Directed Conjugate Addition Reactions

Sdieme 6.23. Di a stereo selective cuprate addition to i9- fiinctionalized enoates 10S—107. 

Interestingly even derivative 113 vtith the carbamate-functionalized stereogenic center in the tS-position exhibited significant levels of diastereoselectivity to give ester 114 (Sdieme 6.24). In this case hov/evep the syn addition product 114 was formed as the major isomer. 

6 Copper-mediated Diastereosefeetive Conjugate Addition and AHyHe Substitution Reactions 

Auxiliary-bound Chiral Michael Acceptors and Auxiliary Chiral Metal Complexes 

Diastereoselective conjugate additions to chiral Michael acceptors in which the part initially bearing the chiral information is removable (ie. a chiral auxiliary) provides a means to synthesize enantiomericalLy pure conjugate adducts. Chiral auxiliaries should ideally be readily available in both enantiomeric forms. They should 

It has been proposed dial a directed cuprate addilioti widi a carbamate or a carbonate serving as a reagenl-directing functional group may account for die stereo-clieniical outcome of diese reactions fsee models 115 and 116 in Sclieme 6.25) [39, 

Entry Enoate Proifoct Yield (%l atili. syti 

204 1 6 Coppei-medloted DIoste.e selectlue Coy gate Additio, o. d Allylic Reoa o. s 

6 Copper-mediated Diastereoselective Conjugate Addition and Allylic Substitution Reactions 

Most of the useful auxiliaries are chiral amine or alcohol derivatives readily available from the chiral pool, and most of them possess rigid cyclic or bicyclic structures to allow efEcient differentiation of the two competing diastereomorphic transition states. In some cases, additional rigidity was achieved with the aid of an external chelating Lewis acid (entries 6, 10, 12). In certain cases, however, acyclic auxiliaries may also be useful (see entry 15). 

As well as organic chiral auxiliaries, organometallic fragments have found some application as chiral auxiliaries in conjugate addition reactions. Particularly noteworthy are chiral molybdenum allyl complexes [69], chiral iron complexes [70], and planar chiral arene chromium species [71]. 

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Cooke, M.P., Jr., and Jaw. J.Y.. Cyclopropane derivatives through charge-directed conjugate addition reactions of unsaturated acylphosphoranes.. /. Org. Chem.. 51, 758, 1986. 

These compounds are not isolated, but used directly in situ for conjugate addition reactions (15-24). Another method for the preparation of such reagents (but with Zn instead of Li) allows them to be made from a-acetoxy halides ... 

This chapter will begin with a discussion of the role of chiral copper(I) and (II) complexes in group-transfer processes with an emphasis on alkene cyclo-propanation and aziridination. This discussion will be followed by a survey of enantioselective variants of the Kharasch-Sosnovsky reaction, an allylic oxidation process. Section II will review the extensive efforts that have been directed toward the development of enantioselective, Cu(I) catalyzed conjugate addition reactions and related processes. The discussion will finish with a survey of the recent advances that have been achieved by the use of cationic, chiral Cu(II) complexes as chiral Lewis acids for the catalysis of cycloaddition, aldol, Michael, and ene reactions. 

Oxazoline-directed conjugate addition of nucleophiles to a naphthalene nucleus is one of the most useful methods to prepare dihydronaphthalenes. Since Meyers last comprehensive review, the focus has been directed to stereoselective synthesis of these important compounds. Meyers laboratory has continued their preeminence in this field and has expanded the scope and applications of this reaction. 

As with mechanism, the stereochemical outcome of tandem vicinal difunctionalization is dependent upon the individual bond-forming steps in the sequence. The conjugate addition reaction is quite sensitive to the steric environment of the a,(3-unsaturated substrate, so that the bond-forming process at the 3-carbon adheres to steric approach control factors the 5-methoxycarbonyl substituent of (5) directs axial attack of a bis(dimethylphenylsilyl)copperlithium reagent so that only the 3,5-trans adduct is formed... 

The highly enantioselective direct conjugate addition of ketones to nitroalkenes has been promoted by a chiral primary amine-thiourea catalyst (7).31 The observed anti diastereoselectivity has suggested participation of a (Z)-enamine intermediate, given (g) the complementary diastereoselectivity obtained in analogous reactions involving (E)-enamines generated from secondary amine catalysts. 

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