Enantioselective ethylation of aldehydes with 1,3-N-donor ligands derived from (+)-camphoric acid

Article abstract of DOI:10.1016/j.tetasy.2009.12.012

Derivatives of (+)-camphoric acid were prepared by a short and simple synthetic sequence and proved to be excellent ligands for the enantioselective ethylation of benzaldehyde with diethylzinc, with ees of up to 96% being obtained. The most efficient liga

Full text of DOI:10.1016/j.tetasy.2009.12.012

Tetrahedron: Asymmetry 21 (2010) 62–68
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Tetrahedron: Asymmetry
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Enantioselective ethylation of aldehydes with 1,3-N-donor ligands derived
from (+)-camphoric acid
*
Dina Murtinho , M. Elisa Silva Serra, A. M. d’A. Rocha Gonsalves
Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3004-535 Coimbra, Portugal
a r t i c l e i n f o
a b s t r a c t
Article history:
Derivatives of (+)-camphoric acid were prepared by a short and simple synthetic sequence and proved to
be excellent ligands for the enantioselective ethylation of benzaldehyde with diethylzinc, with ees of up
to 96% being obtained. The most efficient ligand was tested with several aromatic aldehydes and ees of up
to 99% were observed. Structural features of the ligands are determinant for achieving high
enantioselectivities.
Received 5 November 2009
Accepted 21 December 2009
Available online 11 January 2010
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
amide type ligands, via one or two additional steps. Synthetic pro-
cedures leading to chiral ligands are often laborious, hence the
The alkylation of aldehydes with dialkylzinc allows for the syn-
thesis of chiral secondary alcohols, essential components in the
preparation of pharmaceuticals, agrochemicals and perfumes,
amongst others.1–3
Although many types of ligands have been used for the enantio-
selective alkylation of aldehydes, amino alcohols are the most cur-
rently used. Diamine ligands and derivatives have received less
attention, although there are various examples of good ees ob-
tained with this type of ligands.4–9 A considerable amount of work
has been reported in the literature on the use of 1,2-bidentate li-
gands, while 1,3- and 1,4-bidentate ligands have been less used
and studied.10–12
In contrast to 1,2-ligands, which form a five-membered chelate
with the zinc atom in the transition state, 1,3- and 1,4-ligands form
conformationally flexible six- or seven-membered catalytic che-
lates with the Zn atom. In these types of ligands, the rigidity of
the structure is of particular importance in order to limit the con-
formational freedom of the catalytic species.12,13 Ligands with rigid
skeletons, such as cyclic or bicyclic structures, are good candidates
to be used.
development of short and simple synthetic sequences is of added
value in the design of new ligands.
Although a great number of N,N0-disulfonated and diacylated
chiral amines have been tested in the enantioselective alkylation
with diethylzinc, especially in the presence of Ti(OiPr)4,17–20 there
are fewer reports in the literature on the use of monosulfonated or
monoacylated amines.1,7,21,22
Urabe et al.23 reported the use of a dialkylated diamine, a dia-
mide and some dialkylaminoamides derived from (+)-camphoric
acid in the reaction of benzaldehyde with several organometallic
reagents, including diethylzinc. The best result (81% yield, 93%
ee) was obtained with ligand 9, in the alkylation of benzaldehyde
with diethylzinc, at 0 °C, using toluene as a solvent. To the best
of our knowledge this is the only study that reports the use of dia-
mine type (+)-camphoric acid derivatives in the enantioselective
alkylation of aldehydes with diethylzinc.
2. Results and discussion
2.1. Ligands synthesis
Our approach to the development of new ligands for asymmet-
ric catalysis, namely for the enantioselective alkylation and
trimethylsilylcyanation of aromatic aldehydes,14,15 was based on
the use of (+)-camphoric acid as the source of chirality for the syn-
thesis of salen ligands for the trimethylsilylcyanation of benzalde-
hyde.16 (+)-Camphoric acid allows the preparation of a 1,3-diamine
directly in one step, by the Schmidt reaction. This diamine can eas-
ily be converted into several derivatives, namely sulfonamide and
Diamine 1 [(1R,3S)-1,3-diamino-1,2,2-trimethylcyclopentane]
was prepared from commercial (+)-camphoric acid, according to a
previously described procedure.24 Monosulfonamides 2 and 3
were obtained by the reaction of 1 equiv of tosyl chloride or
(+)-camphorsulfonyl chloride, respectively, with an excess of
diamine 1, in ethanol, at room temperature. Aminoamide 4 and
aminocarbamate 5 were synthesized in an analogous way, using
benzoylchlorideand benzylchloroformate, respectively(Scheme1).
The substitution occurs preferentially at the amine group with less
steric hindrance, which allows for the introduction of different sub-
stituents at the two amino groups.
* Corresponding author. Tel.: +351 239854478; fax: +351 239827703.
E-mail address: dmurtinho@ci.uc.pt (D. Murtinho).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.12.012

D. Murtinho et al. / Tetrahedron: Asymmetry 21 (2010) 62–68
63
Ligand 11 was obtained from compound 4 by alkylation with
ethyl iodide in refluxing ethanol, using potassium carbonate as
a base (Scheme 4). The corresponding diethylated ligand 12
proved more difficult to synthesize: the resulting product was al-
ways a mixture of mono and diethylated compounds. Attempts to
improve the yield of the diethylated compound by using a large
excess of ethyl iodide or dimethylformamide as a solvent did
not lead to a significant improvement in yield. Therefore, this
compound was prepared in refluxing ethanol using a 10-fold ex-
cess of ethyl iodide.
NaN3/H2SO4
COOH
HOOC
H2N
NH2
CHCl3 55-60 ºC
1
(1R,3S )-
R=
RCl
EtOH, rt
H3C
SO2
2
3
O
Ligand 7 was reduced with L-selectrideÒ, using a described pro-
cedure,20 in order to obtain the exo compound 13, Scheme 5.
Our first attempt to prepare ligand 14, by reaction of 3 and ethyl
iodide, always gave low yields and a mixture of product and re-
agent, which were difficult to separate by column chromatography
on silica gel. We therefore decided to prepare this ligand starting
from compound 11. Hydrolysis of the benzoyl group followed by
reaction with (1S)-(+)-10-camphorsulfonyl chloride allowed us to
obtain the desired product 15 (Scheme 6).
