{"history":[],"article":{"id":"65a51e28-0cb5-4255-85cd-d9b153b246c5","title":"Elias James Corey","slug":"elias-james-corey","content":":::summary\n![Corey in 2007](https://upload.wikimedia.org/wikipedia/commons/a/a2/E.J.Coreyx240.jpg)\n**Name:** E.J. Corey \n**Image Size:** 240px \n**Birth Name:** Elias James Corey \n**Birth Date:** July 12, 1928 \n**Birth Place:** [Methuen, Massachusetts](https://bliptext.com/articles/methuen-massachusetts), U.S. \n**Alma Mater:** [Massachusetts Institute of Technology](https://bliptext.com/articles/massachusetts-institute-of-technology) ([BS](https://bliptext.com/articles/b-s), [PhD](https://bliptext.com/articles/phd)) \n**Doctoral Advisor:** [John C. Sheehan](https://bliptext.com/articles/john-c-sheehan) \n**Thesis Title:** The synthesis of N,N-diacylamino acids and analogs of penicillin \n**Thesis Year:** 1951 \n**Thesis Url:** http://www.worldcat.org/oclc/30308926 \n**Notable Students:** [Phil Baran](https://bliptext.com/articles/phil-baran) · [Rajender Leleti](https://bliptext.com/articles/rajender-leleti) · [Eric Block](https://bliptext.com/articles/eric-block) · [Dale L. Boger](https://bliptext.com/articles/dale-l-boger) · [Weston T. Borden](https://bliptext.com/articles/weston-t-borden) · [David E. Cane](https://bliptext.com/articles/david-e-cane) · [Rick L. Danheiser](https://bliptext.com/articles/rick-l-danheiser) · [William L. Jorgensen](https://bliptext.com/articles/william-l-jorgensen) · [John Katzenellenbogen](https://bliptext.com/articles/john-katzenellenbogen) · [Alan P. Kozikowski](https://bliptext.com/articles/alan-p-kozikowski) · [Bruce H. Lipshutz](https://bliptext.com/articles/bruce-h-lipshutz) · [David Liu](https://bliptext.com/articles/david-r-liu) · [Gojko Lalic](https://bliptext.com/articles/gojko-lalic) · [Albert Meyers](https://bliptext.com/articles/albert-meyers) · [K. C. Nicolaou](https://bliptext.com/articles/k-c-nicolaou) · [Ryōji Noyori](https://bliptext.com/articles/ry-ji-noyori) · [Gary H. Posner](https://bliptext.com/articles/gary-h-posner) · [Bengt I. Samuelsson](https://bliptext.com/articles/bengt-i-samuelsson) · [Dieter Seebach](https://bliptext.com/articles/dieter-seebach) · [Vinod K. Singh](https://bliptext.com/articles/vinod-k-singh) · [Brian Stoltz](https://bliptext.com/articles/brian-stoltz) · [Hisashi Yamamoto](https://bliptext.com/articles/hisashi-yamamoto) · [Ramakanth Sarabu](https://bliptext.com/articles/ramakanth-sarabu) · [Jin-Quan Yu](https://bliptext.com/articles/jin-quan-yu) \n**Known For:** [Retrosynthetic analysis](https://bliptext.com/articles/retrosynthetic-analysis) · [Synthon](https://bliptext.com/articles/synthon) · [Corey–Bakshi–Shibata catalyst](https://bliptext.com/articles/cbs-catalyst) · [Corey–Chaykovsky reaction](https://bliptext.com/articles/johnson-corey-chaykovsky-reaction) · [Corey–Fuchs reaction](https://bliptext.com/articles/corey-fuchs-reaction) · [Corey–Gilman–Ganem oxidation](https://bliptext.com/articles/corey-gilman-ganem-oxidation) · [Corey–House synthesis](https://bliptext.com/articles/corey-house-synthesis) · [Corey–Itsuno reduction](https://bliptext.com/articles/corey-itsuno-reduction) · [Corey–Kim oxidation](https://bliptext.com/articles/corey-kim-oxidation) · [Corey–Link reaction](https://bliptext.com/articles/corey-link-reaction) · [Corey–Nicolaou macrolactonization](https://bliptext.com/articles/corey-nicolaou-macrolactonization) · [Corey–Peterson olefination](https://bliptext.com/articles/peterson-olefination) · [Corey–Seebach reaction](https://bliptext.com/articles/corey-seebach-reaction) · [Corey–Suggs reagent](https://bliptext.com/articles/pyridinium-chlorochromate) · [Corey–Winter olefin synthesis](https://bliptext.com/articles/corey-winter-olefin-synthesis) · [LHASA](https://bliptext.com/articles/lhasa) \n**Website:** http://chemistry.harvard.edu/people/e-j-corey \n**Field:** [Organic chemistry](https://bliptext.com/articles/organic-chemistry) \n**Work Institutions:** [University of Illinois at Urbana–Champaign](https://bliptext.com/articles/university-of-illinois-at-urbana-champaign) [Harvard University](https://bliptext.com/articles/harvard-university) \n**Prizes:** [ACS Award in Pure Chemistry](https://bliptext.com/articles/acs-award-in-pure-chemistry) (1960) · [Ernest Guenther Award](https://bliptext.com/articles/ernest-guenther-award) (1968) · [Centenary Medal](https://bliptext.com/articles/centenary-medal) (1971) · [Linus Pauling Award](https://bliptext.com/articles/linus-pauling-award) (1973) · [George Ledlie Prize](https://bliptext.com/articles/george-ledlie-prize) (1973) · [Arthur C. Cope Award](https://bliptext.com/articles/arthur-c-cope-award) (1976) · [William H. Nichols Medal](https://bliptext.com/articles/william-h-nichols-medal) (1977) · [Franklin Medal](https://bliptext.com/articles/franklin-medal) (1978) · [Chemical Pioneer Award](https://bliptext.com/articles/chemical-pioneer-award) (1981) · [Lewis S. Rosenstiel Award](https://bliptext.com/articles/lewis-s-rosenstiel-award) (1981) · [Paul Karrer Gold Medal](https://bliptext.com/articles/paul-karrer-gold-medal) (1982) · [Tetrahedron Prize](https://bliptext.com/articles/tetrahedron-prize) (1983) · [Willard Gibbs Award](https://bliptext.com/articles/willard-gibbs-award) (1984) · [Wolf Prize in Chemistry](https://bliptext.com/articles/wolf-prize-in-chemistry) (1986) · [National Medal of Science](https://bliptext.com/articles/national-medal-of-science) (1988) · [Japan Prize](https://bliptext.com/articles/japan-prize) (1989) · [Nobel Prize in Chemistry](https://bliptext.com/articles/nobel-prize-in-chemistry) (1990) · [ForMemRS](https://bliptext.com/articles/fellow-of-the-royal-society) (1998) · [Priestley Medal](https://bliptext.com/articles/priestley-medal) (2004) \n:::\n\n# \n**Elias James Corey** (born July 12, 1928) is an American [organic chemist](https://bliptext.com/articles/organic-chemistry).\nIn 1990, he won the [Nobel Prize in Chemistry](https://bliptext.com/articles/nobel-prize-in-chemistry) \"for his development of the theory and methodology of [organic synthesis](https://bliptext.com/articles/organic-synthesis)\", specifically [retrosynthetic analysis](https://bliptext.com/articles/retrosynthetic-analysis).\nRegarded by many as one of the greatest living chemists, he has developed numerous synthetic [reagents](https://bliptext.com/articles/reagents), methodologies and total syntheses and has advanced the science of organic synthesis considerably.\n\n# Biography\nE.J. Corey (the surname was anglicized from [Levantine Arabic](https://bliptext.com/articles/levantine-arabic) [Khoury](https://bliptext.com/articles/khoury), meaning priest) was born to [Lebanese Greek Orthodox Christian](https://bliptext.com/articles/lebanese-greek-orthodox-christians) immigrants Fatima (née Hasham) and Elias Corey in [Methuen, Massachusetts](https://bliptext.com/articles/methuen-massachusetts), 50 km north of Boston.\nHis mother changed his name from William to \"Elias\" to honor his father, who died eighteen months after Corey's birth.\nHis widowed mother, brother, two sisters, aunt and uncle all lived together in a spacious house, struggling through the [Great Depression](https://bliptext.com/articles/great-depression).\nAs a young boy, Corey was independent and enjoyed sports such as baseball, football, and hiking.