Efficient kinetic resolution of (±)-1,2-O-isopropylidene-3,6-di-O- benzyl-myo-inositol with the lipase B of Candida antarctica

Article abstract of DOI:10.1016/j.tetasy.2010.12.006

(±)-1,2-O-Isopropylidene-3,6-di-O-benzyl-myo-inositol is a relevant starting material in the synthesis of inositol phosphates and their analogs. In this study, we disclose our efforts toward an efficient methodology for the kinetic resolution of this comp

Full text of DOI:10.1016/j.tetasy.2010.12.006

Tetrahedron: Asymmetry 21 (2010) 2899–2903
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Efficient kinetic resolution of ( )-1,2-O-isopropylidene-3,6-di-O-benzyl-myo-i-
nositol with the lipase B of Candida antarctica
Aline G. Cunha a, Angelo A. T. da Silva b, Antônio J. R. da Silva b, Luzineide W. Tinoco b, Rodrigo V. Almeida a,
a
Ricardo B. de Alencastro c, Alessandro B. C. Simas b, , Denise M. G. Freire
⇑
a Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, RJ, Brazil
(UFRJ), Instituto de Quómica (IQ), Programa de Pós-Graduação em Bioquímica, Departamento de Bioquímica, Brazil
b UFRJ, Núcleo de Pesquisas de Produtos Naturais (NPPN), Brazil
c UFRJ, IQ, Departamento de Química Orgânica, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
( )-1,2-O-Isopropylidene-3,6-di-O-benzyl-myo-inositol is a relevant starting material in the synthesis of
inositol phosphates and their analogs. In this study, we disclose our efforts toward an efficient method-
ology for the kinetic resolution of this compound by lipase B of Candida antarctica (Novozym 435). This
reaction selectively affords L-(ꢀ)-1,2-O-isopropylidene-5-O-acetyl-3,6-di-O-benzyl-myo-inositol. From a
conversion of 34% with EtOAc as an acylating agent, the use of vinyl acetate increased the yield to over
49%, while maintaining a very high ee (>99%). The combination of the latter reagent with TBME as a sol-
vent accelerates the reaction.
Received 30 September 2010
Accepted 2 December 2010
Available online 11 January 2011
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
We have recently found that racemic ( )-1,2-O-isopropylidene-
3,6-di-O-benzyl-myo-inositol ( )-1 (Scheme 1), despite its steric
Chiral myo-inositol derivatives, such as d-1,4,5-myo-inositol
trisphosphate, play key roles in cellular signal transductions.1 For
this reason, such substances are important tools in cell biology
investigations. Moreover, inositols hold promise in the develop-
ment of drugs.
myo-Inositol itself, an accessible achiral substance, is the most
used precursor for its chiral derivatives. As this strategy implies
the formation of racemic intermediates, resolution is commonly
required. It is noteworthy that most routes for the enantioselective
synthesis still rely on the resolution by derivatization (formation of
diastereomers).1–3 Although these strategies are effective, the need
of steps for the introduction and removal of the chiral auxiliary
naturally makes them even more costly.
hindrance, could be resolved by a lipase.6 Substance ( )-17,8 is a
relevant precursor of biologically active myo-inositol derivatives.9
Thus, the lipase B of Candida antarctica (Novozym 435) con-
verted diol ( )-1 into monoacetate (ꢀ)-2 in 34% yield and >99%
ee.6 The acylation was found to be highly regioselective, occurring
at the C-5 hydroxyl group. Based on this preliminary result, theo-
retical models were developed for the rationalization of the ob-
served regio- and enantioselectivities. To the best of our
knowledge, no such bulky myo-inositol derivative bearing two
types of protecting group, such as ( )-1, has previously been em-
ployed as a substrate for lipases.
This result encouraged us to improve this kinetic resolution.
Herein, we report the results of this investigation. We also disclose
the synthesis of ( )-2, which streamlined the determination of the
enantiomeric excess of (ꢀ)-2.
The use of enzymes in synthesis, especially lipases, is very
attractive due to the possibility of engaging unnatural substrates
in highly selective and efficient reactions catalyzed by these bio-
catalysts. Moreover, such transformations can be run under mild
conditions.4
O
Despite the clear potential, lipases have not been well explored
O
OBn
O
in the chemoenzymatic syntheses of myo-inositols.5
Novozym 435,
AcOEt, 48h
OH
OAc
OBn
OH
O
BnO
OBn
34% (-)-2
OH
( )-1
⇑
Corresponding author. Tel.: +55 21 2562 6792; fax: +55 21 2562 6795.
