Silylcuprates 1,4-addition

Allylsilanes in which the silyl group is at the more substituted end of the allyl system have been prepared by a reaction sequence involving the conjugate addition of silylcuprates to a, jS-unsat-urated esters followed by reduction and dehydration via selenoxide elimination38. 

This reagent reacts with a,/3-unsaturated ketones to give kinetic products of exclusive 1,4-addition (2). With cyclic substrates, a strong preference for axial addition is observed, as is a susceptibility to steric hindrance. Transformation into the corresponding silylcuprate species permits conjugate addition to a wider variety of a,/3-unsaturated substrates (3,4). 

The 1,4-addition of RCu to a diene compound can generate allylcopper species, which is active toward electrophiles.53 The silylcupration of 1,3-dienes with PhMe2SiCuCNLi56 followed by reaction with C02 yielded the /3,7-unsaturated carboxylic acids 110 as shown in Scheme 39.57 The carboxylation took place regioselectively at the 7-position of the cr-allylcopper intermediate 113. 

Scheme 3.3. Conjugate addition reactions of silylcuprates and zincates in the presence and absence ofTMSCI [43].

The silylcuprate conjugate addition reaction has been used for the protection of an enone double bond, which can be regenerated with CuBr2 [22a], and for the strategic introduction of the silyl substituent for stereocontrol and regiocontrol purposes. Enantiopure 5-trimethylsilyl-2-cyclohexenone can be prepared by conjugate addition reaction [44] and the appropriate enantiomer has been converted into a number of natural products (Scheme 3.4) [38]. These synthetic strategies exploit... 

Scheme 3.S. Silylcuprate conjugate addition in syntheses of (+)-compactin, (-l-)-mevinolin, and (+)-pravastatin [45].

Scheme 3.6. Diastereoselectivity in silylcuprate conjugate addition-alkylation (alkyl halides) or protonation reactions with a,/S-enoates [46],...

Scheme 3.7. Diastereoselective formation of /S-silyl ( )- or (Z)-ester enolates by silylcuprate conjugate addition followed by alkylation with aldehydes [49]. Stereoselective synthesis of ( )-and (Z)-allyl silanes [50].

Silylcuprates have been reported to undergo reactions with a number of miscellaneous Michael acceptors [65]. Conjugate addition to 3-carbomethoxy acyl pyri-dinium salts [65a] affords 4-silyl-l,4-dihydropyridines. Oxidation with p-chlorand generates a 4-acyl pyridinium salt that gives the 4-silylnicotinate upon quenching with water, and methyl 4-silyl-2-substituted dihydronicotinates upon quenching with nucleophiles (nucleophilic addition at the 6-position). The stabilized anion formed by conjugate addition to an a, j8-unsaturated sulfone could be trapped intramolecularly by an alkyl chloride [65b]. 

The (diastereoselective) conjugate addition of silylcuprate reagents to a variety of chiral derivatives of a,(3-unsaturated carboxylic acids can be used to prepare optically active p-silyl esters.258 259 Best results are obtained with substrates of type (25). The (related) p-silyl ketones, which also constitute valuable building blocks for (acyclic) stereoselective synthesis, are now accessible in high ee via palladium-catalyzed enantioselective 1,4-disiiylation of a,p-unsaturated ketones (Scheme 76).260... 

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