\nHe attended a Catholic elementary school and [Lawrence High School](https://bliptext.com/articles/lawrence-high-school-massachusetts) in [Lawrence, Massachusetts](https://bliptext.com/articles/lawrence-massachusetts).\nAt the age of 16 Corey entered [MIT](https://bliptext.com/articles/mit), where he earned both a [bachelor's degree](https://bliptext.com/articles/bachelor-s-degree) in 1948 and a [Ph.D.](https://bliptext.com/articles/doctor-of-philosophy) under Professor [John C. Sheehan](https://bliptext.com/articles/john-c-sheehan) in 1951.\nUpon entering MIT, Corey's only experience with science was in mathematics, and he began his college career pursuing a degree in engineering.\nAfter his first chemistry class in his sophomore year he began rethinking his long-term career plans and graduated with a bachelor's degree in chemistry.\nImmediately thereafter, at the invitation of Professor John C. Sheehan, Corey remained at MIT for his Ph.D. After his graduate career he was offered an appointment at the [University of Illinois at Urbana–Champaign](https://bliptext.com/articles/university-of-illinois-at-urbana-champaign), where he became a full professor of chemistry in 1956 at the age of 27.\nHe was initiated as a member of the Zeta chapter of [Alpha Chi Sigma](https://bliptext.com/articles/alpha-chi-sigma) at the University of Illinois in 1952.\nIn 1959, he moved to [Harvard University](https://bliptext.com/articles/harvard-university), where he is currently an emeritus professor of organic chemistry with an active Corey Group research program.\nHe chose to work in organic chemistry because of \"its intrinsic beauty and its great relevance to human health\".\nHe has also been an advisor to Pfizer for more than 50 years.\nAmong numerous honors, Corey was awarded the [National Medal of Science](https://bliptext.com/articles/national-medal-of-science) in 1988, the [Nobel Prize in Chemistry](https://bliptext.com/articles/nobel-prize-in-chemistry) in 1990, and the [American Chemical Society](https://bliptext.com/articles/american-chemical-society)'s greatest honor, the [Priestley Medal](https://bliptext.com/articles/priestley-medal), in 2004.\n\n# Major contributions\n\n## Reagents\nCorey has developed several new synthetic reagents:

[PCC (pyridinium chlorochromate)](https://bliptext.com/articles/pyridinium-chlorochromate), also referred to as the **Corey-Suggs reagent**, is widely used for the oxidation of [alcohols](https://bliptext.com/articles/alcohol-chemistry) to corresponding [ketones](https://bliptext.com/articles/ketone) and [aldehydes](https://bliptext.com/articles/aldehyde).\nPCC has several advantages over other commercial oxidants.\nAn air-stable yellow solid, it is only slightly hygroscopic.\nUnlike other oxidizing agents, PCC requires only about 1.5 equivalents to complete a single oxidation (scheme 1).\nIn the reaction, the alcohol nucleophilically displaces chlorine from the electropositive [chromium](https://bliptext.com/articles/chromium)(VI) metal.\nThe [chloride](https://bliptext.com/articles/chloride) [anion](https://bliptext.com/articles/anion) then acts as a base to afford the aldehyde product and chromium(IV).\nThe slightly acidic character of PCC makes it useful for cyclization reactions with alcohols and [alkenes](https://bliptext.com/articles/alkene) (Scheme 2).\nThe initial oxidation yields the corresponding aldehyde, which can then undergo a [Prins reaction](https://bliptext.com/articles/prins-reaction) with the neighboring [alkene](https://bliptext.com/articles/alkene).\nAfter elimination and further oxidation, the product is a cyclic [ketone](https://bliptext.com/articles/ketone).\nConversely, powdered [sodium acetate](https://bliptext.com/articles/sodium-acetate) co-reagent inhibits reaction after formation of the aldehyde.\nPCC's oxidatory robustness has also rendered it useful in the realm of total synthesis (Scheme 3).\nThis example illustrates that PCC is capable of performing a Dauben oxidative rearrangement with tertiary alcohols through a [3,3]-sigmatropic rearrangement.\n
t-Butyldimethylsilyl ether (TBS), triisopropylsilyl ether (TIPS), and methoxyethoxymethyl (MEM) are popular alcohol [protecting groups](https://bliptext.com/articles/protecting-group).\nThe development of these protecting groups allowed the synthesis of several [natural products](https://bliptext.com/articles/natural-product) whose [functional groups](https://bliptext.com/articles/functional-group) could not withstand standard chemical transformations.\nAlthough the synthetic community attempts to minimize the use of protecting groups, it is still rare that a published natural-product synthesis omits them entirely.\nSince 1972 the TBS group has become the most popular [silicon](https://bliptext.com/articles/silicon) protecting group (Scheme 4).\nTBS is stable to [chromatography](https://bliptext.com/articles/chromatography) and labile enough to cleave under basic and acidic conditions.\nMore importantly, TBS [ethers](https://bliptext.com/articles/ether) are stable to such carbon nucleophiles as Grignard reagents and enolates.\n[CSA (Camphorsulfonic acid)](https://bliptext.com/articles/camphorsulfonic-acid) selectively removes a primary TBS ether in the presence of TIPS and tertiary TBS ethers.\nOther TBS deprotection methods include acids (also Lewis acids), and [fluorides](https://bliptext.com/articles/fluoride).\nTIPS protecting groups provide increased selectivity of primary over secondary and tertiary alcohol protection.\nTheir ethers are more stable under acidic and basic conditions than TBS ethers, but less labile for deprotection.\nThe most common cleavage reagents employ the same conditions as TBS ether, but longer reaction times.\nUsually TBAF severs TBS ethers, but the hindered TBS ether above survives primary TIPS removal (scheme 5).\nThe MEM protecting group was first described by Corey in 1976.\nThis protecting group is similar in reactivity and stability to other alkoxy methyl ethers under acidic conditions.\nAcidic conditions usually accomplish cleavage of MEM protecting groups, but coordination with metal halides greatly enhances lability (scheme 6).\n
1,3-[Dithianes](https://bliptext.com/articles/dithiane) are a temporary modification of a [carbonyl](https://bliptext.com/articles/carbonyl) group that reverses their reactivity in displacement and addition reactions.\nDithianation introduced [umpolung](https://bliptext.com/articles/umpolung) chemistry, now a key concept in organic synthesis.\nThe formations of dithianes can be accomplished with a Lewis acid (scheme 7) or directly from carbonyl compounds.\nThe pKa of dithianes is approximately 30, allowing deprotonation with an alkyl lithium reagent, typically [n-butyllithium](https://bliptext.com/articles/n-butyllithium).\nThe reaction between dithianes and aldehydes is now known as the [Corey-Seebach reaction](https://bliptext.com/articles/corey-seebach-reaction).\nThe dithiane, once deprotonated, serves as an acyl anion, attacking incoming [electrophiles](https://bliptext.com/articles/electrophile).\nDithiane deprotection, usually with HgO, constructs a ketone product.\n
Corey also commenced detailed studies on cationic polyolefin cyclizations utilized in enzymatic production of [cholesterol](https://bliptext.com/articles/cholesterol) from simpler plant terpenes.\nCorey established the details of the remarkable cyclization process by first studying the biological synthesis of sterols from squalene.

