A. Torres-Gavil a´ n et al. / Tetrahedron: Asyꢀꢀetry 18 (2007) 2621–2624
2623
these scaled conditions, better yields than those obtained in
the sꢀall scale experiꢀent for the enantioꢀerically pure
for the N-[(R±-(+±-1-phenylethyl]decanaꢀide. To identify
each enantioꢀer, a standard of N-[(S±-(ꢀ±-1-phenyl-
ethyl]decanaꢀide enantioꢀer was cheꢀically synthesized.
2
2
(
R±-1 aꢀine were observed (98%± in 48 h (Scheꢀe 2±.
The enzyꢀatic hydrolysis herein described results in better
yields than those already reported for the selective hydroly-
4.4. Structure determination
2
3
sis of arylaꢀides. Indeed, conversion yields of 98% were
obtained in the hydrolysis of (R±-3 aꢀide in 48 h, while
in general 7–10 days are required to obtain siꢀilar yields
1
13
H NMR and C NMR spectra were obtained using a
Bruker Ultra Shield spectroꢀeter run at 300 MHz and
75 MHz, respectively. Eleꢀental analysis was obtained in
a Therꢀofinnigan EA 112 instruꢀent. High resolution
1
in lipase-catalyzed hydrolysis of aꢀides.
ꢀ
ass spectroꢀetry analyses (FAB+± were perforꢀed on a
3
. Conclusion
Jeol JMS-SX 102A ꢀass spectroꢀeter. Xenon was used
as the boꢀbarding gas with an energy of 10 kV using
PEG 600 as internal standard and 3-nitrobenzyl alcohol
as the ꢀatrix. Optical rotations were deterꢀined in a
10 cꢀ, 1 ꢀl cell, Perkin–Elꢀer-341 polariꢀeter. All ꢀelting
points were deterꢀined in an Electrotherꢀal MEL-TEMP
apparatus and are uncorrected.
In conclusion, the whole lipase-catalyzed ‘easy-on, easy-off’
strategy described here considers an integrated synthesis–
hydrolysis process where both enantioꢀerically pure (R±-
1
and (S±-1 aꢀines are obtained in good yields and high
enantioꢀeric excess. This strategy involves not only a sin-
gle biocatalyst in an effective two step resolution process,
but also it is successfully applied to the resolution of PhEA,
one of the ꢀost powerful interꢀediates used in industrial
asyꢀꢀetric synthesis as a chiral adjuvant and as a ligand
in asyꢀꢀetric catalysis. We are currently working on an
extension of this effective enzyꢀatic resolution process
for other aꢀines, alcohols, and aꢀino-alcohols.
4.4.1. Chemical synthesis of N-[(S)-(ꢀ)-1-phenyl-
ethyl]decanamide (S)-3. A stirred solution of capric acid
2 (1.0 g, 1.1 ꢀl, 5.8 ꢀꢀol± in 100 ꢀl of CH Cl was treated
2
2
3
with 1.29 g (6.3 ꢀꢀol± of DCC, 0.04 g (0.4 ꢀꢀol± of
DMAP, and 0.81 ꢀl (0.76 g, 6.3 ꢀꢀol± of (S±-(ꢀ±-1-phen-
ylethylaꢀine (S±-1. The ꢀixture was stirred overnight
and then filtered and concentrated in vacuo. Flash Chro-
ꢀ
atography was packed with silica gel 230–400 ꢀesh
4. Experimental
(Macherey-Nagel, D u¨ ren, Gerꢀany± and eluted with
9
0:10 hexane/ethanol, afforded the pure N-[(S±-(ꢀ±-1-phen-
4
.1. Materials
ylethyl]decanaꢀide enantioꢀer [(S±-3] as a white powder.
Yield after isolation 81%, white powder, ꢀp = 50–52 ꢁC,
2
D
4
1
Methanol (99%± and 2-ꢀethyl-2-butanol (2M2B, 99.7%±
were purchased froꢀ J.T. Baker (Edo. De M e´ xico, M e´ xi-
co±. Tetrahydrofuran (>99%±, (± ±-1-phenylethylaꢀine
½aꢁ ¼ ꢀ64:7 (c 0.7, CHCl ±.
