Microwave-assisted conversion of carbonyl compounds into formylated secondary amines: New contribution to the Leuckart reaction mechanism in N-methylformamide

Article abstract of DOI:10.1016/j.tetlet.2013.01.097

The reductive amination of several carbonyl compounds (Leuckart reaction) has been performed using N-methylformamide and microwave technology. Under these conditions, a new mechanism is proposed via the initial formation of an imine, followed by reduction

Full text of DOI:10.1016/j.tetlet.2013.01.097

Tetrahedron Letters 54 (2013) 1835–1838
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Microwave-assisted conversion of carbonyl compounds into formylated
secondary amines: new contribution to the Leuckart reaction mechanism
in N-methylformamide
⇑
⇑
Fructuoso Barba , Javier Recio, Belen Batanero
Department of Organic Chemistry, University of Alcalá, 28871 Alcalá de Henares, Madrid, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
The reductive amination of several carbonyl compounds (Leuckart reaction) has been performed using N-
methylformamide and microwave technology. Under these conditions, a new mechanism is proposed via
the initial formation of an imine, followed by reduction to the amine by ‘in situ’ generated formic acid,
and further formylation of the amine. Using this methodology, the formyl derivatives of several second-
ary amines were obtained in good to excellent yields.
Received 3 December 2012
Revised 17 January 2013
Accepted 23 January 2013
Available online 31 January 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Reductive amination
Leuckart reaction
Microwave technology
Redox process
Formylation of amines
The Leuckart reaction is a process commonly used for the
reductive amination of aldehydes and ketones.1 When formamide
is used in the reaction, the N-formyl derivatives of the amines
are obtained, instead of the free amines.2
Formamides are regarded as useful intermediates in organic
and medicinal chemistry.3,4 In fact they have found many impor-
tant applications in organic synthesis, in reactions such as allyla-
tions,5 hydrosilylations,6 the Vilsmeier reaction,7 etc.
amines. The second objection is the proposed transfer of hydride
proceeding from the formic acid formed in the reaction.
In recent years, microwave-assisted organic synthesis (MAOS)
has became a very rapidly developing area of chemistry, as it pro-
vides a number of advantages over the standard heating tech-
niques, such as cleaner reactions, improved product yields,
shorter reaction times, easy work-ups and solvent-free reaction
conditions.10
A single universal mechanism for the Leuckart reaction has not
been established yet. There seems to be a general acceptance that
the mechanism involves an initial addition of ammonium formate,
formamide or substituted formamide to the carbonyl function de-
rived from an aldehyde or ketone, to yield an unstable carbinol-
amine intermediate, which then suffers either reduction,
dehydration to an imine, or formylation to the formic ester.8 The
following step involves a hydrogen transfer to the substrate via hy-
dride from the formic acid generated or added to the reaction.9
However, these mechanistic proposals have some uncertainties
that make further experimental considerations regarding the Leu-
ckart reaction process welcome. The first objection to the mecha-
nistic proposals is the acceptance of formamide as the
nucleophile toward the carbonyl group of the substrate, even when
it is well known the low nucleophilicity of amides compared to
In the literature, there are several examples of reactions using
MAOS via decomposition of formamides.11 For example, the Leuck-
art reaction employing formamide and a series of ketones has been
previously reported12 to proceed with excellent yields by micro-
wave irradiation.
In the present Letter, a reasonable and novel pathway to the
Leuckart reaction is postulated without the assumption of the pre-
viously mentioned inconveniences. This pathway is supported by
recent experimental results employing N-methylformamide and
MAOS. As far as we know, only one paper has been published to
date concerning the Leuckart reaction between N-methylforma-
mide and ketones.13
Results and discussion
The amine formylation is a well known reaction, both in the
presence14 and in the absence15 of catalyst. We have carried out
the microwave (MW) heating of benzylamine in formic acid for
10 min, in the absence of catalyst, and quantitative formylated
amine was obtained. On the other hand, when this MW-reaction
⇑
Corresponding authors. Tel.: +34 91 8854617/2517; fax: +34 91 8854686.
E-mail addresses: fructuoso.barba@uah.es (F. Barba), belen.batanero@uah.es (B.
Batanero).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.01.097

1836
F. Barba et al. / Tetrahedron Letters 54 (2013) 1835–1838
Table 2
is performed with the Schiff base: PhAN@CHAPh, the expected N-
benzyl-N-phenylformamide was formed as the main product.
