Corey reagent, functionalization

One of the important functionalizations of the keto function is the epoxidation using the Corey reagent (dimethylsulfoniumethylide in DMSO and THF) as reported by Qelas and Gelas (41,42) (Scheme 10). 

The electrophilic reactivity of the j3-carbon in an a/S-unsaturated aldehyde is reversed in l,3-bis(methylthio)allyl-lithium (151), derived by metallation of l,3-bis(methylthio)-2-methoxypropane with lithium di-isopropylamide this reagent functions as the synthetic equivalent of the unknown p-formylvinyl anion (152) in the preparation of a number of ay -unsaturated aldehydes, as exemplified in Scheme 72. Corey has utilized this reagent further in a total synthesis of prostaglandin p2 . 

Corey and Chaykovsky had discovered that dimethyl sulfoxide is converted to methyl-sulfinyl carbanion upon treatment with sodium hydride114 and that this conjugate base of DMSO reacts with various electrophiles115. This finding has opened up various reactions with a-sulfmyl carbanions derived from sulfoxides, since the sulfinyl function can be removed either by thermolysis or by subjecting the compound to reductive desulfurization. Thus a-sulfmyl carbanions have become versatile synthetically useful reagents. 

A more subtle example of identical functional groups with different steric enviroment is found in the intermediate H which Corey [8] uses in the synthesis of fumagillin (13). The two identical secondary hydroxyl groups in the cyclohexane derivative H can be differentiated by using a bulky reagent since the axially disposed hydroxyl group is less accesible than the one which is equatorially disposed and can be chemoselectively methylated (12) in the presence of sodium rert-amylate (Scheme 12.2). 

If the presence of sensitive functional groups poses problems of chemose-lectivity in the use of hard allylic metal reagents, allylboronate derivatives also can be accessed by a milder transmetalation of allylic tin species with boron halides.This approach has been used by Corey in the synthesis of chiral bis(sulfonamido)boron reagents such as the medially 1 reagent 15 (Eq. 19) (see section Chiral Boronate Derivatives ). ... 

Wittig reagents can represent enolates of unsymmetrical ketones. From Corey s work on arachidonic acid metabolites18 comes the coupling between the aldehyde 92 and the phosphonium salt 93. This is very impressive as both components have multiple functionality and there is no loss of stereochemical integrity even though the Wittig reaction is done in aqueous NaOH. 

The pioneering studies by Itsuno [1] and Corey [2] on the development of the asymmetric hydroboration of ketones using oxazaborolidines have made it possible to easily obtain chiral secondary alcohols with excellent optical purity [3]. Scheme 1 shows examples of Corey s (Corey-Bakshi-Shibata) CBS reduction. When oxazaborolidines 1 were used as catalysts (usually 0.01-0.1 equiv), a wide variety of ketones were reduced by borane reagents with consistently high enan-tioselectivity [2]. The sense of enantioselection was predictable. Many important biologically active compounds and functional materials have been synthesized using this versatile reaction [2-4]. 

Corey s double activation procedure (Method 2) does not use an external reagent to activate the functional group, but effects cyclization by heating a solution of the 2-pyridinethiol ester of a hydroxy acid for a prolonged period. Several pieces of evidence point to the intermediacy of 2 in this lactonization.10 If one accepts this intermediate, it follows that a hydroxy(2-pyridinethiolJ ester, heavily substituted near the reaction centers (i.e., near the hydroxyl and acyl groups), would encounter a high... 

The reagent was used by Corey and Kim in an improved synthesis of prostaglandins. Thus oxidation of the hydroxy acid (5) to the keto acid (6) was effected in > 90% yield with ase of N-cblorosuccinimide-dimethyl sulfide. The oxidation had been carried out previously with Jones reagent at —20° in about 70% yield. The carboxyl function... 

Functional group manipulation now gives the aldehyde 173 ready for addition to the vinyl-lithium reagent 165. The product was trapped as the MEM (methoxy-ethoxy-methyl-) derivative 174 in a very high yield but without any stereoselectivity. Fortunately, Corey already knew how to control the stereochemistry at the two OH groups by oxidation to ketones and stereoselective reduction so the synthesis could be completed. 

Oxidation of alcohols. This stable reagent, prepared from t-BuNH2 by N,N-dichlorination and then treatment with PhSAc, functions in the same fashion as the reactive species generated in the Swem and Corey-Kim oxidations. With which efficient oxidation of alcohols is performed in dichloromethane in the presence of DBU (11 examples, 90-99%). ... 

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