Total synthesis of (R)-sarkomycin via asymmetric rhodium-catalyzed conjugate addition.
(R)-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.
Fachbereich Chemie, Philipps-Universität Marburg , 35032 Marburg, Germany.
Johannes
J
Westmeier
Steffen
S
Kress
Christopher
C
Pfaff
Paultheo
P
von Zezschwitz
D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry; D008872:Microwaves; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
D002264:Carboxylic Acids; D003517:Cyclopentanes; D012238:Rhodium; C092083:sarkomycin A