Ligands 4 and 9 are known compounds, prepared by Urabe
et al.23 Ligand 4, as far as we know, has not been tested in the enan-
tioselective alkylation of benzaldehyde; ligand 9 was used for com-
parative purposes. All ligands were obtained with moderate to
good yields.
SO2
RHN
NH2
O
O
(1S,3R)-2-5
O
4
5
Scheme 1. Synthesis of chiral ligands.
Disulfonamides 6 and 7 were prepared by the reaction of dia-
mine 1 with 2.2 equiv of the corresponding sulfonyl chloride, in
the presence of triethylamine, Scheme 2.
RCl, NEt3
RHN
NHR
(1R,3S)-6-7
NH
H N
2
2
CH2Cl2, rt
(1R,3S)-1
2.2. Enantioselective alkylations
We began to test our ligands in the enantioselective alkylation
of benzaldehyde with diethylzinc, using our previously optimized
conditions.25 The reactions were carried out in dry cyclohexane
at 0 °C in the presence of 15% chiral ligand (Scheme 7). The results
obtained are shown in Table 1.
H C
SO
2
3
R=
7
O
6
SO
2
All ligands tested proved to be efficient in promoting the ethy-
lation reaction, with conversions ranging from 34% to 98%. For
some ligands, in addition to the desired chiral alcohol, 1-phenyl-
1-propanol, benzyl alcohol was formed as a by-product. The forma-
tion of benzyl alcohol has been observed by others and is the result
of a secondary process in which benzaldehyde is reduced by the
zinc alkoxide of the ethylation product, 1-phenyl-1-propanoxide.26
The results shown in Table 1, with respect to ligands 2–4 with
only one substituted amine group, suggest that higher conversions
and low reactions times are obtained when an amido rather than a
sulfonyl group is present in the ligand. An improved enantiomeric
excess (75%) was obtained with ligand 3, due to the two additional
stereogenic centres from the camphorsulfonyl moiety. Lower con-
versions and ee were obtained with disulfonamides 6 and 7 due to
the presence of two bulky substituent groups. The presence of a
less sterically demanding dimethyl substituent, as in ligands 8–
10, allows for an improvement in conversions, amount of chiral
product and ee. The presence of a carbamate group is more bene-
Scheme 2. Synthesis of chiral disulfonamides.
Dimethylation of compounds 2, 4 and 5, with formic acid and
formaldehyde, according to a described procedure,23 gave ligands
8–10, Scheme 3.
HCOOH/HCHO
RHN
NH2
RHN
N(CH3)2
reflux
(1S,3R)-2,4,5
(1S,3R)-8,9,10
O
O
O
SO2
R=
8
9
10
Scheme 3. Synthesis of the dimethylated ligands.
O
N
H
NHEt
O
(1S,3R)-11
EtI, K2CO3
N
H
NH2
EtOH, reflux
O
(1S,3R)-4
N
H
NEt2
(1S,3R)-12
Scheme 4. Synthesis of the ethylated ligands.

64
D. Murtinho et al. / Tetrahedron: Asymmetry 21 (2010) 62–68
O
ficial than a sulfonyl group, but the ee is lower in comparison to
when an amide group is present.
O
S
O
S
With these results in hand, we decided to prepare ligands 11
and 12 with one amide moiety and one or two ethyl substituent
groups in order to introduce a slightly more bulky group than
methyl to determine if the enantioselectivity of the process could
be improved upon. The presence of one ethyl group turned out
to be beneficial in terms of ee. With this ligand the reaction is very
fast, with a conversion of 95% after 6 h, no formation of the benzyl
alcohol and an ee of 96%. The presence of two ethyl groups seems
detrimental. The conversion is very low, indicating that the zinc
does not coordinate properly with the ligand, possibly due to its
excessive steric bulk.
NH
N
H
O
O
O
(1R,3S)-7
L-Selectride®
-78º C (1h), rt (2h)
HO
O
O
S
S
Moreover, compound 13, a tetradentate ligand obtained by
reduction of the carbonyl groups of ligand 7, showed low enanti-
oselectivity, probably because it requires the presence of
titanium.
NH
N
H
O
O
OH
(1R,3S)-13
Scheme 5. Synthesis of disulfonamide 13.
Similarly to ligand 11, the presence of an ethyl group in ligand
15 reduces the reaction time and drastically improves the conver-
sion, chiral product formation and enantiomeric excess (90%, 100%
and 92%, respectively) of the catalytic process. Consequently, it
seems that the presence of one ethyl group is highly advantageous
for this type of ligand.
Using our best ligand, 11, we tested other reaction solvents: tol-
uene, ethyl ether and dichloromethane. The catalyst loading was
also studied. The results are summarized in Table 2.
O
HCl/H2O
H2N
NHEt
N
H
NHEt
reflux
(1S,3R)-11
(1R,3S)-14
The best solvent for ligand 11 was found to be cyclohexane, as
shown in Table 2. The best results in terms of conversion and ee
were obtained with non-coordinating solvents, cyclohexane and
toluene. Decreasing the ligand loading resulted in a slight decrease
in reaction conversion. With 5 mol % ligand 11, an ee of 95% and a
conversion of 90% were obtained.
The good results obtained with ligand 11 led us to examine its
efficiency with a series of other aldehydes using our best reaction
conditions (0 °C, 15 mol % catalyst and cyclohexane as solvent).
The results are shown in Table 3.
SO2Cl
K2CO3, EtOH
O
O
O
S
NHEt
N
H
O
(1S,3R)-15
Scheme 6. Synthesis of ligand 15.
All aldehydes showed good conversions. With the exception of
o-chlorobenzaldehyde, all of the ee were excellent. In all cases,
the absolute configuration of the major enantiomer was assigned
as (S) by comparison of the retention times with reported values
or by determining the sign of the specific rotation of the isolated
reaction.27–29 Even bulky substrates, such as 1- and 2-naphthalde-
hyde gave excellent ee, 96% and 92%, respectively. The best ee was
obtained for m-methylbenzaldehyde, 99%.
OH
O
15 mol% ligand
Et2Zn
H
+
Cyclohexane, 0 ºC
Scheme 7. Asymmetric addition of diethylzinc to benzaldehyde.
Attempts to alkylate aliphatic aldehydes, such as dodecanal in
the presence of ligand 11 were unsuccessful. Only 16% conversion
was obtained after a reaction time of 24 h.
