CDCl3) δ 149.2, 128.2, 126.6, 125.7, 83.0, 35.8, 24.8, 24.7, 21.3
(C attached to quadrupole B not observed).
(ca. 25% overall) from a similar experiment using 10 mol % of
I2 for activation of 16 followed by treatment with KHF2 and
coupling with p-nitroiodobenzene/PdCl2(dppf). These results
implicate a second hydroboration event as the reason for the
apparent reduction7 but do not clarify the role of iodine
stoichiometry.
Procedures for Tables 1 and 2. For Table 1, entries 1, 2, 5, 9,
10, and 11, and for Table 2, entries, 1-4, 6, 8, and 9, the procedure
for formation of 5 was followed. For Table 1, entries 3 and 4, after
stirring was completed, the solution was transferred by cannula into
sodium hydroxide (5 mL, 1 M) at 0 °C.
Studies described here define the optimum conditions for
conversion of alkenes into monoalkylborane products using the
activated pyridine borane reagent 1. Also presented is a method
for the formation of pinacol boronates directly from hydrobo-
ration mixtures. Alternative reagents for hydroboration are
known that allow conversion to monoalkyl-boronic acid deriva-
tives, including the recently developed Snieckus di(isopropyl-
prenyl)borane8 as well as haloboranes9 or catechol borane under
metal catalysis.10 Hydroboration using PyBH2I (1) is a simple
alternative that readily provides purifiable pinacol boronates in
most cases and works best for the more hindered 1,2-di- or
trisubstituted alkenes where competition by the second hy-
droboration stage is disfavored.
For Table 1, entry 7, and Table 2, entries 5 and 7, the solution
was cooled to 0 °C, sodium hydroxide (15 mL, 1 M) was added,
the solution was warmed to room temperature, and then a solution
of pinacol (1.32 g, 11.1 mmol) in CH2Cl2 (15 mL) was added and
the resulting solution stirred for 15 h.
For Table 1, entry 8, the solution was cooled to 0 °C, sodium
hydroxide (30 mL, 1 M) was added, the solution was warmed to
room temperature, and then a solution of pinacol (2.64 g, 22.2
mmol) in CH2Cl2 (30 mL) was added and the resulting solution
stirred for 15 h.
Oxazaborolidine 10. A solution of pyridine borane (220 µL,
2.2 mmol) in CH2Cl2 (5 mL) was cooled to 0 °C. Iodine (280 mg,
1.1 mmol) was added, and the solution was stirred at 0 °C until
gas evolution ceased. The solution was warmed to room temper-
ature, and styrene (252 µL, 2.2 mmol) was added. After being stirred
for 2 h, the solution was cooled to 0 °C, methanol (6.5 mL) was
added very slowly, and the solvent was removed under vacuum.
The solid residue was dissolved in THF (3 mL), then 2-picolinic
acid (295 mg, 2.4 mmol), water (6 mL), and ethanol (6 mL) were
added, and the solution was brought to reflux (15 h). The solution
was concentrated, the residual solid was partitioned between CH2Cl2
and water, and the water layer was extracted with CH2Cl2, dried
(Na2SO4), and concentrated. The crude products were purified by
flash chromatography using 2/1 ether/hexanes to yield 142 mg
Experimental Section
Pinacol Boronate Ester 5. A solution of pyridine borane (330
µL, 3.3 mmol) in CH2Cl2 (15 mL) was cooled to 0 °C. Iodine (419
mg, 1.65 mmol) was added in several portions, and the solution
was stirred at 0 °C until gas evolution ceased. The solution was
warmed to room temperature, and ꢀ-methylstyrene (285 µL, 2.2
mmol) was added. Stirring was continued until the reaction was
complete based on TLC assay (2 h). The solution was cooled to 0
°C, sodium hydroxide (5 mL, 1 M) was added, the mixture was
warmed to room temperature, and then a solution of pinacol (440
mg, 3.7 mmol) in CH2Cl2 (5 mL) was added and stirred for 15 h.
The resulting mixture was added to H2O (10 mL), extracted with
ether, dried (Na2SO4), and concentrated (aspirator). The crude
products were purified by flash chromatography using 2% ether in
hexanes to yield 520 mg (96%) of 510b as a colorless oil: 1H NMR
(400 MHz, CDCl3) δ 7.28 (m, 4H), 7.17 (m, 1H), 2.28 (t, J ) 8.3
Hz, 1H), 1.99 (m, 1H), 1.78 (m, 1H), 1.24 (m, 12H), 0.91 (t, J )
7.9 Hz, 3H); aminor doublet (ca. 8-10% relative to the 0.91 triplet)
at δ 0.97 was also resolved, tentatively assigned to the inseparable
regioisomeric pinacol boronate; 13C NMR (100 MHz, CDCl3; only
the major regioisomer 5 detected) δ 143.4, 128.4, 128.2, 125.1,
83.2, 34.4, 25.9, 24.7, 24.6, 14.0.
