Elias James Corey (born July 12, 1928) is an American organic chemist. In 1990, he won the Nobel Prize in Chemistry "for his development of the theory and methodology of organic synthesis", specifically retrosynthetic analysis.E. J. Corey, X-M. Cheng, The Logic of Chemical Synthesis, Wiley, New York, 1995, .
Biography E.J. Corey (the surname was anglicized from Levantine Arabic Khoury, meaning priest) was born to Lebanese Greek Orthodox Christian immigrants Fatima (née Hasham) and Elias Corey in Methuen, Massachusetts, north of Boston.Elias James Corey – Autobiography . nobelprize.org His mother changed his name from William to "Elias" to honor his father, who died eighteen months after Corey's birth. His widowed mother, brother, two sisters, aunt and uncle all lived together in a spacious house, struggling through the Great Depression. As a young boy, Corey was independent and enjoyed sports such as baseball, football, and hiking. He attended a Catholic elementary school and Lawrence High School in Lawrence, Massachusetts.
At the age of 16 Corey entered MIT, where he earned both a bachelor's degree in 1948 and a Ph.D. under Professor John C. Sheehan in 1951. Upon entering MIT, Corey's only experience with science was in mathematics, and he began his college career pursuing a degree in engineering. After 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. Immediately 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, where he became a full professor of chemistry in 1956 at the age of 27. He was initiated as a member of the Zeta chapter of Alpha Chi Sigma at the University of Illinois in 1952.Fraternity – Awards – Hall of Fame – Alpha Chi Sigma In 1959, he moved to Harvard University, and in 1967 he was appointed the Sheldon Emory Professor and became a Guggenheim Fellow (1968-69). During his time at Harvard, Corey synthesised around 100 molecules, which previously had been only found in nature. At Harvard, Corey is currently an emeritus professor of organic chemistry; his group maintains an active research program. He chose to work in organic chemistry because of "its intrinsic beauty and its great relevance to human health". He has also been an advisor to Pfizer for more than 50 years.
Among numerous honors, Corey was awarded the National Medal of Science in 1988,National Science Foundation – The President's National Medal of Science the Nobel Prize in Chemistry in 1990, and the American Chemical Society's greatest honor, the Priestley Medal, in 2004.
Major contributions
Reagents Corey has developed several new synthetic reagents: Pyridinium chlorochromate (PCC), also known as the Corey–Suggs reagent, is widely used for the oxidation of alcohols to corresponding ketones and aldehydes. PCC has several advantages over other commercial oxidants. An air-stable yellow solid, it is only slightly hygroscopic. Unlike other oxidizing agents, PCC requires only about 1.5 equivalents to complete a single oxidation (scheme 1).
In the reaction, the alcohol nucleophilically displaces chlorine from the electropositive chromium(VI) metal. The chloride anion then acts as a base to afford the aldehyde product and chromium(IV).
The slightly acidic character of PCC makes it useful for cyclization reactions with alcohols and alkenes (Scheme 2).
The initial oxidation yields the corresponding aldehyde, which can then undergo a Prins reaction with the neighboring alkene. After elimination and further oxidation, the product is a cyclic ketone. Conversely, powdered sodium acetate co-reagent inhibits reaction after formation of the aldehyde.
PCC's oxidative robustness has also rendered it useful in the realm of total synthesis (Scheme 3). This example illustrates the Babler oxidation reaction, in which tertiary allylic alcohols undergo a [3,3]-sigmatropic rearrangement.
t-Butyldimethylsilyl ether (TBS), triisopropylsilyl ether (TIPS), and methoxyethoxymethyl (MEM) are popular alcohol protecting groups. The development of these protecting groups allowed the synthesis of several natural products whose functional groups could not withstand standard chemical transformations. Although the synthetic community attempts to minimize the use of protecting groups, it is still rare that a published natural-product synthesis omits them entirely.
Since 1972 the TBS group has become the most popular silicon protecting group (Scheme 4). TBS is stable to chromatography and labile enough to cleave under basic and acidic conditions. More importantly, TBS ethers are stable to such carbon nucleophiles as Grignard reagents and enolates.Kocienski, P.J. Protecting Groups; Georg Thieme Verlag: Germany, 2000
CSA (Camphorsulfonic acid) selectively removes a primary TBS ether in the presence of TIPS and tertiary TBS ethers. Other TBS deprotection methods include acids (also Lewis acids), and fluorides.
TIPS protecting groups provide increased selectivity of primary over secondary and tertiary alcohol protection. Their ethers are more stable under acidic and basic conditions than TBS ethers, but less labile for deprotection. The most common cleavage reagents employ the same conditions as TBS ether, but longer reaction times.
Usually TBAF severs TBS ethers, but the hindered TBS ether above survives primary TIPS removal (scheme 5).
The MEM protecting group was first described by Corey in 1976. This protecting group is similar in reactivity and stability to other alkoxy methyl ethers under acidic conditions. Acidic conditions usually accomplish cleavage of MEM protecting groups, but coordination with metal halides greatly enhances lability (scheme 6).
