Corey in 2007
Elias James Corey
July 12, 1928
Methuen, Massachusetts, United States
|Alma mater||Massachusetts Institute of Technology|
|Known for||Retrosynthetic analysis|
|Doctoral advisor||John C. Sheehan|
Elias James "E.J." 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. Regarded by many as one of the greatest living chemists, he has developed numerous synthetic reagents, methodologies and total syntheses and has advanced the science of organic synthesis considerably.
Organic chemistry is a subdiscipline of chemistry that studies the structure, properties and reactions of organic compounds, which contain carbon in covalent bonding. Study of structure determines their chemical composition and formula. Study of properties includes physical and chemical properties, and evaluation of chemical reactivity to understand their behavior. The study of organic reactions includes the chemical synthesis of natural products, drugs, and polymers, and study of individual organic molecules in the laboratory and via theoretical study.
The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature, peace, and physiology or medicine. This award is administered by the Nobel Foundation, and awarded by Royal Swedish Academy of Sciences on proposal of the Nobel Committee for Chemistry which consists of five members elected by Academy. The award is presented in Stockholm at an annual ceremony on December 10, the anniversary of Nobel's death.
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 of the most important branches of organic chemistry. There are several main areas of research within the general area of organic synthesis: total synthesis, semisynthesis, and methodology.
E.J. Corey (the surname was anglicized from the Lebanese Arabic Khoury , meaning priest) was born to Christian Lebanese immigrants in Methuen, Massachusetts, 50 km (31 mi) north of Boston. His mother changed his name to "Elias" to honor his father, who died eighteen months after Corey's birth. His widowed mother, brother, two sisters and an aunt and uncle all lived together in a spacious house, struggling through the Great Depression. As a young boy, Corey was rather independent and enjoyed sports such as baseball, football, and hiking. He attended a Catholic elementary school and Lawrence High School in Lawrence, Massachusetts.
Lebanon, officially known as the Lebanese Republic, is a country in Western Asia. It is bordered by Syria to the north and east and Israel to the south, while Cyprus is west across the Mediterranean Sea. Lebanon's location at the crossroads of the Mediterranean Basin and the Arabian hinterland facilitated its rich history and shaped a cultural identity of religious and ethnic diversity. At just 10,452 km2, it is the smallest recognized sovereign state on the mainland Asian continent.
Arab Christians are Arabs of the Christian faith. Many are descended from ancient Arab Christian clans that did not convert to Islam, such as the Kahlani Qahtanite tribes of Yemen who settled in Transjordan and Syria, as well as Arabized Christians, such as Melkites and Antiochian Greek Christians. Arab Christians, forming Greek Orthodox and Greek Catholic communities, are estimated to be 520,000–703,000 in Syria, 221,000 in Jordan, 134,130 in Israel and around 50,000 in Palestine. There is also a sizable Arab Christian Orthodox community in Lebanon and marginal communities in Iraq, Turkey and Egypt. Emigrants from Arab Christian communities make up a significant proportion of the Middle Eastern diaspora, with sizable population concentrations across the Americas, most notably in Argentina, Brazil, Chile, Mexico, Venezuela, Colombia, and the US.
Methuen is a statutory city and an Atlantic resort town in Essex County, Massachusetts, United States. The population was 47,255 at the 2010 census. Methuen lies along the northwestern edge of Essex County, just east of Middlesex County and just south of Rockingham County, New Hampshire. The irregularly-shaped town is bordered by Haverhill to the northeast, North Andover to the east, Lawrence and Andover to the south, Dracut to the west, Pelham, New Hampshire to the northwest, and Salem, New Hampshire to the north. Methuen is located 30 miles (48 km) north-northwest of Boston and 25 miles (40 km) south-southeast of Manchester, New Hampshire.
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, 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.
A bachelor's degree or baccalaureate is an undergraduate academic degree awarded by colleges and universities upon completion of a course of study lasting three to seven years. In some institutions and educational systems, some bachelor's degrees can only be taken as graduate or postgraduate degrees after a first degree has been completed. In countries with qualifications frameworks, bachelor's degrees are normally one of the major levels in the framework, although some qualifications titled bachelor's degrees may be at other levels and some qualifications with non-bachelor's titles may be classified as bachelor's degrees.
