Solvent-free synthesis of racemic α-aminonitriles

Article abstract of DOI:10.1055/s-2007-965974

A very simple one-step, environmentally friendly procedure for the synthesis of α-aminonitriles from aldehydes and ketones, using trimethylsilyl cyanide in the absence of solvent, is reported. The active catalyst of this three-component (Strecker) reaction was the amine employed in the transformation. In general, aldehydes react more rapidly than ketones and give almost quantitative yields of the corresponding α-aminonitriles in less than fifteen minutes. However, only cyclic ketones afford the corresponding α-aminonitriles in excellent chemical yields under these conditions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-965974

1230
PAPER
Solvent-Free Synthesis of Racemic a-Aminonitriles
S
olvent-Free Synth
l
esis of
e
R
acemic
a
j
-Amino
a
nitriles ndro Baeza, Carmen Nájera,* José M. Sansano
Departamento de Química Orgánica and Instituto de Síntesis Orgánica (ISO), Facultad de Ciencias, Universidad de Alicante,
Apdo. 99, 03080 Alicante, Spain
Fax +34(96)5903549; E-mail: cnajera@ua.es
Received 2 February 2007
es the use of a catalyst to achieve successful results was
necessary [e.g., La(O-i-Pr)3, Sc(OTf)3, BiCl3, NiCl2,
RuCl3, Cu(OTf)2, sulfonium salts, organocatalysts,5
Lewis bases such as Et3N,5f and even montmorillonite
Abstract: A very simple one-step, environmentally friendly proce-
dure for the synthesis of a-aminonitriles from aldehydes and ke-
tones, using trimethylsilyl cyanide in the absence of solvent, is
reported. The active catalyst of this three-component (Strecker) re-
action was the amine employed in the transformation. In general, al- KSF6 or iodine7]. To the best of our knowledge there are
dehydes react more rapidly than ketones and give almost
only two processes where the presence of the catalyst
quantitative yields of the corresponding a-aminonitriles in less than
could be avoided; in both cases the solvent became cru-
fifteen minutes. However, only cyclic ketones afford the corre-
cial, acting as a catalyst.8
sponding a-aminonitriles in excellent chemical yields under these
conditions.
On the other hand, the absence of solvent in organic syn-
thesis and the employment of a small excess of reagent
make procedures simpler, saves energy, and prevents sol-
vent waste, hazards, and toxicity. In this sense a solvent-
free synthesis of a-aminonitriles employing excess carbo-
nyl compound (aldehyde or ketone) was reported in
1985.9 This reaction cannot be considered as a one-pot,
three-component process because a preformed imine was
used, formed by heating the reaction mixture at 100 °C,
and then an excess of trimethylsilyl cyanide was required
to obtain the desired nitriles after heating at 100 °C. Re-
cently, the first effective three-component Strecker reac-
tion in the absence of solvents has been reported,
however, the presence of magnesium bromide–diethyl
ether complex as a Lewis acid catalyst was also neces-
sary.10 Continuing our research in solvent-free organic
synthesis and based on the experience in an analogous re-
action for obtaining O-protected cyanohydrins,11 here we
reported a three-component Strecker reaction in the ab-
sence of solvent and catalyst, avoiding waste reagents and
workup protocols.
Key words: addition reactions, Strecker synthesis, catalysis,
aminonitriles, green chemistry, solvent-free
The Strecker reaction, which allows the synthesis of a-
aminonitriles, was discovered in 1850;1 it was the first re-
ported multicomponent reaction.2 The advantages of
Strecker-type reactions have attracted many chemists to
focus on the design of suitable asymmetric and nonracem-
ic versions of this efficient a-amino acid (a-AA) synthe-
sis.3 One of the most remarkable features of this process is
the easy accessibility of very important proteinogenic and
nonproteinogenic a-amino acid derivatives, especially
arylglycines, which are very difficult to obtain by other
preparative methods. In addition, the resulting a-aminoni-
triles, proposed as prebiotic precursors to porphyrins, cor-
rins, nicotinic acids, and nucleic acids by Eschenmoser,3b
have been employed as precursors of iminium ions in the
synthesis of natural products and heterocyclic com-
pounds. The corresponding a-metalated a-aminonitriles
(masked acyl anion equivalents)4 have been used in the
generation of multiple polyfunctional structures such as
diamines, amino alcohols, enamines, and carbonyl com-
pounds.
