Department of Chemistry and Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, United States.
J Am Chem Soc. 2021 Dec 8;143(48):20084-20089. doi: 10.1021/jacs.1c11060. Epub 2021 Nov 23.
We report the convergent total synthesis of (±)-hamigeran M, enabled by five C-H functionalization reactions and proceeding in 11 steps in 3.9% overall yield. The C-H functionalizations include a hydroxy-directed C-H borylation, one C-H metalation-1,2-addition, one C-H metalation-Negishi coupling, a late-stage oxazole-directed C-H borylation-oxidation, and one electrophilic bromination. Two of these five C-H functionalizations forged strategic C-C bonds in the seven-membered ring of hamigeran M. The oxazole-directed C-H borylation-oxidation was unprecedented and ensured a late-stage hydroxylation. Other key steps include a tandem Suzuki reaction-lactonization to join the cyclopentane building block with the aromatic moiety and a hydrogen-atom transfer reaction to reduce a challenging tetrasubstituted double bond.
我们报告了（±）-hamigeran M 的会聚全合成，该合成通过五个 C-H 官能化反应实现，总收率为 3.9%，历经 11 步。这些 C-H 官能化反应包括一个羟基导向的 C-H 硼化反应、一个 C-H 金属化-1,2-加成反应、一个 C-H 金属化-Negishi 偶联反应、一个晚期唑导向的 C-H 硼化-氧化反应和一个亲电溴化反应。这五个 C-H 官能化反应中的两个在 hamigeran M 的七元环中形成了战略性的 C-C 键。唑导向的 C-H 硼化-氧化反应是前所未有的，确保了晚期的羟基化。其他关键步骤包括串联 Suzuki 反应-内酯化，将环戊烷砌块与芳香部分连接起来，以及氢原子转移反应，以还原具有挑战性的四取代双键。
