pubs.acs.org/joc
based on Cr,3 Sm,4 Mn,5 Zn,6 Cd,7 Sn,8 or In9 have been
Titanocene(III)-Promoted Barbier-type Crotylation
of Carbonyl Compounds
developed. Among them, those in which the active metal is in
a homogeneous phase present some advantages derived from a
better control of the reaction conditions and reproducibility.
One remarkable example of this case is the anti stereoselective
Cr(II)-mediated3 crotyl additions, although it is restricted to
aldehydes as electrophiles. Therefore, the development of a
general regioselective and stereoselective Barbier-type crotyl
addition under homogeneous conditions is desirable.
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Iris Sancho-Sanz, Delia Miguel, Alba Millan,
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Rosa E. Estevez, Juan L. Oller-Lopez,
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Enrique Alvarez-Manzaneda, Rafael Robles,
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Juan M. Cuerva, and Jose Justicia*
Department of Organic Chemistry, Faculty of Sciences,
University of Granada, C. U. Fuentenueva s/n,
18071 Granada, Spain
SCHEME 1. General Crotylation Reaction under Barbier
Conditions
Received November 13, 2010
In this sense, we have recently described that Cp2TiCl, a
mild single-electron transfer (SET) reagent extensively stud-
11
ied by RajanBabu and Nugent,10 Gansauer, and our
€
group,12 is able to promote mild, chemo- and regioselective
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hedron Lett. 1996, 37, 7049–7052.
A mild, highly regio- and stereoselective method for the
crotylation of aldehydes and ketones mediated/catalyzed
by titanocene(III) is described. Optimized conditions
permit the selective generation of γ-adducts in high yields
together with high stereoselectivity, with a predominance
of anti stereoisomers.
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Regio- and stereoselective addition of crotyl metals to
carbonyl compounds allows the creation of two new adjacent
stereogenic centers in only one step (see Scheme 1), which is an
important process in organic synthesis.1 Within this context,
Barbier-type protocols,2 in which the crotyl metal intermedi-
ates are generated “in situ” from the crotyl halide and the cor-
responding metal, are attractive from a practical point of view
because prior preparation of the organometallic intermediate
is circumvented. Thus, for example, Barbier-type protocols
€
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~ ꢀ
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732 J. Org. Chem. 2011, 76, 732–735
Published on Web 12/29/2010
DOI: 10.1021/jo102269d
r
2010 American Chemical Society