The total synthesis of (-)-cyanthiwigin F by means of double catalytic enantioselective alkylation.
Double catalytic enantioselective transformations are powerful synthetic methods that can facilitate the construction of stereochemically complex molecules in a single operation. In addition to generating two or more stereocentres in a single reaction, multiple asymmetric reactions also impart increased enantiomeric excess to the final product in comparison with the analogous single transformation. Furthermore, multiple asymmetric operations have the potential to independently construct several stereocentres at remote points within the same molecular scaffold, rather than relying on pre-existing chiral centres that are proximal to the reactive site. Despite the inherent benefits of multiple catalytic enantioselective reactions, their application to natural product total synthesis remains largely underutilized. Here we report the use of a double stereoablative enantioselective alkylation reaction in a concise synthesis of the marine diterpenoid (-)-cyanthiwigin F (ref. 8). By employing a technique for independent, selective formation of two stereocentres in a single stereoconvergent operation, we demonstrate that a complicated mixture of racemic and meso diastereomers may be smoothly converted to a synthetically useful intermediate with exceptional enantiomeric excess. The stereochemical information generated by means of this catalytic transformation facilitates the easy and rapid completion of the total synthesis of this marine natural product.
Enquist
John A
JA
The Arnold and Mabel Beckman Laboratories of Chemical Synthesis, Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC164-30, Pasadena, California 91125, USA.
Stoltz
Brian M
BM
D000478:Alkylation; D000818:Animals; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry
D001688:Biological Products; D004224:Diterpenes; D007659:Ketones; C530546:cyanthiwigin F