Jason S Chen1, Andrew M Romine2, Kin S Yang2, Malkanthi K Karunananda2, Keary M Engle2. 1. Automated Synthesis Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States. 2. Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Abstract
A weakly coordinating monodentate heteroaryl thioether directing group has been developed for use in Pd(II) catalysis to orchestrate key elementary steps in the catalytic cycle that require conformational flexibility in a manner that is difficult to accomplish with traditional strongly coordinating directing groups. This benzothiazole thioether, (BT)S, directing group can be used to promote oxidative Heck reactivity of internal alkenes providing a wide range of products in moderate to high yields. To demonstrate the broad applicability of this directing group, an arene C-H olefination method was also successfully developed. Reaction progress kinetic analysis provides insights into the role of the directing group in each reaction, which is supplemented with computational data for the oxidative Heck reaction. Furthermore, this (BT)S directing group can be transformed into a number of synthetically useful functional groups, including a sulfone for Julia olefination, allowing it to serve as a "masked olefin" directing group in synthetic planning. In order to demonstrate this synthetic utility, natural products (+)-salvianolic acid A and salvianolic acid F are formally synthesized using the (BT)S directed C-H olefination as the key step.
A weakly coordinating monodentate heteroaryl thioether directing group has been developed for use inn class="Chemical">Pd(II) catalysis to orchestrate key elementary steps in the catalytic cycle that require conformational flexibility in a manner that is difficult to accomplish with traditional strongly coordinating directing groups. This benzothiazole thioether, (BT)S, directing group can be used to promote oxidative Heck reactivity of internal alkenes providing a wide range of products in moderate to high yields. To demonstrate the broad applicability of this directing group, an arene C-H olefination method was also successfully developed. Reaction progress kinetic analysis provides insights into the role of the directing group in each reaction, which is supplemented with computational data for the oxidative Heck reaction. Furthermore, this (BT)S directing group can be transformed into a number of synthetically useful functional groups, including a sulfone for Juliaolefination, allowing it to serve as a "masked olefin" directing group in synthetic planning. In order to demonstrate this synthetic utility, natural products (+)-salvianolic acid A and salvianolic acid Fare formally synthesized using the (BT)S directed C-H olefination as the key step.
Authors: Andrew M Romine; Matthew J Demer; Milan Gembicky; Arnold L Rheingold; Keary M Engle Journal: Organometallics Date: 2021-04-30 Impact factor: 3.837