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Total Synthesis of Haliclonin A
Author(s) -
Jin Yuan,
Orihara Kensuke,
Kawagishi Fumiki,
Toma Tatsuya,
Fukuyama Tohru,
Yokoshima Satoshi
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202016343
Subject(s) - chemistry , moiety , aldehyde , total synthesis , metathesis , cyclopropanation , alkylation , enone , stereoselectivity , intramolecular force , cyclohexanone , acetal , epoxide , enamine , ring closing metathesis , diene , stereochemistry , ring (chemistry) , birch reduction , organic chemistry , catalysis , polymerization , polymer , natural rubber
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.