ORGANIC
LETTERS
2011
Vol. 13, No. 7
1793–1795
Access to Enantiomerically Enriched
cis-2,3-Disubstituted Azetidines via
Diastereoselective Hydrozirconation
Tarun K. Pradhan, K. Syam Krishnan, Jean-Luc Vasse,* and Jan Szymoniak*
ꢀ
Institut de Chimie Moleculaire de Reims, CNRS (UMR 6229) and Universite de Reims,
51687 Reims Cedex 2, France
ꢀ
jean-luc.vasse@univ-reims.fr; jan.szymoniak@univ-reims.fr
Received February 2, 2011
ABSTRACT
An asymmetric variant of the hydrozirconation reaction has been established starting from Boc-protected chiral allylic amines. The resulting
diastereoselectively formed N-functionalized organozirconiums can be considered as promising chirons. In this case, they have been
transformed into enantiomerically enriched cis-2,3-disubstituted azetidines through a iodination/cyclization sequence.
Azetidines are valuable building blocks for the prepara-
tion of both naturally occurring1 and synthetic molecules2
of biological interest and for the design of new organo-
catalysts3 or ligands.4 One of the modern mimicking
approaches to enhance recognition of biological receptors
is based on conformational constraint. Therefore, small-
size rings, and among them the azetidine framework,
constitute potent tools for SAR studies.5 Although several
syntheses of azetidine derivatives have been reported,6 the
development of simplesyntheticstrategiesopening the way
to optically pure compounds is still important.
The hydrozirconation of alkenes with the Schwartz
reagent, Cp2Zr(H)Cl, is a well-known reaction with
important synthetic potential, owing to wide functional
group tolerance, as well as marked regioselectivity and syn-
stereoselectivity.7,8 It represents one of the most practical
methods for the formation of C-Zr bonds, which can be
further transmetalated, linking zirconium chemistry with
that of many other metals. In this context, an almost total
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K.; Ishiyama, H.; Takahashi, Y.; Ito, J.; Mikami, Y.; Kobayashi, J.
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10.1021/ol200323r
2011 American Chemical Society
Published on Web 03/08/2011