Journal of the American Chemical Society
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with 3-bromopyridine as the coupling partner in 99% yield (NSERC) Discovery Grant RGPIN-06438, the Canada
1
2
3
4
5
6
7
8
using Pd(dba)2/PCy3 in a biphasic toluene/KOH aqueous
mixture. A second Suzuki–Miyaura coupling was achieved on
boronate 3u in 81% yield. The product of this reaction succes-
sively underwent TBAF-mediated deprotection of the TBS
group to provide the free alcohol 8 in 96% yield (Scheme 3).
Foundationꢀfor Innovation Leaders Opportunity Funds
227346, the Canada Research Chair Program CRC-227346,
theꢀ FRQNT Team Grant PR-190452, the FRQNT Centre in
Green Chemistry and Catalysis (CGCC) Strategic Cluster
RS-171310, and Université de Montréal. The authors are
grateful to S. Goudreau and É. Lévesque for helpful discus-
sions and suggestions.
In summary, we have developed a highly efficient boro-
cyclopropanation using a novel boromethylzinc carbenoid.
This reaction generally proceeds with good yields and
selectivities with a wide range of alkenes. The product are
versatile building blocks to access polysubstituted cyclo-
propane derivatives in a stereocontrolled fashion. Further
work is in progress to expand this reaction into an enanti-
oselective version.
9
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10
11
12
13
14
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Scheme 3. Post-functionalization of Borocyclopropane
Derivatives
5
OH
Bpin
3-Pyr
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OR2
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R1
R1
2007, 107, 3117.
6
3l: R1 = n-Pr; R2 = Bn
3a: R1 = Ph; R2 = Bn
3u: R1 = Ph; R2 = TBS
de Meijere, A.; Khlebnikov, A. F.; Sünnemann, H. W.; Frank, D.;
5: R1 = nPr
6: R1 = Ph
70%
99%
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(c)
Ph
Ph
(d)
OTBS
R1
7: R1 = Ph
OH
R1
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8: R1 = Ph
81%
96%
a H2O2 (30%, 2 equiv), NaOH (aq) (1 equiv), THF, 0 °C, 30
min.10a b Pd(dba)2 (5 mol %), PCy3 (10 mol %), 3-
bromopyridine (2 equiv), KOH (3 N) (6 equiv), toluene,
115 °C, 20 h. c Pd(dba)2 (7 mol %), PCy3 (15 mol %), iodo-
benzene (2 equiv), KOH (3 N) (6 equiv), toluene, 115 °C, 20
h. d TBAF (1.2 equiv), THF, 0 °C to rt, 110 min.
9
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ASSOCIATED CONTENT
11
Supporting Information. Experimental procedures, com-
pound characterization data, and NMR spectra for new com-
pounds. This material is available free of charge via the Inter-
Zhong, C. M.; Kunii, S.; Kosaka, Y.; Sawamura, M.; Ito, H. J. Am.
Chem. Soc. 2010, 132, 11440.
12
Takai, K.; Toshikawa, S.; Inoue, A.; Kokumai, R.; Hirano, M. J. Organ-
omet. Chem. 2007, 692, 520.
13
For an alternative approach to cyclopropylborinate derivatives see:
Zimmer, L. E.; Charette, A. B. J. Am. Chem. Soc. 2009, 131, 15624.
For the preparation of dichloromethylboronate and related Finkelstein
reaction of chloromethylboronate see: a) Wuts, P. G. M.; Thompson, P.
A. J. Organomet. Chem. 1982, 234, 137. b) Raheem, I. T.; Goodman, S.
N.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 706.
AUTHOR INFORMATION
Corresponding Author
14
Funding Sources
15
The dichloromethylboronic acid was synthesized according literature
procedure14a-b whereas the corresponding pinacol boronate was synthe-
sized by a modified procedure: Cl2CHB(OH)2 (1 equiv), pinacol (1.05
equiv), MgSO4, DCM, rt, 18h, 88% yield (for a complete procedure see
Supporting Information).
No competing financial interests have been declared.
ACKNOWLEDGMENT
16
a) Langer, F.; Schwink, L.; Devasagayaraj, A.; Chavant, P.-Y.; Knochel,
This work was supported through funding from the Natural
Science and EngineeringꢀResearch Council of Canada
P. J. Org. Chem. 1996, 61, 8229. b) Bolm, C., Rudolph, J. J. Am. Chem.
Soc. 2002, 124, 14850. c) Li, H.; Carroll, P. J.; Walsh, P. J. J. Am. Chem.
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