First dynamic kinetic resolution of selenium-containing chiral amines catalyzed by palladium (Pd/BaSO4) and Candida antartica lipase (CAL-B)

Article abstract of DOI:10.1016/j.tetlet.2009.05.022

An efficient method for chemoenzymatic dynamic kinetic resolution of selenium-containing chiral amines (organoselenium-1-phenylethanamines) has been developed, leading to the corresponding amides in excellent enantioselectivities and high isolated yields.

Full text of DOI:10.1016/j.tetlet.2009.05.022

Tetrahedron Letters 50 (2009) 4331–4334
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Tetrahedron Letters
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First dynamic kinetic resolution of selenium-containing chiral amines
catalyzed by palladium (Pd/BaSO4) and Candida antartica lipase (CAL-B)
*
Leandro H. Andrade , Alexandre V. Silva, Eliane C. Pedrozo
Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes, 748, CEP 05508-900, São Paulo, SP, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient method for chemoenzymatic dynamic kinetic resolution of selenium-containing chiral
amines (organoselenium-1-phenylethanamines) has been developed, leading to the corresponding
amides in excellent enantioselectivities and high isolated yields. This one-pot procedure employs two dif-
ferent types of catalysts: Pd on barium sulphate (Pd/BaSO4) as racemization catalyst and lipase (CAL-B) as
the resolution catalyst.
Received 4 April 2009
Revised 7 May 2009
Accepted 11 May 2009
Available online 18 May 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
(Pd/BaSO4) as racemization catalyst and lipase (CAL-B) as biocata-
lyst for kinetic resolution through enantioselective acylation.
Chiral organoselenium compounds have demonstrated impor-
tant applications in organic synthesis, especially as catalysts in
asymmetric reactions.1a–c Thus, some synthetic tools have been ap-
plied to synthesize organoselenium compounds in enantiomeri-
cally pure form. Among them, we can mention the use of chiral
precursors,2a,b and more recently, enantioselective synthesis med-
iated by enzymes.3a–c In the search for practical ways to generate
selenium-containing chiral compounds, we turned our attention
to bioreduction of organoselenoacetophenones mediated by alco-
hol dehydrogenases3a and kinetic resolution of organoseleno-
phenylethanols mediated by lipase.3b,3c Encouraged by the excel-
lent results obtained by CAL-B as biocatalyst in the enantioselec-
tive acylation of organoseleno-phenylethanols, we decided to
study the enzymatic kinetic resolution of organoselenium-1-phen-
ylethanamines through enantioselective acylation. In fact, by using
this enzymatic approach, the enantiopure organoselenium amides
were obtained in excellent enantiomeric excess (>99%).4 However,
enzymatic kinetic resolution has a drawback, the yield is limited to
a maximum 50%. An excellent alternative to achieve 100% yield is
the use of a chemoenzymatic protocol, the Dynamic Kinetic Reso-
lution (DKR).5a,b This methodology has been shown to be very use-
ful to obtain enantiomerically pure amines and amides in up to
100% yield.6 This protocol makes use of a catalyst to racemize
the amine and a biocatalyst to perform the kinetic resolution.
The catalysts usually employed for racemization are ruthe-
nium,6b–d iridium,6e thiols and AIBN,6f palladium6g–i and Raney
nickel and cobalt.6j The kinetic resolution of the amines can be per-
formed by enantioselective acylation mediated by lipases. There-
fore, now, we report the first application of the DKR to obtain
selenium-containing chiral amides using Pd on barium sulphate
2. Results and discussion
2.1. Synthesis of the organoselenium-1-phenylethanamines
(RS-4a–f)
The organoselenium-1-phenylethanamines (RS-4a–f) were pre-
pared from commercially available ortho-, meta-, and para-amino-
acetophenones as described in Scheme 1.
