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-β-functionalized γ,δ-unsaturated
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 Nα-protected amino acids with biologically
interesting functional groups were prepared for the first time.