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Diastereoselective Rhodium‐Catalyzed [(3+2+2)] Carbocyclization Reactions with Tethered Alkynylidenecyclopropanes: Synthesis of the Tremulane Sesquiterpene Natural Products
Author(s) -
Evans P. Andrew,
Dushnicky Molly J.,
Cho Dasol,
Majhi Jadab,
Choi Seulhui,
Pipaliya Bhavin V.,
Inglesby Phillip A.,
Baik MuHyun
Publication year - 2021
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.202000482
Subject(s) - chemistry , stereocenter , diastereomer , rhodium , stereochemistry , intramolecular force , sesquiterpene , allene , ligand (biochemistry) , cope rearrangement , asymmetric induction , combinatorial chemistry , catalysis , enantioselective synthesis , organic chemistry , biochemistry , receptor
The development of a diastereoselective intramolecular rhodium‐catalyzed [(3+2+2)] carbocyclization reactions of allyl ester‐tethered alkynylidenecyclopropanes (ACPs) for the construction of the 5,7,5‐tricyclic scaffold of the tremulane sesquiterpene natural products is described. This work illustrates that the stereoelectronic nature of the phosphite ligand is critical for attaining high levels of stereocontrol, which is supported by density functional theory (DFT) studies that indicate the migratory insertion step favors the formation of the cis ‐diastereoisomer. Consequently, several strategies were devised to access the thermodynamically more stable trans ‐diastereoisomer for the synthesis of the tremulanes; however, the attempts to either switch the sense of stereocontrol in the carbocyclization reaction or epimerize the C7 stereocenter of the cycloadduct provided only modest improvements. Hence, we elected to highlight the synthetic utility of this strategy with the development of concise and highly efficient syntheses of (±)‐ epi ‐tremulenolide A, (±)‐ epi ‐tremulenediol A and (±)‐ epi ‐ceriponol D.