Corey epoxidation

Ring expansion by one carbon atom, for instance by the use of a Tiffeneau-Dem-janov rearrangement, provides access to the series of odd-numbered macrocyclic systems. The precursor is readily available through cyanhydrin formation and hydrogenation, or Corey epoxidation and epoxide ring-opening with ammonia... 

Regioselectivity of C—C double bond formation can also be achieved in the reductiv or oxidative elimination of two functional groups from adjacent carbon atoms. Well estab llshed methods in synthesis include the reductive cleavage of cyclic thionocarbonates derivec from glycols (E.J. Corey, 1968 C W. Hartmann, 1972), the reduction of epoxides with Zn/Nal or of dihalides with metals, organometallic compounds, or Nal/acetone (seep.lS6f), and the oxidative decarboxylation of 1,2-dicarboxylic acids (C.A. Grob, 1958 S. Masamune, 1966 R.A. Sheldon, 1972) or their r-butyl peresters (E.N. Cain, 1969). 

In the last fifteen years macrolides have been the major target molecules for complex stereoselective total syntheses. This choice has been made independently by R.B. Woodward and E.J. Corey in Harvard, and has been followed by many famous fellow Americans, e.g., G. Stork, K.C. Nicolaou, S. Masamune, C.H. Heathcock, and S.L. Schreiber, to name only a few. There is also no other class of compounds which is so suitable for retrosynthetic analysis and for the application of modem synthetic reactions, such as Sharpless epoxidation, Noyori hydrogenation, and stereoselective alkylation and aldol reactions. We have chosen a classical synthesis by E.J. Corey and two recent syntheses by A.R. Chamberlin and S.L. Schreiber as examples. 

The Corey-Chaykovsky reaction entails the reaction of a sulfur ylide, either dimethylsulfoxonium methylide (1, Corey s ylide, sometimes known as DMSY) or dimethylsulfonium methylide (2), with electrophile 3 such as carbonyl, olefin, imine, or thiocarbonyl, to offer 4 as the corresponding epoxide, cyclopropane, aziridine, or thiirane. ... 

Epoxidation of aldehydes and ketones is the most profound utility of the Corey-Chaykovsky reaction. As noted in section 1.1.1, for an a,P-unsaturated carbonyl compound, 1 adds preferentially to the olefin to provide the cyclopropane derivative. On the other hand, the more reactive 2 generally undergoes the methylene transfer to the carbonyl, giving rise to the corresponding epoxide. For instance, treatment of P-ionone (26) with 2, derived from trimethylsulfonium chloride and NaOH in the presence of a phase-transfer catalyst Et4BnNCl, gave rise to vinyl epoxide 27 exclusively. ... 

Isolated carbonyls always give epoxides from the Corey-Chaykovsky reaction. Take the aldehyde substrate as an example. Spiro epoxide 30 was produced from the reaction of trisnorsqualene aldehyde 28 (R20 represents the polyene side-chain with 20 carbons) with substituted sulfur ylide 29, prepared in situ from cyclopropyldiphenylsulfonium tetrafluoroborate and KOH. " For the epoxidation of ketones, the Corey-Chaykovsky reaction works well for diaryl- (31), arylalkyl- (32), ... 

The Corey-Chaykovsky reaction incited some applications in medicinal chemistry. During the synthesis of analogs of fluconazole, an azole antifungal agent, treatment of 49 with 1 led to the corresponding epoxide, which was subsequently... 

Corey s ylide (1), as the methylene transfer reagent, has been utilized in ring expansion of epoxide 75 and arizidine 77 to provide the corresponding oxetane 76 and azetidine 78, respectively. 

Corey s sulfonium ylide methodology32 was then adopted. As shown in Scheme 7-51, conversion of ketone 161 to spiroepoxide 165 proceeded with high yield, and a Lewis acid-induced epoxide opening gave the desired allylic alcohol 164 with perfect yield. 

E. J. Corey, F.-Y. Zhang, Mechanism and Conditions for Highly Enantioselective Epoxidation of a,p-Enones Using Charge-Accelerated Catalysis by a Rigid Quaternary Ammonium Salt , Org. Lett. 1999,1,1287-1290. 

Along with catalytic asymmetric epoxidation, the related dihydroxylation of olefins is another venerable catalytic enantioselective process that is widely used by the modern organic chemist. An application of this important transformation may be found in Corey s 1994 preparation of optically pure 109 (Scheme 16), an intermediate in Corey s 1985 total synthesis of ovalicin.1181 The catalytic asymmetric dihydroxylation that affords 108 solves one of the most challenging problems in the total synthesis installment of the tertiary alcohol center with the appropriate relative and absolute stereochemistry. 

Palucki, M. Jacobsen-Katsuki epoxidation In Name Reactions in Heterocyclic Chemistry, Li, J. J. Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2005, 29—43. (Review). 

Polycyclic oxasqualenoid glabrescol was synthesized by Corey and coworkers in order to confirm its structure. Several pentaoxacyclic compounds were synthesized via epoxidation with ketone 26 followed by cyclizations [90]. Finally, compound 48 was synthesized to match the properties of the naturally occurring glabrescol, leading to the determination of the stereochemistry of glabrescol (Scheme 7) [91]. 

A weak base such as glycine added to [HMIMjPFg has also been reported to catalyze a Knoevenagel reaction of malononitrile and benzaldehyde 110). A KOH-treated [BMIMjPFg also provides a suitable medium for the Corey-Chaykovsky epoxidation of enones and cyclopropanation of aldehydes using trimethyl sulfonium iodide (///). 

In a marked contrast to the lighter pnictogen (P, As, Sb) elements, this class of bismuth ylides readily undergoes Corey-Chaycovsky-type epoxidations with aromatic, aliphatic, and ot,(3-unsaturated aldehydes to afford the corresponding... 

Scheme 6.30 Typical epoxides obtained from the Corey-Chaykovsky epoxidation of aldehydes catalyzed by urea 16.

Also, the reaction pathways of the Corey-Chaykovsky epoxidation reaction have been compared quantum-chemically <1999JOC4596>. As models for one transition state, 1,3-oxathiane compounds such as 52, suitably substituted to allow comparison with experiment (Equation 3), were calculated and these predicted both the absolute stereochemistry of the main product 53 and the distribution of the other stereoisomers, as supported by experimental results. Thus, this theoretical study was able to identify the transition state which proved to be responsible for the stereoselectivity of the catalytic Corey-Chaykovsky epoxidation reaction. 

SCHEME 29. Corey mechanism of Ti-catalyzed epoxidation of allylic alcohols. 

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