Tertiary and Quaternary Carbon Bond Formation

A general method for the diastereoselective formation of adjacent quaternary carbon atoms is a challenging process that has many inherent problems. Due to steric issues, alkylation and substitution reactions often fall short as sufficient means to construct these complex molecules [14]. Gilbert and Kelly were extremely 

1 1 mixture of trimethylsilylchloride (TMSCl) and triethylamine. It was observed that by adding hexamethylphosphoramide (HMPA) after the addition of TMSCl the yield increased from 55 to 76%. The Carroll rearrangement of the newly formed silyl ketene acetal proceeded smoothly after the reaction mixture was warmed to 40 °C and the resulting acid 8 was converted directly into the methyl ester 9 in good overall yield (76%). 

30 and 31 smoothly rearranged into ketones 32 and 33 in 65 and 70% yields, respectively. Ozonolysis and subsequent methylation of the resulting acids gave the desired diketoesters 34 and 35, which were converted into the enantiomeri-cally pure side chain alcohols 27a and 27b in three additional steps. 

Z-j0-keto ester 58, but proved to be unsuccessful. When 58 was treated with 2 eq. of LDA no desired product was obtained. When the silyl ketene acetal of 58 was formed and heated under reflux, only a very small amount of 56 and 57 was obtained. This mixture, when subjected to ozonolysis and acetylation, gave a 1.5 1 mixture of 52 and 54. 

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