\n# [700px | upload.wikimedia.org/wikipedia/commons/b/b9/PCC///mechanism.png]\n# [reactivity of PCC under acidic conditions | upload.wikimedia.org/wikipedia/commons/2/27/PCC///under///acidic///conditions2.png]\n# [[3,3] rearrangement with PCC | upload.wikimedia.org/wikipedia/commons/8/87/PCC///rearrangement3.png]\n# [500px | upload.wikimedia.org/wikipedia/commons/4/40/TBS///primary///deprotection4.png]\n# [550px | upload.wikimedia.org/wikipedia/commons/f/f8/Primary///TIPS///deprotection5.png]\n# [600px | upload.wikimedia.org/wikipedia/commons/e/e8/MEM///Zn///deprotection6.png]\n# [350px | upload.wikimedia.org/wikipedia/commons/0/0a/Dithiane///formation7.png]\n# [650px | upload.wikimedia.org/wikipedia/commons/a/a1/1%2C2-dithiane///addition8.png]\n\n## Methodology\nSeveral reactions developed in Corey's lab have become commonplace in modern synthetic organic chemistry.\nAt least 302 methods have been developed in the Corey group since 1950.\nSeveral reactions have been named after him:

[Corey-Itsuno reduction](https://bliptext.com/articles/corey-itsuno-reduction), also known as the Corey-Bakshi-Shibata reduction, is an enantioselective reduction of ketones to alcohols through an oxazaborolidine [catalyst](https://bliptext.com/articles/catalysis), with various boranes as the stoichiometric reductant.\nThe Corey group first demonstrated [the catalyst's](https://bliptext.com/articles/cbs-catalyst) synthesis using borane and the chiral amino acid [proline](https://bliptext.com/articles/proline) (scheme 9).\nLater, Corey demonstrated that substituted boranes were easier to prepare and much more stable.\nThe reduction mechanism begins with the oxazoborolidine, only slightly basic at [nitrogen](https://bliptext.com/articles/nitrogen), coordinating to a borane reductant (scheme 10).\nPoor donation from the nitrogen to the boron leaves the Lewis acidity mostly intact, allowing coordination to the ketone substrate.\nThe complexation of the substrate occurs from the most accessible lone pair of the [oxygen](https://bliptext.com/articles/oxygen), restricting rotation around the B-O bond due to the sterically neighboring phenyl group.\nMigration of the hydride from borane to the electrophilic ketone center occurs via a 6-membered ring transition state, leading to a four-membered ring intermediate, ultimately providing the chiral product and regeneration of the catalyst.\nThe reaction has also been of great use to natural products chemists (scheme 11).\nThe synthesis of dysidiolide by Corey and co-workers was achieved via an enantioselective CBS reduction using a borane-dimethylsulfide complex.\n
[Corey-Fuchs alkyne synthesis](https://bliptext.com/articles/corey-fuchs-reaction) is the synthesis of terminal [alkynes](https://bliptext.com/articles/alkyne) through a one-carbon homologation of aldehydes using [triphenylphosphine](https://bliptext.com/articles/triphenylphosphine) and carbon tetrabromide.\nThe mechanism is similar to that of a combined [Wittig reaction](https://bliptext.com/articles/wittig-reaction) and [Appell reaction](https://bliptext.com/articles/appell-reaction).\nReacting a phosphorus ylide formed in situ with the aldehyde substrate yields a dibromoolefin.\nOn treatment with two equivalents of n-butyllithium, lithium halogen exchange and deprotonation yields a lithium acetylide species that undergoes hydrolysis to yield the terminal alkyne product (scheme 12).\nMore recent developments include a modified procedure for one-pot synthesis.\nThis synthetic transformation has been proven successful in the total synthesis (+)-taylorione by W.J. Kerr and co-workers (scheme 13).\n
The [Corey–Kim oxidation](https://bliptext.com/articles/corey-kim-oxidation) was a new conversion of alcohols into corresponding aldehydes and ketones.\nThis combination of N-chlorosuccinimidosulfonium chloride (NCS), dimethylsulfide (DMS), and [triethylamine](https://bliptext.com/articles/triethylamine) (TEA) offers a less toxic alternative to chromium-based oxidations.\nThe Corey-Kim reagent is formed in situ when the succinimide and sulfide react to form a dimethylsuccinimidosulfonium chloride species (scheme 14).\nTriethylamine deprotonates the alkoxysulfonium salt at the α position to afford the oxidized product.\nThe reaction accommodates a wide array of functional groups, but allylic and benzylic alcohols are typically transformed into chlorides instead.\nIts application in synthesis is based on the mild protocol conditions and functional and protecting group compatibility.\nIn the total synthesis of ingenol, Kuwajima and co-workers exploited the Corey-Kim oxidation by selectively oxidizing the less hindered secondary alcohol(scheme 15).\n
[Corey-Winter olefination](https://bliptext.com/articles/corey-winter-olefination) is a stereospecific transformation of 1,2-diols to alkenes involving the diol substrate, thiocarbonyldiimidazole, and excess trialkylphosphite.\nThe exact mechanism is unknown, but has been narrowed down to two possible pathways.\nThe thionocarbonate and trialkylphosphite either form a phosphorus ylide or carbenoid intermediate.\nThe reaction is stereospecific for most substrates unless the product would lead to an exceedingly strained structure, as discovered when Corey et al attempted to form sterically hindered trans alkenes in certain 7-membered rings.\nStereospecfic alkenes are present in several natural products as the method continues to be exploited to yield a series of complex substrates.\nProfessor T.K.M Shing et al used the Corey-Winter olefination reaction to synthesize (+)-Boesenoxide (scheme 16).\n
CBS-type enantioselective [Diels–Alder reaction](https://bliptext.com/articles/diels-alder-reaction) has been developed using a similar scaffold to the enantioselective CBS reduction.\nAfter the development of this reaction the CBS reagent proved to be a very versatile reagent for a series of several powerful synthetic transformations.\nThe use of a chiral Lewis acid such as the CBS catalyst includes a broad range of unsaturated [enones](https://bliptext.com/articles/enone) substrates.\nThe reaction likely proceeds via a highly organized 6-membered ring pre-transition state to deliver highly enantio-enriched products (scheme 17).\nThis transition state likely occurs because of favorable pi-stacking with the phenyl substituent.\nThe enantioselectivity of the process is facilitated from the diene approaching the dienophile from the opposite face of the phenyl substituent.\nThe Diels-Alder reaction is one of the most powerful transformations in synthetic chemistry.\nThe synthesis of natural products using the Diels-Alder reaction as a transform has been applied especially to the formation of six-membered rings(scheme 18).\n
[Corey-Nicolaou macrolactonization](https://bliptext.com/articles/corey-nicolaou-macrolactonization) provides the first method for preparing medium-to-large-size [lactones](https://bliptext.com/articles/lactone).\nPreviously, intermolecular outcompeted intramolecular lactonization even at low concentrations.\nOne big advantage of this reaction is that it is performed under neutral conditions allowing the presence of acid and base-labile functional groups.\nAs of 2016, rings of 7–44 members have been successfully synthesized using this method.\nThe reaction occurs in the presence of 2,2'-dipyridyl disulfide and triphenylphosphine with reflux of a nonpolar solvent such as [benzene](https://bliptext.com/articles/benzene).\nThe mechanism begins with formation of the 2-pyridinethiol ester (scheme 19).\nProton-transfer provides a dipolar intermediate in which the alkoxide [nucleophile](https://bliptext.com/articles/nucleophile) attacks the electrophilic carbonyl center, providing a tetrahedral intermediate that yields the macrolactone product.\nOne of the first examples of this protocol was applied to the total synthesis of [zearalenone](https://bliptext.com/articles/zearalenone) (scheme 20).\n
The [Johnson-Corey-Chaykovsky reaction](https://bliptext.com/articles/johnson-corey-chaykovsky-reaction) synthesizes [epoxides](https://bliptext.com/articles/epoxide) and [cyclopropanes](https://bliptext.com/articles/cyclopropane).\nThe reaction forms a sulfur ylide in situ that reacts with enones, ketones, aldehydes, and [imines](https://bliptext.com/articles/imine) to form corresponding epoxides, cyclopropanes, and [aziridines](https://bliptext.com/articles/aziridines).\nTwo sulfur ylide variants have been employed that give different chemeoselective products (scheme 21).The dimethylsulfoxonium methylide provides epoxides from ketones, but yields the cyclopropanes when enones are employed.\nDimethylsulfonium methylide transforms ketones and enones to the corresponding epoxides.\nDimethylsulfonium methylide is much more reactive and less stable than dimethylsulfoxonium methylide, so it is generated at low temperatures.\n
Based on their reactivity, another distinct advantage of these two variants is that kinetically they provide a difference in diastereoselectivity.\nThe reaction is very well established, and enantioselective variants (catalytic and stoichiometric) have also been achieved.\nFrom a retrosynthetic analysis standpoint, this reaction provides a reasonable alternative to conventional epoxidation reactions with alkenes (scheme 22).\nDanishefsky utilized this methodology for the synthesis of taxol.\nDiastereoselectivity is established by 1,3 interactions in the transition state required for epoxide closure.\n