E-mail address: abcsimas@nppn.ufr.br (A.B.C. Simas).
Scheme 1. Kinetic resolution of ( )-1 catalyzed by Novozym 435 in AcOEt.
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.12.006

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A. G. Cunha et al. / Tetrahedron: Asymmetry 21 (2010) 2899–2903
O
O
O
O
O
O
OBn
OAc
OPMB
c
OBn
OH
b
OBn
OAc
BnO
BnO
BnO
OPMB
( )-4
OH
( )-6 86%
( )-2 45%
O
O
a
OBn
OH
BnO
OH
( )-1
O
O
O
O
O
O
OBn
OPMB
OBn
OPMB
c
b
OBn
OH
BnO
BnO
BnO
OH
( )-5
OAc
( )-7 99%
OAc
( )-3 44%
Scheme 2. Synthesis of ( )-2 and regiosomer ( )-3: Reagents and conditions (a) (i) Bu2SnO, MeOH/PhMe 1:1, 100 °C, 3 h; (ii) PMBBr, TBAB, DIPEA, PhMe, 100 °C, 11 h, 81%
(4:5 ratio = 63:37, by 1H NMR); (b) DMAP, Ac2O, pyridine, 0 °C?rt, overnight; (c) DDQ, CH2Cl2/H2O 9:1, 0 °C?rt, 2 h.
were not separable by chromatography (silica gel). Thus, we de-
vised the chemical synthesis of ( )-2 from ( )-1 (Scheme 2). This
substance was monoprotected with PMBBr via the stannylene
derivative7,10 affording a mixture of regioisomeric mono-PMB
ethers 4 and 5, which were then separated. The 1H NMR spectra
of these compounds were correlated with those of the known
tri-benzyl ethers 8 and 9, respectively (Fig. 1), indicating that the
protection occurred as shown. Triether 5 was then acetylated and
then the PMB group was cleaved by DDQ,11,12 leading to desired
hydroxyacetate ( )-2. Regioisomer 3 was prepared in a similar
manner. The NMR spectra of ( )-2 and ( )-3 confirmed the previ-
ous structural assignment of (ꢀ)-2 by 2D-NMR experiments.6
2. Results and discussion
2.1. Synthesis of ( )-2
The direct acylation of ( )-1 with Ac2O by the usual procedure
under controlled conditions (Et3N, DMAP, CH2Cl2, ꢀ20 °C) afforded
a roughly 1:1 mixture of monoacetates, along with a minor amount
of the diacetate derivative. The monoacetates in such a mixture
2.2. Solvent selection for the resolution of ( )-1 by Novozym 435
An investigation into the effect of solvents on the performance
of the resolution of ( )-1 (acylation with EtOAc) catalyzed by Nov-
ozym 435 was carried out. The conditions for determining the ee
(Fig. 2, see Section 4) and configuration of (ꢀ)-2 were established
in a previous work.6 It is known that the solvent affects both en-
zyme activity and selectivity in the complex mechanism involving
interactions among the enzyme, the substrate (ligand) and the
reaction medium. The literature has already shown a strong sol-
vent influence on enantioselectivity.13,14 The choice of toluene,
Figure 1. Comparison of NMR (400 MHz, CDCl3) data of ( )-4 and ( )-5 to those of
corresponding tribenzyl ethers ( )-8 and ( )-9.
Figure 2. HPLC analysis of (ꢀ)-2 and ( )-2 (see Section 4).

A. G. Cunha et al. / Tetrahedron: Asymmetry 21 (2010) 2899–2903
2901
Table 2
40
35
30
25
20
15
10
5
Conversion (c), enantiomeric excess (ee) and enantioselectivity (E) in the resolution of
( )-1 with different acylating agents by Novozym 435
Acylating agent
Solvent
( )-1
Time (h) c (%) eep (%)
E
Vinyl acetate
TBME
Vinyl acetate
TBME
24
48
24
48.0 >99
49.9 >99
43,8 >99
>100
>100
>100
Isopropenyl
acetate
Isopropenyl
acetate
TBME
48
45.3 >99
>100
EtOAc
24
24
28.3 >99
33.6 >99
>100
>100
EtOAc
0
0
10
20
Time (hours)
30
40
50
50
45
40
35
30
25
20
15
10
5
EtOAc
TBME
Dichloromethane
Chloroform
THF
Toluene
1,4-Dioxane
Figure 3. Time course of conversion in the resolution of ( )-1 with EtOAc catalyzed
by Novozym 435 in different solvents.
