Communications
DOI: 10.1002/anie.201007351
Asymmetric Catalysis
Activation of Vinyl Iodides for the Highly Enantioselective Addition to
Aldehydes**
Albert M. DeBerardinis, Mark Turlington, and Lin Pu*
Grignard and organolithium reagents can be directly pre-
pared from organohalides and are of great importance in
organic synthesis. However, the high reactivity of these
reagents makes it difficult to develop enantioselective cata-
lysts for their nucleophilic addition to carbonyls to generate
chiral alcohols.[1–3] In the past two decades, the use of
organozinc reagents in asymmetric catalysis has been studied
extensively.[4,5] Organozinc reagents are generally less reac-
tive and more tolerant of functional groups than Grignard and
organolithium reagents. These characteristics have allowed
the rapid development of enantioselective catalysts for the
asymmetric organozinc addition to carbonyls. Among these
studies, several highly enantioselective catalysts were found
for the asymmetric addition of vinylzinc compounds to
carbonyls to generate chiral allylic alcohols.[6–9] In these
reports, the vinylzinc reagents were prepared by using
methods such as the hydrozirconation[6] or hydroboration[7]
of alkynes with subsequent transmetallation, vinyl boronic
acids or esters,[8] and the nickel-catalyzed addition of ZnMe2
to alkynes.[9] The hydrozirconation and hydroboration of
terminal alkynes generate alkenylzirconiums and alkenylbo-
ranes, respectively, which upon treatment with alkylzinc
reagents can form the corresponding alkenylzinc reagents.
These reagents in the presence of chiral ligands have been
shown to be very useful for the asymmetric addition to
carbonyls.[6,7]
it was not known whether this strategy was applicable to vinyl
iodides. Herein, we report the discovery of a highly enantio-
selective catalyst for the reaction of vinyl iodides with
aldehydes through the direct conversion of vinyl iodides
into vinylzinc reagents in the presence of ZnEt2. This method
allows the synthesis of substituted and functionalized allylic
alcohols with high enantiomeric purity under very mild
reaction conditions.
We first examined the reaction of a vinyl iodide, (E)-1-
iodo-1-phenyl-1-pentene, with c-C6H11CHO in the presence
of ZnEt2 (Scheme 1). This led to the formation of the
corresponding allylic alcohol in only a 17% yield. The
reactions of other vinyl iodides with aldehydes were also
tested and these reactions normally gave low yields of product
except for a few cases. These results indicate that the vinylzinc
reagents prepared directly from the vinyl iodides generally
have low reactivity toward aldehydes.
However, the use of the hydrozirconation and hydro-
boration of terminal alkynes has limitations. For example,
these methods cannot be applied to make cycloalkenylzinc
reagents and only terminal alkynes are used in most cases.
Preparation of vinylzinc reagents directly from vinyl halides
would avoid these limitations. There is no report yet on the
catalytic asymmetric reaction of carbonyl compounds with
vinylzinc reagents that are prepared directly from vinyl
halides without using the magnesium or lithium reagents,
which are less tolerant of functional groups.[10] In 2004,
Knochel and co-workers demonstrated that aryl iodides can
be converted into arylzinc compounds by using ZniPr2,[11] but
Scheme 1. Reaction of vinyl iodides with aldehydes in the presence of
ZnEt2. The reaction was carried out using method D in the Supporting
Information without using a chiral ligand. The yields are of the isolated
product. [a] Step 1 was performed at RT and run for 8 h. acac=acetyl-
acetonate, NMP=N-methyl-2-pyrrolidone, TBS=tert-butyldimethylsilyl.
[*] Dr. A. M. DeBerardinis, M. Turlington, Prof. L. Pu
Department of Chemistry, University of Virginia
Charlottesville, VA 22904-4319 (USA)
Fax: (+1)434-924-3710
Recently, we reported a one-step synthesis of a class of
amine-containing H8-binol ligands by using the Mannich-type
reaction of H8-binol with secondary amines and paraformal-
dehyde (Scheme 2).[12] Among these compounds, (S)-1 was
found to catalyze the highly enantioselective arylzinc addition
to aldehydes in a number of cases.[12] We investigated the use
of (S)-1 to promote the reaction of vinyl iodides with
aldehydes in the presence of ZnEt2. We were pleased to
find that using 10 mol% of (S)-1 can catalyze the reaction of
E-mail: lp6n@virginia.edu
[**] The partial support of the US National Science Foundation (CHE-
0717995 and ECCS-0708923) for this work is gratefully acknowl-
edged.
Supporting information (detailed synthesis and characterization
data for the preparation of the vinyl iodides and allylic alcohols) for
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 2368 –2370