Elias James Corey
Elias James Corey 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.
Biography
E.J. Corey was born to Lebanese Greek Orthodox Christian immigrants Fatima and Elias Corey in Methuen, Massachusetts, north of Boston. 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. In 1959, he moved to Harvard University, and in 1967 he was appointed the Sheldon Emory Professor and became a Guggenheim Fellow. 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, 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, 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.
The slightly acidic character of PCC makes it useful for cyclization reactions with alcohols and alkenes.
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. This example illustrates the Babler oxidation reaction, in which tertiary allylic alcohols undergo a -sigmatropic rearrangement.
File:PCC rearrangement3.png|700px|center| rearrangement with PCC
- t-Butyldimethylsilyl ether, triisopropylsilyl ether, and methoxyethoxymethyl 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.
CSA selectively removes a primary TBS ether in the presence of TIPS and tertiary TBS ethers. Other TBS deprotection methods include 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.
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 .
- 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 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
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.
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. 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. 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. 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.
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.
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.
The Corey–Kim oxidation was a new conversion of alcohols into corresponding aldehydes and ketones. This combination of N-chlorosuccinimidosulfonium chloride, dimethylsulfide, and triethylamine 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.
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.
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.
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.
This transition state likely occurs because of favorable pi-stacking with the phenyl substituent. The enantioselectivity of the process is facilitated from the diene approaching the dienophile from the opposite face of the phenyl substituent.
The Diels-Alder reaction is one of the most powerful transformations in synthetic chemistry. The synthesis of natural products using the Diels-Alder reaction as a transform has been applied especially to the formation of six-membered rings.
Corey-Nicolaou macrolactonization provides the first method for preparing medium-to-large-size lactones. Previously, intermolecular outcompeted intramolecular lactonization even at low concentrations. One big advantage of this reaction is that it is performed under neutral conditions allowing the presence of acid and base-labile functional groups. As of 2016, rings of 7–44 members have been successfully synthesized using this method.
The reaction occurs in the presence of 2,2'-dipyridyl disulfide and triphenylphosphine with reflux of a nonpolar solvent such as benzene. The mechanism begins with formation of the 2-pyridinethiol ester. Proton-transfer provides a dipolar intermediate in which the alkoxide nucleophile attacks the electrophilic carbonyl center, providing a tetrahedral intermediate that yields the macrolactone product.
One of the first examples of this protocol was applied to the total synthesis of zearalenone.
The Johnson-Corey-Chaykovsky reaction synthesizes epoxides and cyclopropanes. The reaction forms a sulfur ylide in situ that reacts with enones, ketones, aldehydes, and imines to form corresponding epoxides, cyclopropanes, and aziridines. Two sulfur ylide variants have been employed that give different chemoselective products.The dimethylsulfoxonium methylide provides epoxides from ketones, but yields the cyclopropanes when enones are employed. Dimethylsulfonium methylide transforms ketones and enones to the corresponding epoxides. Dimethylsulfonium methylide is much more reactive and less stable than dimethylsulfoxonium methylide, so it is generated at low temperatures.
Based on their reactivity, another distinct advantage of these two variants is that kinetically they provide a difference in diastereoselectivity. The reaction is very well established, and enantioselective variants have also been achieved. From a retrosynthetic analysis standpoint, this reaction provides a reasonable alternative to conventional epoxidation reactions with alkenes. Danishefsky utilized this methodology for the synthesis of taxol. Diastereoselectivity is established by 1,3 interactions in the transition state required for epoxide closure.