O
O
O
(ii)
(i)
RSe
R
H2N
3a, R = 4'-EtSe (63%)
3b, R = 4'-MeSe (53%)
3c, R = 4'-n-BuSe (75%)
3d, R = 4'-PhCH2Se (71%)
3e, R = 3'-EtSe (78%)
3f, R = 2'-EtSe (65%)
2a, R = 4'-NCSe (64%)
2b, R = 3'-NCSe (28%)
2c, R = 2'-NCSe (68%)
1a, 4'-NH2
1b, 3'-NH2
1c, 2'-NH2
NH2
(iii, iv)
RSe
(RS)-4a, R = 4'-EtSe (73%)
(RS)-4b, R = 4'-MeSe (73%)
(RS)-4c, R = 4'-n-BuSe (19%)
(RS)-4d, R = 4'-PhCH2Se (21%)
(RS)-4e, R = 3'-EtSe (39%)
(RS)-4f, R = 2'-EtSe (63%)
Scheme 1. Reagents and conditions: (i) NaNO2, HCl 2 M, pH 4.3, 0 °C, then KSeCN,
1 h; (ii) RBr, NaBH4, MeOH, 0 °C, 2 h; (iii) Ti(OCH(CH3)2)4, NH3/EtOH (2 M), 12 h; (iv)
NaBH4, 12 h, rt.
* Corresponding author. Tel.: +55 11 3091 2287; fax: +55 11 3815 5579.
E-mail address: leandroh@iq.usp.br (L.H. Andrade).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.05.022

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L. H. Andrade et al. / Tetrahedron Letters 50 (2009) 4331–4334
Table 2
Initially, the in situ preparation of diazonium salts from ortho-,
Enzymatic kinetic resolution of 1-(ethylselenium)phenylethanamines (RS)-4e–fa
meta-, and para-aminoacetophenones followed by the addition of
KSeCN afforded the corresponding selenocyanate acetophenones
2a–c (up to 68% yield).4 The next step was the alkylation of the
selenium atom using NaBH4 and alkyl halide to give ortho-, meta-,
and para-organoselenium acetophenones 3a–f (up to 78% yield).
After the alkylation step, we carried out the reductive amination
of the organoselenium acetophenones 3a–f to afford the organose-
lenium-1-phenylethanamines 4a–f (up to 73% yield).
O
O
NH2
HN
R
NH2
O
R
CAL-B
+
EtSe
(RS)-4e-f
Substrate
EtSe
EtSe
(R)-5e,f,j,k
(S)-4e,f
Entry
R
(R)-5 eeb (%)
(S)-4 eed (%)
ce
Ef
1
2
3
4
4e, 30-EtSe
4e, 30-EtSe
4f, 20-EtSe
4f, 20-EtSe
Me
MeOCH2
Me
>99
81c
>98
70c
38
59
8
38
42
8
>200
17
107
9
2.2. Evaluation of different acyl donors for the enzymatic
kinetic resolution of organoselenium-1-phenylethanamines
MeOCH2
47
40
Before starting the dynamic kinetic resolution of organosele-
nium-1-phenylethanamines RS-4a–f, a screening test was per-
formed to choose the most appropriate acyl donor for the kinetic
resolution (KR) via enantioselective acylation catalyzed by lipase
(CAL-B).10 The selected acyl donors for this study were ethyl meth-
oxyacetate, ethyl acetate, dimethyl carbonate, ethyl benzoate, and
vinyl benzoate.
a
Reaction conditions: (RS)-4e,
f (0.2 mmol), CAL-B (20 mg), acyl donor
(0.8 mmol), hexane (1 mL), 30 °C, and 48 h.10
ee determined by chiral HPLC analysis.11
b
c
d
e
f
ee determined after hydrolysis and derivatization with acetic anhydride.
ee determined after derivatization with acetic anhydride.
Conversion: c = ees/(ees + eep).
E = ln{(1 ꢁ ees)/(1 + ees/eep)}/ln{(1 + ees)/(1 + ees/eep)}.7
The 1-(4-ethylselenium)phenylethanamine (RS-4a) was se-
lected as model substrate and hexane as solvent. The results are
summarized in Table 1.
performed the enzymatic kinetic resolution of the compounds 4e
and 4f with ethyl methoxyacetate and ethyl acetate as acyl donors.
The results are summarized in Table 2.
As can be seen in Table 1, the use of ethyl methoxyacetate, ethyl
acetate, and dimethyl carbonate as acyl donors for the KR of the
(RS)-4a gave the amide (S)-5a in excellent ee (>99%) and enantio-
meric ratio (E >200). In relation to the conversion, dimethyl car-
bonate as acyl donor gave the product (R)-5 with 13% conversion,
and with ethyl acetate the conversion value was 18%. When ethyl
methoxyacetate was used the conversion increased to 36%, and no
reaction was observed with ethyl benzoate and vinyl benzoate as
acyl donors.
