Synthesis and peptide coupling of protected 2-pyrrolylalanine

2-Pyrrolylalanine has been synthesized in two protected forms and applied in the solution-phase synthesis of a dipeptide. (2S)-N-(Boc)-N′-(phenylsulfonyl)- and (2S)-N,N′-bis-(phenylsulfonyl)-3-(2-pyrrolyl)alanines (7 and 9) were obtained, respectively, in 14% and 13% overall yields and six and seven steps from oxazolidine β-methyl ester 1, which was derived from l-aspartic acid. Homoallylic ketone 2 was obtained from a copper-catalyzed cascade addition of vinylmagnesium bromide to 1 and converted into pyrrolylalanines 7 and 9 by a sequence featuring subsequent olefin oxidation and Paal-Knorr condensation. Protected pyrrolylalanine 9 was then introduced into a dipeptide.