Table 1
Enantioselective alkylation of benzaldehyde catalyzed by 2–4, 6–13, 15a
Ligand
Time (h)
Conversionb (%)
1-Phenyl-1-propanolc (%)
eed (%)
3. Conclusion
2
3
4
6
7
24
24
6
24
24
24
6
6
6
24
24
6
52
48
90
49
52
72
98
97
95
34
57
90
53
89
100
64
90
78
41 (S)
75 (S)
68 (S)
21 (S)
62 (S)
57 (S)
90 (S)e
76 (S)
96 (S)
37 (S)
21 (S)
92 (S)
A new series of 1,3-chiral ligands has been easily prepared
from natural (+)-camphoric acid, in a two- or three-step se-
quence. The ligands were tested in the enantioselective ethyla-
tion of benzaldehyde, showing excellent enantioselectivities (up
to 96%). Some structural features of the ligands are determinant
in order to achieve high enantioselectivities, namely the pres-
ence of a bulky substituent in the amine group with less steric
hindrance, at the 3-position of the cyclopentane ring, and an
ethyl substituent in the amino group with more steric hindrance.
The use of our best ligand, 11, for the alkylation of other aro-
matic aldehydes with diethylzinc showed excellent ee (up to
99% for m-methylbenzaldehyde). Further studies are currently
in progress in order to extend the application of these and other
(+)-camphoric acid derived ligands to other useful asymmetric
transformations.
8
9
96
10
11
12
13
15
100
100
52
67
100
a
Reactions were carried out in cyclohexane, at 0 °C, using 0.15 mmol of chiral
ligand, 1 mmol of benzaldehyde and 2 mmol of diethylzinc (1 M in hexane).
b
Determined by GC.
Relative to converted benzaldehyde.
Determined by GC on a chiral column; the major enantiomer is indicated in
c
d
parentheses.
e
Ligand described by Urabe et al. (under their conditions 81% yield, 93% ee).

D. Murtinho et al. / Tetrahedron: Asymmetry 21 (2010) 62–68
65
Table 2
Asymmetric ethylation of benzaldehyde catalyzed by 11, with various solvents and catalyst loadingsa
Solvent
Catalyst (mol %)
Conversionb (%)
1-Phenyl-1-propanolc (%)
eed (%)
Cyclohexane
Diethyl ether
Dichloromethane
Toluene
Cyclohexane
Cyclohexane
15
15
15
15
10
5
95
40
55
76
91
90
100
99
100
100
100
100
96 (S)
92 (S)
91 (S)
95 (S)
95 (S)
95 (S)
a
b
c
Reactions were carried out at 0 °C for 6 h, using 1 mmol of benzaldehyde and 2 mmol of diethylzinc (1 M in hexane).
Determined by GC.
Relative to converted benzaldehyde.
d
Determined by GC on a chiral column; the major enantiomer is indicated in parentheses.
Table 3
reported values and by determining the sign of the specific rotation
of the isolated reaction.
Asymmetric ethylation of different aldehydes catalyzed by 11a
Aldehyde
Conversionb (%)
eec (%)
4.2. Synthesis of chiral ligands
o-Methylbenzaldehyde
m-Methylbenzaldehyde
p-Methylbenzaldehyde
m-Methoxybenzaldehyde
o-Chlorobenzaldehyde
p-Chlorobenzaldehyde
p-Nitrobenzaldehyde
1-Naphthaldehyde
73
88
87
82
95
100
92
70
92 (S)
99 (S)
95 (S)
92 (S)
72 (S)
93 (S)
90 (S)
96 (S)
92 (S)
The syntheses of compounds 1, 4 and 9 have already been
described.23,24
4.2.1. General procedure for the synthesis of compounds 2–5
To a stirred solution of diamine 1 (1.42 g, 10 mmol) in dry ethanol
(25 mL) was added, at 0 °C under an inert atmosphere, a solution of
the sulfonyl chloride, benzoyl chloride or benzyl chloroformate
(4 mmol) in dry ethanol (20 mL). The reaction mixture was stirred
overnight at room temperature. The solvent was evaporated and
the reaction mixture was treated with NaHCO3 (saturated solution)
to basic pH. The aqueous phase was extracted three times with
dichloromethane and the joint organic phases were washed with
water, brine and dried over anhydrous Na2SO4. After evaporating
the solvent, the product was purified as described below.
2-Naphthaldehyde
71
a
Reactions were carried out at 0 °C for 6 h, using 1 mmol of aldehyde and
2 mmol of diethylzinc (1 M in hexane).
b
Determined by GC.
Determined by GC on a chiral column.
c
4. Experimental
4.1. General
4.2.1.1. N-((1S,3R)-3-Amino-2,2,3-trimethylcyclopentyl)-4-
Commercially available compounds were used without further
purification. All solvents were dried prior to use following standard
procedures. Diethylzinc (Aldrich) was used as a 1 M solution in
hexane. Benzaldehyde was distilled prior to use and stored over
4 Å molecular sieves. Melting points were determined using a Elec-
trothermal Melting Point Apparatus (values are uncorrected). Opti-
cal rotations were measured with an Optical Activity AA-5
polarimeter. NMR spectra were recorded on a Bruker AMX 300
(300 and 75.5 MHz for 1H and 13C, respectively) or a Bruker Avance
III 400 MHz (100 MHz for 13C). TMS was used as the internal stan-
dard and chemical shifts are given in ppm. Elemental analyses
were carried out on a Fisons Instruments EA 1108 CHNS-O elemen-
tal analyzer. GC analyses were recorded on an HP 5890A instru-
methylbenzenesulfonamide 2.
The product was purified by
silica gel column chromatography (dichloromethane/methanol
90:10) to afford a white solid, which was recrystallized from
CH2Cl2/hexane (56%). Mp 59–61 °C; ½a D25
¼ þ15 (c 1.0, CH2Cl2). IR
ꢀ
(KBr, cmꢁ1): 3125, 2958, 2925, 1400, 1315, 1154, 1094, 664, 559.