TBME (tert-butyl methyl ether), CHCl3, CH2Cl2, THF, 1,4-dioxane,
and EtOAc as solvents in our assays took into account both the sub-
strate solubility and the stability of that commercial enzyme. The
progress of the resolution reactions catalyzed by lipase in such
media was investigated (Fig. 3).
We found that the more hydrophobic solvents enhanced the con-
version rate in the resolution of ( )-1. The initial rates were higher in
0
0
10
20
30
40
50
toluene (0.206
Lower rates were observed when less hydrophobic solvents were
mol minꢀ1 gꢀ1
employed: CHCl3 (0.060 CH2Cl2 (0.042
mol minꢀ1 gꢀ1
) and 1,4-dioxane
l l
mol minꢀ1 gꢀ1) and TBME (0.602 mol minꢀ1 gꢀ1).
Time (hours)
EtOAc
Isopropenyl acetate
TBME/Isopropenyl acetate
Vinyl acetate
TBME/Vinyl acetate
TBME/EtOAc
l
l
)
l
mol minꢀ1 gꢀ1), THF (0,028
(0.006
l
mol minꢀ1 gꢀ1). Conversions to acetate (ꢀ)-2 followed this
Figure 4. Time course of conversion in the resolution of ( )-1 catalyzed by
Novozym 435 in different acylating agents.
trend (Table 1). The more hydrophilic solvents arguably remove
the H2O molecules bound to the enzyme surface, which modifies
its structure. The result of this is a change in activity and enantiose-
lectivity.15 However, the reaction in EtOAc, a more hydrophilic sol-
agent, with either vinyl acetate or isopropenyl acetate with the res-
olution of ( )-1. We sought higher efficiency in these reactions,
meaning high conversions to (ꢀ)-2, while maintaining its high
ee. As TBME had previously performed well, we also assayed com-
binations of this solvent with the acylating agents.
As expected, alkenyl acetates performed much better than
EtOAc (Table 2, Fig. 4). The use of vinyl and isopropenyl acetate
led to higher conversions, with vinyl acetate affording the best re-
sults. The ee of (ꢀ)-2 remained high in these cases. The use of
TBME as solvent, along with the same reagents, brought about
higher rates. Conversions were not as high as in the reaction with
vinyl acetate as solvent. Thus, our data demonstrate that both the d
and l [in the form of l-(-)-2] enantiomorphs of 1 may be obtained in
high ee.
vent as well, showed high initial rates (0.468 l
mol minꢀ1 gꢀ1) and
conversions (after 24 h). In this case, as the solvent itself is the acyl-
ating agent, it led to an equilibrium shift in favor of (ꢀ)-2 formation.
High ee (>99%) and enantioselectivity (E >100) were obtained in
all cases (Table 1). The conversion degree was not improved upon
when AcOEt was used as the acylating agent.
2.3. Acylating agent selection for the resolution of ( )-1 by
Novozym 435
As acylations catalyzed by lipases involve the formation of an
acyl-enzyme intermediate, the nature of the acylating agent has
a strong effect on the enzyme activity. The use of vinylic esters
as these reagents has the advantage of forming carbonyl by-prod-
ucts, instead of alcohols, which makes those reactions irreversible.
It also results in higher conversion rates.16,17 Thus, we studied the
effect of the replacement of AcOEt, as a solvent and/or an acylating
3. Conclusion
We have disclosed the conditions for a very efficient kinetic res-
olution of racemic myo-inositol derivative 1 with Novozym 435.
This compound is a relevant precursor of inositol derivatives. The
use of vinyl acetate as an acylating agent enabled high conversion
to monoester (ꢀ)-2 while maintaining high enantioselectivity.
Moreover, the use of TBME as a solvent in combination with vinyl
acetate proved to be an alternative condition.