A Doctor of Philosophy is the highest university degree that is conferred after a course of study by universities in most English-speaking countries. PhDs are awarded for programs across the whole breadth of academic fields. As an earned research degree, those studying for a PhD are usually required to produce original research that expands the boundaries of knowledge, normally in the form of a thesis or dissertation, and defend their work against experts in the field. The completion of a PhD is often a requirement for employment as a university professor, researcher, or scientist in many fields. Individuals who have earned a Doctor of Philosophy degree may, in many jurisdictions, use the title Doctor or, in non-English-speaking countries, variants such as "Dr. phil." with their name, although the proper etiquette associated with this usage may also be subject to the professional ethics of their own scholarly field, culture, or society. Those who teach at universities or work in academic, educational, or research fields are usually addressed by this title "professionally and socially in a salutation or conversation." Alternatively, holders may use post-nominal letters such as "Ph.D.", "PhD", or "DPhil". It is, however, considered incorrect to use both the title and post-nominals at the same time.
John Clark Sheehan was an American organic chemist whose work on synthetic penicillin led to tailor-made forms of the drug. After nine years of hard work at the Massachusetts Institute of Technology (M.I.T.), he became the first to discover a practical method for synthesizing penicillin V. While achieving total synthesis, Sheehan also produced an intermediate compound, 6-aminopenicillanic acid, which turned out to be the foundation of hundreds of kinds of synthetic penicillin. Dr. Sheehan's research on synthetic penicillin paved the way for the development of customized forms of the lifesaving antibiotic that target specific bacteria. Over the four decades he worked at M.I.T., Sheehan came to hold over 30 patents, including the invention of ampicillin, a commonly used semi-synthetic penicillin that is taken orally rather than by injection. His research covered not only penicillin, but also peptides, other antibiotics, alkaloids, and steroids.
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.
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 sciences, biology, chemistry, engineering, mathematics and physics. The twelve member presidential Committee on the National Medal of Science is responsible for selecting award recipients and is administered by the National Science Foundation (NSF).
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 nearly 157,000 members at all degree levels and in all fields of chemistry, chemical engineering, and related fields. It is the world's largest scientific society by membership. The ACS is a 501(c)(3) non-profit organization and holds a congressional charter under Title 36 of the United States Code. Its headquarters are located in Washington, D.C., and it has a large concentration of staff in Columbus, Ohio.
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 who immigrated to the United States of America in 1794. The ACS formed in 1876, spearheaded by a group of chemists who had met two years previously in Priestley's home.
E.J. Corey has developed several new synthetic reagents:
Pyridinium chlorochromate (PCC) is a yellow-orange salt with the formula [C5H5NH]+[CrO3Cl]-. It is a reagent in organic synthesis used primarily for oxidation of alcohols to form carbonyls. A variety of related compounds are known with similar reactivity. Although no longer widely used, PCC offers the advantage of the selective oxidation of alcohols to aldehydes or ketones, whereas many other reagents are less selective.
In chemistry, an alcohol is any organic compound in which the hydroxyl functional group (–OH) is bound to a carbon. The term alcohol originally referred to the primary alcohol ethanol, which is used as a drug and is the main alcohol present in alcoholic beverages. An important class of alcohols, of which methanol and ethanol are the simplest members, includes all compounds for which the general formula is CnH2n+1OH. It is these simple monoalcohols that are the subject of this article.
In chemistry, a ketone is an organic compound with the structure RC(=O)R', where R and R' can be a variety of carbon-containing substituents. Ketones and aldehydes are simple compounds that contain a carbonyl group. They are considered "simple" because they do not have reactive groups like −OH or −Cl attached directly to the carbon atom in the carbonyl group, as in carboxylic acids containing −COOH. Many ketones are known and many are of great importance in industry and in biology. Examples include many sugars (ketoses) and the industrial solvent acetone, which is the smallest ketone.
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(VI) metal displacing chlorine. 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).