The trial reaction was performed with freshly distilled
benzaldehyde, aniline (1.05 equiv), and trimethylsilyl cy-
anide (1.05 equiv) (Scheme 1). The aminonitrile 1a was
obtained quantitatively after three minutes as a crude
compound with >92% purity (Table 1, entry 1). Easily re-
movable amino groups, such as 4-methoxyphenyl and
benzyl, were next introduced from the corresponding
amine, obtaining aminonitriles 1b and 1c, respectively, in
excellent yields and purity and in very short reaction times
(Table 1, entries 2 and 3). The same reaction occurred
when allylamine was used, giving 1d in quantitatively
yield in only three minutes (Table 1, entry 4). The use of
symmetrically or unsymmetrically substituted secondary
amines led to a slight increase in the reaction time
(Table 1, entries 6–8) without a decrease in the yield.
Although enantioselective processes were unknown until
the mid-1990s, the popular synthesis of racemic a-amino-
nitriles is very well known. It is generally based on the use
of preformed imines and subsequent addition of hydrogen
cyanide, trimethylsilyl cyanide, or another cyanide source
in the presence of a catalyst, although direct processes are
also known. The latter are a more attractive route than se-
quential reactions, and efforts have been focused on de-
veloping easier methods to obtain a-aminonitriles.
Numerous examples of two- or three-component reac-
tions have been reported over the last few years; in all cas-
When 4-chlorobenzaldehyde, isobutyraldehyde, 3-phe-
nylpropanal, or a,b-unsaturated aldehydes, such as (E)-
cinnamaldehyde and (E)-oct-2-enal were allowed to react
with primary amines the corresponding a-aminonitriles
SYNTHESIS 2007, No. 8, pp 1230–1234
Advanced online publication: 28.02.2007
DOI: 10.1055/s-2007-965974; Art ID: Z03107SS
© Georg Thieme Verlag Stuttgart · New York
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x
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Solvent-Free Synthesis of Racemic a-Aminonitriles
1231
NR3R4
mixture of the amine and the aldehyde was allowed to re-
act for five minutes prior to the addition of the cyanide
source in order to minimize the large amount of cyanohy-
drin obtained when all the reagents were mixed simulta-
neously. Compound 1p was only isolated in 74% yield,
probably due to the slow formation of the imine and steric
repulsion between bulky dibenzylamine and the a-
branched aldehyde (Table 1, entry 16).
O
TMSCN (1.05 equiv)
R3NHR4 (1.05 equiv)
R1
R2
R1
R2
CN
1
Scheme 1 Synthesis of a-aminonitriles 1
were obtained in high yields in short reaction times, inde-
pendently of the amine employed. (Table 1, entries 9–15,
17). A lower yield and longer reaction time were observed
when the secondary amine dibenzylamine reacted with
isobutyraldehyde (Table 1, entry 16). In this example, the
Ketones reacted very slowly with benzylamine and the re-
action was incomplete despite the longer reaction times.
In particular, acetophenone gave very poor yield of nitrile
Table 1 Synthesis of Racemic a-Aminonitriles 1
Entry
1
R1
R2
H
NR3R4
Time (min)
Product
1a
1b
1c
Yielda (%)
99
Ph
NHPh
3
7
2
Ph
H
NH(C6H4-4-OMe)
NHBn
99
3
Ph
H
3
99
4
Ph
H
NHCH2CH=CH2
NHCHPh2
NBn2
3
1d
1e
99
5
Ph
H
3
99
6
Ph
H
10
10
5
1f
98
7
Ph
H
NMeBn
pyrrolidin-1-yl
NHBn
1g
1h
1i
95
8
Ph
H
98
9
4-ClC6H4
H
5
93b
98
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
(E)-CH=CHPh
(E)-CH=CHPh
(E)-CH=CHPh
(E)-CH=CH(CH2)4Me
i-Pr
H
NHPh
5
1j
H
NHBn
3
1k
1l
99
H
NBn2
12
5
90
H
NHBn
1m
1n
1o
1p
1q
1r
95
H
NHPh
3
99
i-Pr
H
NHBn
3
99
i-Pr
H
NBn2
15
10
35
20
20
18
13
12
9
74b,c
98
CH2CH2Ph
Ph
H
NHBn
Me
Me
Me
Et
NHBn
21b,c,d
–
CH=CH2
NHBn
1s
CH=CHPh
Et
NHBn
1t
2b,c,d
77b,c,d
98b,d
97
NHBn
1u
1v
1we
1x
1y
–(CH2)4–
NHBn
–(CH2)2C(t-Bu)(CH2)2–
–(CH2)2O(CH2)2–
–(CH2)2S(CH2)2–
NHBn
NHBn
99b,d
98b,c,d
NHBn
11
a Isolated crude compounds (>92% purity by 1H NMR).