Table 1
Conversion (c), enantiomeric excess (ee) and enantioselectivity (E) in the resolution of
( )-1 with EtOAc in different solvents by Novozym 435
Solvent
( )-1
Time (h)
c (%)
eep (%)
E
EtOAc
TBME
Toluene
Chloroform
Dichloromethane
THF
24
24
12
48
24
24
48
33.6
28.3
16.7
12.0
11.0
7.1
>99
>99
>99
>99
>99
>99
>99
>100
>100
>100
>100
>100
>100
>100
4. Experimental
4.1. Resolution of ( )-1
The enzymatic reactions were realized in closed thermostatized
flasks containing ( )-1 (5 mg), acylating agent (1.0 mL), and
1,4-Dioxane
7.2

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A. G. Cunha et al. / Tetrahedron: Asymmetry 21 (2010) 2899–2903
Novozym 435 (50 mg) in the solvent (1.5 mL) at 30 °C. Aliquots
were taken after 0.5, 2, 6, 12, 24, and 48 h and analyzed by HPLC.
The physical data of product L-(ꢀ)-2 were reported in the previous
(t, 1H, J = 8.3 Hz), 7.29–7.41 (m, 10H). 13C NMR (100.62 MHz,
CDCl3), d 21.1, 25.4, 27.4, 70.4, 72.8, 72.9, 73.5, 75.3, 77.0,
78.5, 79.1, 106.5, 127.6, 127.7, 128.1, 128.3, 128.6, 137.8, 138.1,
work:6
[a]
D = ꢀ8.1 (c 0.65, CDCl3); 1H NMR (400 MHz, CDCl3), d
171.0; Anal. Calcd for
C, 68.05; H, 6.64.
C25H30O7: C, 67.86; H, 6.83. Found:
1.37 (s, 3H), 1.53 (s, 3H), 2.10 (s, 3H), 3.68–3.75 (m, 2H), 4.05 (t,
1H, J = 8.65 Hz), 4.24 (t, 1H, J = 6.01 Hz), 4.42 (dd, 1H, J = 3.62
5.97 Hz), 4.70–4.84 (m, 4H), 4.89 (t, 1H, J = 8.22 Hz), 7.28–7.41
(m, 10H). 13C NMR (100.62 MHz, CDCl3), d 21.1, 25.4, 27.4, 70.4,
72.8, 72.9, 73.5, 75.2, 76.9, 78.5, 79.0, 106.5, 127.6, 127.7, 128.1,
128.3, 128.6, 137.8, 138.1, 171.0. EM-ESI: m/z = 465.1 [M+Na]+.
4.4.2. ( )-1,2-O-Isopropylidene-4-O-acetyl-3,6-di-O-benzyl-myo-
inositol ( )-3
The procedure in Section 4.4.1 was followed in the reaction of
( )-7 (0.012 g) to afford ( )-3 (0.0049 g; 44%) 1H NMR (400 MHz,
CDCl3), d 1.38 (s, 3H), 1.56 (s, 3H), 2.11 (s, 3H), 3.58 (t, 1H,
J = 8.1 Hz), 3.73–3.81 (m, 2H), 4.22 (td, 1H, J = 1.9 6.2 Hz), 4.37–
4.39 (m, 1H), 4.67–4.92 (m, 4H), 5.28 (td, 1H, J = 1.5 8.0 Hz),
7.28–7.40 (m, 10H).
4.2. HPLC analysis of conversion of ( )-1 to (ꢀ)-2
Conversion analyses were done via HPLC on a Shimadzu-C18
column (40 °C in a CTO-20A oven) eluted with an acetonitrile–
H2O (60:40) mixture (0.5 mL/min) by a Shimadzu LC-20AT pump.
A Shimadzu SPD-M20A variable-wavelength UV/vis detector was
employed, with the detection set at 215 nm, and the Shimadzu
LCsolution software was used for chromatogram integration. The
samples to be analyzed were filtered through a 0.45 lm PTFE filter.
The retention times of the substrate ( )-1 and product L-2 were
9.3 min and 15.4 min, respectively.
