Elias James Corey (born July 12, 1928) is an American
organic chemist
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J.; ...
. In 1990, he won the
Nobel Prize in Chemistry
)
, image = Nobel Prize.png
, alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
"for his development of the theory and methodology of
organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...
", specifically
retrosynthetic analysis
Retrosynthetic analysis is a technique for solving problems in the planning of organic syntheses. This is achieved by transforming a target molecule into simpler precursor structures regardless of any potential reactivity/interaction with reagents. ...
.
Regarded by many as one of the greatest living chemists, he has developed numerous synthetic
reagents
In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...
, methodologies and total syntheses and has advanced the science of organic synthesis considerably.
Biography
E.J. Corey (the surname was anglicized from
Levantine Arabic
Levantine Arabic, also called Shami (autonym: or ), is a group of mutually intelligible vernacular Arabic varieties spoken in the Levant, in Syria, Jordan, Lebanon, Palestine, Israel, and Turkey (historically in Adana, Mersin and Hatay on ...
''
Khoury'', meaning ''priest'') was born to
Lebanese Greek Orthodox Christian immigrants Fatima (née Hasham) and Elias Corey in
Methuen, Massachusetts
Methuen () is a 23 square mile (60 km2) city in Essex County, Massachusetts, United States. The population was 53,059 at the 2020 census. Methuen lies along the northwestern edge of Essex County, just east of Middlesex County and just south of ...
, 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
The Great Depression (19291939) was an economic shock that impacted most countries across the world. It was a period of economic depression that became evident after a major fall in stock prices in the United States. The economic contagio ...
. 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
Lawrence is a city located in Essex County, Massachusetts, United States, on the Merrimack River. At the 2020 census, the city had a population of 89,143. Surrounding communities include Methuen to the north, Andover to the southwest, and Nort ...
.
At the age of 16 Corey entered
MIT
The Massachusetts Institute of Technology (MIT) is a private land-grant research university in Cambridge, Massachusetts. Established in 1861, MIT has played a key role in the development of modern technology and science, and is one of the m ...
, where he earned both a
bachelor's degree
A bachelor's degree (from Middle Latin ''baccalaureus'') or baccalaureate (from Modern Latin ''baccalaureatus'') is an undergraduate academic degree awarded by colleges and universities upon completion of a course of study lasting three to six ...
in 1948 and a
Ph.D.
A Doctor of Philosophy (PhD, Ph.D., or DPhil; Latin: or ') is the most common degree at the highest academic level awarded following a course of study. PhDs are awarded for programs across the whole breadth of academic fields. Because it is ...
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
The University of Illinois Urbana-Champaign (U of I, Illinois, University of Illinois, or UIUC) is a public land-grant research university in Illinois in the twin cities of Champaign and Urbana. It is the flagship institution of the Universit ...
, 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
Alpha Chi Sigma () is a professional fraternity specializing in the fields of the chemical sciences. It has both collegiate and professional chapters throughout the United States consisting of both men and women and numbering more than 70,000 mem ...
at the University of Illinois in 1952.
[Fraternity – Awards – Hall of Fame – Alpha Chi Sigma](_blank)
In 1959, he moved to
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
, where he is currently an emeritus professor of organic chemistry with an active Corey Group 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
The National Medal of Science is an honor bestowed by the President of the United States to individuals in science and engineering who have made important contributions to the advancement of knowledge in the fields of behavioral and social scienc ...
in 1988, the
Nobel Prize in Chemistry
)
, image = Nobel Prize.png
, alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
in 1990,
[ and the ]American Chemical Society
The American Chemical Society (ACS) is a scientific society based in the United States that supports scientific inquiry in the field of chemistry. Founded in 1876 at New York University, the ACS currently has more than 155,000 members at all d ...
's greatest honor, the Priestley Medal
The Priestley Medal is the highest honor conferred by the American Chemical Society (ACS) and is awarded for distinguished service in the field of chemistry. Established in 1922, the award is named after Joseph Priestley, the discoverer of oxygen ...
, in 2004.[
]
Major contributions
Reagents
Corey has developed several new synthetic reagents:
* PCC (pyridinium chlorochromate), also referred to as the Corey-Suggs reagent, is widely used for the oxidation of alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
s to corresponding ketone
In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...
s and aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
s. PCC has several advantages over other commercial oxidants.