b Carbonyl compound and amine were allowed to react for 5 min before TMSCN was added.
c The corresponding cyanohydrin was also obtained.
d Amine (1.3 equiv) and TMSCN (1.2 equiv) were added.
e Obtained as a >95:5 cis/trans mixture of diastereomers.
Synthesis 2007, No. 8, 1230–1234 © Thieme Stuttgart · New York

1232
A. Baeza et al.
PAPER
1r (Table 1, entry 18) and reactions of a,b-unsaturated ke- In order to avoid the use of hazardous trimethylsilyl cya-
tones failed under these reaction conditions. In the case of nide, we thought it might be possible to replace it with
methyl vinyl ketone (Table 1, entry 19), Michael-type ad- acetone cyanohydrin (1.05 equiv) in the reaction of ben-
dition products of the amine to the conjugated system and zaldehyde and benzylamine (1.05 equiv). Under these
1
unidentified products were detected by H NMR of the new reaction conditions the corresponding a-aminonitrile
crude material. In contrast, when 4-phenylbut-3-en-2-one 1a was obtained after 20 minutes in 91% conversion (de-
1
was used, the cyanohydrin product was obtained as the termined by H NMR), unfortunately the crude mixture
major product (Table 1, entry 20). Nonaromatic acyclic was not very clean and some unidentified products were
and cyclic aliphatic ketones are more appropriate sub- observed.
strates for this solvent-free Strecker reaction, thus pentan-
3-one gave the desired nitrile 1u in 77% yield (Table 1,
entry 21) and the corresponding cyanohydrin in 23%
yield. Cyclopentanone and 4-tert-butylcyclohexanone
Other cyanide sources such as diethyl cyanophosphonate,
methyl cyanoformate, or benzoyl cyanide were also uti-
lized instead of trimethylsilyl cyanide as cyanide source in
the Strecker-type reaction of benzaldehyde and benzy-
gave excellent yields of 1v and 1w, respectively, in 12–13
lamine. In these reactions neither a-aminonitriles (free
minutes (Table 1, entries 22, 23). Heterocyclic aliphatic
base or N-protected) nor cyanohydrin products were ob-
ketones, such as tetrahydro-4H-pyran-4-one and tetrahy-
tained. Presumably a large amount of amine reacts with
the cyanide source, causing total decomposition, which
dro-4H-thiopyran-4-one, were used and gave the corre-
sponding Strecker adducts 1x and 1y in excellent yields
and in short reaction times (Table 1, entries 24, 25). The
reactive ketones depicted in Table 1 (entries 21–25) react-
ed with trimethylsilyl cyanide (1.2 equiv) and benzyl-
amine (1.3 equiv) and the aldehyde/benzylamine mixture
was always stirred for five minutes before the addition of
trimethylsilyl cyanide, except for the 4-tert-butylcyclo-
hexanone, which reacted under the same reaction condi-
tions as the aldehydes. In the latter case, the product 1w
was obtained as a >95:5 cis/trans mixture of diastereo-
mers [by chemical shifts and NMR experiments (NOE-
SY)] (Table 1, entry 23, and Scheme 2).
was observed by 1H NMR and 13C NMR analysis. The ad-
dition of potassium cyanide to benzaldehyde in presence
of ammonium chloride or ammonium hydroxide to give
the corresponding free a-aminonitrile was also assessed,
leading in both cases to a complex mixture of products as
occurred under the published reaction conditions.9
The presence of hydrogen cyanide in commercial trimeth-
ylsilyl cyanide, as we have already demonstrated by 13C
NMR in previous work,11,12 seems to be crucial in the re-
action pathway since it could activate the carbonyl com-
pound, acting as a Brønsted acid, favoring imine
1
formation. This was affirmed by two simultaneous H
NMR experiments performed in deuterochloroform. In
the first, equimolecular amounts of benzaldehyde and
benzylamine were mixed, and in the second the same
components and trimethylsilyl cyanide were allowed to
react. In the first and second experiments, it was observed
that the imine formation and the generation of a-aminoni-
trile, respectively, took place in very short reaction times.
