Catalytic Anti-Markovnikov Transformations of Hindered Terminal Alkenes Enabled by Aldehyde-Selective Wacker-Type Oxidation
A new strategy for the functionalization of sterically hindered terminal olefins is reported. Alkenes bearing quaternary carbons at the allylic or homoallylic position are readily oxidized to the corresponding aldehydes by palladium/copper/nitrite catalysis. A broad range of functional groups including esters, nitriles, silyl ethers, vinylogous esters, ketones, lactones, and β-ketoesters are tolerated under the reaction conditions. The crude aldehyde products can be transformed further, enabling direct conversion of hindered terminal alkenes to various other synthetically useful functional groups, resulting in formal anti-Markovnikov hydroamination, among other transformations.
Additional Information© 2016 American Chemical Society. Received: August 25, 2016. Publication Date (Web): September 27, 2016. This manuscript is dedicated to Professor Samuel J. Danishefsky on the occasion of his 80th birthday. This work was supported by the NSF under the CCI Center for Selective C–H Functionalization, CHE-1205646. Additional financial support was provided by Caltech and Novartis. Dr. Mona Shahgholi and Naseem Torian are acknowledged for assistance with high-resolution mass spectrometry. Dr. Yiyang Liu, Nicholas R. O'Connor, Dr. Allen Y. Hong, and Prof. Wen-Bo Liu are acknowledged for contributions to substrate preparation. Beau P. Pritchett is thanked for preparation of the Ohira–Bestmann reagent. The authors declare no competing financial interest.
Supplemental Material - ja6b08788_si_001.pdf