Hydroboration of Ketones
417
added as a co-solvent in order to improve stirrability and enhance
aqueous phase extracted twice with 30 mL of ether. The organic
phase was dried with sodium sulfate and after evaporation of
the solvent, the residue was distilled. 14 was crystallized from
cyclohexane. The form of the major compound of the respec-
tive enantiomeric mixture was determined by measuring the
rotational power of the product mixture at room temperature
◦
mixing at −78 C. So the best results were achieved with the
Lewis acid ZnI2 in a 1:1 solvent mixture of lactic acid methyl
◦
ester and THF at −78 C. The respective ee values and distilled
yields of the alcohols 2, 4b, and 10 to 14 are listed in Table 6.
◦
◦
Conclusion
(25 C) (Schmidt+Haensch Kreispolarimeter). 11: bp 112 C;
1
70 mg, 40% yield; ee 43%; [α]D = −2.65 (c 0.068, CHCl3)
Solvent-induced chiral hydroboration of ketones was strongly
enhanced by zinc halides, and less so by other Lewis acids. We
believe it is a remote possibility that, before the reaction, BH3
forms a more selective reagent with the zinc salts. From the
results of the influence of the molecular structure of the inducing
solvent, we conclude that there should be only one hydrogen
bridging functional group – located at the chiral centre. It is
likely that further interaction of the carbonyl group is valuable
for substances that contain an aromatic ring. π–π stacking may
be responsible for its orientation and one may speculate about
the influence of the outer sphere of the solvent cage in which the
transition state occurs.
◦
[19]
◦
Lit. [α]D = +5 neat (S)-form.
12: bp 120 C; 270 mg, 60%
◦
yield; ee 61%; [α]D = −4.63 (c 0.11, CHCl3) Lit. [α]D = +8.7
neat (S)-form.[
20]
◦
1
3: bp 189 C; 515 mg, 82% yield; ee 39%; [α]D = −3.3
◦
[21]
(
6
c 0.206, CHCl3) Lit. [α]D = +5.3 neat (S)-form.
14: mp
◦
7–68 C (from cyclohexane); 460 mg, 49% yield; ee 47%;
◦
[
(
α]D = +2.3 (c 0.7, CHCl3) Lit. [α]D = −29.2 c(benzene) 0.22
S)-form.[
22]
Acknowledgements
We thank N. Schön for helpful discussions. S. H. Hüttenhain is grateful for
financial support from the ZFE Hochschule Darmstadt.
Experimental
The chiral solvents 4a, b, e, f, and h were bought from
Sigma/Aldrich and used as they were. Substances 4c and 4d
were made from 1-tert-butoxypropan-2-ol and substance 4g was
made from hexan-2-ol according to ref. [18].
The Lewis acids and the boran/THF complex were from
Merck and used without further purification.
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Inatwo-neckedflask, oneclosedbyaseptum, theotherequipped
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ture by a syringe (0.5 h). The reaction mixture was kept at that
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(
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◦ −1
890 II/autosampler 6890 (250 C); He 1 mL min , Cyclodex
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5
◦
◦
B (Agilent), FID (300 C); 2 isotherm 130 C, retention times
◦
(
R)-(+) 8.384 min; (S)-(−) 8.735 min; 4b isotherm 80 C, reten-
(
b) C. Baudequin, D. Brégeon, J. Levillain, F. Guillen,
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tion times (R)-(+) 7.766 min; (S)-(−) 8.229 min; 10 isotherm
◦
4
1
5
0 C, retention times (R)-(−) 7.254 min; (S)-(+) 7.484 min;
3
◦
1 isotherm 70 C, retention times (R)-(−) 5.534 min; (S)-(+)
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◦
.647 min; 12 isotherm 70 C, retention times (R)-(−) 8.072 min;
◦
(
1
S)-(+) 8.674 min; 13 isotherm 100 C, retention times (R)-(−)
◦
9.489 min; (S)-(+) 19.885 min; 14 isotherm 150 C, retention
[
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times (S)-(−) 40.854 min; (R)-(+) 41.431 min.
For identification, the homochiral forms (S)2, (R)10, and
(
S)15 were bought from Sigma/Aldrich. For the other alcohols,
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[
9. doi:10.1039/B411922C
◦
stirred for 10 min at 50 C to hydrolyze the remaining lactic acid
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