B-Alkyl Suzuki-Miyaura Cross-Coupling Reactions
for 30 min. The resulting white solid was purified by dissolu-
tion in acetone and precipitation with Et2O to give 945 mg of
a white solid, 72% yield: 1H NMR (acetone-d6) δ -0.09 (s, 9H),
-0.5 (m, 2H); 13C NMR (acetone-d6) δ 6.27 (m), 1.3; 19F NMR
(DMSO-d6) δ -132.0 (m); 11B NMR (DMSO-d6) δ 7.9 (m).
mmol) was dissolved in MeCN (20 mL) and KHF2 (800 mg,
11.2 mmol, 3.1 equiv) was added at room temperature followed
by the addition of water (2.5 mL) over 1 h. The mixture was
extracted several times with acetone, and the extracts were
combined, concentrated, and then held under high vacuum for
1 h. The resulting white solid was purified by dissolving in
hot MeCN and precipitating with Et2O, providing a white solid
(700 mg, 75%), mp 183 °C: 1H NMR (acetone-d6) δ 8.02 (dd, J
) 7.0 and 1.3 Hz, 2H), 7.59 (t, J ) 6.2 Hz, 1H), 7.48 (t, J ) 7.3
Hz, 2H), 4.23 (t, J ) 7.3 Hz, 2H), 1.70 (quint, J ) 7.9 Hz, 2H),
0.24 (br s, 2H); 13C NMR (acetone-d6) δ 167.0, 133.5, 132.2,
130.1, 129.3, 69.2, 25.9, 23.4; 19F NMR (acetone-d6) δ -141.8
(m); 11B NMR (acetone-d6) δ 8.35 (br s).
P ot a ssiu m 3-(p -Tolylsu lfon yla m in o)p r op ylt r iflu or o-
bor a te (3d ). The compound was prepared following the above
procedure, starting with 705 mg (3.3 mmol) of allylamine,
p-tolylsulfonamide, pinacolborane (1.0 g, 5.6 mmol, 1.7 equiv),
and 1 mol % Rh(PPh3)3Cl. The boronic ester derivative was
isolated as a colorless oil (820 mg, 60%): 1H NMR (CDCl3) δ
7.68 (d, J ) 8.1 Hz, 2H), 7.24 (d, J ) 8.1 Hz, 2H), 4.88 (br t,
1H, NH), 2.88-2.84 (m, 2H), 2.37 (s, 3H), 1.54-1.51 (m, 2H),
1.21 (s, 6H), 1.18 (s, 6H), 0.69 (t, J ) 6.5 Hz, 2H); 11B NMR
(CDCl3) δ 21.9 (m). A part of the boronic ester (500 mg, 1.4
mmol, 1 equiv) was treated with 400 mg of KHF2 (4.2 mmol,
3 equiv) following the same procedure as above. After recrys-
tallization in CHCl3 the corresponding potassium trifluorobo-
rate 3d was obtained as a white solid (320 mg, 75% yield), mp
120 °C: 1H NMR (DMSO-d6) δ 7.65-7.63 (AA′, 2H), 7.37-
7.35 (BB′, 2H), 7.14 (br t, J ) 1.1 Hz, 1H, NH), 2.58-2.55 (m,
2H), 2.37 (s, 3H), 1.23 (quint, J ) 7.7 Hz, 2H), -0.16 to -0.21
(m, 2H); 13C NMR (acetone-d6) δ 143.3, 139.6, 130.2, 128.1,
47.3, 26.5, 25.3 (m), 21.4; 19F NMR (acetone-d6) δ -140.3 (br
s); 11B NMR (acetone-d6) δ 8.25 (br s).