One of these advantages is that the compound is available as an air-stable yellow solid that is not very hygroscopic. Unlike other oxidizing agents, PCC can accomplish single oxidations with only about 1.5 equivalents (scheme 1). The alcohol performs nucleophilic attack to the electropositive chromium
Chromium is a chemical element with the symbol Cr and atomic number 24. It is the first element in group 6. It is a steely-grey, lustrous, hard, and brittle transition metal.
Chromium metal is valued for its high corrosion resistance and hardne ...
(VI) metal displacing chlorine. The chloride
The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride salts ...
anion
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
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 alkene
In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond.
Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
s (Scheme 2).
The initial oxidation yields the corresponding aldehyde, which can then undergo a Prins reaction
The Prins reaction is an organic reaction consisting of an electrophilic addition of an aldehyde or ketone to an alkene or alkyne followed by capture of a nucleophile or elimination of an H+ ion. The outcome of the reaction depends on reaction c ...
with the neighboring alkene
In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond.
Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
. After elimination and further oxidation, the product is a cyclic ketone
In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...
. If this product is undesired, powdered sodium acetate
Sodium acetate, CH3COONa, also abbreviated Na O Ac, is the sodium salt of acetic acid. This colorless deliquescent salt has a wide range of uses.
Applications
Biotechnological
Sodium acetate is used as the carbon source for culturing bacteria ...
can be used as a buffer to achieve only initial oxidation. The robustness of PCC as an oxidizing agent has also rendered it useful in the realm of total synthesis (Scheme 3). This example illustrates that PCC is capable of performing a ''Dauben oxidative rearrangement'' with tertiary alcohols through a ,3sigmatropic rearrangement.
*''t''-Butyldimethylsilyl ether (TBS), triisopropylsilyl ether (TIPS), and methoxyethoxymethyl (MEM): are popular alcohol protecting group
A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis.
In many ...
s. The development of these protecting groups allowed the synthesis of several natural product
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical syn ...
s that did not have the functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...
compatibility to withstand standard chemical transformations. Although the synthetic community is now moving away from the use of protecting groups it is still rare that a published synthesis of a natural product omits them. Since 1972 the TBS group has become the most popular silicon
Silicon is a chemical element with the symbol Si and atomic number 14. It is a hard, brittle crystalline solid with a blue-grey metallic luster, and is a tetravalent metalloid and semiconductor. It is a member of group 14 in the periodic tab ...
protecting group. TBS is stable to chromatography
In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system (a ...
and labile enough for cleavage under basic and acidic conditions. More importantly, TBS ether
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be c ...
s are stable to some carbon nucleophiles such as Grignard reagents and enolates.
In the field of complex molecule synthesis, TBS has been widely used as one of the most versatile of the silicon-based protecting groups (scheme 4). The use of CSA provides selective removal of a primary TBS ether in the presence of tertiary TBS ether and TIPS ethers. Other means of TBS deprotection include acids (also Lewis acids), and fluoride
Fluoride (). According to this source, is a possible pronunciation in British English. is an inorganic, monatomic anion of fluorine, with the chemical formula (also written ), whose salts are typically white or colorless. Fluoride salts typ ...
s. TIPS protecting groups were also pioneered by Corey and provide increased selectivity of primary alcohol protection over secondary and tertiary alcohol protection. TIPS ethers are more stable under acidic and basic conditions, the disadvantage of this protecting group over TBS ethers being that the group is less labile for deprotection. The most common reagents used for cleavage employ the same conditions as TBS ether, but longer reaction times are generally needed.
Usually TBS ethers are severed by TBAF, but the hindered TBS ether above survives the reaction conditions upon 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. Cleavage of MEM protecting groups is usually accomplished under acidic conditions, but coordination with metal halides greatly enhances lability via assisted cleavage (scheme 6).
*1,3-Dithiane
A dithiane is a heterocyclic compound composed of a cyclohexane core structure wherein two methylene bridges (-- units) are replaced by sulfur centres. The three isomeric parent heterocycles are 1,2-dithiane, 1,3-dithiane and 1,4-dithiane.