Chromium is a chemical element with 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 boasts a high usage rate as a metal that is able to be highly polished while resisting tarnishing. Chromium is also the main additive in stainless steel, a popular steel alloy due to its uncommonly high specular reflection. Simple polished chromium reflects almost 70% of the visible spectrum, with almost 90% of infrared light being reflected. The name of the element is derived from the Greek word χρῶμα, chrōma, meaning color, because many chromium compounds are intensely colored.
The chloride ion is the anion Cl−. It is formed when the element chlorine gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride salts such as sodium chloride are often very soluble in water. It is an essential electrolyte located in all body fluids responsible for maintaining acid/base balance, transmitting nerve impulses and regulating fluid in and out of cells. Less frequently, the word chloride may also form part of the "common" name of chemical compounds in which one or more chlorine atoms are covalently bonded. For example, methyl chloride, with the standard name chloromethane is an organic compound with a covalent C−Cl bond in which the chlorine is not an anion.
In organic chemistry, an alkene is an unsaturated hydrocarbon that contains at least one carbon–carbon double bond. The words alkene and olefin are often used interchangeably (see nomenclature section below). Acyclic alkenes, with only one double bond and no other functional groups, known as mono-enes, form a homologous series of hydrocarbons with the general formula CnH2n. Alkenes have two hydrogen atoms fewer than the corresponding alkane (with the same number of carbon atoms). The simplest alkene, ethylene (C2H4), with the International Union of Pure and Applied Chemistry (IUPAC) name ethene, is the organic compound produced on the largest scale industrially. Aromatic compounds are often drawn as cyclic alkenes, but their structure and properties are different and they are not considered to be 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. If this product is undesired, powdered sodium acetate 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 [3,3]-sigmatropic rearrangement.
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 fluorides. 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).
The pKa of dithianes is approximately 30, allowing deprotonation with an alkyl lithium reagent, typically n-butyllithium. 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 electrophiles. 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.
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:
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 [nitrogen], 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 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.
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 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).
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).
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. The mechanism begins with formation of the 2-pyridinethiol ester (scheme 19). 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 (scheme 20).
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.
E. J. Corey and his research group have completed many total syntheses. At least 265 compounds have been synthesized in the Corey group since 1950.
His 1969 total syntheses of several prostaglandins 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 chemist. 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:
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). His books include:
Among the hundreds of graduate students supervised by Corey was Jason Altom.Altom's suicide caused controversy because he explicitly blamed Corey, his research advisor, for his suicide. Corey was devastated and bewildered by Altom's death. 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. Corey is quoted as stating: "That letter doesn't make sense. At the end, Jason must have been delusional or irrational in the extreme." Corey also is on record as stating that 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."
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.
The American Foundation for Suicide Prevention (AFSP) cited The New York Times article on Altom's suicide as an example of problematic reporting,and suggested that Corey was unfairly scapegoated. According to The Boston Globe , Altom's suicide note indicated fear that his career hopes were doomed, but The Globe also cited students and professors as saying that Altom actually retained Corey's support.
As of 2010, approximately 700 people have been Corey Group members. A database of 580 former members and their current affiliation was developed for Corey's 80th birthday in July, 2008.
When awarded the Priestley Medal in 2004, E. J. Corey created a controversy with his claim to have inspired Robert Burns Woodward prior to the development of the Woodward–Hoffmann rules. 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 in the journal Angewandte Chemie . 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.
E.J. Corey has received more than 40 major awards including the Linus Pauling Award (1973), Franklin Medal (1978), Tetrahedron Prize (1983), Wolf Prize in Chemistry (1986), National Medal of Science (1988), Japan Prize (1989), Nobel Prize in Chemistry (1990), Roger Adams Award (1993), and the Priestley Medal (2004).He was inducted into the Alpha Chi Sigma Hall of Fame in 1998. As of 2008, he has been awarded 19 honorary degrees from universities around the world including Oxford University (UK), Cambridge University (UK), and National Chung Cheng University. 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.