1H NMR (400 MHz, CDCl3) d: 0.81 (s, 3H), 0.91 (s, 3H), 1.07 (s,
3H), 1.39–1.51 (m, 2H), 1.62–1.70 (m, 1H), 1.90–1.94 (m, 1H),
2.41 (s, 3H), 3.35–3.39 (m, 1H), 7.26 (d, 2H, J 8.1), 7.73 (d, 2H, J
8.1). 13C NMR (100 MHz, CDCl3) d: 17.13, 21.50, 24.63, 26.14,
37.84, 47.53, 61.88, 63.92, 126.85, 129.44, 139.46, 142.49. GC–MS
(EI) m/z: 296 (M+, 1%), 225 (5), 155 (8), 126 (100), 110 (24), 91
(27), 70 (35), 57 (11). HRMS (EI+, [M+H]+) m/z: calcd for
(C15H25N2O2S) 297.1637; found 297.1639.
ment coupled to an HP 3396A integrator using
a capillary
column (Supelcowax 10, 30 m, 0.25 i.d., 0.25 m). Infrared spectra
l
4.2.1.2. N-((1S,3R)-3-Amino-2,2,3-trimethylcyclopentyl)-1-
were recorded on a Thermo Scientific Nicolet 6700 FTIR. Mass
spectra were recorded on an HP 5973 MSD chromatograph with
70 eV (EI), Agilent 6890 series, equipped with an HP-5MS column
((1S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesul-
fonamide 3.
The product was purified by silica gel column
chromatography (dichloromethane/methanol 95:5) to afford a
(30 m d 0.25 mm d 0.25
l
m) or on a Fisons Instruments-Platform
white solid (63%). Mp 170 °C (sublimes); ½a D25
¼ þ45 (c 1.0,
ꢀ
with an APCI probe coupled to a Thermo Separation Spectra Series
P200 chromatograph.
CH2Cl2). IR (KBr, cmꢁ1): 3377, 3303, 2962, 1738, 1722, 1456,
1419, 1333, 1321, 1150, 1095, 1055, 888, 569, 529. 1H NMR
(400 MHz, CDCl3) d: 0.89 (s, 3H), 0.90 (s, 3H), 1.00 (s, 3H), 1.11
(s, 3H), 1.12 (s, 3H), 1.38–1.50 (m, 3H), 1.56–1.64 (m, 1H), 1.68–
1.84 (m, 3H); 2.00–2.10 (m, 2H), 2.23–2.32 (m, 1H), 2.35–2.42
(m, 1H), 2.47–2.55 (m, 1H), 2.90 (d, 1H, J 14.8) 3.45 (d, 1H, J
14.8), 3.54 (d, 1H, J 6.8). 13C NMR (100 MHz, CDCl3) d: 17.39,
19.85, 20.00, 24.38, 25.27, 26.16, 26.94, 30.76, 37.83, 42.72,
42.79, 47.30, 47.94, 51.03, 58.79, 61.86, 63.97, 215.76. GC–MS
(EI) m/z: 356 (M+, 2%), 339 (14), 215 (70), 151 (26), 124 (100),
108 (85), 93 (18), 81 (27), 67 (18), 55 (16). HRMS (EI+, [M+H]+)
m/z: calcd for (C18H33N2O3S) 357.2212; found 357.2209.
Alkylation reactions were carried out under an inert atmo-
sphere using standard Schlenk-type techniques. Reaction products
were identified by comparison with authentic commercially ac-
quired samples and by GC/MS analysis. Catalytic experiments were
repeated in order to confirm the results. Enantiomeric excesses
were determined by using a chiral c-cyclodextrin capillary column
(FS-Lipodex-E, 25 m, 0.25 i.d.) from Machery-Nagel using hydrogen
as carrier gas, on an HP 5890A instrument coupled to an HP 3396A
integrator. The absolute configuration of the major enantiomers
was determined by comparison of the retention times with

66
D. Murtinho et al. / Tetrahedron: Asymmetry 21 (2010) 62–68
4.2.1.3. N-((1S,3R)-3-Amino-2,2,3-trimethylcyclopentyl)benz-
amide 4. The product was purified by silica gel column chro-
7.5 mL of HCl 2 M were added and the solution was evaporated un-
der reduced pressure. The residue was dissolved in water and
NaOH 15% was added to basic pH. The resulting mixture was ex-
tracted several times with dichloromethane. The joint organic
phases were dried over anhydrous Na2SO4. After evaporating the
solvent, the product was purified as described below.
matography (diethyl ether/triethylamine 80:2) to afford a low
melting solid (90%).
½
a 2D5
ꢀ
¼ þ80 (c 1.5, CH2Cl2). 1H NMR
(400 MHz, CDCl3) d: 0.95 (s, 3H), 0.96 (s, 3H), 1.16 (s, 3H), 1.54–
1.65 (m, 2H), 1.82–1.89 (m, 1H), 2.25–2.34 (m, 1H), 4.36 (approx.
t, 1H, J 8.4), 7.38–7.45 (m, 3H), 7.78–7.80 (m, 2H), 8.75 (d, 1H, J
7.8).
4.2.3.1. N-((1S,3R)-3-(Dimethylamino)-2,2,3-trimethylcyclopen-
tyl)-4-methylbenzene-sulfonamide 8.
The product was
white solid was obtained
¼ þ20 (c 1.0, CH2Cl2). IR (KBr,
4.2.1.4. Benzyl (1S,3R)-3-amino-2,2,3-trimethylcyclopentylcar-
recrystallized in CH2Cl2/hexane. A
bamate 5.
The product was purified by silica gel column chro-
(44%). Mp 191 °C (sublimes); ½a D25
ꢀ
matography (dichloromethane/methanol 95:5) to afford an oil
(81%). The product was used directly in the next step. 1H NMR
(400 MHz, CDCl3) d: 0.88 (s, 6H), 1.09 (s, 3H), 1.49–1.60 (m, 2H),
1.66–1.78 (m, 1H), 2.15–2.25 (m, 1H), 3.82–3.87 (m, 1H), 5.06 (d,
1H, J 12.6), 5.10 (d, 1H, J 12.6), 6.57 (d, 1H, J 9.2), 7.26–7.35 (m, 5H).
cmꢁ1): 3292, 3251, 2969, 2820, 2777, 1438, 1345, 1323, 1161,
1077, 914, 817, 667, 566, 550. 1H NMR (300 MHz, CDCl3) d: 0.84
(s, 3H), 0.89 (s, 3H), 0.95 (s, 3H), 1.38–1.47 (m, 1H), 1.61–1.80
(m, 3H), 2.16 (s, 6H), 2.42 (s, 3H), 3.35–3.38 (m, 1H), 4.60 (d, 1H,
J 10.1), 7.29 (d, 2H, J 8.2), 7.75 (d, 2H, J 8.2). 13C NMR (100 MHz,
CDCl3) d: 11.21, 17.18, 21.54, 22.43, 27.55, 36.53, 40.14, 47.25,
62.46, 66.18, 126.99, 129.63, 138.41, 143.17. GC–MS (EI) m/z:
324 (M+, 2%), 169 (6), 154 (100), 98 (21), 86 (13), 69 (7), 56 (6).
