Total Synthesis of Haliclonin A

The total synthesis of haliclonin A was accomplished. Starting from 3,5‐dimethoxybenzoic acid, a functionalized cyclohexanone fused to a 17‐membered ring was prepared through a Birch reduction/alkylation sequence, ring‐closing metathesis, intramolecular cyclopropanation, and stereoselective 1,4‐addition of an organocopper reagent to an enone moiety. Reductive C−N bond formation via an N,O‐acetal forged the 3‐azabicyclo[3.3.1]nonane core. The allyl alcohol moiety was constructed by a sequence involving stereoselective α‐selenylation of an aldehyde via an enamine, syn‐elimination of a selenoxide, and allylation of the aldehyde with an allylboronate. Formation of the 15‐membered ring containing a skipped diene was achieved by ring‐closing metathesis, and final transformations led to the synthesis of haliclonin A. A synthesis of a tetracyclic natural product, haliclonin A, was achieved. The cyclohexane ring was derived from 3,5‐dimethoxybenzoic acid, which was elaborated via Birch reduction, intramolecular cyclopropanation, and a reaction with an organocopper reagent. The lactam ring was constructed via reductive C−N bond formation. The two macrocyclic rings were formed via ring‐closing metathesis.