1,3 ...
s were pioneered by E.J. Corey in 1965 as a temporary modification of a carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...
group in displacement and addition reactions. The formation of dithiane was the initial development that introduced Umpolung
In organic chemistry, umpolung () or polarity inversion is the chemical modification of a functional group with the aim of the reversal of polarity of that group. This modification allows secondary reactions of this functional group that would oth ...
chemistry and is widely used for inversion of reactivity. 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
''n''-Butyllithium C4H9Li (abbreviated ''n''-BuLi) is an organolithium reagent. It is widely used as a polymerization initiator in the production of elastomers such as polybutadiene or styrene-butadiene-styrene (SBS). Also, it is broadly emp ...
. The reaction with dithianes and aldehydes is now known as the Corey-Seebach reaction. The dithiane once deprotonated serves as an acyl anion used to attack incoming electrophile
In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carries ...
s. After deprotection of the dithiane, usually with HgO, a ketone product is observed from the masked acyl dithiane anion. The utility of such reactions has expanded the field of organic synthesis by allowing synthetic chemists to use Umpolung disconnections in total synthesis (scheme 8). 1,3-dithianes are also used as protecting groups for carbonyl compounds expressing the versatility and utility of this functional group.
*In addition, Corey commenced detailed studies on cationic polyolefin cyclizations utilized in enzymatic production of cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
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. 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 utilizing an oxazaborolidine catalyst
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
and various boranes as the stoichiometric reductant. The Corey group first demonstrated the synthesis of the catalyst using borane and chiral aminoalcohols. The reaction uses the chiral amino acid proline
Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...
and in the presence of borane leads to the CBS catalyst
The CBS catalyst or Corey–Bakshi–Shibata catalyst is an Chiral synthesis, asymmetric catalyst derived from proline. It finds many uses in organic reactions such as the CBS reduction, Diels-Alder reactions and (3+2) cycloadditions. Pro ...
(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 oxazoborolidine being only slightly basic at itrogen coordinating with the stoichiometric borane of the boron amine complex(scheme 10). Lack of donation from the nitrogen to the boron increases its Lewis acidity, allowing coordination with the ketone substrate. The complexation of the substrate occurs from the most accessible lone pair of the oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...
leading to restricted 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 alkyne
\ce
\ce
Acetylene
\ce
\ce
\ce
Propyne
\ce
\ce
\ce
\ce
1-Butyne
In organic chemistry, an alkyne is an unsaturated hydrocarbon containing at least one carbon—carbon triple bond. The simplest acyclic alkynes with only one triple bond and n ...
s through a one-carbon homologation of aldehydes using triphenylphosphine
Triphenylphosphine (IUPAC name: triphenylphosphane) is a common organophosphorus compound with the formula P(C6H5)3 and often abbreviated to P Ph3 or Ph3P. It is widely used in the synthesis of organic and organometallic compounds. PPh3 exists a ...
and carbon tetrabromide. The mechanism is similar to that of the Wittig reaction
The Wittig reaction or Wittig olefination is a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide called a Wittig reagent. Wittig reactions are most commonly used to convert aldehydes and ketones to alkenes. Most o ...
by the formation of a phosphorus ylide An ylide or ylid () is a neutral dipolar molecule containing a formally negatively charged atom (usually a carbanion) directly attached to a heteroatom with a formal positive charge (usually nitrogen, phosphorus or sulfur), and in which both atoms h ...
with triphenylphosphine and carbon tetrabromide. Reacting the phosphorus ylide with the aldehyde substrate yields a dibromoolefin.
On treatment with two equivalents of ''n''-buLi, lithium halogen exchange and deprotonation yields a lithium acetylide species that undergoes hydrolysis to yield the terminal alkyne product (scheme 12). More recently, a one-pot synthesis using a modified procedure has been developed. 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
The Corey–Kim oxidation is an oxidation reaction used to synthesise aldehydes and ketones from primary and secondary alcohols. It is named for American chemist and Nobel Laureate Elias James Corey and Korean-American chemist Choung Un Kim.
...
was a newly developed transformation for the conversion of alcohols into corresponding aldehydes and ketones. This process offers a less toxic alternative to chromium based oxidations with the use of ''N''-chlorosuccinimidosulfonium chloride (NCS), dimethylsulfide (DMS), and triethylamine
Triethylamine is the chemical compound with the formula N(CH2CH3)3, commonly abbreviated Et3N. It is also abbreviated TEA, yet this abbreviation must be used carefully to avoid confusion with triethanolamine or tetraethylammonium, for which TEA ...