Encouraged by the results presented in Table 1, we decided to
apply ethyl methoxyacetate and ethyl acetate as acyl donors on
the kinetic resolution of the organoselenium amines 4e and 4f
(Table 2). It is worth to mention that dimethyl carbonate is a good
acylant agent for amines because the formed carbamate can be
easily transformed into the free amine. In spite of this important
characteristic, this compound cannot be applied in the DKR be-
cause the acylated product (carbamate) is not stable in the racemi-
zation conditions required for this process.8
When ethyl acetate was used as acyl donor the ee values for the
products 5e (98%) and 5f (99%) were similar to those observed for
organoselenium amide 5a (Table 1, entry 1). In contrast, the con-
version value for the ortho isomer 4f (8%) was significantly lower
than that for the meta isomer 4e (38%) (Table 2, entries 1 and 3).
The low conversion in the kinetic resolution of 4f can be attributed
to the selenium–nitrogen interaction (Seꢀ ꢀ ꢀN).9 Due to this interac-
tion, the nucleophilicity of the amine group decreases and, conse-
quently, a low conversion can be observed. The same interaction
cannot occur when the selenium atom is at the para or meta posi-
tion of the aromatic ring.
In comparison with the substrate (RS)-4a (Table 1, entry 5), we
can observe that the KR of (RS)-4e and (RS)-4f with ethyl meth-
oxyacetate and CAL-B had lower E-values (Table 2, entries 2 and
4) than those reactions with ethyl acetate as acyl donor. In view
of these results, we selected ethyl acetate as acyl donor to be em-
ployed on the DKR of organoselenium amines.
In order to evaluate the influence of different acyl donors to-
ward 1-phenylethanamines containing the ethylselenium group
attached to the meta and ortho position of the aromatic ring, we
2.3. Dynamic kinetic resolution of organoselenium-1-
phenylethanamines (4a–f)
Table 1
As palladium catalyst, Pd/BaSO4, can be used for racemization of
amines,6g,h initially, we performed a racemization test with the
enantiomerically enriched substrate 4a. By using the (S)-4a,
40 mol % of Pd/BaSO4 (5% Pd), toluene at 70 °C under hydrogen
(1 atm), and after 48 h, the racemic amine was observed. Thus,
we decided to investigate the dynamic kinetic resolution of the
amine (RS)-4a in a more detailed way (Table 3).12
As mentioned in Table 3 (entries 1–3), the first reaction condi-
tion tested was similar to that used in the kinetic resolution of
the 1-(ethylselenium)phenylethanamines (Section 2.2), ethyl ace-
tate as acyl donor, lipase of Candida antartica (CAL-B) and toluene
at 30 °C under hydrogen atmosphere (1 atm).
Moreover, the effect of the reaction time (24, 48, and 120 h) in
the DKR of the (R,S)-4a was evaluated (Table 3, entries 1–3). The
product (R)-5a was obtained in moderate yield (11–38%) but with
excellent enantiomeric excess (91–99%). Then, the same reaction
condition was applied to a higher temperature, 50 °C (Table 3, en-
tries 4–6). Indeed, with the increase of the temperature we almost
duplicated the yield of the product (R)-5a. A long reaction time
(120 h) for both temperatures (30 and 50 °C) resulted in a decrease
Influence of acyl donor on the kinetic resolution of amine (RS)-4a mediated by CAL-Ba
O
O
NH2
HN
R2
+
R1
NH2
O
CAL-B
R2
EtSe
EtSe
EtSe
(RS)-4a
R1
)-5
(R
(S)-4a
Entry
R2
(R)-5 eeb (%)
(S)-4a eed (%)
ce
Ef
1
2
3
4
5
Et
Et
Vinyl
Me
Et
Me
Ph
Ph
MeO
MeOCH2
99
—
22
—
—
15
55
18
—
—
13
36
>200
—
—
>200
>200
—
99c
99c
a
Reaction conditions: (RS)-4a (0.2 mmol), CAL-B (20 mg), acyl donor (0.8 mmol),
hexane (1 mL), 30 °C, 48 h.10
ee determined by chiral HPLC analysis.11
ee determined after hydrolysis and derivatization with acetic anhydride.
ee determined after derivatization with acetic anhydride.
b
c
d
e
Conversion: c = ees/(ees + eep).