P ota ssiu m 3-Ch lor op r op yltr iflu or obor a te (3a ). To a
mixture of allyl chloride (1.4 g, 16 mmol) and HSiEt3 (2.0 g,
17 mmol) was added a solution of BCl3 (1 M in hexane, 18
mL, 18 mmol) at -78 °C under an argon atmosphere. The
resulting suspension was stirred at this temperature for 30
min, after which it was allowed to warm to room temperature
for 1 h. The mixture was cooled to 0 °C, and water (30 mL)
and ether (30 mL) were slowly added. The suspension was
stirred for 30 min and then extracted with ether. The combined
extracts were dried over MgSO4 and filtered. After removal of
the solvent the white solid was purified by crystallization,
affording 1.4 g of the boronic acid. A part of the resulting
boronic acid (850 mg, 7 mmol) was dissolved in ether (20 mL),
and KHF2 (2.30 g, 29.4 mmol) was added followed by the
addition of water (1 mL) over 1 h. The mixture was extracted
with acetone and the combined extracts were concentrated
and then held under high vacuum for 30 min. The resulting
white solid was purified by dissolving in hot acetone and
precipitating with Et2O, providing a white solid (1.03 g, 5.6
mmol, 80% yield), mp >290 °C: 1H NMR (DMSO-d6) δ 3.48
(t, J ) 7.7 Hz, 2H), 1.57 (quint, J ) 7.7 Hz, 2H), 0.01 (m, 2H);
13C NMR (DMSO-d6) δ 49.8, 30.9, 17.4 (m); 19F NMR (DMSO-
d6) δ -137.7 (m); 11B NMR (DMSO-d6) δ 5.22.
P otassiu m 3-P h en ylsu lfen ylpr opyltr iflu or obor ate (3b).
To a solution of allyl phenyl sulfide (1.0 g, 6.6 mmol, 1 equiv)
in CH2Cl2 (25 mL) was added a solution of HBBr2‚SMe2 (1 M
in CH2Cl2, 13.3 mL, 13.3 mmol, 2 equiv). The resulting
suspension was stirred at reflux for 24 h and then allowed to
cool to room temperature. The mixture was cooled further to
0 °C, and water and ether were slowly added. The suspension
was stirred for 30 min, extracted with ether, dried over MgSO4,
and filtered. After removal of the solvent the white solid was
purified by crystallization in ether/hexane, providing 1.0 g of
the boronic acid (80% yield): 1H NMR (CDCl3) δ 7.32-7.23
(m, 4H), 7.11 (t, J ) 1.2 Hz, 1H), 2.97-2.92 (m, 2H), 1.82-
1.74 (m, 2H), 1.02-0.0 (m, 2H); 11B NMR (CDCl3) δ 33.5 (m).
A part (770 mg, 3.9 mmol) of the resulting boronic acid
derivative was dissolved in ether (20 mL), and KHF2 (915 mg,
11.7 mmol, 3 equiv) was added followed by the addition of
water (1 mL) over 1 h. The mixture was extracted several
times with acetone, and the combined extracts were concen-
trated and then held under high vacuum for 30 min. The
resulting white solid was purified by dissolving in hot acetone
and precipitating with ether, affording 3b as a flaky white solid
(935 mg, 93% yield), mp 289 °C: 1H NMR (DMSO-d6) δ 7.27-
7.23 (m, 4H), 7.11 (t, J ) 1.2 Hz, 1H), 2.83 (t, J ) 7.8 Hz, 2H),
1.47-1.44 (m, 2H), 0.07-0.05 (m, 2H); 13C NMR (DMSO-d6) δ
137.7, 128.7, 127.2, 124.7, 35.4, 25.8; 19F NMR (DMSO-d6) δ
-136.7; 11B NMR (DMSO-d6) δ 5.73.
