New Routes to Lipophilic Amino Acids: Synthesis of Alkynyl and Fluoro-Containing Alanine Derivatives

Branched alpha-amino acids incorporating an alkynyl group have been prepared by copper-catalysed reaction of a serine-derived organozinc reagent with bromoallenes. Substantial improvements to our previously reported Negishi cross-coupling of the serine-derived organozinc reagent with cycloalkenyl triflates are possible using a combination of LiCl and SPhos as ligand. Finally, we report a preliminary example of addition of HF to cycloalkenyl alanine derivatives, leading to the corresponding tertiary fluoride.