Asymmetric total synthesis of (-)-lingzhiol via a Rh-catalysed [3+2] cycloaddition
Rong Long1, Jun Huang1, Wenbin Shao2
11] Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China [2] Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Beijing National Laboratory for Molecular Science (BNLMS), and Peking-Tsinghua Center for Life Sciences and Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China [3].
Abstract:
The development of efficient reactions for the one-pot construction of bicyclic ring systems bearing two quaternary carbon centres at their bridgehead positions represents a significant challenge to synthetic chemistry. The development of new methods capable of overcoming this challenge is highly desirable, because this motif can be found in a wide range of natural products with significant biological activities. Herein, we report an efficient [3+2] cycloaddition reaction between an enal and an alleno rhodium species, which was generated in situ from the corresponding enynol via a retro metal-propargylation reaction, to give [3.3.0] and [3.4.0] bicyclic systems bearing two quaternary atoms at their bridgehead positions. The developed chemistry has been successfully applied to the asymmetric total synthesis of natural product (-)-lingzhiol (4) for the first time in 17 steps.
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