4.4.3. ( )-1,2-O-Isopropylidene-3,6-di-O-benzyl-4-O-(40-
methoxybenzyl)-myo-inositol ( )-4 and ( )-1,2-O-
isopropylidene-3,6-di-O-benzyl-5-O-(40-methoxybenzyl)-myo-
inositol ( )-5
At first, Bu2SnO (0.066 g; 0.26 mmol) and diol ( )-1 (0.101 g;
0.25 mmol) in a 1:1 toluene/CH3OH mixture (4.0 mL) under stir-
ring and Ar were heated to 100 °C for 3 h. Additional dry toluene
(5.0–10.0 mL) was added and evaporated to dryness once more un-
der vacuum. The residue had the trace amounts of solvent removed
under high vacuum (40 min) and to this material, TBAB (0.048 g;
0.15 mmol), toluene (21.0 mL), and PMBBr (0.08 mL; 0.56 mmol)
were added sequentially. Then, the resulting mixture was stirred
at 120 °C for 11 h. Next, the volatiles were partially removed under
vacuum and the obtained mixture was subjected directly to flash
chromatography (elution with ethyl acetate/hexane mixtures).
This yielded ( )-4 and ( )-5 and a mixture of both compounds
(0.106 g combined; 81%, ( )-4/( )-5 = 63:37, by 1H NMR). Com-
pound ( )-4: IR (KBr) mmax cmꢀ1 3467 (b), 3051, 3031, 2936,
2908, 2877, 2837, 1613, 1586, 1514, 1455, 1381, 1371, 1302,
1248, 1218, 1112, 1083, 1065, 1029, 868, 821, 738, 699; 1H NMR
(400 MHz, CDCl3), d 1.38 (s, 3H), 1.53 (s, 3H), 2,66 (1OH, b), 3.51
(t, 1H, J = 9,78 Hz), 3.67–3.72 (m, 2H), 3.75–3.81 (several signals,
6H, impurity), 3.83 (s, 3H), 4.12 (t, 1H, J = 6.23 Hz), 4.31 (dd, 1H,
J = 4.04 5.38 Hz), 6.89–6.93 (m, 2H), 7.28–7.39 (m, 12H). Com-
pound ( )-5: IR (KBr) mmax cmꢀ1 3464 (l), 3063, 3031, 2988, 2935,
2908, 2879, 2837, 1613, 1586, 1514, 1497, 1455, 1381, 1371,
1302, 1248, 1219, 1173, 1111, 1084, 1066, 1035, 868, 822, 738,
699; 1H NMR (400 MHz, CDCl3), d 1.36 (s, 3H), 1.50 (s, 3H), 2,63
(1OH, b), 3.29 (t, 1H, J = 9.04 Hz), 3.57 (dd, 1H, J = 3.55 9.66 Hz),
3.70 (dd, 1H, J = 6.85 8.80 Hz), 3.82 (s, 3H), 4.04 (t, 1H,
J = 9.42 Hz), 4.13 (t, 1H, J = 6.48 Hz), 4.32 (t, 1H, J = 4.40 Hz),
4.64–4.94 (m, 6H), 6.87–6.93 (m, 2H), 7.28–7.44 (m, 12H).
4.3. Determination of ee and E
Chromatographic determinations of the enantiomeric excesses
(ee) of L-(ꢀ)-2 were carried out on the same equipment mentioned
above using a Chiralcel OD-H column (5
with a 9:1 hexane–2-propanol (0.8 mL/min). Retention times of the
l
m; 4.6 ꢁ 250 mm) eluted
enantiomers: D-2 (15.7 min), L-2 (22.3 min).
The enantiomeric ratio E was calculated by using the equation
of Chen et al.18 as given below:
ln½1 ꢀ cð1 þ eepÞꢂ
E ¼
ð1Þ
ln½1 ꢀ cð1 ꢀ eepÞꢂ
where
½Pꢂ þ ½Qꢂ
C ¼
¼ extent of conversion
ð2Þ
ð3Þ
½Aꢂ0 þ ½Bꢂ0
½Pꢂ ꢀ ½Qꢂ
eep ¼
¼ enantiomeric purity of product P
½Pꢂ þ ½Qꢂ
where A and B stand for substrate, and P and Q are products,
respectively.