It is noteworthy that in the second experiment a small pro-
portion of cyanohydrin compound was detected as conse-
quence of the dilution in deuterochloroform, which makes
the process slower, favoring the irreversible side reaction.
In addition, the amine (in very slight excess) could acti-
vate hydrogen cyanide, by formation of an ammonium
salt, and increase the reaction rate.11 On the other hand,
the high proportion of cyanohydrin obtained in some cas-
es could be explained because the amine itself catalyzes
the process,11 which is favored when the imine formation
is slow as described above.
NHBn
CN
tBu
TMSCN2
O
cis-1w
(1.05 equiv)
tBu
CN
BnNH2
(1.05 equiv)
NHBn
tBu
trans-1w
Scheme 2 Synthesis of the a-aminonitriles derived from 4-tert-
butylcyclohexanone
The reaction using aromatic ketones and benzo-con-
densed cyclic ketones, such as indanone and a-tetralone,
gave cyanohydrins exclusively under the reaction condi-
tions described. For these unsuccessful examples we de-
cided to use the conditions that used a sequential reaction
by mixing the ketone and the amine at 100 °C for one
minute followed by reaction of the resulting mixture with
trimethylsilyl cyanide at 100 °C for 15 minutes.9 Thus, In accordance with these observations and the reactivity
acetophenone gave a 71% of 1r and a-tetralone afforded observed, we can conclude that new conditions for the
a-aminonitrile 1z (Figure 1) in 69% yield (both obtained synthesis of a-aminonitriles from aldehydes and aliphatic
after column chromatography).
ketones have been developed. This environmentally
friendly, one-pot reaction proceeds at room temperature,
without solvent, with the minimum amounts of reagents,
and avoiding the typical workup; the crude reaction prod-
uct did not require any further purification. This proce-
dure, which reduces the amount of the cyanide reagents to
the minimum and proceeds under mild conditions without
PhHN
CN
1z
Figure 1
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PAPER
Solvent-Free Synthesis of Racemic a-Aminonitriles
1233
MS (EI): m/z (%) = 173 ([M – HCN]+, 41), 172 (19), 91 (100).
HRMS: m/z [M – HCN]+ calcd for C12H15N: 173.1204; found:
the presence of a catalyst, could potentially be applied at
an industrial level.
173.1199.
Spectroscopic and physical data for know compounds corresponded
to those given in the literature: 1a,6 1b,13 1c,6 1d,14 1e,15 1f,5a 1g,5a
1h,5g 1i,8b 1j,6 1k,16 1l,5a 1n,8a 1o,8b 1p,17 1r,18 and 1u.19 All new
compounds were fully characterized.
1-(Benzylamino)-4-tert-butylcyclohexanecarbonitrile (1w)
Colorless prisms; mp 81–82 °C (hexane); Rf = 0.70 (n-hexane–
EtOAc, 4:1).
IR (KBr): 3316, 2252, 1479, 1467, 1454 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.89 [s, 9 H, C(CH3)3], 1.25–1.47
(m, 4 H, CH2), 1.52–1.63 (br m, 2 H, CH, NH), 1.83, 2.16 (2 m,
2 × 2 H, CH2), 3.93 (s, 2 H, CH2Ph), 7.29–7.38 (m, 5 H, ArH).
13C NMR (75 MHz, CDCl3): d = 23.8 (CH2), 27.5 [C(CH3)3], 32.3
[C(CH3)3], 36.7 (CH2), 47.3 (CH), 48.8 (CH2Ph), 58.1 (CCN),
122.0 (CN), 127.4, 128.4, 128.6, 139.4 (ArC).
MS (EI): m/z (%) = 243 ([M – HCN]+, 26), 228 (48), 186 (18), 158
(18), 91 (100).