Anal. Calcd for C17H28N2O2S: C, 62.93; H, 8.70; N, 8.63; S, 9.88.
Found: C, 62.76; H, 9.08; N, 8.37; S, 10.38.
4.2.2. General procedure for the synthesis of compounds 6 and
7
To a stirred solution of diamine 1 (0.71 g, 5 mmol) in dry dichlo-
romethane (50 mL) and triethylamine (1.53 mL, 11 mmol) was
added, at 0 °C in an inert atmosphere, a solution of the sulfonyl
chloride (11 mmol) in dry dichloromethane (20 mL). The reaction
mixture was stirred overnight at room temperature. The reaction
mixture was extracted with HCl 2 M and water. The organic phase
was dried over anhydrous Na2SO4. After evaporating the solvent,
the product was purified as described below.
4.2.3.2. N-((1S,3R)-3-(Dimethylamino)-2,2,3-trimethylcyclopen-
tyl)benzamide 9.
The product was recrystallized in CH2Cl2/
hexane to give a white solid (96%). Mp 141–143 °C (lit. 135–
137 °C); ½a 2D5
ꢀ
¼ þ25 (c 1.0, CH2Cl2); [lit. +30 (c 0.6, CHCl3)].23 1H
NMR (300 MHz, CDCl3) d: 1.02 (s, 3H), 1.03 (s, 3H), 1.06 (s, 3H),
1.40–1.50 (m, 1H), 1.60–1.69 (m, 1H), 1.91–1.97 (m, 1H), 2.10–
2.23 (m, 1H), 2.25 (s, 6H), 4.47 (q, 1H, J 9.4), 6.48 (d, 1H, J 9.4),
7.41–7.50 (m, 3H), 7.75–7.78 (m, 2H).
4.2.2.1. N,N0-((1R,3S)-1,2,2-Trimethylcyclopentane-1,3-diyl)-
bis(4-methylbenzene-sulfonamide) 6.
The product was
recrystallized in CHCl3/hexane to give a white solid (35%). Mp
205–206 °C; ½a 2D5
ꢀ
¼ þ30 (c 0.5, CHCl3). IR (KBr, cmꢁ1): 3585,
4.2.3.3. Benzyl (1S,3R)-3-(dimethylamino)-2,2,3-trimethylcycl-
3501, 3246, 2973, 2590, 1455, 1318, 1303, 1160, 1134, 1094,
1079, 816, 708. 1H NMR (300 MHz, CDCl3) d: 0.79 (s, 3H), 0.88 (s,
3H), 0.92–1.04 (m, 1H), 1.09 (s, 3H), 1.47–1.57 (m, 1H), 1.64–1.77
(m, 1H), 2.05–2.15 (m, 1H), 2.41 (s, 3H), 2.43 (s, 3H), 3.25–3.34
(m, 1H), 4.49 (s, 1H), 5.50 (d, 1H, J 10.0), 7.25–7.31 (m, 4H), 7.66
(d, 2H, J 8.3), 7.74 (d, 2H, J 8.3). 13C NMR (75.5 MHz, CDCl3) d:
17.61, 21.47, 21.69, 23.06, 28.45, 33.04, 48.42, 60.81, 68.39,
76.68, 126.98, 127.01, 129.62, 129.71, 138.22, 140.06, 143.26,
143.30. LC–MS (ES+) m/z: 451 [(M+1)+, 100%], 434 (37), 375 (38),
345 (27). Anal. Calcd for C22H30N2S2O4ꢂ1/2H2O: C, 57.49; H, 6.80;
N, 6.09; S, 13.95. Found: C, 57.12; H, 6.54; N, 6.41; S, 13.40.
opentylcarbamate 10.
The product was purified by silica
gel column chromatography (diethyl ether/triethylamine 80:2) to
afford the product as an oil (55%). ½a D25
¼ þ20 (c 1.0, CH2Cl2). IR
ꢀ
(KBr, cmꢁ1): 2966, 1702, 1535, 1396, 1243, 1221, 1049, 1028,
737, 697. 1H NMR (400 MHz, CDCl3) d: 0.89 (s, 3H), 0.96 (s, 3H),
1.02 (s, 3H) 1.27–1.36 (m, 1H), 1.52–1.59 (m, 1H), 1.80–1.88 (m,
1H), 1.90–2.10 (m, 1H), 2.20 (s, 6H), 3.96 (q, 1H, J 9.6), 4.75 (d,
1H, J 9.6), 5.06 (d, 1H, J 12.4), 5.12 (d, 1H, J 12.4), 7.33–7.37 (m,
5H). 13C NMR (100 MHz, CDCl3) d: 11.14, 14.14, 17.06, 22.66,
26.85, 36.65, 40.11, 47.14, 59.59, 66.52, 66.70, 128.13, 128.16,
128.54, 136.58, 156.35. GC–MS (EI) m/z: 304 (M+, 8%), 289 (3),
154 (87), 98 (100), 91 (37), 85 (43), 56 (10). HRMS (EI+, [M]+) m/
z: calcd for (C18H28N2O2) 304.2151; found 304.2137.
4.2.2.2. N,N0-((1R,3S)-1,2,2-Trimethylcyclopentan-1,3-diyl)-bis-
((1S)-(7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methane-
sulfonamide 7.
hexane to give
The product was recrystallized in CH2Cl2/
white solid (48%). Mp 184 °C (sublimes);
4.2.4. General procedure for the synthesis of compounds 11–12
A mixture of compound 4 (2.46 g, 10 mmol), K2CO3 (5.5 g,
40 mmol) and ethyl iodide (3.23 mL, 40 mmol for compound 11
and 8.12 mL, 100 mmol for compound 12), in dry ethanol (60 mL)
was refluxed for 24 h. The resulting solution was cooled to room
temperature and the solvent evaporated under reduced pressure.
