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

• Published in: Chemistry : a European journal Vol. 21; no. 45; pp. 15988 - 15997
• Main Authors: Sohn, Te-ik, Kim, Deukjoon, Paton, Robert S.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 02.11.2015; Wiley Subscription Services, Inc
• Subjects: Asymmetry; Bromination; Chemistry; Chemistry, Multidisciplinary; Chlorination; Natural products; Physical Sciences; Science & Technology; Synthesis; CONVERSION; STRATEGY; ION FORMATION; ALPHA; LAURENCIA; STEREOSELECTIVE SYNTHESIS; MARINE NATURAL-PRODUCTS; microcladallenes; natural products; asymmetric synthesis; total synthesis; CYCLIC ETHERS; synthesis design; PARTICIPATION; CHLORINATION
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201502592

Substrate-controlled asymmetric total syntheses of (+)-microcladallenesA, B, and C have been accomplished based on the proposed structures. The syntheses of microcladallenesA and B confirmed the structures and absolute configurations of both natural products. However, the synthesis of microcladalleneC, which includes seven stereogenic centers and an (R)-bromoallene in its compact C-15 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 -oriented vicinal cis-dichloride function in microcladalleneC was elaborated through a novel tandem Cl-2-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.