Open AccessDefluorodearomatization: A Photocatalytic Birch-Like Reduction That Enables C–C Bond Formation and Provides Access to Unnatural Cannabinoids
Author(s) -
Jon I. Day,
Sascha Grotjahn,
Sameera Senaweera,
Burkhard Koenig,
Jimmie D. Weaver
Publication year - 2021
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.1c00169
Subject(s) - chemistry , photocatalysis , selectivity , combinatorial chemistry , chemical space , hydrogen bond , coupling reaction , drug discovery , nanotechnology , catalysis , organic chemistry , molecule , biochemistry , materials science
Within the framework of discovery chemistry, polyfluorination remains a synthetic challenge despite its ability to provide useful characteristics, such as a reduction in the number of hydrogen bond donors and metabolic stability. Coupling a reversal of this methodology with photocatalysis has been demonstrated to allow the rapid synthesis of previously difficult or impossible targets by starting with fluorines everywhere and selectively removing or functionalizing them. Herein, we demonstrate a novel method to synthesize 1,4-cyclohexadienes through a dearomative photocatalytic C-C coupling reaction. This allows for access to materials that are orthogonal to the selectivity of the Birch reaction and are more functional-group-tolerant. The reaction also allows the efficient synthesis of polyfluorinated cannabinoids. While the yields are modest, the access to the new chemical space provided by the reaction is unprecedented by any means. The trifluorinated analog of THC, 1-deoxy-1,2,4-trifluoro-THC, is synthesized, demonstrating the importance of discovery chemistry and the ability to explore otherwise unknown structure-activity relationships.