Lactols, silylated. reduction

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. 

It appears that the counterion on the alkoxide has some remediating effects. For example, the NaBHq reduction of the lactol affords only the product of silyl migration... 

Completion of the synthesis was readily achieved. Diastereoselective reduction of the ketone was accomplished with (S)-BINOL/LiAlH4. Then, removal of the tether by acidic hydrolysis, which also effected silyl ether deprotection, afforded dihydroxy lactol 223 allowing introduction of the final side chain using a Wittig reaction (Scheme 10-71). 

The 5-lactols and their acetylated derivatives (2, 8) are activated by acid to form oxonium cation intermediates (3, 9), which are attacked by nucleophiles to provide the substituted tetrahydropyrans with good stereoselectivity (Scheme 3) [13]. As the nucleophiles, allylsilane 4 (Hosomi-Sakurai reaction), silyl enol ethers 5 (Mukaiyama aldol) and EtaSiH (reduction) have frequently been used. Since the axial attack of the nucleophiles determines the product s... 

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