Total Synthesis of the Cephanolides (Xie, 2025)

An organic chemistry minilecture on the 'Asymmetric Total Synthesis of Benzenoid Cephalotane-type Diterpenoids Through a Cascade C(sp2) & C(sp3)–H Activation' by Xiangxin Li, Zhaoxu Lu, Shaocong Liu, Mengyao Sun, Shengfu Duan & Zhixiang Xie*. It showcases a spectacular C-H activation cascade to build up the polycyclic core and a range of oxidation chemistries to transform this into several members of the Cephanolide family of diterpenoids. SUPPORT THE CHANNEL ON PATREON:   / simplifyingsynthesis   Socials:   / simplifyingsynthesis     / simplifyingsyn1     / simplifyingsynthesis   References: Nat Commun. 2025, 16, 4674 (This synthesis) Phytochemistry 2021, 192, No. 112939 (Isolation) J. Am. Chem. Soc. 2022 144 (41), 19173-19185(Sarpong Synthesis) Tetrahedron Lett. 1978, 19, 419 (Acetal oxidation) Eur. J. Org. Chem. 2015, 7460–7467 (Demethylation mechanism) Tetrahedron Lett. 1984, 25, 1953−1956 (Suarez oxidation) Synthesis 1971; 1971(10): 501-526 (Hypoiodite formation) Org. Lett. 2022, 24, 41, 7507–7511 (Hu Synthesis) Catal Lett. 2021, 151, 17–26 (Co(OAc)2 Benzylic Oxidation) Molecular Catalysis. 2018, 447, 90–96 (Co(OAc)2 Benzylic Oxidation) Tetrahedron Letters 50 (2009) 3001–3004 (TBCA Bromination)