These experimental results suggested the need to reconsider the
Leuckart reaction mechanism. For this purpose, we run the micro-
wave assisted heating of different carbonyl derivatives in N-meth-
ylformamide (instead of formamide as the classical formylating
agent), the reasons for this will be discussed later.
Obtained yields of 3 and 4 by MW radiation in N-methylformamide
1
Yield of 3 (%)
Yield of 4 (%)
g: Phenanthrene 9,10-dione
h: Benzil
i: Furil
97
5
17
2
6
55
The microwave-assisted Leuckart reaction in N-methylforma-
mide of a series of aldehydes and ketones (1) has thus been per-
formed (Scheme 1) to obtain the reductive formylation products
(2) in good yields, as indicated in Table 1.
and the hydrogen atom formed in the formic acid oxidation are
needed to be close to each other for the coupling to occur. Last step
takes place as indicated in bibliography and mentioned above in
the beginning of the Discussion.
In view of the obtained results, our proposed first step for the
Leuckart reaction is as follows: N-methylformamide, under our
experimental microwave-assisted heating (see Experimental sec-
tion), suffers a heterolytic cleavage to MeANHÀ and HACO+ which,
immediately evolves to methylamine and formic acid by reaction
with the water of hygroscopic N-methylformamide (not previously
dried). Generation of ammonia via thermal decomposition of form-
amide has already been studied under microwave conditions to
provide an efficient tool for the synthesis of nitrogen-containing
heterocycles.16
The obtained methylamine then reacts ‘in situ’ with the car-
bonyl substrates (1) to form the corresponding imines (detected
in all cases). In contrast to the formamide reaction, where ammo-
nia was produced, now the methylated imine is stable enough to
be detected as a minor product. Once these imines are formed they
suffer a redox process by reaction with the generated formic acid
to give the secondary amine through a plausible radical pathway,
as indicated in Scheme 2. At this point, the imine is reduced to
its radical anion at the same time that easy oxidation of formic
acid occurs. It should be noted that anodic oxidation of formic
acid17 at nickel oxide nanoparticle modified electrode is only
+0.25 V (vs Ag/Ag+).
There is enough evidence in the literature to support this mech-
anism: (1) Carbon dioxide formation is indicative of the participa-
tion of formic acid as the reducing agent.18 (2) It has been found,
investigating the reduction of enamines by DACOOH, that hydro-
gen (deuterium) bonded to the carbon of the formic acid suffers
association with the
a
-carbon of the enamine.19 (3) It was found
that both the evolution of carbon dioxide and the formation of
the reduction product occur in equivalent quantities.20 (4) The rate
of reaction is known to decrease by the addition of hydroquinone.
This fact indicates that reduction takes place according to a free-
radical mechanism.21
Exceptions to this microwave-assisted Leuckart reaction were
observed with substrates such as phenanthrene 9,10-dione (1g),
benzil (1h) or furil (1i). In these cases, the corresponding oxazoles
(3) and N-methyl-imidazoles (4) were formed instead of the dou-
ble N-formylated amines. The obtained yields are summarized in
Table 2, and the formation of these heterocycles can be rational-
ized, as indicated in Scheme 3, through the initial attack of methyl-
amine to the carbonyl group to give the imine, and subsequent
cyclization catalyzed by the ‘in situ’ generated formic acid.
Conclusion
It is important to remark that electrons never ‘jump’ within the
reaction media. An electron-transfer reaction between two com-
pounds needs a previous and indispensable adsorption of both
molecules. For this reason, the radical anion of the Schiff base
Several secondary amines, obtained by reduction of certain car-
bonyl imines, were formylated in good to excellent yields employ-
ing microwave methodology and N-methylformamide as the
solvent. Novel experimental results have prompted us to recon-
sider the Leuckart reaction mechanism and to propose a feasible
alternative pathway. On the other hand, when the reaction condi-
tions are applied to 1,2-diketones the corresponding oxazoles (3)
and imidazoles (4) are obtained.
Me
R
O
CHO
R´
microwave
N
H-CO-NHMe
+
R
R´
1
2
Scheme 1. Microwave-assisted Leuckart reaction in N-methylformamide.