Water and dichloromethane were added and the aqueous phase
was extracted several times with dichloromethane. The combined
organic phases were dried over anhydrous Na2SO4. The products
were purified as described below.
a
½
a 2D5
ꢀ
¼ þ40 (c 1.0, CH2Cl2). IR (KBr, cmꢁ1): 3244, 2968, 1732,
1456, 1418, 1395, 1328, 1146, 1080, 1052, 1017, 594, 577. 1H
NMR (300 MHz, CDCl3) d: 0.90 (s, 3H), 0.92 (s, 3H), 1.00 (s, 3H),
1.02 (s, 3H), 1.04 (s, 3H), 1,07 (s, 3H), 1.43 (s, 3H) 1.90–2.18 (m,
12H), 2.29–2.47 (m, 6H), 2.92 (d, 1H, J 6.2), 2.97 (d, 1H, J 6.2),
3.44 (d, 1H, J 15.0), 3.55 (d, 1H, J 15.0), 3.61–3.70 (m, 1H), 5.35
(d, 1H, J 9.2), 5.71 (s, 1H). 13C NMR (100 MHz, CDCl3) d: 17.77,
19.48, 19.73, 19.93, 19.97, 22.18, 23.12, 26.21, 26.33, 26.97,
27.02, 29.72, 34.27, 42.70, 42.78, 42.84, 42.94, 48.42, 48.66,
49.03, 51.38, 53.93, 59.10, 59.37, 61.11, 67.33, 216.26, 218.07. Anal.
Calcd for C28H46N2O6S2: C, 58.92; H, 8.12; N, 4.91. Found: C, 58.75;
H, 8.27; N, 4.72.
4.2.4.1. N-((1S,3R)-3-(Ethylamino)-2,2,3-trimethylcyclopen-
tyl)benzamide 11.
The product was purified by silica gel col-
umn chromatography using diethyl ether as eluent to give a white
solid (67%). Mp 128–129 °C; ½a D25
¼ þ60 (c 1.0, CH2Cl2). IR (KBr,
ꢀ
4.2.3. General procedure for the synthesis of compounds 8–10
To 2 mL (50 mmol) of 98% formic acid, cooled in an ice bath, was
slowly added compound 2, 4 or 5 (10 mmol). To the resulting mix-
ture were added 2.5 mL (30 mmol) of a formaldehyde solution
(34%) and was stirred at reflux overnight. The solution was cooled,
cmꢁ1): 3293, 2960, 2868, 1650, 1579, 1520, 1483, 1351, 703. 1H
NMR (400 MHz, CDCl3) d: 0.95 (s, 3H), 0.99 (s, 3H), 1.08 (s, 3H),
1.16 (t, 3H, J 7.1), 1.51–1.60 (m, 2H), 1.68–1.71 (m, 1H), 1.94–
2.06 (m, 1H), 2.27–2.34 (m, 1H), 2.56–2.61 (m, 1H), 2.65–2.71
(m, 1H), 4.30 (approx. t, 1H, J 8.4), 7.39–7.51 (m, 3H), 7.78–7.80

D. Murtinho et al. / Tetrahedron: Asymmetry 21 (2010) 62–68
67
(m, 2H), 8.89 (d, 1H, J 8.4). 13C NMR (100 MHz, CDCl3) d: 16.59,
16.64, 19.02, 25.31, 30.10, 31.83, 36.33, 48.56, 59.33, 65.90,
126.80, 128.35, 130.89, 135.39, 165.31. GC–MS (EI) m/z: 274 (M+,
7%), 154 (62), 115 (45), 98 (100), 84 (28), 77 (31), 70 (22). Anal.
Calcd for C17H26N2Oꢂ1/2H2O: C, 72.05; H, 9.60; N, 9.88. Found: C,
72.45; H, 9.95; N, 9.80.
inert atmosphere, was added dropwise (+)-camphorsulfonyl chlo-
ride (0.81 g, 3.24 mmol) in dry ethanol (20 mL). The mixture was
stirred overnight at room temperature. The solvent was evapo-
rated, after which water and ethyl acetate were added, and the
reaction mixture was extracted several times with ethyl acetate.
The combined organic phases were washed with water and brine
and dried over anhydrous Na2SO4. After filtration and removal of
the solvent, the product was purified by silica gel column chroma-
tography (diethyl ether/triethylamine 80:2). The product was ob-
4.2.4.2. N-((1S,3R)-3-(Diethylamino)-2,2,3-trimethylcyclopen-
tyl)benzamide 12.
The product was purified by silica gel col-
umn chromatography using diethyl ether as eluent to give 12 as a
tained as a white solid (41%). Mp 58–60 °C; ½a D25
¼ þ55 (c 1.0,
ꢀ
white solid (27%). Mp 119–120 °C; ½a D25
ꢀ
¼ þ70 (c 1.0, CH2Cl2). IR
CH2Cl2). IR (KBr, cmꢁ1): 3219, 2966, 2879, 1729, 1477, 1454,
1372, 1328, 1152, 1116, 1069, 912, 767, 572. 1H NMR (400 MHz,
CDCl3) d: 0.89 (s, 3H), 0.91 (s, 3H), 0.99 (s, 3H), 1.03 (s, 3H), 1.08
(t, 3H, J 7.0), 1.13 (s, 3H), 1.38–1.52 (m, 3H), 1.63–1.73 (m, 2H),
1.90–1.96 (m, 2H), 2.00–2.09 (m, 2H), 2.23–2.32 (m, 1H), 2.34–
2.41 (m, 1H), 2.49–2.63 (3H), 2.88 (d, 1H, J 14.8), 3.44 (d, 1H, J
14.8); 3.38 (d, 1H, J 6.0), 8.82 (br s, 1H). 13C NMR (100 MHz, CDCl3)
d: 16.47, 17.21, 19.01, 19.86, 20.05, 24.92, 25.23, 26.96, 31.08,
32.16, 36.43, 42.74, 42.88, 47.91, 48.29, 51.02, 58.78, 63.76,
65.41, 215.53. GC–MS (EI) m/z: 384 (M+, 1%), 249 (24), 215 (7),
154 (100), 124 (7), 108 (10), 98 (38), 84 (11), 70 (11). Anal. Calcd
for C20H36N2O3Sꢂ1/2H2O: C, 61.03; H, 9.48; N, 7.12; S, 8.15. Found:
C, 60.97; H, 9.27; N, 6.99; S, 6.47.
