Synthesis of (+)-Chokol A by a Tandem Michael-AdditiodDieckmann C ycliza tion

(-)-Chokol A is a fungitoxic modified sesquiterpene isolated from the stromata of timothy grass Phleum prutense infected by the pathogenic fungus Epichloe typhinu. Isolated for the first time in 1985 by Yoshihara et al.C2I, (-)-chokol A and the more active chok01s B, CL3], D and Gl4] have recently received special attention due to their fungitoxic proper tie^[^]. So far, two syntheses for racemic chokol A (12) and two enantioselective ones have been described. In 1986 Oppolzer et al. reported on a 12-step synthesis of racemic chokol with an overall yield of 3%. Key step of this synthesis was a stereoselective magnesiumene reaction. In 1988 Lawler and Simpkins synthesized (k)-chokol A (12) in six steps via a conjugate addition/alkylation reaction in an overall yield of 32%[']. Unfortunately, the use of toxic and carcinogenic HMPTA could not be avoided. Moreover, the conjugate addition step remains problematic since the yield varies between 30-52%. In 1987 Mash presented the first asymmetric synthesis of (-)-chokol A[*]. Key step of this synthesis was a diastereoselective cyclopropanation of a chiral ketal. The overall yield was 9% over 13 steps with an enantiomeric excess of approximately 80%. The last synthesis of (-)-chokol A was described by Suzuki et al. in 1992191. They converted the well-established (R)-2,3-O-isopropylideneglyceraldehyde[lO] in 21 steps into (-)-chokol A with an overall yield of 4%.