Experimental section
The microwave reactions were performed in a Biotage MW
apparatus model Initiator 2.5 at a constant temperature (variable
pressure) of 250 °C for 10 min. Mass spectra (EI, ionizing voltage
70 eV) were registered using a Thermofisher Scientific ITQ900
equipped with a Thermofisher Trace GC-Ultra. IR spectra were ob-
tained, as dispersions in KBr or NaCl, on a Perkin–Elmer Model 583
spectrophotometer. 1H NMR and 13C NMR (300 and 75.4 MHz
respectively) spectra were recorded on a Varian Unity 300 appara-
tus with deuterochloroform as an internal standard. The chemical
shifts are given in ppm. Melting points were determined on a Reic-
hert Thermovar microhot stage apparatus. Elemental analyses
were performed on a Leco CHNS Model 932 analyzer.
Table 1
Obtained yields of 2 by MW radiation in N-methylformamide.
1
Yield of 2 (%)
a: Cyclohexanone
b: Acetophenone
c: Propiophenone
d: 2-Acetylpyridine
e: Thiophene-2-carbaldehyde
f: Benzaldehyde
90
85
88
85
92
90
Me
Me
R
N
+1e-
-1e-
N
General procedure
Me
NH
R
R´
R´
+
CO2
O
A solution of carbonyl compound 1 (1 mmol) in 10 mL of N-
methylformamide (purchased from Aldrich, 99%) was heated at
250 °C under stirring by microwave radiation for ten minutes
and subsequently analyzed by GC–MS and TLC. The residue was
extracted with ether (3Â)/H2O. The organic phase was dried over
R
R´
H. + CO2 + H+
H
OH
Scheme 2. Redox process by reaction of an imine with generated formic acid to
give a secondary amine.

F. Barba et al. / Tetrahedron Letters 54 (2013) 1835–1838
1837
CH2
H
CH3
HO
N
O
O
N
O
CH3NH2
CH2
HCOOH
catalysis
-H+
N
HO
O
1
2 CH3NH2
CH3
N
CH3
aromat.
NH
O
N
N
3
HCOOH(catalyst)
CH3
CH3
H3C
H3C
CH2
N
H3C
N
N
NH
HN
N
N
N
H
aromat.
-H+
Scheme 3. Reaction pathway to explain the formation of Oxazoles (3) and Imidazoles (4).
4
MgSO4 and concentrated by evaporation under reduced pressure.
The resulting residue was chromatographed on silica gel 60 (35–
70 mesh) in a (28 Â 2.5 cm) column, using a mixture CH2Cl2/EtOH
(15:1) as the eluent. The experimental physical and spectroscopical
properties of the new obtained products are summarized below.
Known product properties were coincident with the previously de-
scribed data.
(39), 77 (11). Anal. Calcd for C11H15NO: C, 74.58; H, 8.47; N, 7.91.
Found: C, 74.43; H, 8.12; N, 8.13.
N-Methyl-N-(1-(pyridine-2-yl)ethyl) formamide (2d)
Oil IR (KBr) m
/cmÀ1 = 3052, 2978, 1668, 1588, 1434, 1087, 751.
1H NMR (300 MHz; CDCl3) d (ppm): 1.62 (d, J = 7.0 Hz, 2H) (dupli-
cated signal: 1.72 (d, J = 7.0 Hz, 2H)), 2.75 (s, 3H) (duplicated sig-
nal: 2.84 (s, 3H)), 4.85 (q, J = 7.0 Hz, 1H), (duplicated signal: 5.8
(d, J = 7.0 Hz, 2H)), 7.2–7.4 (m, 2H), 7.6–7.8 (m, 1H), 8.4 (s, 1H).
8.5–8.6 (m, 1H). 13C NMR (75.4 MHz, CDCl3) d: 15.1, 17.1, 26.5,
29.7, 50.8, 58.5, 121.1, 122.4, 122.6, 122.7, 136.7, 136.8, 149.0,
149.4, 158.9, 162.6, 162.8. MS m/z (relative intensity) CI: 205
(M++41, 7), 193 (M++29, 20), 165 (M++1, 58), 137 (100), 106 (58).
Anal. Calcd for C9H12N2O: C, 65.85; H, 7.32; N, 17.08. Found: C,
66.21; H, 7.01; N, 16.79.
