Enones conjugate additions, chlorotrimethylsilane

MeOC6H4, respectively. The titanium enolates were converted into silyl enol ethers 54 by treatment with chlorotrimethylsilane and lithium isopropoxide. Additionally, cyclic enones lb and Ic, and linear enones Id and le, are also good substrates for the asymmetric conjugate addition of phenyltitanium triisopropoxide, giving the corresponding arylation products with over 97% enantioselectivity. 

Besides simple enones and enals, less reactive Michael acceptors like /3,/3-disubstituted enones, as well as a,/3-unsaturated esters, thioesters, and nitriles, can also be transformed into the 1,4-addition products by this procedure.44,44a,46,46a The conjugate addition of a-aminoalkylcuprates to allenic or acetylenic Michael acceptors has been utilized extensively in the synthesis of heterocyclic products.46-49 For instance, addition of the cuprate, formed from cyclic carbamate 53 by deprotonation and transmetallation, to alkyl-substituted allenic esters proceeded with high stereoselectivity to afford the adducts 54 with good yield (Scheme 12).46,46a 47 Treatment with phenol and chlorotrimethylsilane effected a smooth Boc deprotection and lactam formation. In contrast, the corresponding reaction with acetylenic esters46,46a or ketones48 invariably produced an E Z-mixture of addition products 56. This poor stereoselectivity could be circumvented by the use of (E)- or (Z)-3-iodo-2-enoates instead of acetylenic esters,49 but turned out to be irrelevant for the subsequent deprotection/cyclization to the pyrroles 57 since this step took place with concomitant E/Z-isomerization. 

Better stereosdectivities have been noted for conjugate addition reactions to the steroidal enone 95 (Scheme 6.20, Tab. 6.2). Irrespective of the enone geometry, addition of lithium dimethylcuprate provided the anti addition product 96 in hi yid-d and with good diastereoselectivity (Tab. 6.2, entries 1 and 2). Interestin y, addition of chlorotrimethylsilane to the reaction mixture had a dramatic effect. The E isomer of enone 95 still gave the anti addition product 96 with perfect stereoselectivity (entry 3). "With the 2 isomer of the enone, however, the syn addition product 97 was formed in good yield and with hi diastereoselect vity (entry 4)... 

This cuprate also underwent the conjugate addition with acyclic enones, for example, 2-hexene-4-one, to give 5-methyl-3-tridecanone in 47% yield. We have not attempted further optimization. Reaction of this calcium cuprate with a sterically hindered enone, for example, isophorone, produced <3% of the desired compound in 24h. The isolated yield, however, increased to 84% when the additives BF3 etherate and chlorotrimethylsilane [12] were used. In the aryl case, / -tolylcalcium cuprate also underwent this transformation with 2-cyclohexenone to give 3-(p-methylphenyl)cyclohexanone in reasonable yield (Table 9.3). 

The role of chlorotrimethylsilane (TMSCl) in accelraating organocuprate conjugate additions continues to arouse much discussion. It has been proposed that TMSCl acts as a Lewis acid in complexing the enone. However, high level ab initio calculations have shown that such complexation is only a weak dipole-dipole inteaction, and cannot... 

Reaction of the lithium enolate of (1) followed by reaction with chlorotrimethylsilane provides ketene acetal (3). This enol reacts with aldehydes in the presence of a Lewis acid to provide unsaturated esters (eq 7). With conjugated enones, (3) undergoes conjugate addition when Titanium(IV) Chloride is used as catalyst (cf. eq 5). ... 

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