\n# [600px | upload.wikimedia.org/wikipedia/commons/e/e3/CBS///formation9.png]\n# [400px | upload.wikimedia.org/wikipedia/commons/0/03/CBS///mechanism10.png]\n# [550px | upload.wikimedia.org/wikipedia/commons/4/45/CBS///total///synthesis11.png]\n# [550px | upload.wikimedia.org/wikipedia/commons/c/cc/Corey-fuch///reaction12.png]\n# [550px | upload.wikimedia.org/wikipedia/commons/b/ba/Corey-fuch///total///synthesis13.png]\n# [550px | upload.wikimedia.org/wikipedia/commons/c/c0/Corey///kim///ox14.png]\n# [550px | upload.wikimedia.org/wikipedia/commons/2/2b/Corey///kim///ox///synthesis///example15.png]\n# [total synthesis example of corey winter olefination | upload.wikimedia.org/wikipedia/commons/7/7b/Corey-winter///olefination///example16.png]\n# [enantioslective diels-alder transition state | upload.wikimedia.org/wikipedia/commons/e/e6/Diels///alder///TS17.png]\n# [enantioslective diels-alder in total synthesis | upload.wikimedia.org/wikipedia/commons/a/ac/Diels///alder///example///enantioselective18.png]\n# [mechanism of Corey-Nicolaou macrolactonization | upload.wikimedia.org/wikipedia/commons/9/93/Corey-nicolaou///macrolactonization19.png]\n# [macrolactonization total synthesis example | upload.wikimedia.org/wikipedia/commons/8/80/Macrolactonization///example20.png]\n# [corey-chaykovsky selectivity | upload.wikimedia.org/wikipedia/commons/7/70/Corey-chakovsky///reaction21.png]\n# [corey-chaykovsky total synthesis example | upload.wikimedia.org/wikipedia/commons/2/21/Corey-chakovsky///example22.png]\n\n## Total syntheses\nE. J. Corey and his research group have completed many [total syntheses](https://bliptext.com/articles/total-synthesis).\nAt least 265 compounds have been synthesized in the Corey group since 1950.\nHis 1969 total syntheses of several [prostaglandins](https://bliptext.com/articles/prostaglandin) are considered classics.\nSpecifically the synthesis of Prostaglandin F2α presents several challenges.\nThe presence of both cis and trans olefins as well as five asymmetric carbon atoms renders the molecule a desirable challenge for organic chemists.\nCorey's retrosynthetic analysis outlines a few key disconnections that lead to simplified precursors (scheme 23).\nMolecular simplification began first by disconnecting both carbon chains with a Wittig reaction and Horner-Wadsworth Emmons modification.\nThe Wittig reaction affords the cis product, while the Horner-Wadsworth Emmons produces the trans olefin.\nThe published synthesis reveals a 1:1 diastereomeric mixture of the carbonyl reduction using zinc borohydride.\nHowever, years later Corey and co-workers established the CBS reduction.\nOne of the examples that exemplified this protocol was an intermediate in the prostaglandin synthesis revealing a 9:1 mixture of the desired diastereomer (scheme 24).\nThe iodolactonization transform affords an allylic alcohol leading to a key Baeyer-Villiger intermediate.\nThis oxidation regioselectively inserts an oxygen atom between the ketone and the most electron-rich site.\nThe pivotal intermediate leads to a straightforward conversion to the Diels-Alder structural goal, which provides the carbon framework for the functionalized cyclopentane ring.\nLater Corey developed an asymmetric Diels-Alder reaction employing a chiral oxazoborolidine, greatly simplifying the synthetic route to the prostaglandins.\nOther notable syntheses:\n# [600px | upload.wikimedia.org/wikipedia/commons/e/eb/Prostaglandin///retro23.png]\n# [500px | upload.wikimedia.org/wikipedia/commons/5/5f/Prostoglandin///CBS24.png]\n\n## Computer programs\nCorey and his research group created [LHASA](https://bliptext.com/articles/lhasa), a program that uses [artificial intelligence](https://bliptext.com/articles/artificial-intelligence) to discover sequences of reaction which may lead to total synthesis.\nThe program was one of the first to use a graphical interface to input and display chemical structures.\n\n## Publications\nE.J. Corey has more than 1100 publications.\nIn 2002, the American Chemical Society (ACS) recognized him as the \"Most Cited Author in Chemistry\".\nIn 2007, he received the first ACS Publications Division \"Cycle of Excellence High Impact Contributor Award\" and was ranked the number one chemist in terms of research impact by the Hirsch Index ([h-index](https://bliptext.com/articles/h-index)).\nHis books include:\n\n# Altom suicide\n[Jason Altom](https://bliptext.com/articles/jason-altom), one of Corey's students, committed suicide in 1998.\nAltom's suicide caused controversy because he explicitly blamed Corey, his research advisor, for his suicide.\nAltom cited in his 1998 farewell note \"abusive research supervisors\" as one reason for taking his life.\nAltom's suicide note also contained explicit instructions on how to reform the relationship between students and their supervisors.\nAltom was the third member of Corey's lab to commit suicide since 1980.\nCorey was reportedly devastated and bewildered by his student's death.\nCorey said, \"That letter doesn't make sense. At the end, Jason must have been delusional or irrational in the extreme.\"\nCorey also claimed he never questioned Altom's intellectual contributions.\n\"I did my best to guide Jason as a mountain guide would to guide someone climbing a mountain. I did my best every step of the way,\" Corey states.\n\"My conscience is clear. Everything Jason did came out of our partnership. We never had the slightest disagreement.\"\nThe [American Foundation for Suicide Prevention](https://bliptext.com/articles/american-foundation-for-suicide-prevention) (AFSP) cited [The New York Times](https://bliptext.com/articles/the-new-york-times) article on Altom's suicide as an example of problematic reporting, arguing that Altom presented warning signs of depression and suicidal ideation and that the article had scapegoated Corey despite a lack of secondary evidence that the advisor's behavior had contributed to Altom's distress.\nAccording to [The Boston Globe](https://bliptext.com/articles/the-boston-globe), students and professors said Altom actually retained Corey's support.\n\n# Corey Group members\nAs of 2010, approximately 700 people have been Corey Group members including notable students [Eric Block](https://bliptext.com/articles/eric-block),\n[Dale L. Boger](https://bliptext.com/articles/dale-l-boger), [Weston T. Borden](https://bliptext.com/articles/weston-t-borden), [David E. Cane](https://bliptext.com/articles/david-e-cane), [Rick L. Danheiser](https://bliptext.com/articles/rick-l-danheiser), [William L. Jorgensen](https://bliptext.com/articles/william-l-jorgensen), [John Katzenellenbogen](https://bliptext.com/articles/john-katzenellenbogen), [Alan P. Kozikowski](https://bliptext.com/articles/alan-p-kozikowski), [Bruce H. Lipshutz](https://bliptext.com/articles/bruce-h-lipshutz), [David R. Liu](https://bliptext.com/articles/david-r-liu), [Albert Meyers](https://bliptext.com/articles/albert-meyers), [K. C. Nicolaou](https://bliptext.com/articles/k-c-nicolaou), [Ryōji Noyori](https://bliptext.com/articles/ry-ji-noyori), [Gary H. Posner](https://bliptext.com/articles/gary-h-posner), [Bengt I. Samuelsson](https://bliptext.com/articles/bengt-i-samuelsson), [Dieter Seebach](https://bliptext.com/articles/dieter-seebach), [Vinod K. Singh](https://bliptext.com/articles/vinod-k-singh), [Brian Stoltz](https://bliptext.com/articles/brian-stoltz), [Alice Ting](https://bliptext.com/articles/alice-y-ting), [Hisashi Yamamoto](https://bliptext.com/articles/hisashi-yamamoto), [Phil Baran](https://bliptext.com/articles/phil-baran) and [Jin-Quan Yu](https://bliptext.com/articles/jin-quan-yu).\nA database of 580 former members and their current affiliation was developed for Corey's 80th birthday in July 2008.\n\n# Woodward–Hoffmann rules\nWhen awarded the Priestley Medal in 2004, E. J. Corey created a controversy with his claim to have inspired [Robert Burns Woodward](https://bliptext.com/articles/robert-burns-woodward) prior to the development of the [Woodward–Hoffmann rules](https://bliptext.com/articles/woodward-hoffmann-rules).\nCorey wrote:\n\"On May 4, 1964, I suggested to my colleague R. B. Woodward a simple explanation involving the symmetry of the perturbed (HOMO) molecular orbitals for the stereoselective cyclobutene → 1,3-butadiene and 1,3,5-hexatriene → cyclohexadiene conversions that provided the basis for the further development of these ideas into what became known as the Woodward–Hoffmann rules.\"\nThis was Corey's first public statement on his claim that starting on May 5, 1964, Woodward put forth Corey's explanation as his own thought with no mention of Corey and the conversation of May 4.\nCorey had discussed his claim privately with Hoffmann and close colleagues since 1964.\nCorey mentions that he made the Priestley statement \"so the historical record would be correct\".\nCorey's claim and contribution were publicly rebutted by [Roald Hoffmann](https://bliptext.com/articles/roald-hoffmann) in the journal [Angewandte Chemie](https://bliptext.com/articles/angewandte-chemie).\nIn the rebuttal, Hoffmann states that he asked Corey over the course of their long discussion of the matter why Corey did not make the issue public.