1,3-Dithianes are a temporary modification of a carbonyl group that reverses their reactivity in displacement and addition reactions. Dithianation introduced umpolung chemistry, now a key concept in organic synthesis.
The formations of dithianes can be accomplished with a Lewis acid (scheme 7) or directly from carbonyl compounds.
The pKa of dithianes is approximately 30, allowing deprotonation with an alkyl lithium reagent, typically n-butyllithium.
The reaction between dithianes and aldehydes is now known as the Corey-Seebach reaction. The dithiane, once deprotonated, serves as an acyl anion, attacking incoming electrophiles. Dithiane deprotection, usually with HgO, constructs a ketone product.
Corey also commenced detailed studies on cationic polyolefin cyclizations utilized in enzymatic production of cholesterol from simpler plant terpenes. Corey established the details of the remarkable cyclization process by first studying the biological synthesis of sterols from squalene.
Methodology Several reactions developed in Corey's lab have become commonplace in modern synthetic organic chemistry. At least 302 methods have been developed in the Corey group since 1950.See the Methods tab Several reactions have been named after him: Corey-Itsuno reduction, also known as the Corey-Bakshi-Shibata reduction, is an enantioselective reduction of ketones to alcohols through an oxazaborolidine catalyst, with various boranes as the stoichiometric reductant.
The Corey group first demonstrated the catalyst's synthesis using borane and the chiral amino acid proline (scheme 9).Kürti, L.; Czakó, B. Strategic Applications of Named Reactions in Organic Synthesis; Elsevier: Burlington, 2005.Corey, E.J.; Kürti, L. Enantioselective Chemical Synthesis; Direct Book Publishing: Dallas, 2010
Later, Corey demonstrated that substituted boranes were easier to prepare and much more stable.
The reduction mechanism begins with the oxazaborolidine, only slightly basic at nitrogen, coordinating to a borane reductant (scheme 10). Poor donation from the nitrogen to the boron leaves the Lewis acidity mostly intact, allowing coordination to the ketone substrate. The complexation of the substrate occurs from the most accessible lone pair of the oxygen, restricting rotation around the B-O bond due to the sterically neighboring phenyl group.
Migration 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.
The reaction has also been of great use to natural products chemists (scheme 11). The synthesis of dysidiolide by Corey and co-workers was achieved via an enantioselective CBS reduction using a borane-dimethylsulfide complex.
Corey-Fuchs alkyne synthesis is the synthesis of terminal alkynes through a one-carbon homologation of aldehydes using triphenylphosphine and carbon tetrabromide.Corey, E.J.; Fuch, P.L. Tetrahedron Lett. 1972, 3769 The mechanism is similar to that of a combined Wittig reaction and Appel reaction. Reacting a phosphorus ylide formed in situ with the aldehyde substrate yields a dibromoolefin.Eymery et al Synthesis 2000, 185
On 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).
More recent developments include a modified procedure for one-pot synthesis.
This synthetic transformation has been proven successful in the total synthesis (+)-taylorione by W.J. Kerr and co-workers (scheme 13).
The Corey–Kim oxidation was a new conversion of alcohols into corresponding aldehydes and ketones. This combination of N-chlorosuccinimidosulfonium chloride (NCS), dimethylsulfide (DMS), and triethylamine (TEA) offers a less toxic alternative to chromium-based oxidations.
The Corey-Kim reagent is formed in situ when the succinimide and sulfide react to form a dimethylsuccinimidosulfonium chloride species (scheme 14).
Triethylamine deprotonates the alkoxysulfonium salt at the α position to afford the oxidized product. The reaction accommodates a wide array of functional groups, but allylic and benzylic alcohols are typically transformed into chlorides instead.
Its application in synthesis is based on the mild protocol conditions and functional and protecting group compatibility. In the total synthesis of ingenol, Kuwajima and co-workers exploited the Corey-Kim oxidation by selectively oxidizing the less hindered secondary alcohol(scheme 15).
Corey-Winter olefination is a stereospecific transformation of 1,2-diols to alkenes involving the diol substrate, thiocarbonyldiimidazole, and excess trialkylphosphite.
The exact mechanism is unknown, but has been narrowed down to two possible pathways. The thionocarbonate and trialkylphosphite either form a phosphorus ylide or carbenoid intermediate.
The 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.
Stereospecfic alkenes are present in several natural products as the method continues to be exploited to yield a series of complex substrates. Professor T.K.M Shing et al used the Corey-Winter olefination reaction to synthesize (+)-Boesenoxide (scheme 16).
CBS-type enantioselective Diels–Alder reaction has been developed using a similar scaffold to the enantioselective CBS reduction. After the development of this reaction the CBS reagent proved to be a very versatile reagent for a series of several powerful synthetic transformations. The use of a chiral Lewis acid such as the CBS catalyst includes a broad range of unsaturated enones substrates.
The reaction likely proceeds via a highly organized 6-membered ring pre-transition state to deliver highly enantio-enriched products (scheme 17).