1
984
Synlett
Y.-J. Kim et al.
Letter
pase has been reported.11 We have confirmed that the ac-
tivity and selectivity of Novozyme 435® catalyzed acetyla-
tion did not decrease during 21 days continuous
production. Our reaction system is a very useful approach
for kinetic resolution and suitable for large-scale reaction
with a biocatalyst.
García-Verdugo, E.; Luis, S. V. ACS Catal. 2012, 2, 1976. (d) Sahin,
S.; Mäki-Arvela, P.; Kangas, M.; Eränen, K.; Wärnnå, J.; Salmi, T.;
Murzin, D. Y. Kinet. Catal. 2012, 53, 673. (e) Strompen, S.; Weiß,
M.; Gröger, H.; Hilterhaus, L.; Liese, A. Adv. Synth. Catal. 2013,
355, 2391. (f) Wiles, C.; Hammond, M. J.; Watts, P. Beilstein J.
Org. Chem. 2009, 5, 27. (g) Žnidaršič-Plazl, P.; Plazl, I. Process
Biochem. 2009, 44, 1115.
In summary, kinetic resolution of (±)-cis-1-amino-2-in-
danol was successfully carried out by lipase-catalyzed N-
acetylation with high enantioselectivity. We could obtain
enantiomerically pure N-acetyl-aminoindanol with a rela-
tively short reaction time, higher productivity, and an easy
workup process in a continuous-flow system. This method
led to the complete conversion of (±)-cis-1-amino-2-inda-
nol with >99% of enantiomeric excess in 64 minutes resi-
dence time at a flow rate of 0.1 mL/min. Furthermore, chiral
amine 1 and amide 2 are expected to be converted easily
into their N-acetylated form 2 or O-acetylated form 3. And
acetamide 2 could be transformed reversely into amine 1 by
lipase under conditions without an acyl donor. All of these
compounds could be utilized as functionalized chiral build-
ing blocks.
(6) Tomin, A.; Hornyánszky, G.; Kupai, K.; Dorkó, Z.; Ürge, L.;
Darvas, F.; Poppe, L. Process Biochem. (Oxford, U.K.) 2010, 45,
859.
(7) de Miranda, A. S.; Miranda, L. S.; de Souza, R. O. Org. Biomol.
Chem. 2013, 11, 3332.
(
8) (a) Dorsey, B. D.; Levin, R. B.; McDaniel, S. L.; Vacca, J. P.; Guare,
J. P.; Darke, P. L.; Zugay, J. A.; Emini, E. A.; Schleif, W. A. J. Med.
Chem. 1994, 37, 3443. (b) Vieth, M.; Cummins, D. J. J. Med. Chem.
2000, 43, 3020. (c) Kheffache, D.; Guemmour, H.; Dekhira, A.;
Benaboura, A.; Ouamerali, O. J. Mol. Model. 2013, 19, 4837.
9) (a) Hong, Y.; Gao, Y.; Nie, X.; Zepp, C. M. Tetrahedron Lett. 1994,
(
35, 6631. (b) Kobayashi, T.; Tanaka, K.; Miwa, J.; Katsumura, S.
Tetrahedron: Asymmetry 2004, 15, 185. (c) Palmer, M.;
Walsgrove, T.; Wills, M. J. Org. Chem. 1997, 62, 5226.
(d) Andreana, P. R.; Liu, C. C.; Schreiber, S. L. Org. Lett. 2004, 6,
4231.
(10) Boros, Z.; Falus, P.; Márkus, M.; Weiser, D.; Oláh, M.;
Hornyánszky, G.; Nagy, J.; Poppe, L. J. Mol. Catal. B: Enzym. 2013,
8
5, 119.
(11) Frings, K.; Koch, M.; Hartmeier, W. Enzyme Microb. Technol.
999, 25, 303.
12) Gotor-Fernández, V.; Busto, E.; Gotor, V. Adv. Synth. Catal. 2006,
48, 797.
13) Chen, C. S.; Fujimoto, Y.; Girdaukas, G.; Sih, C. J. J. Am. Chem. Soc.
982, 104, 7294.
