ORGANIC
LETTERS
2013
Vol. 15, No. 6
1414–1417
NHCÀCu-Catalyzed Protoboration
of Monosubstituted Allenes.
Ligand-Controlled Site Selectivity,
Application to Synthesis and Mechanism
Fanke Meng, Byunghyuck Jung, Fredrik Haeffner, and Amir H. Hoveyda*
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill,
Massachusetts 02467, United States
Received February 12, 2013
ABSTRACT
Two types of NHCÀCu complexes catalyze protoborations of terminal allenes to afford valuable 1,1- or trisubstituted vinylboron species with
high site selectivity and stereoselectivity. The scope of the method, application to natural product synthesis, and mechanistic basis for the
observed selectivity trends are presented.
Vinylboron compounds are used in a myriad of applica-
tions in chemical synthesis, most notably as cross-coupling
partners;1 development of methods for efficient and stereo-
selective preparation of such entities thus constitutes a
compelling objective. Catalytic variants would be espe-
cially valuable, as the opportunity for accessing different
selectivity profiles then becomes feasible through adjust-
ment of catalyst structures. Herein, we outline protocols
for efficient conversion of alkyl- and aryl-substituted
allenes to either of the two possible vinylboron isomers,
depending on the NHCÀCu complex used (Figure 1).
Reactions are promoted by complexes derived from com-
mercially available imidazolium salts and proceed after
8.0 h at 22 °C to afford (pin)B-substituted olefins in up to
92% yield and >98% site selectivity and stereoselectivity
(pin = pinacolato). We demonstrate utility through
synthesis of the C1ÀC10 fragment of a macrolide anti-
biotic elansolid A. Mechanistic rationales for the varying
trends in selectivity and efficiency are provided.
In 2011, we demonstrated that by altering the structure
ofthe NHC ligand of a Cu-basedcatalyst, terminal alkynes
may be efficiently converted to R- or β-vinylboron entities
(Figure 1).2 Reactions involve site-selective addition of an
NHCÀCuÀB(pin) complex followed by protonation of
the vinylcopper intermediate by MeOH (net protobora-
tion).3 More recently, as shown in Figure 1, in conjunction
with studies regarding NHCÀCu-catalyzed enantioselec-
tive allylic substitution reactions, we showed that the
resulting allenes undergo Cu-catalyzed allene protobora-
tion to afford 1,1-disubstituted vinylboron products with
∼90:10 selectivity.4,5 Considering the value of either iso-
meric form and the limited number of available protocols
(1) For applications of vinylboron compounds in CÀC bond forma-
tion, see: (a) Hall, D. G. In Boronic Acids: Preparation and Applications
in Organic Synthesis and Medicine; WileyÀVCH: Weinheim, 2005. (b)
Tobisu, M.; Chatani, N. Angew. Chem., Int. Ed. 2009, 48, 3565. For
syntheses of cyclic and acyclic vinylborons by Pd-catalyzed cross-
coupling reactions involving vinyl bromides and triflates, see: (c) Takagi,
J.; Takahashi, K.; Ishiyama, T.; Miyaura, N. J. Am. Chem. Soc. 2002,
124, 8001. For a review on applications of vinyltrifluoroboron species,
accessed via vinylborons, see: (d) Molander, G. A.; Ellis, N. Acc. Chem.
Res. 2007, 40, 275.
(2) Jang, H.; Zhugralin, A. R.; Lee, Y.; Hoveyda, A. H. J. Am. Chem.
Soc. 2011, 133, 7859.
(3) For synthesis of vinylboron compounds by Cu-catalyzed proto-
boration of alkynes (in addition to ref 2), see: (a) Kim, H. R.; Jung, I. G.;
Yoo, K.; Jang, K.; Lee, E. S.; Yun, J.; Son, S. U. Chem. Commun. 2010,
46, 758. (b) Semba, K.; Fujihara, T.; Terao, J.; Tsuji, Y. Chem.;Eur. J.
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2012, 18, 4179. (c) Moure, A. L.; Arrayas, R. G.; Gardenas, D. J.;
Alonso, I.; Carretero, J. C. J. Am. Chem. Soc. 2012, 134, 7219. (d) Park,
J. K.; Ondrusek, B. A.; McQuade, D. T. Org. Lett. 2012, 14, 4790.
r
10.1021/ol4004178
Published on Web 03/05/2013
2013 American Chemical Society