Pinacol Boronate Ester 6 (Table 1, Entry 6). A solution of
pyridine borane (660 µL, 6.6 mmol) in CH2Cl2 (15 mL) was cooled
to 0 °C. Iodine (838 mg, 3.3 mmol) was added in several portions,
and the solution was stirred at 0 °C until gas evolution ceased.
The solution was warmed to room temperature, and R-methylstyrene
(285 µL, 2.2 mmol) was added. Stirring was continued until the
reaction was complete based on TLC (2 h). The solution was cooled
to 0 °C, sodium hydroxide (10 mL, 1 M) was added, the solution
was warmed to room temperature, and then a solution of pinacol
(880 mg, 7.4 mmol) in CH2Cl2 (10 mL) was added and the resulting
solution stirred for 15 h. The same workup and purification as
described above gave 334 mg (62%) of 610b as a colorless oil: 1H
NMR (400 MHz, CDCl3) δ 7.30 (m, 4H), 7.19 (m, 1H), 3.10 (m,
1H), 1.31 (d, J ) 7.4 Hz, 3H), 1.18 (m, 14H); 13C NMR (100 MHz,
1
(38%) of 10 as a colorless oil: IR (CDCl3) 1737 cm-1; H NMR
(400 MHz, CDCl3) δ 8.20 (m, 3H), 7.61 (m, 1H), 7.15 (m, 4H),
7.06 (m, 6H), 2.62 (m, 2H), 2.18 (m, 2H), 1.28 (m, 2H), 1.00 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 163.5, 145.4, 143.8, 142.1,
140.3, 128.1, 128.0, 127.8, 125.1, 123.4, 30.7, 24.2; 11B NMR (128
MHz, CDCl3) δ 10.1; ESMS m/z (relative intensity) 366.1 (M +
Na, 100); HRMS m/z calcd for C22H22BNO2 (M + Na) 366.1641,
found 366.1624.
Pinacol Boronate 15. A solution of iodine (51 mg, 0.20 mmol)
in CH2Cl2 (6.3 mL) was added slowly to amine borane 12 (73 mg,
0.39 mmol) in CH2Cl2 (6.3 mL) and stirred for 2 h. The solution
was cooled to 0 °C, NaOH (1.25 mL, 1 M) was added followed by
pinacol (188 mg, 1.6 mmol) in CH2Cl2 (2.2 mL), and the mixture
was stirred overnight. The solution was added to water (10 mL),
extracted with ether, dried over Na2SO4, and concentrated. The
residue was placed under high vacuum (0.1 Torr) to remove excess
pinacol and gave 114 mg (97% recovery, >95% major component
by NMR assay) of 15 as a colorless oil, not purified further due to
instability to silica gel chromatography: IR (CDCl3) 2975 cm-1
;
1H NMR (300 MHz, CDCl3) δ 7.27 (m, 5H), 3.72 (m, 2H), 2.61
(m, 2H), 1.87 (s, 1H), 1.61 (m, 1H), 1.50 (m, 1H), 1.46 (m, 1H),
1.30 (m, 1H), 1.15 (m, 13H), 0.86 (t, J ) 7.4 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 139.4, 128.4, 128.2, 127.1, 82.0, 53.3, 48.4,
30.7, 25.0, 24.9, 24.2, 13.9; 11B NMR (160 MHz, CDCl3) δ 29.8;
ESMS m/z (relative intensity) 304.2 (M + H, 100); HRMS calcd
for C18H30BNO2 (M+) 303.2370, found 303.2367.
Acknowledgment. This work was supported by the NIH
(GM067146).
(7) Isolation of alcohols from alkyne hydroboration followed by oxidative
cleavage has been attributed to the formation of 1,1-diboro intermediates and
subsequent nucleophile-induced deboronation: Brown, H. C.; Zweifel, G. J. Am.
Chem. Soc. 1961, 83, 3834.
(8) Kalinin, A. V.; Scherer, S.; Snieckus, V. Angew. Chem., Int. Ed. 2003,
42, 3399.
(9) Josyula, K. V. B.; Gao, P.; Hewitt, C. Tetrahedron Lett. 2003, 44, 7789,
and references therein.
(10) (a) Review: Crudden, C. M.; Edwards, D. Eur. J. Org. Chem. 2003,
4695. (b) Cipot, J.; Vogels, C. M.; McDonald, R.; Westcott, S. A.; Stradiotto,
M. Organometallics 2006, 25, 5965.
Supporting Information Available: General experimental,
citation of known compounds, characterization data for entries
4 and 5 of Table 1, and copies of 1H NMR and 13C NMR spectra
for new compounds. This material is available free of charge
JO8020049
9510 J. Org. Chem. Vol. 73, No. 23, 2008