C O M M U N I C A T I O N S
Scheme 2. Influence of NHC Structure on Site Selectivity and
Enantioselectivity of Boron-Copper Additionsa
2), resulting in the formation of secondary vinylboronates 19a and
19b as the major isomers (18/19 ) 17:83 and 10:90, respectively). In
contrast, when imidazolinium sulfonate 3 is used, 18a and 18b are
produced predominantly (18/19 ) 89:11).10 Control experiments
indicate that secondary boronates (e.g., 19) undergo Cu-catalyzed
hydroboration less readily and afford products with substantially lower
enantiomeric purity (with the Cu complex of 3). For example, treatment
of a pure sample of 5 with the conditions in Scheme 1 results in 13%
conversion to 6, which is formed in only 55:45 er. The high
enantioselectivity afforded by the NHC-Cu complex derived from 3
is thus partly due to its ability to promote preferential formation of
the terminal vinylboronates selectively. Consistent with the above
findings, chiral monodentate NHC-Cu complexes 20 and 21 (Scheme
2) give rise to less efficient and nonselective transformations. The basis
for the site selectivity in NHC-Cu-catalyzed alkyne hydroborations
is under investigation.
The diboronates obtained through the present method are versatile,
providing access to other useful enantiomerically enriched molecules.
The example in eq 4 involving diboronate 15 and ꢀ-bromoenone 22
is illustrative; site-selective Pd-catalyzed cross-coupling11 of the less
hindered C-B bond followed by oxidation of the remaining alkylbo-
ronate delivers 23 in 72% yield without loss of enantiomeric purity
(96.5:3.5 er).
a Conversions for reactions with 0.9 equiv of 1 are based on the amount of
this reagent and determined by 1H NMR analysis. Mes ) (2,4,6)-trimethylphenyl.
Graduate Fellow. We thank Frontier Scientific, Inc. for generous gifts
of reagent 1. The mass spectrometry facilities at Boston College are
supported by the NSF (DBI-0619576).
Supporting Information Available: Experimental procedures and
spectral and analytical data for all products. This material is available free
References
(1) Lee, Y.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 3160.
(2) Dang, L.; Lin, Z.; Marder, T. B. Organometallics 2008, 27, 4443, and
references cited therein.
(3) For selected reviews regarding catalytic diboron additions to alkenes
(including enantioselective variants), see: (a) Beletskaya, I.; Moberg, C.
Chem. ReV. 2006, 106, 2320. (b) Burks, H. E.; Morken, J. P. Chem.
Commun. 2007, 4717. (c) Dang, L.; Lin, Z.; Marder, T. B. Chem. Commun.
2009, 3987. See the Supporting Information for additional reviews.
(4) For Rh-catalyzed enantioselective hydroborations (up to 89.5:10.5 er) of a
vinylboronate [(E)-2-(phenylethenyl)-1,3,2-dioxaborolane], see: Wiesauer,
C.; Weissensteiner, W. Tetrahedron: Asymmetry 1996, 7, 5.
Enantiomerically enriched diboronates can be synthesized through
catalytic diborations of terminal alkenes with 1 equiv of 1 or the derived
biscatecholate3,6 (vs 2 equiv as used in this study). Bis(pinacolato)di-
boron is, however, commercially available in ample quantities and
inexpensive. The alternative protocols require the use of chiral
phosphines and salts of precious metals (e.g., Pt-, Pd- or Rh-based),
which are significantly more costly than CuCl. Finally, as demonstrated
through the synthesis of unsaturated diboronate 25 (eq 5), the present
approach complements the above-mentioned protocols involving alkene
substrates;3,6 the Cu-catalyzed reaction thus allows for chemoselective
diboration of an alkyne in the presence of an olefin (<2% reaction of
the alkene).
(5) For Pt- and Pd-catalyzed double hydrosilylation of arylacetylenes, see:
Shimada, T.; Mukaide, K.; Shinohara, A.; Han, J. W.; Hayashi, T. J. Am.
Chem. Soc. 2002, 124, 1584.
(6) For selected recent reports regarding catalytic enantioselective diboration
of terminal alkenes, see: Rh-catalyzed: (a) Morgan, J. B.; Miller, S. P.;
Morken, J. P. J. Am. Chem. Soc. 2003, 125, 8702. (b) Trudeau, S.; Morgan,
J. B.; Shrestha, M.; Morken, J. P. J. Org. Chem. 2005, 70, 9538.
Pt-catalyzed: (c) Kliman, L. T.; Mlynarski, S. N.; Morken, J. P. J. Am.
Chem. Soc. 2009, 131, 13210. Enantiomerically enriched diboronates have
been prepared by Rh- or Ir-catalyzed hydrogenations of bisborylalkenes.
See: (d) Morgan, J. B.; Morken, J. P. J. Am. Chem. Soc. 2004, 126, 15338.
(e) Paptchikhine, A.; Cheruku, P.; Engman, M.; Andersson, P. G. Chem.
Commun. 2009, 5996.
(7) For a recent review of Rh- and Ir-catalyzed enantioselective alkene
hydroboration, see: (a) Carroll, A.-M.; O’Sullivan, T. P.; Guiry, P. J. AdV.
Synth. Catal. 2005, 347, 609. For a recent Cu-catalyzed hydroboration of
monosubstituted styrenes (with pinacolborane), see: (b) Noh, D.; Chea, H.;
Ju, J.; Yun, J. Angew. Chem., Int. Ed. 2009, 48, 6062.
(8) N-Heterocyclic Carbenes in Transition Metal Catalysis; Glorious, F., Ed.;
Springer-Verlag: Berlin, 2007.
(9) For representative examples where bidentate Cu-based NHC sulfonates have
been utilized in enantioselective C-C bond formation, see: (a) Brown,
M. K.; Hoveyda, A. H. J. Am. Chem. Soc. 2008, 130, 12904. (b) Lee, Y.;
Akiyama, K.; Gillingham, D. G.; Brown, M. K.; Hoveyda, A. H. J. Am.
Chem. Soc. 2008, 130, 446. For structural attributes of related Zn- and
Al-based complexes, see: (c) Lee, Y.; Li, B.; Hoveyda, A. H. J. Am. Chem.
Soc. 2009, 131, 11625.
Development of other NHC-Cu-catalyzed boron-copper additions
and examination of mechanistic issues are in progress.
(10) For a study regarding variations in the site selectivity of boron-copper
additions to terminal alkynes (not catalytic), see: Takahashi, K.; Ishiyama,
T.; Miyaura, N. J. Organomet. Chem. 2001, 625, 47.
(11) Doucet, H. Eur. J. Org. Chem. 2008, 2013.
Acknowledgment. Financial support was provided by the NSF
(CHE-0715138) and the NIH (GM-47480). Y.L. is an AstraZeneca
JA9089928
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