Isopinocampheylchloroborane for Asymmetric Hydroboration
J . Org. Chem., Vol. 61, No. 15, 1996 5147
mmol) was added at 0 °C. The 11B NMR spectrum of the
reaction mixture showed 85% of IpcBHCl and 15% of IpcBCl2.
The solution was 0.83 M in hydride and 1.10 M in chloride.
Typ ica l P r oced u r e for th e Exa m in a tion of th e Ra te
a n d En a n tiom er ic Excess for th e Hyd r obor a tion of
2-Meth yl-2-bu ten e w ith Ip cBH2 in EE. Optically pure
IpcBH2 (1.20 M, 8.3 mL, 10 mmol) in EE was made according
to the literature procedure.5 For reactions other than in EE,
solvent EE was removed (13 mmHg, 25 °C, 20-30 min) and
replaced by the same volume of either pentane, CH2Cl2, or THF
(8.3 mL). The 11B NMR spectrum was recorded (Table 1) and
the solution analyzed for hydride content.18 The solution was
cooled to 0 °C, and 2-methyl-2-butene (10 mmol) was added
at that temperature. The rate of the reaction was followed at
fixed time intervals by the 11B NMR spectrum of an aliquot
(∼0.10-0.20 mL) after methanolysis with cold (-10 °C)
methanol (∼0.40-0.50 mL).9a,16 At the end of the reaction,
the mixture was methanolyzed and subjected to alkaline
peroxide oxidation.7,9b The resultant product alcohol, 3-methyl-
2-butanol, was separated from the isopinocampheol by a short-
path distillation, derivatized as the menthyl carbonate,28a and
analyzed on the capillary GC (SPB-5 column, 30 m at 140 °C
isothermal temperature) for its percentage enantiomeric excess
(Table 2). The results of these reactions are graphically
represented in Figure 1. These results are also provided in
Table 6 (supporting information).
presence of IpcBCl2 in the asymmetric hydroboration of
prochiral alkenes has no significant effect on the chiral
outcome of the reaction (Table 5).
In conclusion, we have demonstrated that the IpcBHCl
reagent can be conveniently synthesized by a number of
simple methods. However, for practical purposes, we
recommend method B for the asymmetric hydroboration
since IpcBCl2 can be prepared conveniently in almost
quantitative yield and stored at room temperature for
considerable periods of time without noticeable change.26
The present study will help in developing practical
procedures for the synthesis of structurally varied chiral
hindered 2-organylapoisopinylhaloboranes of consider-
able promise in the area of asymmetric synthesis via
chiral organoboranes. Our preliminary results for asym-
metric hydroboration with 2-ethylapoisopinylchlorobo-
rane (EapBHCl) and with IpcBHBr reagents are quite
promising.27 This research is in progress and will be
reported shortly.
Exp er im en ta l Section
All glassware was dried overnight at 140 °C, assembled hot,
and cooled to ambient temperature in a stream of nitrogen.18
All reactions were performed under static pressure of dry
nitrogen. The 11B NMR spectra were recorded at 96 MHz and
were referenced to BF3‚EE.
Typ ica l P r oced u r e for th e Exa m in a tion of Ra te a n d
En a n tiom er ic Excess for th e Hyd r obor a tion of 2-Meth yl-
2-bu ten e w ith Ip cBHCl, Obta in ed fr om th e Rea ction of
o
Ip cBH2 w ith Ip cBCl2 a t 0 C in Rep r esen ta tive Solven ts.
5
19a,b
Ma ter ia ls. IpcBH2 and IpcBCl2
were prepared using
To a cold (0 °C) solution of optically pure IpcBH2 (1.20 M, 4.2
mL, 5.0 mmol), prepared in 9.0 mL of pentane or CH2Cl2 or
THF as mentioned above, was added neat, optically pure
IpcBCl2 (5.0 mmol) via syringe. The reaction mixture was
stirred for 5 min, and the 11B NMR spectrum of an aliquot
was recorded16 (results are given in Table 7, supplementary
information). The active hydride (∼1.00 M) and chloride
contents of the solution were determined.18 To the reaction
mixture was added 2-methyl-2-butene (10 mmol) at 0 °C, and
the rate of the reaction was followed at that temperature as
described in the preceding experiment. The rate of hydrobo-
ration at 24 °C was determined by the direct measurement of
dialkylchloroborane (δ 72-74) evident in the 11B NMR spec-
trum. The results of these reactions are graphically shown
in Figures 2 and 3. The results are given in Table 8
(supporting information).
literature procedures. Trimethylsilane, dry EE, DMS, and
pentane were used as obtained. Dichloromethane and THF
were distilled from phosphorous pentoxide and sodium ben-
zophenone ketyl, respectively, prior to use.
Hydr obor ation of r-P in en e with BH2Cl‚SMe2 in CH2Cl2.
