Diastereoselective synthesis of 2-alkylated 4-silyloxyproline esters

Abstract

Treatment of the 4-silyloxy-N-Boc-L-proline methyl ester 1 with allyl bromide in the presence of LDA in THF at −78 °C gives a mixture of the (2S,4R)- and (2R,4R)-2-(prop-2-enyl)-4-silyloxy-N-Boc-L-proline esters 2a and 2b in 75% combined yield in the ratio 53 ∶ 47. In contrast, similar treatment of the (−)- and (+)-menthyl esters 5 and 6 gives a mixture of allylated products 7a,b and 8a,b in the ratio 75 ∶ 25 and 89 ∶ 11, respectively. Reaction of 6 with methyl iodide and propyl iodide also give the corresponding 2-alkylated esters 16a and 16b in a highly diastereoselective manner (94 ∶ 6 and 93 ∶ 7, respectively).