Journal of the American Chemical Society, Vol.143, No.2, 687-692, 2021
Rapid Construction of Tetralin, Chromane, and Indane Motifs via Cyclative C-H/C-H Coupling: Four-Step Total Synthesis of (+/-)-Russujaponol F
The development of practical C-H/C-H coupling reactions remains a challenging yet appealing synthetic venture because it circumvents the need to prefunctionalize both coupling partners for the generation of C-C bonds. Herein we report a cyclative C(sp(3))-H/C(sp(2))-H coupling reaction of free aliphatic acids enabled by a cyclopentane-based mono-N-protected beta-amino acid ligand. This reaction uses inexpensive sodium percarbonate (Na2CO3 center dot 1.5H(2)O(2)) as the sole oxidant and generates water as the only byproduct. A range of biologically important scaffolds, including tetralins, chromanes, and indanes, can be easily prepared by this protocol. Finally, the synthetic application of this methodology is demonstrated by the concise total synthesis of (+/-)-russujaponol F in a four-step sequence starting from readily available phenylacetic acid and pivalic acid through sequential functionalizations of four C-H bonds.