Enantioselective total synthesis of epothilones A and B using multifunctional asymmetric catalysis

An enantioselective total synthesis of epothilones A (1) and B (2) using mu ltifunctional asymmetric catalysis such as a cyanosilylation of an aldehyde , an aldol reaction of an unmodified ketone with an aldehyde, and a protona tion in the conjugate addition of a thiol to an alpha,beta -unsaturated thi oester has been achieved. We divided 1 and 2 into fragment A, fragment B, a nd fragment C. A catalytic asymmetric synthesis of fragments A and B was ac complished using a catalytic asymmetric cyanosilylation as a key step. An e nantiocontrolled synthesis of fragment C was achieved in two ways. One is t he use of a direct catalytic asymmetric aldol reaction of an unmodified ket one with an aldehyde as a key step, and the other utilizes a catalytic asym metric protonation in the conjugate addition of a thiol to an alpha,beta -u nsaturated thioester as a key step. Suzuki cross-coupling of fragment A wit h fragment C followed by Yamaguchi lactonization as key steps led to an ena ntiocontrolled synthesis of epothilone A (1). On the other hand, Suzuki cro ss-coupling of fragment B with fragment C followed by Yamaguchi lactonizati on accomplished an enantiocontrolled synthesis of epothilone B (2).