f
E = ln{(1 ꢁ ees)/(1 + ees/eep)}/ln{(1 + ees)/(1 + ees/eep)}.7

L. H. Andrade et al. / Tetrahedron Letters 50 (2009) 4331–4334
4333
Table 3
Dynamic kinetic resolution of amine (RS)-4a using Pd/BaSO4 (5% Pd) and CAL-Ba
Table 4
Dynamic kinetic resolution of organoselenium-1-phenylethanamines (RS)-4a–fa
NHAc
NH2
Entry Substrate
Product
%
½ ꢂ
a 2D5
Pd-BaSO4 (5% Pd)
CAL-B, EtOAc
Isolated
yieldb (%
ee)
toluene, H2 (1 atm)
EtSe
EtSe
(R)-5a
(R)-5a
Yield (%)
(RS)-4a
NH2
NHAc
NHAc
Entry
T (°C)
Time (h)
Pd/BaSO4 (mol %)
1
74 (>99) +102.77
(c 0.59,
eeb (%)
EtSe
EtSe
1
2
3
4
5
6
7
8
9
10
11
12
13
14
30
30
30
50
50
50
50
50
50
50
70
70
70
70
24
48
120
24
48
120
48
48
60
60
40
40
40
40
40
40
10
30
10
30
40
40
40
10
>99
>99
91
>99
>99
61
>99
>99
>99
>99
>99
>99
75
11
22
38
32
39
61
26
36
47
43
23
57
22
74
EtOAc)
(R)-5a
(R)-5b
(RS)-4a
NH2
2
3
4
5
6
76 (>99) +96.39 (c
0.78,
MeSe
MeSe
EtOAc)
(RS)-4b
24
48
120
48
NH2
NHAc
>99
77 (>99) +51.12 (c
3.08,
n-BuSe
n-BuSe
a
Reaction conditions: (RS)-4a (0.2 mmol), CAL-B (60 mg), ethyl acetate
(2 ꢃ 0.8 mmol), and toluene (4 mL).12
EtOAc)
(R)-5c
(R)-5d
(RS)-4c
b
ee determined by chiral HPLC analysis.11
NH2
NHAc
72 (>99) +65.68 (c
1.32,
of the enantiomeric excess of the (R)-5a. Based on these results, we
decided to study the influence of different amounts of palladium
catalyst (Table 3, entries 7–10). Using 10 or 30 mol % of catalyst,
after 48 and 60 h reaction time, we obtained the product in up to
47% yield and >99% ee (Table 3, entry 9).
From these results, we expected that an increase in the temper-
ature could lead to a higher yield without compromising the
enantioselectivity. In this way, DKR of the (RS)-4a was performed
at 70 °C, in different reaction times 24, 48, and 120 h with 10
and 40 mol % of Pd/BaSO4 (Table 3, entries 11–14). The DKR with
10 mol % of Pd/BaSO4 (48 h, 70 °C) gave (R)-5a in high yield and
excellent enantiomeric excess (Table 3, entry 14: 74% yield, >99%
ee).
PhCH2Se
EtSe
PhCH2Se
EtSe
EtOAc)
(RS)-4d
NH2
NHAc
87 (>99) +88.67 (c
0.21,
EtOAc)
(RS)-4e
(R)-5e
NH2
NHAc
30 (>99) +21.77 (c
0.50,
With the optimized reaction condition in hands, we carried out
the DKR of additional organoselenium-1-phenylethanamines (RS)-
4b–f (Table 4).
SeEt
SeEt
EtOAc)
(R)-5f
(RS)-4f
As shown in Table 4, entries 1–5, in spite of the difference of the
organoselenium group attached to the aromatic ring, in all cases,
the amides (5a–f) were obtained in good yield and excellent enan-
tiomeric excess. However, DKR of the compound (RS)-4f, which
contains ethylselenium group attached to the ortho position of
the aromatic ring, produced the organoselenium amide 5f in low
yield as observed in the KR study (Section 2.2). The unreacted
amine (RS)-4f was recovered. From these results, we also verify
that the DKR conditions, which employ palladium, are compatible
with the organoselenium compounds and no deselenization was
observed.
