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Formal Synthesis of Sarain A: Intramolecular Cycloaddition of an Eight‐Membered Cyclic Nitrone to Construct the 2‐Azabicyclo[3.3.1]nonane Framework
Author(s) -
Higo Takuya,
Ukegawa Tomoya,
Yokoshima Satoshi,
Fukuyama Tohru
Publication year - 2015
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.201501633
Subject(s) - stereocenter , cycloaddition , nitrone , enantioselective synthesis , bicyclic molecule , intramolecular force , stereochemistry , chemistry , pyrrolidine , ring (chemistry) , aldol reaction , organic chemistry , catalysis
An enantioselective route to the tetracyclic skeleton of sarain A has been developed. Asymmetric reduction of an ynone introduced a chiral center which was transferred to the contiguous tertiary stereogenic centers through an Ireland–Claisen rearrangement. The 2‐azabicyclo[3.3.1]nonane framework was constructed by an unprecedented intramolecular cycloaddition of an eight‐membered cyclic nitrone. Using the steric bias of the bicyclic system, the quaternary carbon atom was constructed by a stereoselective aldol reaction. Further ring formations were performed by ring‐closing metathesis for the 13‐membered ring and an iodoamidation reaction for the pyrrolidine ring. The present synthesis has successfully provided an alternative route to the late‐stage intermediate of Overman’s synthesis.