4.4. Physical data
4.4.1. ( )-1,2-O-Isopropylidene-5-O-acetyl-3,6-di-O-benzyl-myo-
inositol ( )-2
4.4.4. ( )-1,2-O-Isopropylidene-4-O-acetyl-3,6-di-O-benzyl-5-O-
(40-methoxybenzyl)-myo-inositol ( )-6
At first, DDQ (0.197, 0.868 mmol) was added in 3 portions every
30 min to PMB-ether ( )-6 (0.202 g, 0.114 mmol) dissolved in a
stirred 9:1 CH2Cl2/H2O mixture (2.0 mL), the first one at 0 °C. After
2 h from the start, the reaction mixture was cooled again to 0 °C
and a satd aq NaHCO3 soln (10 mL) was added. After 5 min, the
resulting mixture was warmed to rt and the product was extracted
with CH2Cl2 (40 mL). The organic phase was washed with distilled
H2O (20 mL) twice, dried over Na2SO4 and filtered. The volatiles
were evaporated under vacuum and the resulting residue was
purified by flash chromatography (elution with ethyl acetate/hex-
ane mixtures) leading to ( )-2 (0.0471 g; 45%). IR (KBr) mmax cmꢀ1
3524, 3448 (b), 2976, 2931, 2915, 1724 (F), 1638, 1498, 1454, 1379,
1367, 1253, 1241, 1217, 1151, 1109, 1061, 1029, 874, 731, 696; 1H
NMR (400 MHz, CDCl3), d 1.37 (s, 3H), 1.53 (s, 3H), 2.10 (s, 3H), 2.81
(1OH, b), 3.67–3.75 (m, 2H), 4.04 (t, 1H, J = 8.7 Hz), 4.23 (t, 1H,
J = 6.0 Hz), 4.41 (dd, 1H, J = 3.85 5.4 Hz), 4.70–4.83 (m, 4H), 4.89
A stirred solution of compound ( )-4 (0.167 g; 0.321 mmol) and
DMAP (0.079 g; 0,064 mmol) in pyridine (30 mL) under Ar was
cooled to 0 °C and treated with Ac2O (0.25 mL; 2.650 mmol). After
15 min, the reaction mixture was allowed to warm to rt. Then, a
satd aq NaHCO3 soln (10 mL) was added to the mixture at 0 °C.
After 5 min, the resulting mixture was allowed to warm back to
rt. The product was isolated (AcOEt as solvent) and purified accord-
ing the usual procedure (see Section 4.4.1), yielding ( )-6 (0.156 g;
86%). IR (KBr) mmax cmꢀ1 3479 (b), 3064, 3032, 2989, 2936, 2908,
2885, 2838, 1743 (w), 1613, 1586, 1514, 1455, 1380, 1371, 1302,
1246, 1219, 1173, 1158, 1084, 1073, 1029, 868, 822, 738, 698; 1H
NMR (400 MHz, CDCl3), d 1.38 (s, 3H), 1.55 (s, 3H), 1.99 (s, 3H),
3.72 (dd, 1H, J = 6.5 8.6 Hz), 3.80–3.83 (m, 4H), 3.90 (t, 1H,
J = 8.3), 4.19 (t, 1H, J = 6.11), 4.35 (dd, 1H, J = 3.7 5.7 Hz), 4.60–
4.84 (m, 6H), 5.03 (t, 1H, J = 8.3 Hz), 6.88–6.90 (m, 2H), 7.23–7.40
(m, 12H).

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4.4.5. ( )-1,2-O-Isopropylidene-5-O-acetyl-3,6-di-O-benzyl-4-O-
(40-methoxybenzyl)-myo-inositol ( )-7
The procedure in Section 4.4.4 was followed in the reaction of
( )-5 (0.033 g) to afford ( )-7 (0.0397g; 99%). 1H NMR (400 MHz,
CDCl3), d 1.35 (s, 3H), 1.51 (s, 3H), 1.97 (s, 3H), 3.40 (t, 1H, J = 8.6
Hz), 3.66 (dd, 1H, J = 3.6 8.4 Hz), 4.52–4.84 (m, 6H), 5.42 (t, 1H,
J = 8.4 Hz), 6.82–6.84 (m, 2H), 7.17–7.35 (m, 12H).
Acknowledgments
9. (a) Lampe, D.; Mills, S. J.; Potter, B. V. L. J. Chem. Soc., Perkin Trans. 1 1992, 2899–
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FAPERJ and CNPq for funding; CAPES for fellowship (AATS);
Central Analítica/NPPN and CNRMN/IBM for NMR data; Laborató-
rio de Síntese Orgânica Ambiental (IQ-UFRJ) for polarimetric
analysis.
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