(TEA). The Corey-Kim reagent is formed in ''situ'' when NCS and DMS are reacted to form dimethylsuccinimidosulfonium chloride species (scheme 14).
The alkoxy sulfonium salt is deprotonated at the alpha position with triethylamine to afford the oxidized product. The reaction accommodates a wide array of functional groups, but allylic and benzylic alcohols are typically transformed into allylic and benzylic chlorides. 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 mechanism has been narrowed down to two possible pathways, but the exact mechanism is unknown. Specifically, the reaction between the thionocarbonate and the trialkylphosphite proceeds either through the formation of a phosphorus ylide species or a carbenoid intermediate. Nonetheless, the reaction is stereospecific for most substrates unless the product would lead to an exceedingly strained structure. The formation of sterically hindered trans alkenes present in 7-membered rings was attempted by Corey and coworkers, but was unsuccessful even when employing this new synthetic methodology incurring enormous ring strain. More importantly, 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 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).
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(scheme 18).
* Corey-Nicolaou macrolactonization provides the first method for preparing medium to large sized lactone
Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring.
Lactones are formed by intramolecular esterification of the co ...
s. 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. To date rings of 7 to 48 members have been successfully synthesized using this method.
The reaction occurs in the presence of 2,2'-dipyridyl disulfide and triphenylphosphine. The reaction is generally refluxed in a nonpolar solvent such as benzene
Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms, ...
. The mechanism begins with formation of the 2-pyridinethiol ester (scheme 19). Proton-transfer provides a dipolar intermediate in which the alkoxide nucleophile
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
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
Zearalenone (ZEN), also known as RAL and F-2 mycotoxin, is a potent estrogenic metabolite produced by some ''Fusarium'' and ''Gibberella'' species. Specifically, the ''Gibberella zeae ,'' the fungal species where zearalenone was initially detected ...
(scheme 20).
* Johnson-Corey-Chaykovsky reaction is useful for the synthesis of epoxide
In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale for ...
s and cyclopropane
Cyclopropane is the cycloalkane with the molecular formula (CH2)3, consisting of three methylene groups (CH2) linked to each other to form a ring. The small size of the ring creates substantial ring strain in the structure. Cyclopropane itself ...
s. The reaction forms a sulfur ylide in situ that reacts with enones, ketones, aldehydes, and imine
In organic chemistry, an imine ( or ) is a functional group or organic compound containing a carbon–nitrogen double bond (). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bo ...
s to form corresponding epoxides, cyclopropanes, and aziridines
220 px, chemotherapeutic agent by virtue of its antitumour activity. Aziridines are organic compounds containing the aziridine functional group, a three-membered heterocycle with one amine (-NR-) and two methylene bridges (--). The parent compou ...
. Two 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. 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 (catalytic and stoichiometric) have also been achieved. From a retrosynthetic analysis standpoint, this reaction provides a reasonable alternative to conventional epoxidation reactions with alkenes (scheme 22). Danishefsky utilized this methodology for the synthesis of taxol. Diastereoselectivity is established by 1,3 interactions in the transition state required for epoxide closure.
Total syntheses
E. J. Corey and his research group have completed many total syntheses
Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes ...
. At least 265 compounds have been synthesized in the Corey group since 1950.
His 1969 total syntheses of several prostaglandin
The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...
s are considered classics. Specifically the synthesis of Prostaglandin F2α presents several challenges. The presence of both ''cis'' and ''trans'' olefins as well as five asymmetric carbon atoms renders the molecule a desirable challenge for organic chemists. Corey's retrosynthetic analysis outlines a few key disconnections that lead to simplified precursors (scheme 23).
Molecular simplification began first by disconnecting both carbon chains with a Wittig reaction and Horner-Wadsworth Emmons modification. The Wittig reaction affords the ''cis'' product, while the Horner-Wadsworth Emmons produces the ''trans'' olefin. The published synthesis reveals a 1:1 diastereomeric mixture of the carbonyl reduction using zinc borohydride. However, years later Corey and co-workers established the CBS reduction. One 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).
The iodolactonization transform affords an allylic alcohol leading to a key Baeyer-Villiger intermediate. This oxidation regioselectively inserts an oxygen atom between the ketone and the most electron-rich site. The pivotal intermediate leads to a straightforward conversion to the Diels-Alder structural goal, which provides the carbon framework for the functionalized cyclopentane ring. Later Corey developed an asymmetric Diels-Alder reaction employing a chiral oxazoborolidine, greatly simplifying the synthetic route to the prostaglandins.
