Original Mitsunobu-Triggered Sequence Involved in a One-Pot Domino Process toward Tetracyclic Systems Bearing a Bis-N,O-acetal Junction.
Herein is reported an efficient, one-pot domino process through a 1,6-aza-Michael addition-triggered sequence and an original Mitsunobu-type concerted sequence for the synthesis of tetracyclic systems containing a bis-N,O-acetal junction. This methodology led to the construction of four new bonds, the cleavage of three C-O bonds, and the generation of an asymmetric center. Mitsunobu activation afforded final ring closure involving the creation of two bonds, which remains unprecedented among reported Mitsunobu-type sequences. The latter occurred in a regioselective fashion at the challenging C6-position of 2-pyridone intermediates. In the case of adequately substituted enantiopure amino alcohols, up to 95:5 of diastereoisomeric excess was achieved. Computational studies allowed the discrimination of a favored pathway for Mitsunobu sequence and supported the regioselectivity as well as the diastereoselectivity observed for this step.
Normandie Univ, France, UNILEHAVRE, URCOM, EA 3221, FR 3038 CNRS, F-76600 Le Havre, France.
Thomas
T
Lepitre
Université de Reims Champagne Ardenne, Institut de Chimie Moléculaire de Reims, CNRS UMR 7312, UFR de Pharmacie, 51 rue Cognacq-Jay, 51096 Cedex Reims, France.|Multiscale Molecular Modeling Platform, Université de Reims Champagne-Ardenne, UFR Sciences Exactes et Naturelles , F-51687 Cedex 2 Reims, France.
Clement
C
Denhez
Normandie Univ, France; UNIROUEN, Laboratoire SMS EA3233, 1 rue Tesniere, France, F-76821 Mont Saint Aignan, France.
Morgane
M
Sanselme
Normandie Univ, France, UNILEHAVRE, URCOM, EA 3221, FR 3038 CNRS, F-76600 Le Havre, France.
Mohamed
M
Othman
Normandie Univ, France, UNILEHAVRE, URCOM, EA 3221, FR 3038 CNRS, F-76600 Le Havre, France.
Ata Martin
AM
Lawson
Normandie Univ, France, UNILEHAVRE, URCOM, EA 3221, FR 3038 CNRS, F-76600 Le Havre, France.
Adam
A
Daïch