H
NMR (CDCl ,
3
3
300 MHz± d = 0.89 (t, 3H, J = 6.93±, 1.27 (s, 10H±, 1.49
(d, 3H, J = 6.9±, 1.63 (ꢀ, 2H±, 2.17 (t, 2H, J = 7.9±, 5.15
1
3
(
rac-PhEA, 99%±, (S±-(ꢀ±-1-phenylethylaꢀine (P98%±,
(ꢀ, 1H±, 5.77, (d, 1H, J = 7.2±, 7.27–7.36 (ꢀ, 5H±.
C
capric acid (99%± and ꢀolecular sieves (8–12 ꢀesh± were
purchased froꢀ Aldrich (WI, USA±. The lipase B froꢀ
C. antarctica, Novozyꢀ 435 (CaL-B± was obtained froꢀ
Novozyꢀes-M e´ xico A/C (M e´ xico±.
NMR (CDCl , 75.46 MHz± d = 15.4, 21.9, 22.86, 25.95,
3
29.45, 29.46, 29.54, 29.64, 32.05, 37.10, 48.71, 126.37,
127.5, 128.83, 143.49, 172.4. Eleꢀental Anal. Calcd for
C H NO: C, 78.49; H, 10.61; N, 5.09. Found: C, 78.35;
1
8
29
H, 10.99; N, 4.68.
4
.2. HPLC analysis
4.5. Enzymatic reactions
Previous to HPLC analysis, enzyꢀe and ꢀolecular sieves
were separated froꢀ all saꢀples by centrifugation at
4.5.1. Synthesis of N-[(R)-(+)-1-phenylethyl]decanamide
(R)-3. In a general procedure, the reaction was carried
out at 45 ꢁC in ꢀagnetically agitated 7 ꢀl sealed vessels
containing 12.1 ꢀg (0.01 ꢀꢀol± of rac-PhEA rac-1,
17.2 ꢀg (0.01 ꢀꢀol± of capric acid 2, 50 ꢀg of ꢀolecular
sieves and 5 ꢀl of 2M2B previously dehydrated with
ꢀolecular sieves. The reactions were started by the addi-
tion of 50 ꢀg of CaL-B. After 24 h, the N-[(R±-(+±-1-phen-
ylethyl]decanaꢀide enantioꢀer (R±-3 and unreacted 1-
phenylethylaꢀine were recovered in a flash chroꢀatogra-
phy systeꢀ. Coluꢀn was packed with silica gel 230–400
ꢀesh (Macherey-Nagel, D u¨ ren, Gerꢀany± and eluted with
1
700g for 3 ꢀin. The reactions were quantified by HPLC
using a Waters Spherisorb 80-5 ODS-2 coluꢀn (4.6 ·
2
50± ꢀꢀ and a Waters 600E systeꢀ controller (Waters
ꢀ
1
Corp. Milford, MA, USA± with a flow rate of 1 ꢀl ꢀin
.
The effluent was a ꢀethanol–phosphate buffer (20 ꢀM, pH
.8± 70:30 (v/v± solution. The production or consuꢀption
3
of aꢀine in the hydrolysis and synthesis, respectively, was
quantified with a water 996 photodiode array detector at
2
06 nꢀ.
4
.3. Chiral HPLC analysis
90:10 hexane/ethanol.
Enantioꢀeric excesses of the aꢀide were quantified by
chiral HPLC with a CHIRALCEL OJ-H coluꢀn (4.6 ·
Yield after isolation 95%, white powder, ꢀelting point 45–
2
4
1
2
50 ꢀꢀ± (Chiral Technologies Inc., West Chester PA,
47 ꢁC, ½aꢁ ¼ þ67:5 (c 0.7, CHCl ±. H NMR (CDCl ,
D
3
3
USA±. The effluent was n-heptane/ethanol 97:3 (v/v± with
300 MHz± d = 0.89 (t, 3H, J = 6.93±, 1.27 (s, 10H±, 1.49
(d, 3H, J = 6.9±, 1.63 (ꢀ, 2H±, 2.17 (t, 2H, J = 7.9±, 5.15
ꢀ
1
a flow rate of 1 ꢀl ꢀin . The retention tiꢀe for the N-
(S±-(ꢀ±-1-phenylethyl]decanaꢀide is 8.7 ꢀin and 7.5 ꢀin
1
3
[
(ꢀ, 1H±, 5.77, (d, 1H, J = 7.2±, 7.27–7.36 (ꢀ, 5H±.
C