The absolute configuration of the amides 5a–f was attributed as
follows: The enantiomerically pure organoselenium amides 5a–f
were treated with n-butyllithium in THF to afford the enantiome-
rically pure N-(1-phenylethyl)acetamide (Scheme 2). These
samples were compared by chiral GC analysis to the (R)- and
(S)-N-(1-phenylethyl)acetamide samples prepared from commer-
cially available (R)- and (S)-1-phenylethanamine.
a
Reaction conditions: (RS)-4a–f (0.2 mmol), CAL-B (60 mg), ethyl acetate
(2 ꢃ 0.8 mmol), toluene (4 mL), H2 (1 atm), 10 mol % Pd/BaSO4 (5% Pd) (42 mg).12
ee determined by chiral HPLC analysis.11
b
O
O
HN
*
HN
*
1- n-BuLi/THF, 0 ºC
2- H2O
RSe
(R) or (S)-5a-f
(R) or (S)- N-(1-phenylethyl)acetamide
Scheme 2. Deselenization of the organoselenium amides 5a–f using n-BuLi.
ciently applied to selenium-containing chiral amines in order
to achieve these compounds in high yield and enantioselectiv-
ity. The organoselenium groups were compatible with the DKR
conditions employed. We expect that this chemoenzymatic
protocol will prove to be useful in the synthesis of chiral sele-
nium compounds.
3. Conclusion
In summary, we have demonstrated that the dynamic ki-
netic resolution mediated by palladium and lipase can be effi-

4334
L. H. Andrade et al. / Tetrahedron Letters 50 (2009) 4331–4334
the organoselenium amides, was hydrolyzed by reacting the amide with
Acknowledgments
aqueous HCl solution (2 mL, 2 M) at 90 °C for 6 h. After this period, the aqueous
phase was extracted with CH2Cl2 (5 mL). The organic layer was washed with
brine (3 mL) and dried over MgSO4. The organic layer was further acetylated
The authors would like to thank CNPq, CAPES and FAPESP for
financial support.
with acetic anhydride for further HPLC analysis.In addition,
a saturated
aqueous NaOH solution was added to the aqueous solution (2) until pH 10.
The resulting solution was extracted with CH2Cl2 (3 ꢃ 2 mL). The organic
phases were combined and washed with brine (3 mL), dried over MgSO4. The
solvent was removed in vacuum and the residue, containing the
organoselenium amines, was acetylated with acetic anhydride for further
HPLC analysis.
References and notes
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L.; Lüdtke, D. S.; Vargas, F.; Braga, R. C. Synlett 2006, 1453–1466; (c) Braga, A. L.;
Lüdtke, D. S.; Vargas, F. Curr. Org. Chem. 2006, 18, 1921–1938.
2. (a) Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini, C.; Marini, F.; Bagnoli, L.;
Temperini, A. Tetrahedron: Asymmetry 2000, 11, 4645–4650; (b) Braga, A. L.;
Schneider, P. H.; Paixão, M. W.; Deobald, A. M.; Peppe, C.; Bottega, D. P. J. Org.
Chem. 2006, 71, 4305–4307.
3. (a) Andrade, L. H.; Omori, A. T.; Porto, A. L. M.; Comasseto, J. V. J. Mol. Catal. B:
Enzym. 2004, 29, 47–54; (b) Comasseto, J. V.; Omori, A. T.; Porto, A. L. M.;
Andrade, L. H. Tetrahedron Lett. 2004, 45, 473–476; (c) Omori, A. T.; Assis, L. F.;
Andrade, L. H.; Comasseto, J. V.; Porto, A. L. M. Tetrahedron: Asymmetry 2007, 18,
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5. (a) Huerta, F. F.; Minidis, A. B. E.; Bäckvall, J.-E. Chem. Soc. Rev. 2001, 30, 321–
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11. HPLC analysis for determination of the enantiomeric excess (ee): The enantiomeric
purities of the organoselenium amides 5a–f were measured by HPLC analysis.
The analysis was carried out on Chiralcel OD-H column and the peaks were
detected by a UV detector at 254 nm. Eluent: hexane/isopropanol (95:5), flow
rate: 1.0 mL/min. Retention times:(RS)-N-(1-(4-(Ethylselanyl)phenyl)ethyl)
acetamide (5a): (R)-5a = 20.44 min; (S)-5a = 24.93 min.(RS)-N-(1-(4-(Methyl-
selanyl)phenyl)ethyl)acetamide (5b): (R)-5b = 25.11 min; (S)-5b = 31.68 min.