\nCorey responded that he thought such a public disagreement would hurt Harvard and that he would not \"consider doing anything against Harvard, to which I was and am so devoted.\"\nCorey also hoped that Woodward himself would correct the historical record \"as he grew older, more considerate, and more sensitive to his own conscience.\"\nWoodward died suddenly of a heart attack in his sleep in 1979.\n\n# Awards and honors\nE.J. Corey has received more than 40 major awards including the [Linus Pauling Award](https://bliptext.com/articles/linus-pauling-award) (1973), [Franklin Medal](https://bliptext.com/articles/franklin-medal) (1978), [Tetrahedron Prize](https://bliptext.com/articles/tetrahedron-prize) (1983), [Wolf Prize in Chemistry](https://bliptext.com/articles/wolf-prize-in-chemistry) (1986), [National Medal of Science](https://bliptext.com/articles/national-medal-of-science) (1988), [Japan Prize](https://bliptext.com/articles/japan-prize) (1989), [Nobel Prize in Chemistry](https://bliptext.com/articles/nobel-prize-in-chemistry) (1990), Golden Plate Award of the [American Academy of Achievement](https://bliptext.com/articles/academy-of-achievement) (1991), Roger Adams Award (1993), and the [Priestley Medal](https://bliptext.com/articles/priestley-medal) (2004).\nHe was inducted into the [Alpha Chi Sigma](https://bliptext.com/articles/alpha-chi-sigma) Hall of Fame in 1998.\nAs of 2008, he has been awarded 19 honorary degrees from universities around the world including [Oxford University](https://bliptext.com/articles/oxford-university) (UK), [Cambridge University](https://bliptext.com/articles/cambridge-university) (UK), and [National Chung Cheng University](https://bliptext.com/articles/national-chung-cheng-university).\nIn 2013, the E.J. Corey Institute of Biomedical Research (CIBR) opened in Jiangyin, Jiangsu Province, China.\nCorey was elected a [Foreign Member of the Royal Society (ForMemRS) in 1998](https://bliptext.com/articles/list-of-fellows-of-the-royal-society-elected-in-1998).","current_revision":null,"created_by":"kACnuQmH5k9Nr5VNVEpVeg7XpvUmMctD","created_at":"2025-01-25T18:31:32.017Z","updated_at":"2025-01-25T18:31:32.017Z","search_vector":"'corey':3 'elia':1 'jame':2","search_content":" \n \n**Name:** E.J. Corey \n**Image Size:** 240px \n**Birth Name:** Elias James Corey \n**Birth Date:** July 12, 1928 \n**Birth Place:** [Methuen, Massachusetts](https://bliptext.com/articles/methuen-massachusetts), U.S. \n**Alma Mater:** [Massachusetts Institute of Technology](https://bliptext.com/articles/massachusetts-institute-of-technology) ([BS](https://bliptext.com/articles/b-s), [PhD](https://bliptext.com/articles/phd)) \n**Doctoral Advisor:** [John C. Sheehan](https://bliptext.com/articles/john-c-sheehan) \n**Thesis Title:** The synthesis of N,N-diacylamino acids and analogs of penicillin \n**Thesis Year:** 1951 \n**Thesis Url:** http://www.worldcat.org/oclc/30308926 \n**Notable Students:** [Phil Baran](https://bliptext.com/articles/phil-baran) · [Rajender Leleti](https://bliptext.com/articles/rajender-leleti) · [Eric Block](https://bliptext.com/articles/eric-block) · [Dale L. Boger](https://bliptext.com/articles/dale-l-boger) · [Weston T. Borden](https://bliptext.com/articles/weston-t-borden) · [David E. Cane](https://bliptext.com/articles/david-e-cane) · [Rick L. Danheiser](https://bliptext.com/articles/rick-l-danheiser) · [William L. Jorgensen](https://bliptext.com/articles/william-l-jorgensen) · [John Katzenellenbogen](https://bliptext.com/articles/john-katzenellenbogen) · [Alan P. Kozikowski](https://bliptext.com/articles/alan-p-kozikowski) · [Bruce H. Lipshutz](https://bliptext.com/articles/bruce-h-lipshutz) · [David Liu](https://bliptext.com/articles/david-r-liu) · [Gojko Lalic](https://bliptext.com/articles/gojko-lalic) · [Albert Meyers](https://bliptext.com/articles/albert-meyers) · [K. C. Nicolaou](https://bliptext.com/articles/k-c-nicolaou) · [Ryōji Noyori](https://bliptext.com/articles/ry-ji-noyori) · [Gary H. Posner](https://bliptext.com/articles/gary-h-posner) · [Bengt I. Samuelsson](https://bliptext.com/articles/bengt-i-samuelsson) · [Dieter Seebach](https://bliptext.com/articles/dieter-seebach) · [Vinod K. Singh](https://bliptext.com/articles/vinod-k-singh) · [Brian Stoltz](https://bliptext.com/articles/brian-stoltz) · [Hisashi Yamamoto](https://bliptext.com/articles/hisashi-yamamoto) · [Ramakanth Sarabu](https://bliptext.com/articles/ramakanth-sarabu) · [Jin-Quan Yu](https://bliptext.com/articles/jin-quan-yu) \n**Known For:** [Retrosynthetic analysis](https://bliptext.com/articles/retrosynthetic-analysis) · [Synthon](https://bliptext.com/articles/synthon) · [Corey–Bakshi–Shibata catalyst](https://bliptext.com/articles/cbs-catalyst) · [Corey–Chaykovsky reaction](https://bliptext.com/articles/johnson-corey-chaykovsky-reaction) · [Corey–Fuchs reaction](https://bliptext.com/articles/corey-fuchs-reaction) · [Corey–Gilman–Ganem oxidation](https://bliptext.com/articles/corey-gilman-ganem-oxidation) · [Corey–House synthesis](https://bliptext.com/articles/corey-house-synthesis) · [Corey–Itsuno reduction](https://bliptext.com/articles/corey-itsuno-reduction) · [Corey–Kim oxidation](https://bliptext.com/articles/corey-kim-oxidation) · [Corey–Link reaction](https://bliptext.com/articles/corey-link-reaction) · [Corey–Nicolaou macrolactonization](https://bliptext.com/articles/corey-nicolaou-macrolactonization) · [Corey–Peterson olefination](https://bliptext.com/articles/peterson-olefination) · [Corey–Seebach reaction](https://bliptext.com/articles/corey-seebach-reaction) · [Corey–Suggs reagent](https://bliptext.com/articles/pyridinium-chlorochromate) · [Corey–Winter olefin synthesis](https://bliptext.com/articles/corey-winter-olefin-synthesis) · [LHASA](https://bliptext.com/articles/lhasa) \n**Website:** http://chemistry.harvard.edu/people/e-j-corey \n**Field:** [Organic chemistry](https://bliptext.com/articles/organic-chemistry) \n**Work Institutions:** [University of Illinois at Urbana–Champaign](https://bliptext.com/articles/university-of-illinois-at-urbana-champaign) [Harvard University](https://bliptext.com/articles/harvard-university) \n**Prizes:** [ACS Award in Pure Chemistry](https://bliptext.com/articles/acs-award-in-pure-chemistry) (1960) · [Ernest Guenther Award](https://bliptext.com/articles/ernest-guenther-award) (1968) · [Centenary Medal](https://bliptext.com/articles/centenary-medal) (1971) · [Linus Pauling Award](https://bliptext.com/articles/linus-pauling-award) (1973) · [George Ledlie Prize](https://bliptext.com/articles/george-ledlie-prize) (1973) · [Arthur C. Cope Award](https://bliptext.com/articles/arthur-c-cope-award) (1976) · [William H. Nichols Medal](https://bliptext.com/articles/william-h-nichols-medal) (1977) · [Franklin Medal](https://bliptext.com/articles/franklin-medal) (1978) · [Chemical Pioneer Award](https://bliptext.com/articles/chemical-pioneer-award) (1981) · [Lewis S. Rosenstiel Award](https://bliptext.com/articles/lewis-s-rosenstiel-award) (1981) · [Paul Karrer Gold Medal](https://bliptext.com/articles/paul-karrer-gold-medal) (1982) · [Tetrahedron Prize](https://bliptext.com/articles/tetrahedron-prize) (1983) · [Willard Gibbs Award](https://bliptext.com/articles/willard-gibbs-award) (1984) · [Wolf Prize in Chemistry](https://bliptext.com/articles/wolf-prize-in-chemistry) (1986) · [National Medal of Science](https://bliptext.com/articles/national-medal-of-science) (1988) · [Japan Prize](https://bliptext.com/articles/japan-prize) (1989) · [Nobel Prize in Chemistry](https://bliptext.com/articles/nobel-prize-in-chemistry) (1990) · [ForMemRS](https://bliptext.com/articles/fellow-of-the-royal-society) (1998) · [Priestley Medal](https://bliptext.com/articles/priestley-medal) (2004) \n \n\n# \n**Elias James Corey** (born July 12, 1928) is an American [organic chemist](https://bliptext.com/articles/organic-chemistry).\nIn 1990, he won the [Nobel Prize in Chemistry](https://bliptext.com/articles/nobel-prize-in-chemistry) \"for his development of the theory and methodology of [organic synthesis](https://bliptext.com/articles/organic-synthesis)\", specifically [retrosynthetic analysis](https://bliptext.com/articles/retrosynthetic-analysis).\nRegarded by many as one of the greatest living chemists, he has developed numerous synthetic [reagents](https://bliptext.com/articles/reagents), methodologies and total syntheses and has advanced the science of organic synthesis considerably.\n\n# Biography\nE.J. Corey (the surname was anglicized from [Levantine Arabic](https://bliptext.com/articles/levantine-arabic) [Khoury](https://bliptext.com/articles/khoury), meaning priest) was born to [Lebanese Greek Orthodox Christian](https://bliptext.com/articles/lebanese-greek-orthodox-christians) immigrants Fatima (née Hasham) and Elias Corey in [Methuen, Massachusetts](https://bliptext.com/articles/methuen-massachusetts), 50 km north of Boston.\nHis mother changed his name from William to \"Elias\" to honor his father, who died eighteen months after Corey's birth.\nHis widowed mother, brother, two sisters, aunt and uncle all lived together in a spacious house, struggling through the [Great Depression](https://bliptext.com/articles/great-depression).\nAs a young boy, Corey was independent and enjoyed sports such as baseball, football, and hiking.\nHe attended a Catholic elementary school and [Lawrence High School](https://bliptext.com/articles/lawrence-high-school-massachusetts) in [Lawrence, Massachusetts](https://bliptext.com/articles/lawrence-massachusetts).