Reductive silylation Tetrabutylammonium fluoride

Chlorophenyl)glutarate monoethyl ester 87 was reduced to hydroxy acid and subsequently cyclized to afford lactone 88. This was further submitted to reduction with diisobutylaluminium hydride to provide lactol followed by Homer-Emmons reaction, which resulted in the formation of hydroxy ester product 89 in good yield. The alcohol was protected as silyl ether and the double bond in 89 was reduced with magnesium powder in methanol to provide methyl ester 90. The hydrolysis to the acid and condensation of the acid chloride with Evans s chiral auxiliary provided product 91, which was further converted to titanium enolate on reaction with TiCI. This was submitted to enolate-imine condensation in the presence of amine to afford 92. The silylation of the 92 with N, O-bis(trimethylsilyl) acetamide followed by treatment with tetrabutylammonium fluoride resulted in cyclization to form the azetidin-2-one ring and subsequently hydrolysis provided 93. This product was converted to bromide analog, which on treatment with LDA underwent intramolecular cyclization to afford the cholesterol absorption inhibitor spiro-(3-lactam (+)-SCH 54016 94. 

In analogy to the preparation of the cyclopropanone hemiacetal 3 (vide supra, Eq. (1)7), reductive cyclization of the piperidide of 3-chloropropionic acid 193 with sodium in ether in the presence of ClSiMe3, gave the 1-piperidino-l-trimethylsilyloxy-cyclopropane 194 a which was converted to the cyclopropanol 194 b upon treatment with methanolic tetrabutylammonium fluoride. Both 194 a and 194 b can be used for the ready generation of cyclopropane derivatives thus the silyl ether 194a could be reacted directly with the vinylic Grignard reagents 195 to provide the vinyl cyclopropane derivative 196, (Eq. (61)128). 

Numerous organometal additions onto ene-sulfones are reported. A sulfonyl group secures powerful activation, and moreover, it can be readily removed by reduction or elimination. This makes the sulfonyl function a cherished auxiliary in natural product synthesis. A rational entry to d-(+)-carbacyclin (in 4.7% overall yield by a triply convergent synthesis) exemplifies the approach. The addition of the silyl-protected trans-(5)-3-hydroxy-l-octenyllithium onto cyclopentenyl phenyl sulfone 162 triggers a condensation with the allyl chloride tail. The carbacyclin skeleton constructed, the sequence is terminated by protodesilylation (using tetrabutylammonium fluoride hydrate), reductive removal (with lithium) of benzyl and benzenesulfinyl, and selective oxidation of the primary alcohol site (Scheme 1-117). ... 

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