Journal of the American Chemical Society
Communication
enantiomerically enriched amino alcohols in a highly enantiose-
lective and readily separable manner but also is operationally
simple and features a low catalyst loading. In addition, there is no
need to rigorously exclude air or to use transition metals. As
acetalization is one of the most fundamental methods for the
protection of a hydroxy group, its successful application to kinetic
resolution has opened doors to a new frontier for the production
of enantiomerically enriched compounds from racemic mixtures.
(d) Sun, Z.; Winschel, G. A.; Borovika, A.; Nagorny, P. J. Am. Chem. Soc.
2
2
012, 134, 8074−8077. (e) Nagorny, P.; Sun, Z.; Winschel, G. A. Synlett
̌
́
013, 24, 661−665. (f) Kim, J. H.; Coric, I.; Vellalath, S.; List, B. Angew.
Chem., Int. Ed. 2013, 52, 4474−4477. (g) Chen, Z.; Sun, J. Angew. Chem.,
Int. Ed. 2013, 52, 13593−13596.
(
8) For site selective acetalization of carbohydrates, see: Mensah, E.;
Camasso, N.; Kaplan, W.; Nagorny, P. Angew. Chem., Int. Ed. 2013, 52,
2932−12936.
9) As shown in the following scheme, the formed acetal is
1
(
thermodynamically much more stable than the alcohol and enol ether.
ASSOCIATED CONTENT
■
*
S
Supporting Information
Representative experimental procedure, spectroscopic data,
determination of the absolute stereochemistry of 2e, and
mechanistic studies on kinetic resolution of racemic amino
(10) For kinetic resolution through esterification using chiral
phosphoric acid catalysts, see: (a) Mandai, H.; Murota, K.; Mitsudo,
K.; Suga, S. Org. Lett. 2012, 14, 3486−3489. (b) Harada, S.; Kuwano, S.;
Yamaoka, Y.; Yamada, K.; Takasu, K. Angew. Chem., Int. Ed. 2013, 52,
1
(
0227−10230.
11) Screening of enol ethers was also conducted. See Supporting
Information (SI) in details.
12) Screening of chiral phosphoric acids was also conducted. See SI in
AUTHOR INFORMATION
(
Notes
details.
The authors declare no competing financial interest.
(13) Schoepf, C.; Wuest, W. Justus Liebigs Ann. Chem. 1959, 626, 150−
1
54.
(
(
14) Formed acetal 4e was obtained as a ca. 1:1 diastereomeric mixture.
15) Other factors that caused the reduction of the s value at high
concentration also cannot be ruled out at this point.
16) The acetalization rate was reproduced well in the presence of MS
A.
17) (R)-1a was employed instead of (R)-1b, because the acetalization
rate of (R)-1a was higher than that of (R)-1b in those substrates without
any detrimental effect on the individual s values.
(18) Application of the resolution system to a racemic 1,3-amino
alcohol as well as the substrate possessing a tertiary alkyl amine moiety
resulted in the low s values. See SI in details.
ACKNOWLEDGMENTS
■
This work was partially supported by a Grant-in-Aid for Scientific
Research on Innovative Areas “Advanced Molecular Trans-
formations by Organocatalysts” from MEXT, Japan.
(
4
(
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