The aldol reaction is a means of forming carbon–carbon bonds in organic chemistry. Discovered independently by the Russian chemist Alexander Borodin in 1869 and by the French chemist Charles-Adolphe Wurtz in 1872, the reaction combines two carbonyl compounds to form a new β-hydroxy carbonyl compound. These products are known as aldols, from the aldehyde + alcohol, a structural motif seen in many of the products. Aldol structural units are found in many important molecules, whether naturally occurring or synthetic. For example, the aldol reaction has been used in the large-scale production of the commodity chemical pentaerythritol and the synthesis of the heart disease drug Lipitor.
An enamine is an unsaturated compound derived by the condensation of an aldehyde or ketone with a secondary amine. Enamines are versatile intermediates.
Organolithium reagents are organometallic compounds that contain carbon – lithium bonds. They are important reagents in organic synthesis, and are frequently used to transfer the organic group or the lithium atom to the substrates in synthetic steps, through nucleophilic addition or simple deprotonation. Organolithium reagents are used in industry as an initiator for anionic polymerization, which leads to the production of various elastomers. They have also been applied in asymmetric synthesis in the pharmaceutical industry. Due to the large difference in electronegativity between the carbon atom and the lithium atom, the C-Li bond is highly ionic. Owing to the polar nature of the C-Li bond, organolithium reagents are good nucleophiles and strong bases. For laboratory organic synthesis, many organolithium reagents are commercially available in solution form. These reagents are highly reactive, and are sometimes pyrophoric.
The Claisen rearrangement is a powerful carbon–carbon bond-forming chemical reaction discovered by Rainer Ludwig Claisen. The heating of an allyl vinyl ether will initiate a [3,3]-sigmatropic rearrangement to give a γ,δ-unsaturated carbonyl.
The Corey–Itsuno reduction, also known as the Corey–Bakshi–Shibata (CBS) reduction, is a chemical reaction in which an achiral ketone is enantioselectively reduced to produce the corresponding chiral, non-racemic alcohol. The oxazaborolidine reagent which mediates the enantioselective reduction of ketones was previously developed by the laboratory of Itsuno and thus this transformation may more properly be called the Itsuno-Corey oxazaborolidine reduction.
Aflatoxin total synthesis concerns the total synthesis of a group of organic compounds called aflatoxins. These compounds occur naturally in several fungi. As with other chemical compound targets in organic chemistry, the organic synthesis of aflatoxins serves various purposes. Traditionally it served to prove the structure of a complex biocompound in addition to evidence obtained from spectroscopy. It also demonstrates new concepts in organic chemistry and opens the way to molecular derivatives not found in nature. And for practical purposes, a synthetic biocompound is a commercial alternative to isolating the compound from natural resources. Aflatoxins in particular add another dimension because it is suspected that they have been mass-produced in the past from biological sources as part of a biological weapons program.
Silyl ethers are a group of chemical compounds which contain a silicon atom covalently bonded to an alkoxy group. The general structure is R1R2R3Si−O−R4 where R4 is an alkyl group or an aryl group. Silyl ethers are usually used as protecting groups for alcohols in organic synthesis. Since R1R2R3 can be combinations of differing groups which can be varied in order to provide a number of silyl ethers, this group of chemical compounds provides a wide spectrum of selectivity for protecting group chemistry. Common silyl ethers are: trimethylsilyl (TMS), tert-butyldiphenylsilyl (TBDPS), tert-butyldimethylsilyl (TBS/TBDMS) and triisopropylsilyl (TIPS). They are particularly useful because they can be installed and removed very selectively under mild conditions.
The Jacobson–Corey–Chaykovsky reaction is a chemical reaction used in organic chemistry for the synthesis of epoxides, aziridines, and cyclopropanes. It was discovered in 1961 by A. William Johnson and developed significantly by E. J. Corey and Michael Chaykovsky. The reaction involves addition of a sulfur ylide to a ketone, aldehyde, imine, or enone to produce the corresponding 3-membered ring. The reaction is diastereoselective favoring trans substitution in the product regardless of the initial stereochemistry. The synthesis of epoxides via this method serves as an important retrosynthetic alternative to the traditional epoxidation reactions of olefins.