\nAt the age of 16 Corey entered [MIT](https://bliptext.com/articles/mit), where he earned both a [bachelor's degree](https://bliptext.com/articles/bachelor-s-degree) in 1948 and a [Ph.D.](https://bliptext.com/articles/doctor-of-philosophy) under Professor [John C. Sheehan](https://bliptext.com/articles/john-c-sheehan) in 1951.\nUpon entering MIT, Corey's only experience with science was in mathematics, and he began his college career pursuing a degree in engineering.\nAfter his first chemistry class in his sophomore year he began rethinking his long-term career plans and graduated with a bachelor's degree in chemistry.\nImmediately thereafter, at the invitation of Professor John C. Sheehan, Corey remained at MIT for his Ph.D. After his graduate career he was offered an appointment at the [University of Illinois at Urbana–Champaign](https://bliptext.com/articles/university-of-illinois-at-urbana-champaign), where he became a full professor of chemistry in 1956 at the age of 27.\nHe was initiated as a member of the Zeta chapter of [Alpha Chi Sigma](https://bliptext.com/articles/alpha-chi-sigma) at the University of Illinois in 1952.\nIn 1959, he moved to [Harvard University](https://bliptext.com/articles/harvard-university), where he is currently an emeritus professor of organic chemistry with an active Corey Group research program.\nHe chose to work in organic chemistry because of \"its intrinsic beauty and its great relevance to human health\".\nHe has also been an advisor to Pfizer for more than 50 years.\nAmong numerous honors, Corey was awarded the [National Medal of Science](https://bliptext.com/articles/national-medal-of-science) in 1988, the [Nobel Prize in Chemistry](https://bliptext.com/articles/nobel-prize-in-chemistry) in 1990, and the [American Chemical Society](https://bliptext.com/articles/american-chemical-society)'s greatest honor, the [Priestley Medal](https://bliptext.com/articles/priestley-medal), in 2004.\n\n# Major contributions\n\n## Reagents\nCorey has developed several new synthetic reagents: \n [PCC (pyridinium chlorochromate)](https://bliptext.com/articles/pyridinium-chlorochromate), also referred to as the **Corey-Suggs reagent**, is widely used for the oxidation of [alcohols](https://bliptext.com/articles/alcohol-chemistry) to corresponding [ketones](https://bliptext.com/articles/ketone) and [aldehydes](https://bliptext.com/articles/aldehyde).\nPCC has several advantages over other commercial oxidants.\nAn air-stable yellow solid, it is only slightly hygroscopic.\nUnlike other oxidizing agents, PCC requires only about 1.5 equivalents to complete a single oxidation (scheme 1).\nIn the reaction, the alcohol nucleophilically displaces chlorine from the electropositive [chromium](https://bliptext.com/articles/chromium)(VI) metal.\nThe [chloride](https://bliptext.com/articles/chloride) [anion](https://bliptext.com/articles/anion) then acts as a base to afford the aldehyde product and chromium(IV).\nThe slightly acidic character of PCC makes it useful for cyclization reactions with alcohols and [alkenes](https://bliptext.com/articles/alkene) (Scheme 2).\nThe initial oxidation yields the corresponding aldehyde, which can then undergo a [Prins reaction](https://bliptext.com/articles/prins-reaction) with the neighboring [alkene](https://bliptext.com/articles/alkene).\nAfter elimination and further oxidation, the product is a cyclic [ketone](https://bliptext.com/articles/ketone).\nConversely, powdered [sodium acetate](https://bliptext.com/articles/sodium-acetate) co-reagent inhibits reaction after formation of the aldehyde.\nPCC's oxidatory robustness has also rendered it useful in the realm of total synthesis (Scheme 3).\nThis example illustrates that PCC is capable of performing a Dauben oxidative rearrangement with tertiary alcohols through a [3,3]-sigmatropic rearrangement.\n \n t-Butyldimethylsilyl ether (TBS), triisopropylsilyl ether (TIPS), and methoxyethoxymethyl (MEM) are popular alcohol [protecting groups](https://bliptext.com/articles/protecting-group).\nThe development of these protecting groups allowed the synthesis of several [natural products](https://bliptext.com/articles/natural-product) whose [functional groups](https://bliptext.com/articles/functional-group) could not withstand standard chemical transformations.\nAlthough the synthetic community attempts to minimize the use of protecting groups, it is still rare that a published natural-product synthesis omits them entirely.\nSince 1972 the TBS group has become the most popular [silicon](https://bliptext.com/articles/silicon) protecting group (Scheme 4).\nTBS is stable to [chromatography](https://bliptext.com/articles/chromatography) and labile enough to cleave under basic and acidic conditions.\nMore importantly, TBS [ethers](https://bliptext.com/articles/ether) are stable to such carbon nucleophiles as Grignard reagents and enolates.\n[CSA (Camphorsulfonic acid)](https://bliptext.com/articles/camphorsulfonic-acid) selectively removes a primary TBS ether in the presence of TIPS and tertiary TBS ethers.\nOther TBS deprotection methods include acids (also Lewis acids), and [fluorides](https://bliptext.com/articles/fluoride).\nTIPS protecting groups provide increased selectivity of primary over secondary and tertiary alcohol protection.\nTheir ethers are more stable under acidic and basic conditions than TBS ethers, but less labile for deprotection.\nThe most common cleavage reagents employ the same conditions as TBS ether, but longer reaction times.\nUsually TBAF severs TBS ethers, but the hindered TBS ether above survives primary TIPS removal (scheme 5).\nThe MEM protecting group was first described by Corey in 1976.\nThis protecting group is similar in reactivity and stability to other alkoxy methyl ethers under acidic conditions.\nAcidic conditions usually accomplish cleavage of MEM protecting groups, but coordination with metal halides greatly enhances lability (scheme 6).\n \n 1,3-[Dithianes](https://bliptext.com/articles/dithiane) are a temporary modification of a [carbonyl](https://bliptext.com/articles/carbonyl) group that reverses their reactivity in displacement and addition reactions.\nDithianation introduced [umpolung](https://bliptext.com/articles/umpolung) chemistry, now a key concept in organic synthesis.\nThe formations of dithianes can be accomplished with a Lewis acid (scheme 7) or directly from carbonyl compounds.\nThe pKa of dithianes is approximately 30, allowing deprotonation with an alkyl lithium reagent, typically [n-butyllithium](https://bliptext.com/articles/n-butyllithium).\nThe reaction between dithianes and aldehydes is now known as the [Corey-Seebach reaction](https://bliptext.com/articles/corey-seebach-reaction).\nThe dithiane, once deprotonated, serves as an acyl anion, attacking incoming [electrophiles](https://bliptext.com/articles/electrophile).\nDithiane deprotection, usually with HgO, constructs a ketone product.\n \n Corey also commenced detailed studies on cationic polyolefin cyclizations utilized in enzymatic production of [cholesterol](https://bliptext.com/articles/cholesterol) from simpler plant terpenes.\nCorey established the details of the remarkable cyclization process by first studying the biological synthesis of sterols from squalene. \n \n# [700px | upload.wikimedia.org/wikipedia/commons/b/b9/PCC///mechanism.png]\n# [reactivity of PCC under acidic conditions | upload.wikimedia.org/wikipedia/commons/2/27/PCC///under///acidic///conditions2.png]\n# [[3,3] rearrangement with PCC | upload.wikimedia.org/wikipedia/commons/8/87/PCC///rearrangement3.png]\n# [500px | upload.wikimedia.org/wikipedia/commons/4/40/TBS///primary///deprotection4.png]\n# [550px | upload.wikimedia.org/wikipedia/commons/f/f8/Primary///TIPS///deprotection5.png]\n# [600px | upload.wikimedia.org/wikipedia/commons/e/e8/MEM///Zn///deprotection6.png]\n# [350px | upload.wikimedia.org/wikipedia/commons/0/0a/Dithiane///formation7.png]\n# [650px | upload.wikimedia.org/wikipedia/commons/a/a1/1%2C2-dithiane///addition8.png]\n\n## Methodology\nSeveral reactions developed in Corey's lab have become commonplace in modern synthetic organic chemistry.\nAt least 302 methods have been developed in the Corey group since 1950.\nSeveral reactions have been named after him: \n [Corey-Itsuno reduction](https://bliptext.com/articles/corey-itsuno-reduction), also known as the Corey-Bakshi-Shibata reduction, is an enantioselective reduction of ketones to alcohols through an oxazaborolidine [catalyst](https://bliptext.com/articles/catalysis), with various boranes as the stoichiometric reductant.\nThe Corey group first demonstrated [the catalyst's](https://bliptext.com/articles/cbs-catalyst) synthesis using borane and the chiral amino acid [proline](https://bliptext.com/articles/proline) (scheme 9).\nLater, Corey demonstrated that substituted boranes were easier to prepare and much more stable.\nThe reduction mechanism begins with the oxazoborolidine, only slightly basic at [nitrogen](https://bliptext.com/articles/nitrogen), coordinating to a borane reductant (scheme 10).\nPoor donation from the nitrogen to the boron leaves the Lewis acidity mostly intact, allowing coordination to the ketone substrate.