Other notable syntheses:
* Longifolene
Longifolene is the common (or trivial) chemical name of a naturally occurring, oily liquid hydrocarbon found primarily in the high-boiling fraction of certain pine resins. The name is derived from that of a pine species from which the compound wa ...
* Ginkgolide
Ginkgolides are biologically active terpenic lactones present in ''Ginkgo biloba''. They are diterpenoids with 20-carbon skeletons, which are biosynthesized from geranylgeranyl pyrophosphate.
Examples
Ginkgolide B
Ginkgolide B, specificall ...
s A and B
* Lactacystin
Lactacystin is an organic compound naturally synthesized by bacteria of the genus '' Streptomyces'' first identified as an inducer of neuritogenesis in neuroblastoma cells in 1991.Omura S, Fujimoto T, Otoguro K, Matsuzaki K, Moriguchi R, Tanaka H ...
* Miroestrol
Miroestrol is a phytoestrogen, a plant-derived chemical that mimics the biological activity of the hormone estrogen. Miroestrol was first reportedly isolated from the Thai herb ''Pueraria mirifica'' in 1960 and thought to be responsible for the ...
* Ecteinascidin 743
* Salinosporamide A
Publications
E.J. Corey has more than 1100 publications. In 2002, the American Chemical Society (ACS) recognized him as the "Most Cited Author in Chemistry". In 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
The ''h''-index is an author-level metric that measures both the productivity and citation impact of the publications, initially used for an individual scientist or scholar. The ''h''-index correlates with obvious success indicators such as winn ...
). His books include:
*
*
*
*
*
Altom suicide
Jason Altom
Jason Altom (6 October 1971 – 15 August 1998) was an American PhD student working in the research group of Nobel laureate Elias James Corey at Harvard University. He killed himself by taking potassium cyanide in 1998, citing in his suicide note ...
, one of Corey's students, committed suicide in 1998. Altom's suicide caused controversy because he explicitly blamed Corey, his research advisor, for his suicide.[
] Altom cited in his 1998 farewell note "abusive research supervisors" as one reason for taking his life. Altom's suicide note also contained explicit instructions on how to reform the relationship between students and their supervisors.
Altom was the third member of Corey's lab to commit suicide since 1980. Corey was reportedly devastated and bewildered by his student's death.[English, Bella. , '']The Boston Globe
''The Boston Globe'' is an American daily newspaper founded and based in Boston, Massachusetts. The newspaper has won a total of 27 Pulitzer Prizes, and has a total circulation of close to 300,000 print and digital subscribers. ''The Boston Glob ...
'' via Archive.org (January 2, 2001). Corey said, "That letter doesn't make sense. At the end, Jason must have been delusional or irrational in the extreme." Corey also claimed he never questioned Altom's intellectual contributions. "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. "My conscience is clear. Everything Jason did came out of our partnership. We never had the slightest disagreement." The American Foundation for Suicide Prevention (AFSP) cited ''The New York Times
''The New York Times'' (''the Times'', ''NYT'', or the Gray Lady) is a daily newspaper based in New York City with a worldwide readership reported in 2020 to comprise a declining 840,000 paid print subscribers, and a growing 6 million paid ...
'' 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. According to ''The Boston Globe
''The Boston Globe'' is an American daily newspaper founded and based in Boston, Massachusetts. The newspaper has won a total of 27 Pulitzer Prizes, and has a total circulation of close to 300,000 print and digital subscribers. ''The Boston Glob ...
'' reporting, students and professors said Altom actually retained Corey's support.
As a result of Altom's death, the Department of Chemistry accepted a proposal allowing graduate students to ask two additional faculty members to play a small advisory role in preparing a thesis.[
]
Corey Group members
As of 2010, approximately 700 people have been Corey Group members including notable students Eric Block,
Dale L. Boger, Weston T. Borden, David E. Cane
David E. Cane (born September 22, 1944) is an American biological chemist. He is Vernon K. Krieble Professor of Chemistry Emeritus and Professor of Molecular Biology, Cell Biology, and Biochemistry Emeritus at Brown University in Providence, R ...