A cold (0 °C) solution of CH2Cl2, containing BH2Cl‚SMe2 (10
mmol) and benzene in CH2Cl2 (1.0 M, 2.0 mL, 2.0 mmol) as
an internal standard, was stirred at 0 °C, and R-pinene (1.36
g, 10 mmol) was added via syringe. The rate of the reaction
1
was followed by H NMR spectra of aliquots (∼0.1 mL) taken
in CDCl3 (0.6 mL) at 24 °C.9a,16 The reaction was over in less
than 10 min, and at that point, the 11B NMR spectrum of an
aliquot showed a mixture of products.17
Rea ction of Ip cBH2 w ith HCl in EE. IpcBH2 in EE was
.
prepared from the reaction of BF3‚EE with IpcBH2 TMEDA
adduct (g99% ee), obtained from (+)-R-pinene of g91% ee.5
To the solution of optically pure IpcBH2 (1.15 M, 8.7 mL, 10
mmol) in EE cooled at -5 °C was added HCl in EE (2.38 M,
4.20 mL, 10 mmol) slowly, and the liberated H2 was measured
(9.5 mmol, 95% in 5 min). The 11B NMR spectrum of the
solution indicated a mixture of 90% IpcBHCl‚EE, and 5% each
of IpcBCl2‚EE and IpcBH2. The molarity of the solution was
conveniently determined by hydride analysis.18 The hydrolysis
of a 1.0 mL aliquot produced 19.2 mL of H2, which corresponds
to 0.77 M. The chloride content was estimated by hydrolyzing
an aliquot and titrating the HCl produced with a standard
aqueous solution of NaOH using phenolphthalein as an
indicator. The solution was 0.79 M in chloride.
Rea ction of Ip cBH2 w ith Ip cBCl2‚EE in EE. To EE (2.70
mL) cooled at -10 °C was slowly added optically pure IpcBCl2
(3.11 mmol) (11B NMR spectrum of IpcBCl2‚EE is a singlet at
δ 17-18). This solution was added to a cold (0 °C) solution of
IpcBH2 (1.15 M, 2.70 mL, 3.11 mmol) in EE and stirred for 15
min. At that point, the 11B NMR spectrum of the reaction
showed a mixture of IpcBHCl (87%) and 6.4% each of IpcBCl2
and IpcBH2. After 24 h, HCl in EE (2.39 M, 0.30 mL, 0.71
Rea ction of a Mixtu r e of r-P in en e a n d Me3SiH w ith
BCl in P en ta n e. BCl3 (2.34 mL, 20 mmol) was dissolved in
pent3ane (15 mL) at -78 °C. To this cold solution was added
a precooled (-78 °C) mixture of R-pinene (2.72 g, 20 mmol)
and Me3SiH (2.96 g, 40 mmol). The progress of the reaction
was monitored by the 11B NMR spectrum taken immediately
(∼1 min); only formation of IpcBCl2 (δ 62) was observedsno
formation of IpcBHCl was evident even after 6 h at -78 °C.
However, very little (∼1-2%) formation of IpcBHCl (br δ
42)19a,b was evident at 0 °C after 24 h. The same results were
obtained when the reaction was carried out with freshly
prepared IpcBCl2 (1.92 g, 8.77 mmol) and Me3SiH (0.65 g, 8.77
mmol) in pentane (8.0 mL) at -78 °C and also at 0 °C.
In Situ Red u ction -Hyd r obor a tion of Ip cBCl2 w ith
Me3SiH in th e P r esen ce of 2-Meth yl-2-bu ten e in P en -
ta n e. In this case the reaction was carried out in the presence
of 2-methyl-2-butene (9.0 mmol) at 0 and -25 °C. The reaction
was over in 24 h at 0 °C and 5 days at -25 °C (as established
by the 11B NMR spectrum of the aliquot after methanolysis).
The usual workup provided 3-methyl-2-butanol in 57% ee and
67% ee, respectively (Table 5). The same reaction was carried
out in CH2Cl2 at 0 and 24 °C, and part of the results are
presented in Table 9 (supporting information).
(26) A sample kept at 24 °C for 4 months under N2 did not show
any observable change by 1H/13C/11B NMR spectroscopy. Also, the
results from the use of this material in asymmetric hydroborations of
alkenes were identical to those obtained with freshly prepared samples.
Similarly, alkaline peroxide oxidation of IpcBCl2 gave isopinocampheol
of g99% ee based on the maximum rotation reported in the literature
(Brown, H. C.; Mandal, A. K.; Yoon, N. M.; Schwier, J . R.; J adhav, P.
K. J . Org. Chem. 1982, 47, 5069).
In Situ Red u ction -Hyd r obor a tion of Ip cBCl2 w ith
Me3SiH in EE a n d THF . To the cold (-10 °C) EE (5.0 mL)
(28) (a) Westley, J . W.; Halpern, B. J . Org. Chem. 1968, 33, 3978.
(b) Dale, J . A.; Dull, D. L.; Mosher, H. S. J . Org. Chem. 1969, 34, 2543.
(29) Whitemore, F. C.; Olewine, J . H. J . Am. Chem. Soc. 1938, 60,
2569.
(27) Dhokte, U. P.; Brown, H. C. Unpublished results.