HRMS: m/z [M – HCN]+ calcd for C17H25N: 243.1987; found:
243.1986.
a-Aminonitriles 1; General Procedure
The corresponding amine (0.525 mmol) and TMSCN (0.525 mmol)
were added sequentially to the carbonyl compound (0.5 mmol) (in
some cases, as indicated in Table 1, the amine and the carbonyl
compound were allowed to react for 5 min before addition of
TMSCN). The mixture was stirred until the reaction was judged to
be complete. The mixture was evaporated to remove excess
TMSCN (Caution! hazardous compound!) and the final pure a-ami-
nonitriles were obtained either by distillation or by crystallization
(hexanes). Only when crude yields were lower than 90% was puri-
fication by flash chromatography necessary to afford the pure com-
pounds (see Table 1).
Anal. Calcd for C18H26N2: C, 80.0; H, 9.7; N, 10.4. Found: C, 79.6;
H, 9.4; N, 10.2.
(E)-2-(Benzylamino)non-3-enenitrile (1m)
Yellow sticky oil; Rf = 0.68 (n-hexane–EtOAc, 4:1).
IR (KBr): 3327, 2254, 1653, 1454, 1381 cm–1.
4-(Benzylamino)tetrahydro-2H-pyran-4-carbonitrile (1x)
White solid; mp 71–73 °C (hexane); Rf = 0.22 (n-hexane–EtOAc,
4:1).
IR (KBr): 3302, 2221, 1477, 1449, 1431 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.60 (br s, 1 H, NH), 1.83, 2.04 (2
m, 2 × 2 H, 2 CH2CCN), 3.70, 3.99 (2 m, 2 × 2 H, 2 CH2O), 3.93 (s,
2 H, CH2NH), 7.26–7.40 (m, 5 H, ArH).
13C NMR (75 MHz, CDCl3): d = 35.9 (CH2CCN), 48.3 (CH2NH),
55.0 (CCN), 63.8 (CH2O), 121.1 (CN), 127.5, 128.3, 128.6, 138.8
(ArC).
1H NMR (300 MHz, CDCl3): d = 0.88 (t, J = 6.7 Hz, 3 H, CH3),
1.24–1.41 (m, 6 H, 3 CH2), 2.07 (m, 2 H, CH2CH), 3.01 (br s, 1 H,
NH), 3.83, 3.99 (2 d, J = 12.9 Hz, 2 × 1 H, CH2Ph), 4.15 (d, J = 5.2
Hz, 1 H, CHCN), 5.50 (dd, J = 5.2, 15.5 Hz, 1 H, CHCHCN), 6.04
(m, 1 H, CH=CHCHCN), 7.26–7.37 (m, 5 H, ArH).
13C NMR (75 MHz, CDCl3): d = 13.9 (CH3), 22.4, 28.3, 31.2, 31.9
(4 CH2), 46.0 (CHCN), 51.0 (CH2Ph), 118.5 (CN), 123.1 (CHCH-
CN), 127.5, 128.3, 128.5, 138.2 (ArC), 136.2 (CH=CHCHCN).
MS (EI): m/z (%) = 215 ([M – HCN]+, 5), 202 (19), 188 (65), 175
(21), 160 (32), 132 (31), 131 (22), 130 (27), 118 (59), 117 (54), 107
(19), 106 (27), 92 (24), 91 (100).
MS (DIP-EI): m/z (%) = 216 ([M]+, 5), 157 (9), 106 (14), 91 (100).
HRMS: m/z [M – HCN]+ calcd for C12H15NO: 189.1154; found:
HRMS: m/z [M]+ calcd for C16H22N2: 242.1783; found: 242.1777.
189.1126.
Anal. Calcd for C13H16N2O: C, 72.2; H, 7.5; N, 13.0. Found: C,
72.2; H, 7.6; N, 12.8.
2-(Benzylamino)-4-phenylbutanenitrile (1q)
Colorless sticky oil; Rf = 0.53 (n-hexane–EtOAc, 4:1).
IR (KBr): 3318, 2225, 1736, 1496, 1454, 1244 cm–1.
4-(Benzylamino)tetrahydro-2H-thiopyran-4-carbonitrile (1y)
Colorless prisms; mp 76–77 °C (hexane); Rf = 0.38 (n-hexane–
EtOAc, 4:1).
IR (KBr): 3309, 2217, 1475, 1453, 1429 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.71 (br s, 1 H, NH), 1.98, 2.34 (2
m, 2 × 2 H, 2 CH2CCN), 2.81 (m, 4 H, 2 CH2O), 3.91 (s, 2 H,
CH2NH), 7.26–7.39 (m, 5 H, ArH).