(RS)-N-(1-(4-(Butylselanyl)phenyl)ethyl)acetamide (5c): (R)-5c = 17.56 min;
(S)-5c = 20.87 min.(RS)-N-(1-(4-(Benzylselanyl)phenyl)ethyl)acetamide (5d):
(R)-5d = 56.46 min;
(S)-5d = 63.76 min.(RS)-N-(1-(3-(Ethylselanyl)phenyl)
ethyl)acetamide (5e): (R)-5e = 19.19 min; (S)-5e = 28.29 min.(RS)-N-(1-(2-
(Ethylselanyl)phenyl)ethyl)acetamide
(5f):
(R)-5f = 16.92 min;
(S)-
5f = 44.46 min.
12. Representative procedure for dynamic kinetic resolution of (RS)-1-((organoselanyl)
phenyl) ethanamines (4a–f): A suspension containing the organoselenium-1-
phenylethanamines (RS)-4a–f (0.2 mmol), Pd-BaSO4 (5% Pd) (42 mg, 10 mol %
Pd), CAL-B (60 mg), and ethyl acetate (78 lL and another 78 lL after 24 h) in
dry toluene (4 mL) was stirred at 70 °C under hydrogen pressure (1 atm). After
48 h, the reaction mixture was cooled to room temperature and filtered and
the remained solid was washed with CH2Cl2 (2 ꢃ 3 mL). The organic phases
were combined and then extracted with an aqueous HCl solution (3 ꢃ 3 mL,
1 M), washed with brine (3 mL), and dried over MgSO4. The solvent was
removed in vacuum and the residue, containing the (R)-organoselenium
amides 5a–f, was analyzed by HPLC. In addition, a saturated aqueous NaOH
solution was added to the resulting acid aqueous phase until pH 10 and it was
then extracted with CH2Cl2 (3 ꢃ 5 mL). The combined organic phases were
washed once with brine (3 mL) and dried over MgSO4. The solvent was
removed in vacuum to give the unreacted organoselenium amines (RS)-4a–f.
All the new compounds synthesized were fully characterized. Selected spectral
data: Compound 5d: Yield: 72%. IR (KBr) cmꢁ1: 3449, 3342, 2971, 1646, 1538,
1494, 1370, 1138, 819, 697, 539, 463, 425. 1H NMR (300 MHz, CDCl3) d: 7.43–
7.39 (d, J = 8 Hz, 2H), 7.28–7.17 (m, 7H), 5.68 (s, 1H), 5.12–5.07 (m, 1H), 4.09
(s, 2H), 1.98 (s, 3H), 1.47–1.45 (d, J = 6, 3H). 13C NMR (75 MHz) d: 169.07,
142.40, 138.47, 133.65, 129.39, 128.83, 128.44, 126.88, 126.84, 48.38, 32.24,
23.46, 21.65. LRMS [EI], m/z (relative abundance): 333 (M+, 29), 318 (1), 274 (4)
200 (4) 120 (3) 91 (100), 65 (5), 43 (4). HRMS [ESI(+)], calcd for
[C17H19NOSe+Na]+: 356.053, found 356.0521; calcd for [C17H19NOSe + K]+:
372.0269, found 372.0266.
8. Hoben, C. E.; Kanupp, L.; Bäckvall, J. Tetrahedron Lett. 2008, 49, 977–979.
9. Iwaoka, M.; Tomoda, S. J. Am. Chem. Soc. 1996, 118, 8077–8084.
10. Representative procedure for kinetic resolution of (RS)-1-((ethylselanyl)phenyl)
ethanamines (4a, 4e and 4f): A suspension containing the organoselenium-1-
phenylethanamines (4a, 4e, or 4f) (0.2 mmol), solvent (1 mL, see tables), CAL-B
(Novozym 435) (60 mg), and the acyl donor (see Table 1) was stirred on a
rotary shaker for 48 h. After this period, the enzyme was filtered off and
washed with CH2Cl2 (5 mL). The organic phase was extracted with an aqueous
HCl solution (3 ꢃ 2 mL, 1 M), affording two solutions: Organic solution (1)
containing the amide and aqueous solution (2) containing the amine
chloridrate. The organic solution (1) was washed with brine (3 mL) and dried
over MgSO4. The solvent was removed in vacuum and the residue, containing