The Holton Taxol total synthesis, published by Robert A. Holton and his group at Florida State University in 1994 was the first total synthesis of Taxol.
Umpolung or polarity inversion in organic chemistry 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 otherwise not be possible. The concept was introduced by D. Seebach and E.J. Corey. Polarity analysis during retrosynthetic analysis tells a chemist when umpolung tactics are required to synthesize a target molecule.
Schwartz's reagent is the common name for the chemical compound with the formula (C5H5)2ZrHCl, sometimes called zirconocene hydrochloride or zirconocene chloride hydride, and is named after Jeffrey Schwartz, a chemistry professor at Princeton University. This metallocene is used in organic synthesis for various transformations of alkenes and alkynes.
Organozinc compounds in organic chemistry contain carbon to zinc chemical bonds. Organozinc chemistry is the science of organozinc compounds describing their physical properties, synthesis and reactions.
The Kornblum–DeLaMare rearrangement is a rearrangement reaction in organic chemistry in which a primary or secondary organic peroxide is converted to the corresponding ketone and alcohol under acid or base catalysis. The reaction is relevant as a tool in organic synthesis and is a key step in the biosynthesis of prostaglandins.
The Rubottom oxidation is a useful, high-yielding chemical reaction between silyl enol ethers and peroxyacids to give the corresponding α-hydroxy carbonyl product. The mechanism of the reaction was proposed in its original disclosure by A.G. Brook with further evidence later supplied by George M. Rubottom. After a Prilezhaev-type oxidation of the silyl enol ether with the peroxyacid to form the siloxy oxirane intermediate, acid-catalyzed ring-opening yields an oxocarbenium ion. This intermediate then participates in a 1,4-silyl migration to give an α-siloxy carbonyl derivative that can be readily converted to the α-hydroxy carbonyl compound in the presence of acid, base, or a fluoride source.
Oseltamivir total synthesis concerns the total synthesis of the antiinfluenza drug oseltamivir marketed by Hoffmann-La Roche under the trade name Tamiflu. Its commercial production starts from the biomolecule shikimic acid harvested from Chinese star anise with a limited worldwide supply. Due to its limited supply, searches for alternative synthetic routes preferably not requiring shikimic acid are underway and to date several such routes have been published. Control of stereochemistry is important: the molecule has three stereocenters and the sought-after isomer is only 1 of 8 stereoisomers.
The Kuwajima Taxol total synthesis by the group of Isao Kuwajima of the Tokyo Institute of Technology is one of several efforts in taxol total synthesis published in the 1990s. The total synthesis of Taxol is considered a landmark in organic synthesis.
Diisopinocampheylborane is an organoborane that is useful for asymmetric synthesis. This colourless solid is the precursor to a range of related reagents. The compound was reported in 1961 by Zweifel and Brown in a pioneering demonstration of asymmetric synthesis using boranes. The reagent is mainly used for the synthesis of chiral secondary alcohols.
Aspidophytine is an indole alkaloid that has attracted a lot of attention from synthetic chemists. An extract of the cockroach plant, aspidophytine is an insecticidal substance particularly effective against cockroaches. It is one of the two components of the dimer haplophytine.
(R)-2-Methyl-CBS-oxazaborolidine is an organoboron catalyst that is used in organic synthesis. This catalyst, developed by Itsuno and Elias James Corey, is generated by heating (R)-(+)-2-(diphenylhydroxymethyl) pyrrolidine along with trimethylboroxine or methylboronic acid. It is an excellent tool for the synthesis of alcohols in high enantiomeric ratio. Generally, 2-10 mol% of this catalyst is used along with borane-tetrahydrofuran (THF), borane-dimethylsulfide, borane-N,N-diethylaniline, or diborane as the borane source. Enantioselective reduction using chiral oxazaborolidine catalysts has been used in the synthesis of commercial drugs such as ezetimibe and aprepitant.
Proline organocatalysis is the use of proline as an organocatalyst in organic chemistry. This theme is often considered the starting point for the area of organocatalysis, even though early discoveries went unappreciated. Modifications, such as MacMillan’s catalyst and Jorgensen's catalysts, proceed with excellent stereocontrol.
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