(KBr, cmꢁ1): 3351, 2968, 1640, 1581, 1493, 1369, 1306, 1194,
1073, 1027, 691. 1H NMR (400 MHz, CDCl3) d: 1.01 (s, 3H), 1.02
(s, 3H), 1.04 (t, 6H, J 7.2), 1.04 (s, 3H), 1.42–1.51 (m, 1H), 1.61–
1.70 (m, 1H), 2.09–2.16 (m, 1H), 2.19–2.28 (m, 1H), 2.55–2.70
(m, 4H), 4.30–4.36 (m, 1H), 7.34 (d, 1H, J 8.4), 7.40–7.50 (m, 3H),
7.76–7.78 (m, 2H). 13C NMR (100 MHz, CDCl3) d: 15.18, 17.28,
19.02, 24.59, 28.77, 35.34, 43.78, 48.98, 58.69, 69.15, 126.84,
128.44, 131.10, 135.29, 166.55. GC–MS (EI) m/z: 302 (M+, 5%),
182 (55), 126 (100), 113 (44), 105 (42), 98 (50), 77 (28). HRMS
(EI+, [M]+) m/z: calcd for (C19H30N2O) 302.2358; found 302.2350.
4.2.4.3. N,N0-((1R,3S)-1,2,2-Trimethylcyclopentan-1,3-diyl)-
bis((1S,2R)-(7,7-dimethyl-2-hydroxybicyclo[2.2.1]heptan-1-
yl)methanesulfonamide 13.
To
a
solution of
7
(0.57 g,
4.2.5. General procedure for enantioselective alkylation
reactions
1 mmol) in dry THF (3 mL) at ꢁ78 °C and under an inert atmo-
sphere was added 1 M L-selectrideÒ in THF (4.5 mL) dropwise.
The reaction mixture was stirred at ꢁ78 °C for 1 h, followed by
2 h at room temperature, then cooled to 0 °C and quenched by
the successive addition of water (1 mL), ethanol (3 mL), 3 M NaOH
(4 mL). 30% aq H2O2 (3 mL) was added dropwise over a 30 min per-
iod. The aqueous phase was saturated with K2CO3 and extracted
with CH2Cl2. The organic phase was dried with anhydrous Na2SO4,
and filtered. Evaporation of the solvent followed by silica gel col-
umn chromatography using AcOEt/hexane (3:2) as eluent affords
To the chiral ligand (0.15 mmol) and benzaldehyde (1 mmol)
under an inert atmosphere, 4 mL of solvent were added. The tem-
perature of the reaction mixture was lowered to 0 °C and diethyl-
zinc (2 mmol, as a 1 M hexane solution) was added. The reaction
was stirred at the same temperature for the appropriate time. After
this time a saturated ammonium chloride solution (1 mL) followed
by 2 M HCl (1 mL) were added and the reaction mixture was ex-
tracted with diethyl ether. The organic phases were washed with
water and brine and dried over anhydrous magnesium sulfate.
The resulting solution was analyzed by GC on a chiral column in or-
der to determine the ee of the 1-phenyl-1-propanol. Conditions:
13 as a white solid (68%). Mp 162 °C (sublimes); ½a D25
¼ þ5 (c 2.0,
ꢀ
CH2Cl2). IR (KBr, cmꢁ1): 3528, 3301, 3277, 2959, 2883, 1741,
1456, 1392, 1317, 1148, 1077, 1058, 1013, 579. 1H NMR
(300 MHz, CDCl3) d: 0.82 (s, 3H), 0.93 (s, 3H), 0.99 (s, 3H), 1.02
(s, 3H), 1.07 (s, 6H), 1.41 (s, 3H), 1.65–2.01 (m, 12H), 2.10–2.65
(m, 6H), 2.84 (d, 1H, J 13.6), 2.92 (d, 1H, J 15.2), 3.22 (d, 1H, J
13.6), 3.49 (d, 1H, J 15.2), 3.53–3.59 (m, 2H), 4.06–4.11 (m, 1H),
4.88 (d, 1H, J 10.3), 5.91 (s, 1H). 13C NMR (100 MHz, CDCl3) d:
17.82, 19.40, 19.91, 19.94, 19.98, 20.56, 21.08, 22.88, 23.12,
23.14, 26.35, 27.02, 27.38, 30.15, 30.66, 33.69, 38.89, 42.71,
42.97, 44.39, 48.72, 49.28, 50.49, 53.62, 54.00, 59.46, 62.11,
68.03. Anal. Calcd for C28H50N2O6S2ꢂ1/2H2O: C, 57.60; H, 8.80; N,
4.80; S, 10.98. Found: C, 57.70; H, 8.87; N, 4.58; S, 12.97.
chiral
c-cyclodextrin capillary column (FS-Lipodex-E, 25 m, 0.25
i.d.) P = 20 psi; 1-phenyl-1-propanol: T = 100 °C, tR (R) = 15.8 min,
tR (S) = 16.3 min; 1-o-tolyl-1-propanol: T = 100 °C, tR (R) = 32.1
min, tR (S) = 35.4 min; 1-m-tolyl-1-propanol: T = 100 °C, tR (R) =
27.4 min, tR (S) = 28.1 min; 1-p-tolyl-1-propanol: T = 100 °C, tR
(R) = 27.5 min, tR (S) = 28.4 min; 1-(m-methoxyphenyl)-1-propa-
nol: T = 110 °C, tR (R) = 53.2 min, tR (S) = 54.9 min; 1-(o-chloro-
phenyl)-1-propan-ol: T = 120 °C, tR (R) = 22.3 min, tR (S) = 20.3
min; 1-(p-chlorophenyl)-1-propan-ol: T = 120 °C, tR (R) = 29.3
min, tR (S) = 30.4 min; 1-(p-nitrophenyl)-1-propanol: T = 130 °C,
tR (R) = 28.5 min, tR (S) = 27.9 min; 1-(1-naphthalenyl)-1-propanol:
T = 140 °C, tR (R) = 61.0 min, tR (S) = 63.8 min; 1-(2-naphthalenyl)-
1-propanol: T = 140 °C, tR (R) = 71.3 min, tR (S) = 72.9 min.
4.2.4.4. N-((1S,3R)-3-(Ethylamino)-2,2,3-trimethylcyclopentyl)-
1-((1S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methane-
sulfonamide 15.