Rep r esen ta tive P r oced u r e for Cr oss-Cou p lin g of P o-
t a ssiu m Met h ylt r iflu or ob or a t e 1 a n d Tr im et h ylsilyl-
m eth yltr iflu or obor a te 2 w ith Ar yl Tr ifla tes or Ar yl
Ha lid es (Meth od A). P r ep a r a tion of 4-Meth yla cetop h e-
n on e46 (4a ). To a suspension of potassium methyltrifluorobo-
rate (1a ) (75 mg, 0.50 mmol), Cs2CO3 (489 mg, 1.50 mmol),
47
PdCl2(dppf)‚CH2Cl2 (36 mg, 0.05 mmol), and 4-acetylphenyl-
triflate (148 mg, 0.55 mmol) in THF (5 mL) was added water
(0.5 mL) under an argon or nitrogen atmosphere. The reaction
mixture was stirred at reflux temperature for 18 h (6-8 h for
trimethylsilylmethyltrifluoroborate 2 or 3 d for alkyltrifluo-
roborates 3a -e), then cooled to room temperature, diluted with
water (10 mL), and extracted with ether. The combined organic
extracts were washed with 1 N HCl (20 mL) and brine (20
mL) and then dried over magnesium sulfate. The solvent was
removed in vacuo, and the crude product was purified by silica
gel column chromatography (eluting with hexane/EtOAc ) 8/1)
to yield 4a (92 mg, 85%): Rf ) 0.47 (EtOAc/hexane ) 1/8); 1H
NMR (CDCl3) δ 7.85 (d, J ) 8.1 Hz, 2H), 7.25 (d, J ) 8.1 Hz,
2H), 2.57 (s, 3H), 2.41 (s, 3H); 13C NMR (CDCl3) δ 197.8, 143.8,
134.7, 129.2, 128.4, 26.5, 21.6.
Gen er a l P r oced u r e for P r ep a r a tion of P ota ssiu m
Alk yltr iflu or obor a tes 3c a n d 3d . P ota ssiu m 3-Ben zoy-
loxyp r op yltr iflu or obor a te (3c). To a solution of allylben-
zoate (1.0 g, 6.2 mmol, 1 equiv) in CH2Cl2 (20 mL) in the
presence of 1 mol % Rh(PPh3)3Cl catalyst was added pina-
colborane (1.0 M THF solution, 1.2 g, 9.2 mmol, 1.5 equiv) at
0 °C. The reaction mixture was allowed to warm to room
temperature and was stirred for 24 h. Water was added and
the mixture was extracted with ether, dried over MgSO4, and
filtered. After removal of the solvent, the boronic ester was
purified by column chromatography (hexane/AcOEt 8/1) to
provide 3c as a colorless oil (1.5 g, 85% yield): 1H NMR (CDCl3)
δ 8.01 (dd, J ) 7.1 and 1.2 Hz, 2H), 7.49 (t, J ) 6.3 Hz, 1H),
7.38 (t, J ) 7.3 Hz, 2H), 4.26 (t, J ) 7.2 Hz, 2H), 1.86-1.83
(m, 2H), 1.22 (s, 3H), 1.21 (s, 3H), 1.20 (s, 3H), 1.19 (s, 3H),
0.89-0.84 (m, 2H); 13C NMR (CDCl3) δ 166.5, 132.6, 130.5,
129.5, 128.1, 83.0, 82.7, 66.6, 24.7, 23.2, 7.3 (m); 11B NMR
(CDCl3) δ 35.04 (m). A part of the resulting product (1.0 g, 3.5
Ack n ow led gm en t. We thank J ohnson & J ohnson,
Merck Research Laboratories, Aldrich Chemical Co.,
Array BioPharma, and J ohnson Matthey for their
generous support, and Dr. Takatoshi Ito for his pre-
liminary work on this project.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails and structural data (NMR spectra) for all compounds
described within the text. This material is available free of
J O0343331
(46) Spectroscopic and physical data of 4a -f, 4h , and 2j-k were
identical to those of authentic samples available from Aldrich.
(47) In the case of potassium alkyltrifluoroborates 3a -e, PdCl2(dppf)
uncomplexed with CH2Cl2 was used. See ref 43.
J . Org. Chem, Vol. 68, No. 14, 2003 5539