Substrate-Controlled Asymmetric Total Syntheses of Microcladallenes A, B, and C Based on the Proposed Structures.

Substrate-controlled asymmetric total syntheses of (+)-microcladallenes A, B, and C have been accomplished based on the proposed structures. The syntheses of microcladallenes A and B confirmed the structures and absolute configurations of both natural products. However, the synthesis of microcladallene C, which includes seven stereogenic centers and an (R)-bromoallene in its compact C15 framework, brought the realization that its proposed structure must be revised. The introduction of C12-bromine into these natural products with retention of configuration relied on TiBr4 -mediated nucleophile-assisting leaving group brominations, the stereochemical outcome of which could be attributed, at least in part, to an oxonium or halonium ion formation-fragmentation sequence through intricate neighboring group participation. In addition, the pivotal β-oriented vicinal cis-dichloride function in microcladallene C was elaborated through a novel tandem Cl2 -induced electrophilic cyclization/imidate chlorination process. The positive rotations of these natural products with an (R)-bromoallene constitute exceptions to Lowe's rule for reasons yet to be determined.