To compound 11 (1.27 g, 4.6 mmol) was
Acknowledgements
added water (5 mL) and concd HCl (7 mL). The mixture was re-
fluxed overnight. After cooling to room temperature, the mixture
was evaporated and water and ethyl acetate were added to the res-
idue. Next, NaOH 1 M was added to the mixture until basic and ex-
tracted several times with ethyl acetate. The combined organic
phases were washed with water and brine and dried over anhy-
drous Na2SO4. After filtration and evaporation of the solvent, an
oil, 14, was obtained and used in the next step without further
purification (77%). 1H NMR (400 MHz, CDCl3) d: 0.78 (s, 3H), 0.80
(s, 3H), 0.97–1.01 (m, 6H), 1.19–1.28 (m, 1H), 1.44–1.52 (m, 1H),
1.61–1.68 (m, 4H), 1.93–2.02 (m, 1H), 2.42–2.52 (m, 1H), 2.56–
2.62 (m, 1H), 2.86–2.89 (m, 1H).
The authors would like to thank Chymiotechnon for financial
support. NMR data was obtained at the Nuclear Magnetic Reso-
nance Laboratory of the Coimbra Chemistry Centre (www.nmrccc.
uc.pt), Universidade de Coimbra, supported in part by Grant REEQ/
481/QUI/2006 from FCT, POCI-2010 and FEDER, Portugal.
References
1. Pu, L.; Yu, H. B. Chem. Rev. 2001, 101, 757–824.
2. Lin, G. Q.; Li, Y. M.; Chan, A. S. C. Principles and Applications of Asymmetric
Synthesis; John Wiley & Sons: New York, 2001.
3. Yus, M.; Ramón, D. J. Pure Appl. Chem. 2005, 77, 2111–2119.
4. Saravanan, P.; Bisai, A.; Baktharaman, S.; Chandrasekhar, M.; Singh, V. K.
Tetrahedron 2002, 58, 4693–4706.
To a mixture of compound 14 (0.55 g, 3.24 mmol) and K2CO3
(0.45 g, 3.24 mmol) in dry ethanol (30 mL), at 0 °C and under an

68
D. Murtinho et al. / Tetrahedron: Asymmetry 21 (2010) 62–68
5. Conti, S.; Falorni, M.; Giacomelli, G.; Soccolini, F. Tetrahedron 1992, 48, 8993–
17. Ramón, D. J.; Yus, M. Chem. Rev. 2006, 106, 2126–2208.
18. Kozakiewicz, A.; Ullrich, M.; Welniak, M.; Wojtczak, A. J. Mol. Catal. A: Chem.
2008, 286, 106–113.
19. Hui, A.; Zhang, J.; Fan, J.; Wang, Z. Tetrahedron: Asymmetry 2006, 17, 2101–
2107.
20. Uang, B. J.; Fu, I. P.; Hwang, C. D.; Chang, C. W.; Yang, C. T.; Hwang, D. R.
Tetrahedron 2004, 60, 10479–10486.
21. Soai, K.; Niwa, S. Chem. Rev. 1992, 833–856.
9000.
6. Richmond, M. L.; Seto, C. T. J. Org. Chem. 2003, 68, 7505–7508.
7. Martins, J. E. D.; Wills, M. Tetrahedron: Asymmetry 2008, 19, 1250–1255.
8. Burguete, M. I.; Escorihuela, S. V. L.; Lledós, A.; Ujaque, G. Tetrahedron 2008, 64,
9717–9724.
9. Cheng, Y. Q.; Bian, Z.; Kang, C. Q.; Guo, H. Q.; Gao, L. X. Tetrahedron: Asymmetry
2008, 19, 1572–1575.
10. Scarpi, D.; Occhiato, E. G.; Guarna, A. Tetrahedron: Asymmetry 2009, 20, 340–
350.
22. González-Sabín, J.; Gotor, V.; Rebolledo, F. Tetrahedron: Asymmetry 2006, 17,
449–454.
11. Olsson, C.; Helgesson, S.; Frejd, T. Tetrahedron: Asymmetry 2008, 19, 1484–
1493.
12. Martínez, A. G.; Vilar, E. T.; Fraile, A. G.; Cerero, S. M.; Ruiz, P. M.; Morillo, C. D.
Tetrahedron: Asymmetry 2007, 18, 742–749.
13. Martínez, A. G.; Vilar, E. T.; Fraile, A. G.; Cerero, S. M.; Maroto, B. L. Tetrahedron:
Asymmetry 2004, 15, 753–756.
23. Urabe, H.; Yamakawa, T.; Sato, F. Tetrahedron: Asymmetry 1992, 3, 5–8.
24. Yang, Z. H.; Wang, L. X.; Zhou, Z. H.; Zhou, Q. L.; Tang, C. C. Tetrahedron:
Asymmetry 2001, 12, 1579–1582.
25. Rocha Gonsalves, A. M. d’A.; Serra, M. E. S.; Murtinho, D.; Silva, V. F.; Matos
Beja, A.; Paixão, J. A.; Ramos Silva, M.; Alte da Veiga, L. J. Mol. Catal. A: Chem.
2003, 195, 1–9.
14. Rocha Gonsalves, A. M. d’A.; Serra, M. E. S.; Murtinho, D. J. Mol. Catal. A: Chem.
2006, 250, 104–113.
15. Serra, M. E. S.; Murtinho, D.; Rocha Gonsalves, A. M. d’A. Appl. Organomet. Chem.
2008, 22, 488–493.
16. Serra, M. E. S.; Murtinho, D.; Goth, A.; Abreu, P. E.; Pais, A. A. C. C.; Rocha
Gonsalves, A. M. d’A. Chirality, in press.
26. Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. Engl. 1991, 30, 49–69.
27. Paleo, M. R.; Cabeza, I.; Sardina, F. J. J. Org. Chem. 2000, 65, 2108–2113.
28. Solà, L.; Reddy, K. S.; Vidal-Ferran, A.; Moyano, A.; Pericàs, M. A.; Riera, A.;
Alvarez-Larena, A.; Piniella, J.-F. J. Org. Chem. 1998, 63, 7078–7082.
29. Vyskocil, S.; Jaracz, S.; Smrcina, M.; Stícha, M.; Hanus, V.; Polasek, M.;
Kocovsky, P. J. Org. Chem. 1998, 63, 7727–7737.