Suzuki-Miyaura Cross-Coupling of Organotrifluoroborates
acetone-d6) δ: 55.6, 52.9, 45.7; 19F-NMR (471 MHz, acetone-d6)
δ -142.68; 11B-NMR (128.37 MHz, acetone-d6) δ 1.13; IR (KBr)
) 3197, 2950, 2805, 1454, 1286, 1150, 1046 cm-1; HRMS (ESI)
calcd for C6H13BF3N2 (M - K) 181.1124, found 181.1120.
General Procedure for Suzuki-Miyaura Cross-Coupling
Reactions of Aryl Electrophiles. Preparation of (Piperidin-1-
ylmethyl)benzene (2a). A Biotage microwave vial was charged
with Pd(OAc)2 (7 mg, 0.03 mmol), XPhos (29 mg, 0.06 mmol),
potassium N-(trifluoroboratomethyl)piperidine (207 mg, 1.01 mmol),
and Cs2CO3 (978 mg, 3.0 mmol). The tube was sealed with a cap
lined with a disposable Teflon septum and evacuated under vacuum
and filled with N2 three times. Chlorobenzene (113 mg, 1.0 mmol),
and THF/H2O (10:1) (0.25 M, 4 mL) were added by syringe and
the reaction was stirred at 80 °C for 24 h, then cooled to rt and
diluted with H2O (2 mL). The reaction mixture was extracted with
CH2Cl2 (3 × 5 mL) or alternatively with EtOAc (3 × 5 mL). The
organic layer was dried (Na2SO4). The solvent was removed in
vacuo, and the crude product was purified by silica gel column
chromatography (elution with hexane/EtOAc/Et3N 4:1:0.05: Rf
0.18) to yield the product as a clear yellow oil in an 85% yield
(150 mg, 0.85 mmol): 1H NMR (500 MHz, CDCl3) δ 7.27-7.31
(m, 3H), 7.22-7.24 (m, 2H), 3.46 (s, 2H), 2.36 (br s, 4H), 1.54-
1.58 (m, 4H), 1.41-1.44 (m, 2H); 13C NMR (125.8 MHz, CDCl3)
δ 138.9, 129.4, 128.3, 127.0, 64.1, 54.7, 26.2, 24.6; IR (neat) )
2932, 2792 cm-1; HRMS (CI) calcd for C12H18N (MH+) 176.1439,
found 176.1431.
added by syringe, and the reaction was stirred at 80 °C for 48 h,
then cooled to rt and diluted with H2O (4 mL). The reaction mixture
was extracted with CH2Cl2 (3 × 5 mL). The organic layer was
dried (Na2SO4). The solvent was removed in vacuo, and the crude
product was purified by basic aluminum oxide column chroma-
tography (elution with hexane/EtOAc/Et3N 36:1:0.2: Rf 0.28) to
yield the product as a clear yellow oil in an 80% yield (342 mg,
1.70 mmol): 1H NMR (500 MHz, CDCl3) δ 7.52 (d, J ) 8.5 Hz,
2H), 7.28-7.31 (m, 2H), 7.24-7.26 (m, 1H), 5.44 (d, J ) 1.7 Hz,
1H), 5.23 (d, J ) 1.6 Hz, 1H), 3.28 (s, 2H), 2.40 (br s, 4H), 1.52-
1.56 (m, 4H), 1.39-1.43 (m, 2H); 13C NMR (125.8 MHz, CDCl3)
δ 144.8, 141.0, 128.2, 127.5, 126.5, 114.9, 63.9, 54.7, 26.3, 24.7.
The spectral data were in agreement with those reported in the
literature.15
Acknowledgment. This work was generously supported by
the National Institutes of Health (GM035249), Amgen, Merck
Research Laboratories, and a Pfizer Summer Undergraduate
Research Fellowship to P.E.G. We also acknowledge Frontier
Scientific and Johnson Matthey for a donation of palladium
catalysts, Professor Stephen L. Buchwald (MIT) for a sample
of phosphine ligands, Dr. Rakesh Kohli (University of Penn-
sylvania) for obtaining high-resolution mass spectra of new
compounds, and the Zeon Corp. for donation of cyclopentyl
methyl ether (CPME).
General Procedure for Suzuki-Miyaura Cross-Coupling
Reactions of Alkenyl Bromides. Preparation of 1-Phenyl-1-
(piperidin-1-ylmethyl)ethylene (9a). A 50 mL round-bottom flask
was charged with Pd(OAc)2 (2.7 mg, 0.012 mmol), XPhos (11.4
mg, 0.024 mmol), potassium N-(trifluoroboratomethyl)piperidine
(430 mg, 2.1 mmol), and Cs2CO3 (1.95 g, 6.0 mmol). The flask
was fitted with a reflux condenser and a rubber septum, evacuated
under vacuum, and purged with N2 three times. R-Bromostyrene
(366 mg, 2.0 mmol) and THF/H2O (10:1) (0.25 M, 8 mL) were
Supporting Information Available: Experimental procedures,
spectral characterization, and copies of 1H, 13C, 11B, and 19F spectra
for all compounds prepared by the method described. This material
JO800183Q
(15) Olofsson, K.; Larhed, M.; Hallberg, A. J. Org. Chem. 2000, 65,
7235-7239.
J. Org. Chem, Vol. 73, No. 6, 2008 2057