13C NMR (75 MHz, CDCl3): d = 24.2 (CH2S), 36.7 (CH2CCN),
48.2 (CH2NH), 56.7 (CCN), 121.0 (CN), 127.5, 128.3, 128.6, 138.8
(ArC).
1H NMR (300 MHz, CDCl3): d = 1.66 (br s, 1 H, NH), 2.06 (q,
J = 7.6 Hz, 2 H, CH2CH), 2.82 (m, 2 H, CH2CH2Ph), 3.45 (t, J = 7.2
Hz, 1 H, CHCN), 3.78, 4.04 (2 d, J = 12.5 Hz, 2 × 1 H, HNCH2Ph),
7.13–7.33 (m, 10 H, ArH).
13C NMR (75 MHz, CDCl3): d = 31.6 (CH2CH2Ph), 35.0 (CH2CH),
48.8 (CHCN), 51.6 (HN-CH2Ph), 120.1 (CN), 126.3, 127.5, 128.3,
128.4, 128.5, 128.6, 138.3, 139.9 (ArC).
MS (EI): m/z (%) = 223 ([M – HCN]+, 36), 132 (77), 105 (19), 91
(100).
HRMS: m/z [M – HCN]+ calcd for C16H17N: 223.1361; found:
243.1355.
MS (EI): m/z (%) = 205 ([M – HCN]+, 23), 177 (17), 91 (100).
HRMS: m/z [M – HCN]+ calcd for C12H15NS: 205.0925; found:
205.0951.
1-(Benzylamino)cyclopentanecarbonitrile (1v)
Colorless solid; mp 43–44 °C (hexane); Rf = 0.59 (n-hexane–
EtOAc, 4:1).
Anal. Calcd for C13H16N2S: C, 67.2; H, 6.9; N, 12.1; S, 13.8. Found:
C, 67.6; H, 6.8; N, 12.0; S, 13.5.
IR (KBr): 3316, 2219, 1496, 1454 cm–1.
1-(Benzylamino)-1,2,3,4-tetrahydronaphthalene-1-carbonitrile
1H NMR (300 MHz, CDCl3): d = 1.64 (br s, 1 H, NH), 1.81–1.90
(m, 6 H, CH2), 2.08–2.17 (m, 2 H, CH2), 3.88 (s, 2 H, CH2Ph), 7.25–
7.37 (m, 5 H, ArH).
(1z)
Brown sticky oil; Rf = 0.43 (n-hexane–EtOAc, 4:1).
IR (KBr): 3314, 2221, 1494, 1453 cm–1.
13C NMR (75 MHz, CDCl3): d = 23.5, 38.9 (2 CH2), 50.1 (CH2Ph),
61.2 (CCN), 122.9 (CN), 127.3, 128.3, 128.5, 139.2 (ArC).
Synthesis 2007, No. 8, 1230–1234 © Thieme Stuttgart · New York

1234
A. Baeza et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 1.97–2.03 (m, 2 H, CH2), 2.16 (br
s, 1 H, NH), 2.65–2.69 (m, 2 H, CH2), 2.83–2.86 (s, 2 H, CH2), 4.72
(s, 2 H, CH2Ph), 7.12 (m, 1 H, ArH), 7.25–7.46 (m, 9 H, ArH).
13C NMR (75 MHz, CDCl3): d = 18.6, 28.2, 28.5 (3 CH2), 49.1
(CH2Ph), 57.7 (CCN), 122.0 (CN), 127.3, 128.3, 128.5, 139.2
(ArC).
MS (EI): m/z (%) = 235 ([M – HCN]+, 83), 234 (100), 91 (75).
HRMS: m/z [M – HCN]+ calcd for C17H17N: 235.1361; found:
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Acknowledgment
This work has been supported by the DGES of the Spanish Ministe-
rio de Educación y Cultura (MEC) (CTQ 2004-00808/BQU) and
Generalitat Valenciana (CTIOIB/2002/320 and GRUPOS03/134
and GV05/144) and by the University of Alicante. A. Baeza thanks
Generalitat Valenciana for a pre-doctoral fellowship.
(11) (a) Baeza, A.; Nájera, C.; Sansano, J. M. ARKIVOC 2005,
(ix), 353; www.arkat.usa.org. (b) Baeza, A.; Nájera, C.;
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Synthesis 2007, No. 8, 1230–1234 © Thieme Stuttgart · New York