ORGANIC
LETTERS
2011
Vol. 13, No. 21
5796–5799
Binaphthol-Catalyzed Asymmetric
Conjugate Arylboration of Enones
Heather M. Turner, Jignesh Patel, Nootaree Niljianskul, and J. Michael Chong*
Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, (GWC)2,
Department of Chemistry, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1
Received September 4, 2011
ABSTRACT
Conjugate addition of arylboronates to R,β-unsaturated ketones may be catalyzed by chiral binaphthols with enantioselectivities of up to 99:1.
Best results were observed with 3,30-dichloro-BINOL. This chemistry was applied to syntheses of intermediates for syntheses of (þ)-indatraline
and (þ)-tolterodine.
The Rh-catalyzed asymmetric conjugate addition of
alkenyl- and arylboronic acids to R,β-unsaturated carbo-
nyl compounds, sometimes referred to as the Hayashiꢀ
Miyaura reaction, has become a very useful synthetic method
since its introduction in 1998.1ꢀ3 More recently, Pd-cata-
lyzed asymmetric conjugate addition of arylboronic acids
has emerged as an excellent method for the construction of
quaternary centers.4 The success of these reactions is due in
part to the low reactivity of arylboronic acids with organic
electrophiles in the absence of transition metal catalysts.
We have previously exploited this low nucleophilicity of
organoborons to develop asymmetric additions of alkynyl-
boronates5 and alkenylboronates6 to R,β-unsaturated
ketones using 3,30-disubstituted binaphthols as catalysts.
While the nature of catalysis using chiral diols is very
different from that using transition metal complexes, both
types of catalysts can provide products with high enantios-
electivity. Since our introduction of binaphthol-catalyzed
reactions of boronates, this chemistry has been extended to
the allylation7 and propargylation8 of ketones; the allyla-
tion of N-acylimines;9 the alkynylation, alkenylation, and
arylation of N-acylimines,10 Petasis reactions;11 and alke-
nylations of acetals.12 The conjugate alkenylboration and
alkynylboration chemistry has been applied to the synth-
esis of natural products.13 However, asymmetric conjugate
arylation has proven tobeelusive. Wenow reportthatcon-
jugate arylborations of enones is possible and can proceed
with high stereoselectivities.
Initial experiments using conditions similar to those found
to be effective for alkenylborations (20 mol % ligand,
CH2Cl2, 40 °C) were not encouraging. With enone 1a as
a test substrate and excess diethyl phenylboronate as a
reagent, reactions using up to 200 mol % of various diols in
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r
10.1021/ol202391r
Published on Web 10/12/2011
2011 American Chemical Society