\nThe complexation of the substrate occurs from the most accessible lone pair of the [oxygen](https://bliptext.com/articles/oxygen), restricting rotation around the B-O bond due to the sterically neighboring phenyl group.\nMigration of the hydride from borane to the electrophilic ketone center occurs via a 6-membered ring transition state, leading to a four-membered ring intermediate, ultimately providing the chiral product and regeneration of the catalyst.\nThe reaction has also been of great use to natural products chemists (scheme 11).\nThe synthesis of dysidiolide by Corey and co-workers was achieved via an enantioselective CBS reduction using a borane-dimethylsulfide complex.\n \n [Corey-Fuchs alkyne synthesis](https://bliptext.com/articles/corey-fuchs-reaction) is the synthesis of terminal [alkynes](https://bliptext.com/articles/alkyne) through a one-carbon homologation of aldehydes using [triphenylphosphine](https://bliptext.com/articles/triphenylphosphine) and carbon tetrabromide.\nThe mechanism is similar to that of a combined [Wittig reaction](https://bliptext.com/articles/wittig-reaction) and [Appell reaction](https://bliptext.com/articles/appell-reaction).\nReacting a phosphorus ylide formed in situ with the aldehyde substrate yields a dibromoolefin.\nOn treatment with two equivalents of n-butyllithium, lithium halogen exchange and deprotonation yields a lithium acetylide species that undergoes hydrolysis to yield the terminal alkyne product (scheme 12).\nMore recent developments include a modified procedure for one-pot synthesis.\nThis synthetic transformation has been proven successful in the total synthesis (+)-taylorione by W.J. Kerr and co-workers (scheme 13).\n \n The [Corey–Kim oxidation](https://bliptext.com/articles/corey-kim-oxidation) was a new conversion of alcohols into corresponding aldehydes and ketones.\nThis combination of N-chlorosuccinimidosulfonium chloride (NCS), dimethylsulfide (DMS), and [triethylamine](https://bliptext.com/articles/triethylamine) (TEA) offers a less toxic alternative to chromium-based oxidations.\nThe Corey-Kim reagent is formed in situ when the succinimide and sulfide react to form a dimethylsuccinimidosulfonium chloride species (scheme 14).\nTriethylamine deprotonates the alkoxysulfonium salt at the α position to afford the oxidized product.\nThe reaction accommodates a wide array of functional groups, but allylic and benzylic alcohols are typically transformed into chlorides instead.\nIts application in synthesis is based on the mild protocol conditions and functional and protecting group compatibility.\nIn the total synthesis of ingenol, Kuwajima and co-workers exploited the Corey-Kim oxidation by selectively oxidizing the less hindered secondary alcohol(scheme 15).\n \n [Corey-Winter olefination](https://bliptext.com/articles/corey-winter-olefination) is a stereospecific transformation of 1,2-diols to alkenes involving the diol substrate, thiocarbonyldiimidazole, and excess trialkylphosphite.\nThe exact mechanism is unknown, but has been narrowed down to two possible pathways.\nThe thionocarbonate and trialkylphosphite either form a phosphorus ylide or carbenoid intermediate.\nThe reaction is stereospecific for most substrates unless the product would lead to an exceedingly strained structure, as discovered when Corey et al attempted to form sterically hindered trans alkenes in certain 7-membered rings.\nStereospecfic alkenes are present in several natural products as the method continues to be exploited to yield a series of complex substrates.\nProfessor T.K.M Shing et al used the Corey-Winter olefination reaction to synthesize (+)-Boesenoxide (scheme 16).\n \n CBS-type enantioselective [Diels–Alder reaction](https://bliptext.com/articles/diels-alder-reaction) has been developed using a similar scaffold to the enantioselective CBS reduction.\nAfter the development of this reaction the CBS reagent proved to be a very versatile reagent for a series of several powerful synthetic transformations.\nThe use of a chiral Lewis acid such as the CBS catalyst includes a broad range of unsaturated [enones](https://bliptext.com/articles/enone) substrates.\nThe reaction likely proceeds via a highly organized 6-membered ring pre-transition state to deliver highly enantio-enriched products (scheme 17).\nThis transition state likely occurs because of favorable pi-stacking with the phenyl substituent.\nThe enantioselectivity of the process is facilitated from the diene approaching the dienophile from the opposite face of the phenyl substituent.\nThe Diels-Alder reaction is one of the most powerful transformations in synthetic chemistry.\nThe synthesis of natural products using the Diels-Alder reaction as a transform has been applied especially to the formation of six-membered rings(scheme 18).\n \n [Corey-Nicolaou macrolactonization](https://bliptext.com/articles/corey-nicolaou-macrolactonization) provides the first method for preparing medium-to-large-size [lactones](https://bliptext.com/articles/lactone).\nPreviously, intermolecular outcompeted intramolecular lactonization even at low concentrations.\nOne big advantage of this reaction is that it is performed under neutral conditions allowing the presence of acid and base-labile functional groups.\nAs of 2016, rings of 7–44 members have been successfully synthesized using this method.\nThe reaction occurs in the presence of 2,2'-dipyridyl disulfide and triphenylphosphine with reflux of a nonpolar solvent such as [benzene](https://bliptext.com/articles/benzene).\nThe mechanism begins with formation of the 2-pyridinethiol ester (scheme 19).\nProton-transfer provides a dipolar intermediate in which the alkoxide [nucleophile](https://bliptext.com/articles/nucleophile) attacks the electrophilic carbonyl center, providing a tetrahedral intermediate that yields the macrolactone product.\nOne of the first examples of this protocol was applied to the total synthesis of [zearalenone](https://bliptext.com/articles/zearalenone) (scheme 20).\n \n The [Johnson-Corey-Chaykovsky reaction](https://bliptext.com/articles/johnson-corey-chaykovsky-reaction) synthesizes [epoxides](https://bliptext.com/articles/epoxide) and [cyclopropanes](https://bliptext.com/articles/cyclopropane).\nThe reaction forms a sulfur ylide in situ that reacts with enones, ketones, aldehydes, and [imines](https://bliptext.com/articles/imine) to form corresponding epoxides, cyclopropanes, and [aziridines](https://bliptext.com/articles/aziridines).\nTwo sulfur ylide variants have been employed that give different chemeoselective products (scheme 21).The dimethylsulfoxonium methylide provides epoxides from ketones, but yields the cyclopropanes when enones are employed.\nDimethylsulfonium methylide transforms ketones and enones to the corresponding epoxides.\nDimethylsulfonium methylide is much more reactive and less stable than dimethylsulfoxonium methylide, so it is generated at low temperatures.\n \n Based on their reactivity, another distinct advantage of these two variants is that kinetically they provide a difference in diastereoselectivity.\nThe reaction is very well established, and enantioselective variants (catalytic and stoichiometric) have also been achieved.\nFrom a retrosynthetic analysis standpoint, this reaction provides a reasonable alternative to conventional epoxidation reactions with alkenes (scheme 22).\nDanishefsky utilized this methodology for the synthesis of taxol.\nDiastereoselectivity is established by 1,3 interactions in the transition state required for epoxide closure.\n \n \n# [600px | upload.wikimedia.org/wikipedia/commons/e/e3/CBS///formation9.png]\n# [400px | upload.wikimedia.org/wikipedia/commons/0/03/CBS///mechanism10.png]\n# [550px | upload.wikimedia.org/wikipedia/commons/4/45/CBS///total///synthesis11.png]\n# [550px | upload.wikimedia.org/wikipedia/commons/c/cc/Corey-fuch///reaction12.png]\n# [550px | upload.wikimedia.org/wikipedia/commons/b/ba/Corey-fuch///total///synthesis13.png]\n# [550px | upload.wikimedia.org/wikipedia/commons/c/c0/Corey///kim///ox14.png]\n# [550px | upload.wikimedia.org/wikipedia/commons/2/2b/Corey///kim///ox///synthesis///example15.png]\n# [total synthesis example of corey winter olefination | upload.wikimedia.org/wikipedia/commons/7/7b/Corey-winter///olefination///example16.png]\n# [enantioslective diels-alder transition state | upload.wikimedia.org/wikipedia/commons/e/e6/Diels///alder///TS17.png]\n# [enantioslective diels-alder in total synthesis | upload.wikimedia.org/wikipedia/commons/a/ac/Diels///alder///example///enantioselective18.png]\n# [mechanism of Corey-Nicolaou macrolactonization | upload.wikimedia.org/wikipedia/commons/9/93/Corey-nicolaou///macrolactonization19.png]\n# [macrolactonization total synthesis example | upload.wikimedia.org/wikipedia/commons/8/80/Macrolactonization///example20.png]\n# [corey-chaykovsky selectivity | upload.wikimedia.org/wikipedia/commons/7/70/Corey-chakovsky///reaction21.png]\n# [corey-chaykovsky total synthesis example | upload.wikimedia.org/wikipedia/commons/2/21/Corey-chakovsky///example22.png]\n\n## Total syntheses\nE. J. Corey and his research group have completed many [total syntheses](https://bliptext.com/articles/total-synthesis).\nAt least 265 compounds have been synthesized in the Corey group since 1950.\nHis 1969 total syntheses of several [prostaglandins](https://bliptext.com/articles/prostaglandin) are considered classics.\nSpecifically the synthesis of Prostaglandin F2α presents several challenges.