Angewandte
Chemie
DOI: 10.1002/anie.201309982
Enantioselective Catalysis
Enantioselective Synthesis of Boron-Substituted Quaternary Carbon
Stereogenic Centers through NHC-Catalyzed Conjugate Additions of
(Pinacolato)boron Units to Enones**
Suttipol Radomkit and Amir H. Hoveyda*
In fond memory of Harry H. Wasserman
Abstract: The first examples of Lewis base catalyzed enantio-
selective boryl conjugate additions (BCAs) that generate
products containing boron-substituted quaternary carbon
stereogenic centers are disclosed. Reactions are performed in
the presence of 1.0–5.0 mol% of a readily accessible chiral
accessible N-heterocyclic carbene (NHC) and commercially
available bis(pinacolato)diboron; cyclic or linear a,b-unsatu-
rated ketones can be used and rigorous exclusion of air or
moisture is not necessary. The desired products are obtained in
63–95% yield and 91:9 to > 99:1 enantiomeric ratio (e.r.). The
special utility of the NHC-catalyzed approach is demonstrated
in the context of an enantioselective synthesis of natural
product antifungal (À)-crassinervic acid.
Scheme 1. Comparison of Cu-catalyzed and Cu-free enantioselective
boron conjugate addition (BCA). B(pin)=(pinacolato)boron.
R
eliable, efficient, and selective catalytic methods for the
synthesis of organoboron compounds are of considerable
catalysis.[12] The lone report on allylic substitutions furnishing
allyl-B(pin) products relies on the use of an enantiomerically
pure Cu-containing complex.[6b] To the best of our knowledge,
there are no examples of Lewis base catalyzed enantioselec-
tive reactions that furnish products with a quaternary B-
substituted carbon center; such transformations would con-
stitute a notable addition to the collection of catalytic
importance.[1] A challenge in organoboron chemistry is the
À
development of catalytic protocols that furnish C B bonds
enantioselectively. There are enantioselective protocols for
boron hydride,[2] diboron,[3] proto-boryl,[4] and conjugate
additions[5] to unsaturated compounds as well as allylic
substitutions[6] that form B-substituted stereogenic centers
and are promoted by transition-metal-containing catalysts;
related boryl additions to imines have been introduced as
well.[7] In the case of boron conjugate addition (BCA)
reactions, chiral Lewis base catalysts provide effective alter-
natives to the Cu-based complexes (Scheme 1);[8] chiral N-
heterocyclic carbenes (NHCs) promote enantioselective
BCA[9] and offer distinctive chemoselectivity profiles that
are otherwise unavailable (Scheme 1).[8d] The large majority
of the above protocols, however, lead to products having
tertiary boron-substituted carbon centers, and the small
number of disclosures focused on the difficult enantioselec-
tive BCA processes that generate boron-substituted quater-
nary carbon centers[10,11] have remained in the domain of Cu
À
enantioselective C B bond-forming processes.
Herein, we disclose the first instances of Lewis base
catalyzed enantioselective BCA transformations that deliver
cyclic or acyclic products with a boron-substituted quaternary
carbon; products are obtained in 63–95% yield and 91:9 to
> 99:1 enantiomeric ratio (e.r.). The catalytic methodꢀs
unique features are highlighted by an enantioselective syn-
thesis of natural product crassinervic acid.
We first probed a number of easily accessible chiral NHCs
that might be used to catalyze the formation of 4a efficiently
and enantioselectively (Table 1). C2-Symmetric carbenes
derived from 1a,b promote the BCA in moderate yield and
enantioselectivity (entries 1 and 2, Table 1). There is complete
substrate consumption in 14 h when C1-symmetric 2a[13] is
used; 4a is obtained in 88:12 e.r. (entry 3, Table 1). Reaction
with the m-iPr-substituted derivative 2b is less efficient and
selective (68% conv., 67:33 e.r.; entry 4, Table 1). When the
NAr moieties of the NHC catalysts are dissymmetric (i.e., 3a–
c in entries 5–7, Table 1), BCA is efficient (> 90% conv.) and
highly enantioselective (> 90:10 e.r.). Transformation with 3c
furnishes 4a in 90% yield and 96:4 e.r. Additional noteworthy
points are:
[*] S. Radomkit, Prof. A. H. Hoveyda
Department of Chemistry, Merkert Chemistry Center
Boston College, Chestnut Hill, MA 02467 (USA)
E-mail: amir.hoveyda@bc.edu
[**] Financial support was provided by the NIH (GM-57212) and the
NSF (CHE-1111074). We thank H. Wu, K. P. McGrath, and Dr. F.
Haeffner for helpful discussions and Frontier Scientific, Inc. for gifts
of B2(pin)2. NHC=N-heterocyclic carbenes.
1) When the reaction is carried out with 1.0 mol% 3c and
5.0 mol% dbu, under conditions otherwise identical to those
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2014, 53, 3387 –3391
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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