, Rick L. Danheiser, William L. Jorgensen, John Katzenellenbogen, Alan P. Kozikowski, Bruce H. Lipshutz Bruce H. Lipshutz (born 1951) is an American chemist. He is a professor at the University of California, Santa Barbara.
Biography
Lipshutz received his undergraduate degree in chemistry from Binghamton University in 1973. His graduate work was supe ...
, David R. Liu, Albert Meyers, K. C. Nicolaou
Kyriacos Costa Nicolaou ( el, Κυριάκος Κ. Νικολάου; born July 5, 1946) is a Cypriot-American chemist known for his research in the area of natural products total synthesis. He is currently Harry C. and Olga K. Wiess Professor of ...
, Ryōji Noyori
is a Japanese chemist. He won the Nobel Prize in Chemistry in 2001, Noyori shared a half of the prize with William S. Knowles for the study of chirally catalyzed hydrogenations; the second half of the prize went to K. Barry Sharpless for his st ...
, Gary H. Posner, Bengt I. Samuelsson
Bengt Ingemar Samuelsson (born 21 May 1934) is a Swedish biochemist. He shared with Sune K. Bergström and John R. Vane the 1982 Nobel Prize for Physiology or Medicine for discoveries concerning prostaglandins and related substances.
Education a ...
, Dieter Seebach
Dieter Seebach is a German chemist known for his synthesis of biopolymers and dendrimers, and for his contributions to stereochemistry. He was born on 31 October 1937 in Karlsruhe. He studied chemistry at the University of Karlsruhe (TH) under ...
, Vinod K. Singh, Brian Stoltz
Brian M. Stoltz is currently a professor of chemistry at the California Institute of Technology. The primary focus of his research is chemical synthesis with an emphasis on expanding the scope of allylic alkylation for the preparation of complex ...
, Hisashi Yamamoto
(born July 16, 1943) is a prominent organic chemist and currently a member of the faculty at the University of Chicago and professor of Chubu University.
Life
Born in Kobe, Japan, Yamamoto earned a B.S. at Kyoto University in 1967 and a Ph.D. ...
, and Jin-Quan Yu
Jin-Quan Yu () is a Chinese-born American chemist. He is the Frank and Bertha Hupp Professor of Chemistry at Scripps Research, where he also holds the Bristol Myers Squibb Endowed Chair in Chemistry. He is a 2016 recipient of the MacArthur Fello ...
. A database of 580 former members and their current affiliation was developed for Corey's 80th birthday in July 2008.
Woodward–Hoffmann rules
When awarded the Priestley Medal in 2004, E. J. Corey created a controversy with his claim to have inspired Robert Burns Woodward
Robert Burns Woodward (April 10, 1917 – July 8, 1979) was an American organic chemist. He is considered by many to be the most preeminent synthetic organic chemist of the twentieth century, having made many key contributions to the subject, e ...
prior to the development of the Woodward–Hoffmann rules The Woodward–Hoffmann rules (or the pericyclic selection rules), devised by Robert Burns Woodward and Roald Hoffmann, are a set of rules used to rationalize or predict certain aspects of the stereochemistry and activation energy of pericyclic reac ...
. Corey wrote:
''"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."''
This 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. Corey had discussed his claim privately with Hoffmann and close colleagues since 1964. Corey mentions that he made the Priestley statement ''"so the historical record would be correct"''.
Corey's claim and contribution were publicly rebutted by Roald Hoffmann
Roald Hoffmann (born Roald Safran; July 18, 1937) is a Polish Americans, Polish-American theoretical chemistry, theoretical chemist who won the 1981 Nobel Prize in Chemistry. He has also published plays and poetry. He is the Frank H. T. Rhodes P ...
in the journal ''Angewandte Chemie
''Angewandte Chemie'' (, meaning "Applied Chemistry") is a weekly peer-reviewed scientific journal that is published by Wiley-VCH on behalf of the German Chemical Society (Gesellschaft Deutscher Chemiker). Publishing formats include feature-length ...
''. In 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. Corey 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." Corey also hoped that Woodward himself would correct the historical record "as he grew older, more considerate, and more sensitive to his own conscience." Woodward died suddenly of a heart attack in his sleep in 1979.
