Total Synthesis of (<i>R</i>)‑Sarkomycin
via Asymmetric Rhodium-Catalyzed Conjugate Addition
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Abstract
(<i>R</i>)-Sarkomycin was prepared using a five-step
total synthesis. Key steps in the enantioselective construction of
the targeted scaffold were a rhodium-catalyzed asymmetric conjugate
alkenyl addition with subsequent silyl trapping and a Mukaiyama aldol
reaction with aqueous formaldehyde. Protection of the hydroxy group
as a THP acetal and oxidative cleavage of the C,C-double bond provided
a stable direct precursor to the natural product. The final liberation
was carried out under slightly acidic conditions in a microwave-assisted
reaction, resulting in a high yield of the “deceptive”
sarkomycin. This represents the shortest enantioselective synthesis
of this rather unstable compound to date and the first to employ asymmetric
catalysis to introduce the stereogenic center