Silylcupration

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. 

Bienz et al. have prepared functionalized a-amino acids containing Si that are derivatives of serine and methionine.191 Saturated and unsaturated 7-trialkylsilyl-substituted a-amino acid derivatives 30-35 have been prepared stereoselectively by Reginato et a/.192 193 The synthetic approach involves a silylcupration of chiral-protected 4-ethynlyloxazolidine (Scheme 5). 

Scheme 3.1. Reactivity profile of silylcuprates with carbon electrophiles [14ej.

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]. 

Scheme 3.16. Silylcupration of alkynes with (t-BuPh2Si)2CuLi-LiCN and electrophilic trapping of the vinylcuprate reagent [69].

Silylcupration also works with 1-aminoalkynes [70], propargyl sulfides [71], prop-argyl amines [14a, 72] - where it has been exploited in the synthesis of saturated and unsaturated y-silyl-a-amino acids (Scheme 3.17) - and propargyl ethers, where... 

Scheme 3.17. Synthesis of functionalized a-amino acids by silylcupration [72a] or stannylcupration [81c] of chiral propargyl amines (Boc = t-butoxycarbonyl TFA = trifluoroacetic acid).

Scheme 3.18. Ring-formation by intramolecular trapping of the vinylcuprates resulting from silylcupration of alkynes with magnesium silylcuprates [75a] or lithium silylcuprates (mCPBA = m-chloroperbenzoic acid) [75bj.

Scheme 3.24. Silylcupration and stannylcupration of allenes under kinetic and thermodynamic control [37c, 67, 95, 96].

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