Acknowledgment
1
This work was financially supported by the Ministry of Trade, Indus-
try & Energy (MOTIE), Republic of Korea (No. N0000582) and the Yon-
sei University Research Fund of 2015.
(
(
(
3
1
14) Flask Reaction – General Procedure
Supporting Information
To a separate small vials containing 0.2 M solutions of (±)-cis-1-
amino-2-indanol (298 mg, 2.0 mmol) in THF–EtOAc (0.5 mL, 50
equiv), Novozyme 435® (20 mg) was added to each vial in one
portion, and the turbid solutions were shaken (125 rpm) at
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380427.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
3
0 °C. After 6 h, 12 h, 24 h, and 48 h, the enzyme was filtered off
from the samples. For HPLC analysis, samples were diluted with
EtOH (0.5 mL).
References and Notes
(
15) (1S,2R)-1-Acetamido-2-indanol (2)
(
(
1) Kagan, H.; Fiaud, J. Top. Stereochem. 1988, 18, 249.
2) (a) Ferreira, E. M.; Stoltz, B. M. J. Am. Chem. Soc. 2001, 123, 7725.
b) Ruble, J. C.; Latham, H. A.; Fu, G. C. J. Am. Chem. Soc. 1997,
19, 1492. (c) Miller, S. J.; Copeland, G. T.; Papaioannou, N.;
20
White solid; [α]
+11.7 (c 0.25, CHCl ). IR (neat): 3444, 3299,
D
3
–1 1
1539 cm . H NMR (400 MHz, CDCl ): δ = 7.22 (s, 4 H), 6.23 (d,
3
(
1
J = 7.2 Hz, NH), 5.32 (dd, J = 8.2, 5.1 Hz, 1 H), 4.57 (td, J = 5.1, 2.3
Hz, 1 H), 3.13 (dd, J =16.5, 5.3 Hz, 1 H), 291 (dd, J = 16.5, 2.1 Hz,
Horstmann, T. E.; Ruel, E. M. J. Am. Chem. Soc. 1998, 120, 1629.
3) (a) Nestl, B. M.; Nebel, B. A.; Hauer, B. Curr. Opin. Chem. Biol.
1
3
1
H), 2.57 (br s, 1 H), 2.07 (s, 3 H). C NMR (100 MHz, CDCl ):
3
(
(
(
δ = 170.9, 140.6, 139.9, 128.2, 127.2, 125.3, 124.5, 73.5, 57.6,
2
2
011, 15, 187. (b) Jaeger, K.-E.; Eggert, T. Curr. Opin. Chem. Biol.
002, 13, 390.
+
3
9.6, 23.3. ESI-HRMS: m/z calcd for C11H14NO2 : 192.1019;
+
found: 192.1016 [M + H] .
4) Hessel, V.; Hardt, S.; Löwe, H.; Müller, A.; Kolb, G. Chemical
Micro Process Engineering; Vol. 1 and 2; Wiley-VCH: Weinheim,
(
16) Continuous-Flow Reaction, General Procedure
Novozyme 435® (2.0 g) was packed into a glass column with an
aluminum heating jacket for maintaining temperature at 30 °C.
The column was fully washed with THF and then fed with a
solution of (±)-cis-1-amino-2-indanol (0.1 M) in EtOAc and THF
2005.
5) (a) Itabaiana, I. Jr.; Gonçalves, K. M.; Zoumpanioti, M.; Leal, I. C.;
de Miranda, L. S.; Xenakis, A.; de Souza, R. O. Org. Process Res.
Dev. 2014, 18, 1372. (b) Junior, I. I.; Flores, M. C.; Sutili, F. K.;
Leite, S. G.; de M. Miranda, L. S.; Leal, I. C.; de Souza, R. O. Org.
Process Res. Dev. 2011, 16, 1098. (c) Porcar, R.; Sans, V.; Ríos-
Lombardía, N.; Gotor-Fernández, V.; Gotor, V.; Burguete, M. I.;
(
1
1:1). At various flow rates (2.0, 1.0, 0.5, 0.25, and 0.1 mL/min),
mL of samples were collected. For HPLC analysis, samples
were diluted with EtOH (0.5 mL).
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Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1981–1984