Awards and honors
E.J. Corey has received more than 40 major awards including the Linus Pauling Award
The Linus Pauling Award is an award recognizing outstanding achievement in chemistry. It is awarded annually by thePuget Sound
Oregon
an
(1973), Franklin Medal
The Franklin Medal was a science award presented from 1915 until 1997 by the Franklin Institute located in Philadelphia, Pennsylvania, U.S. It was founded in 1914 by Samuel Insull
Samuel Insull (November 11, 1859 – July 16, 1938) was a Bri ...
(1978), Tetrahedron Prize The Tetrahedron Prize for Creativity in Organic Chemistry or Bioorganic and Medicinal Chemistry is awarded annually by Elsevier, the publisher of Tetrahedron (journal), Tetrahedron Publications. It was established in 1980 and named in honour of the ...
(1983), Wolf Prize in Chemistry
The Wolf Prize in Chemistry is awarded annually by the Wolf Foundation in Israel. It is one of the six Wolf Prizes established by the Foundation and awarded since 1978; the others are in Agriculture, Mathematics, Medicine, Physics and Arts.
Laure ...
(1986), National Medal of Science
The National Medal of Science is an honor bestowed by the President of the United States to individuals in science and engineering who have made important contributions to the advancement of knowledge in the fields of behavioral and social scienc ...
(1988), Japan Prize
is awarded to people from all parts of the world whose "original and outstanding achievements in science and technology are recognized as having advanced the frontiers of knowledge and served the cause of peace and prosperity for mankind." The P ...
(1989), Nobel Prize in Chemistry
)
, image = Nobel Prize.png
, alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
(1990), Golden Plate Award of the American Academy of Achievement
The American Academy of Achievement, colloquially known as the Academy of Achievement, is a non-profit educational organization that recognizes some of the highest achieving individuals in diverse fields and gives them the opportunity to meet o ...
(1991), Roger Adams Award (1993), and the Priestley Medal
The Priestley Medal is the highest honor conferred by the American Chemical Society (ACS) and is awarded for distinguished service in the field of chemistry. Established in 1922, the award is named after Joseph Priestley, the discoverer of oxygen ...
(2004).[See the E.J. Corey, About E.J. Corey, Major Awards tab
] He was inducted into the Alpha Chi Sigma
Alpha Chi Sigma () is a professional fraternity specializing in the fields of the chemical sciences. It has both collegiate and professional chapters throughout the United States consisting of both men and women and numbering more than 70,000 mem ...
Hall of Fame in 1998.
As of 2008, he has been awarded 19 honorary degrees from universities around the world including Oxford University
Oxford () is a city in England. It is the county town and only city of Oxfordshire. In 2020, its population was estimated at 151,584. It is north-west of London, south-east of Birmingham and north-east of Bristol. The city is home to the ...
(UK), Cambridge University
, mottoeng = Literal: From here, light and sacred draughts.
Non literal: From this place, we gain enlightenment and precious knowledge.
, established =
, other_name = The Chancellor, Masters and Schola ...
(UK), and National Chung Cheng University
National Chung Cheng University (CCU; ) is a national university in Minxiong Township, Chiayi County, Taiwan. CCU is a member of the Association to Advance Collegiate Schools of Business.
History
National Chung Cheng University was the first ...
. In 2013, the E.J. Corey Institute of Biomedical Research (CIBR) opened in Jiangyin, Jiangsu Province, China.
Corey was elected a Foreign Member of the Royal Society (ForMemRS) in 1998.
References
External links
Compiled Works of E.J. Corey
*
Elias James Corey Nobel Lecture
(PDF
Portable Document Format (PDF), standardized as ISO 32000, is a file format developed by Adobe in 1992 to present documents, including text formatting and images, in a manner independent of application software, hardware, and operating systems. ...
)
Podcast interview with E.J. Corey about his Lifelong Pursuit of Learning - May 30, 2018
{{DEFAULTSORT:Corey, Elias James
1928 births
Living people
Members of the United States National Academy of Sciences
20th-century American chemists
21st-century American chemists
Organic chemists
American people of Lebanese descent
Nobel laureates in Chemistry
American Nobel laureates
Harvard University faculty
Wolf Prize in Chemistry laureates
Massachusetts Institute of Technology School of Science alumni
National Medal of Science laureates
Foreign Members of the Royal Society
University of Illinois Urbana-Champaign faculty
People from Methuen, Massachusetts
Lawrence High School (Massachusetts) alumni
Members of the National Academy of Medicine