Thio-Claisen Rearrangement Used in Preparing Anti-β-Functionalized γ,δ-Unsaturated Amino Acids: Scope and Limitations

Multifunctionalized amino acids, especially amino acids with unsaturation, are important, demanding building blocks in peptide chemistry. Here we present a summary of our most recent study using the thio-Claisen rearrangement for the synthesis of anti-beta-functionalized gamma,delta-unsaturated amino amino acids. Investigations on scope, limitations, chemoselectivities and stereoselectivities regarding an FeBr3-catalyzed allylation strategy and a thio-enolate dianion formation strategy for asymmetric thio-Claisen rearrangement are documented. An explanation of the chirality crossover observed between the Eschenmoser-Claisen rearrangement and the thio-Claisen rearrangement is proposed. Novel optically active N-1-protected amino acids with biologically interesting functional groups were prepared for the first time.