\nThe presence of both cis and trans olefins as well as five asymmetric carbon atoms renders the molecule a desirable challenge for organic chemists.\nCorey's retrosynthetic analysis outlines a few key disconnections that lead to simplified precursors (scheme 23).\nMolecular simplification began first by disconnecting both carbon chains with a Wittig reaction and Horner-Wadsworth Emmons modification.\nThe Wittig reaction affords the cis product, while the Horner-Wadsworth Emmons produces the trans olefin.\nThe published synthesis reveals a 1:1 diastereomeric mixture of the carbonyl reduction using zinc borohydride.\nHowever, years later Corey and co-workers established the CBS reduction.\nOne of the examples that exemplified this protocol was an intermediate in the prostaglandin synthesis revealing a 9:1 mixture of the desired diastereomer (scheme 24).\nThe iodolactonization transform affords an allylic alcohol leading to a key Baeyer-Villiger intermediate.\nThis oxidation regioselectively inserts an oxygen atom between the ketone and the most electron-rich site.\nThe pivotal intermediate leads to a straightforward conversion to the Diels-Alder structural goal, which provides the carbon framework for the functionalized cyclopentane ring.\nLater Corey developed an asymmetric Diels-Alder reaction employing a chiral oxazoborolidine, greatly simplifying the synthetic route to the prostaglandins.\nOther notable syntheses:\n# [600px | upload.wikimedia.org/wikipedia/commons/e/eb/Prostaglandin///retro23.png]\n# [500px | upload.wikimedia.org/wikipedia/commons/5/5f/Prostoglandin///CBS24.png]\n\n## Computer programs\nCorey and his research group created [LHASA](https://bliptext.com/articles/lhasa), a program that uses [artificial intelligence](https://bliptext.com/articles/artificial-intelligence) to discover sequences of reaction which may lead to total synthesis.\nThe program was one of the first to use a graphical interface to input and display chemical structures.\n\n## Publications\nE.J. Corey has more than 1100 publications.\nIn 2002, the American Chemical Society (ACS) recognized him as the \"Most Cited Author in Chemistry\".\nIn 2007, he received the first ACS Publications Division \"Cycle of Excellence High Impact Contributor Award\" and was ranked the number one chemist in terms of research impact by the Hirsch Index ([h-index](https://bliptext.com/articles/h-index)).\nHis books include:\n\n# Altom suicide\n[Jason Altom](https://bliptext.com/articles/jason-altom), one of Corey's students, committed suicide in 1998.\nAltom's suicide caused controversy because he explicitly blamed Corey, his research advisor, for his suicide.\nAltom cited in his 1998 farewell note \"abusive research supervisors\" as one reason for taking his life.\nAltom's suicide note also contained explicit instructions on how to reform the relationship between students and their supervisors.\nAltom was the third member of Corey's lab to commit suicide since 1980.\nCorey was reportedly devastated and bewildered by his student's death.\nCorey said, \"That letter doesn't make sense. At the end, Jason must have been delusional or irrational in the extreme.\"\nCorey also claimed he never questioned Altom's intellectual contributions.\n\"I did my best to guide Jason as a mountain guide would to guide someone climbing a mountain. I did my best every step of the way,\" Corey states.\n\"My conscience is clear. Everything Jason did came out of our partnership. We never had the slightest disagreement.\"\nThe [American Foundation for Suicide Prevention](https://bliptext.com/articles/american-foundation-for-suicide-prevention) (AFSP) cited [The New York Times](https://bliptext.com/articles/the-new-york-times) article on Altom's suicide as an example of problematic reporting, arguing that Altom presented warning signs of depression and suicidal ideation and that the article had scapegoated Corey despite a lack of secondary evidence that the advisor's behavior had contributed to Altom's distress.\nAccording to [The Boston Globe](https://bliptext.com/articles/the-boston-globe), students and professors said Altom actually retained Corey's support.\n\n# Corey Group members\nAs of 2010, approximately 700 people have been Corey Group members including notable students [Eric Block](https://bliptext.com/articles/eric-block),\n[Dale L. Boger](https://bliptext.com/articles/dale-l-boger), [Weston T. Borden](https://bliptext.com/articles/weston-t-borden), [David E. Cane](https://bliptext.com/articles/david-e-cane), [Rick L. Danheiser](https://bliptext.com/articles/rick-l-danheiser), [William L. Jorgensen](https://bliptext.com/articles/william-l-jorgensen), [John Katzenellenbogen](https://bliptext.com/articles/john-katzenellenbogen), [Alan P. Kozikowski](https://bliptext.com/articles/alan-p-kozikowski), [Bruce H. Lipshutz](https://bliptext.com/articles/bruce-h-lipshutz), [David R. Liu](https://bliptext.com/articles/david-r-liu), [Albert Meyers](https://bliptext.com/articles/albert-meyers), [K. C. Nicolaou](https://bliptext.com/articles/k-c-nicolaou), [Ryōji Noyori](https://bliptext.com/articles/ry-ji-noyori), [Gary H. Posner](https://bliptext.com/articles/gary-h-posner), [Bengt I. Samuelsson](https://bliptext.com/articles/bengt-i-samuelsson), [Dieter Seebach](https://bliptext.com/articles/dieter-seebach), [Vinod K. Singh](https://bliptext.com/articles/vinod-k-singh), [Brian Stoltz](https://bliptext.com/articles/brian-stoltz), [Alice Ting](https://bliptext.com/articles/alice-y-ting), [Hisashi Yamamoto](https://bliptext.com/articles/hisashi-yamamoto), [Phil Baran](https://bliptext.com/articles/phil-baran) and [Jin-Quan Yu](https://bliptext.com/articles/jin-quan-yu).\nA database of 580 former members and their current affiliation was developed for Corey's 80th birthday in July 2008.\n\n# Woodward–Hoffmann rules\nWhen awarded the Priestley Medal in 2004, E. J. Corey created a controversy with his claim to have inspired [Robert Burns Woodward](https://bliptext.com/articles/robert-burns-woodward) prior to the development of the [Woodward–Hoffmann rules](https://bliptext.com/articles/woodward-hoffmann-rules).\nCorey wrote:\n\"On May 4, 1964, I suggested to my colleague R. B. Woodward a simple explanation involving the symmetry of the perturbed (HOMO) molecular orbitals for the stereoselective cyclobutene → 1,3-butadiene and 1,3,5-hexatriene → cyclohexadiene conversions that provided the basis for the further development of these ideas into what became known as the Woodward–Hoffmann rules.\"\nThis was Corey's first public statement on his claim that starting on May 5, 1964, Woodward put forth Corey's explanation as his own thought with no mention of Corey and the conversation of May 4.\nCorey had discussed his claim privately with Hoffmann and close colleagues since 1964.\nCorey mentions that he made the Priestley statement \"so the historical record would be correct\".\nCorey's claim and contribution were publicly rebutted by [Roald Hoffmann](https://bliptext.com/articles/roald-hoffmann) in the journal [Angewandte Chemie](https://bliptext.com/articles/angewandte-chemie).\nIn the rebuttal, Hoffmann states that he asked Corey over the course of their long discussion of the matter why Corey did not make the issue public.\nCorey responded that he thought such a public disagreement would hurt Harvard and that he would not \"consider doing anything against Harvard, to which I was and am so devoted.\"\nCorey also hoped that Woodward himself would correct the historical record \"as he grew older, more considerate, and more sensitive to his own conscience.\"\nWoodward died suddenly of a heart attack in his sleep in 1979.\n\n# Awards and honors\nE.J. Corey has received more than 40 major awards including the [Linus Pauling Award](https://bliptext.com/articles/linus-pauling-award) (1973), [Franklin Medal](https://bliptext.com/articles/franklin-medal) (1978), [Tetrahedron Prize](https://bliptext.com/articles/tetrahedron-prize) (1983), [Wolf Prize in Chemistry](https://bliptext.com/articles/wolf-prize-in-chemistry) (1986), [National Medal of Science](https://bliptext.com/articles/national-medal-of-science) (1988), [Japan Prize](https://bliptext.com/articles/japan-prize) (1989), [Nobel Prize in Chemistry](https://bliptext.com/articles/nobel-prize-in-chemistry) (1990), Golden Plate Award of the [American Academy of Achievement](https://bliptext.com/articles/academy-of-achievement) (1991), Roger Adams Award (1993), and the [Priestley Medal](https://bliptext.com/articles/priestley-medal) (2004).\nHe was inducted into the [Alpha Chi Sigma](https://bliptext.com/articles/alpha-chi-sigma) Hall of Fame in 1998.\nAs of 2008, he has been awarded 19 honorary degrees from universities around the world including [Oxford University](https://bliptext.com/articles/oxford-university) (UK), [Cambridge University](https://bliptext.com/articles/cambridge-university) (UK), and [National Chung Cheng University](https://bliptext.com/articles/national-chung-cheng-university).\nIn 2013, the E.J. Corey Institute of Biomedical Research (CIBR) opened in Jiangyin, Jiangsu Province, China.\nCorey was elected a [Foreign Member of the Royal Society (ForMemRS) in 1998](https://bliptext.com/articles/list-of-fellows-of-the-royal-society-elected-in-1998).","revisionCount":0},"hasMore":false,"nextCursor":null}

History