N-Benzyl-N-phenylformamide
Mp 44–45 °C [Lit.14 45–46 °C]. 13C NMR (75.4 MHz, CDCl3) d:
48.9, 54.2, 124.1, 126.7, 127.0, 127.5, 127.8, 128.7, 129.6, 136.6,
140.9, 159.4, 162.5. MS m/z (relative intensity) EI: 211 (M+, 80),
210 (M+À1, 21), 194 (6), 166 (9), 91 (100), 77 (7), 65 (24).
N-Cyclohexyl-N-methylformamide (2a)
Oil [Lit.22 Bp 250 °C]. IR (KBr)
m
/cmÀ1 = 2932, 2856, 1668, 1452,
N-Methyl-N-((thiophen-2-yl)methyl)formamide (2e)
1409, 1068, 895, 724. 1H NMR (300 MHz; CDCl3) d (ppm): 1.0–1.8
(m, 10H), 2.72 (s, 3H) (duplicated signal: 2.76 (s, 3H)), 3.1–3.3 (m,
1H), 8.07 (s, 1H). 13C NMR (75.4 MHz, CDCl3) d: 25.4, 25.5, 29.5,
31.3, 50.8, 58.2, 162.4. MS m/z (relative intensity) EI: 141 (M+,
60), 112 (20), 98 (90), 84 (19), 70 (83), 60 (100). IQ: 182 (M++41,
6), 170 (M++29, 20), 142 (M++1, 100), 60 (36).
Oil IR (KBr) m
/cmÀ1 = 3092, 2962, 1672, 1397, 1260, 1079, 713.
1H NMR (300 MHz; CDCl3) d (ppm): 2.58 (s, 3H) (duplicated signal:
2.65 (s, 3H)), 4.31 (s, 2H) (duplicated signal: 4.41 (s, 2H)), 6.6–6.8
(m, 2H), 6.9–7.1 (m, 1H), 7.81 (s, 1H) (duplicated signal: 8.0 (s,
1H)). 13C NMR (75.4 MHz, CDCl3) d: 29.1, 33.7, 42.1, 48.1, 125.4,
125.6, 126.3, 126.5, 126.8, 126.9, 138.0, 138.7, 161.9, 162.1. MS
m/z (relative intensity) EI: 155(M+, 50), 126 (27), 112 (19), 98
(53), 97 (100), 85 (32), 53 (21). Anal. Calcd for C7H9NOS: C,
54.19; H, 5.81; N, 9.03. Found: C, 53.82; H, 5.61; N, 9.07.
N-Methyl-N-(1-phenylethyl)formamide23 (2b)
Oil IR (KBr) m
/cmÀ1 = 3064, 2976, 1669, 1405, 1316, 1081, 913,
737. 1H NMR (300 MHz; CDCl3) d (ppm): 1.5 (d, J = 7.2 Hz, 3H)
(duplicated signal: 1.62 (d, J = 6.9 Hz, 3H)), 2.6 (s, 3H), 4.58 (q,
J = 7.2 Hz, 1H) (duplicated signal: 5.6 (q, J = 6.9 Hz, 1H), 7.2–7.4
(m, 5H), 8.1 (s, 1H) (duplicated signal: 8.35 (s, 1H)). 13C NMR
(75.4 MHz, CDCl3) d: 15.3, 17.9, 26.0, 29.5, 48.7, 56.5, 126.7,
127.3, 127.5, 127.8, 128.5, 128.7, 139.4, 139.5, 162.4, 162.6. MS
m/z (relative intensity) EI: 163 (M+, 29), 162 (M+À1, 100), 120
(20), 105 (19), 77 (18), 51 (11).
N-Benzyl-N-methylformamide (2f)
Oil [Lit.24 Bp (14 Torr) 124–126 °C]. MS m/z (relative intensity)
EI: 149 (M+, 55), 148 (M+À1, 100), 134 (12), 121 (13), 106 (39),
91 (82), 79 (64), 65 (27).
Phenanthro[9,10-d][1,3]oxazole (3g)
N-Methyl-N-(1-phenylpropyl)formamide (2c)
Mp 136–138 °C [Lit.25 137–139 °C]. MS m/z (relative intensity)
EI: 219 (M+, 100), 192 (22), 190 (25), 163 (36), 82 (5).
Oil IR (KBr) m
/cmÀ1 = 3058, 2970, 1674, 1409, 1089, 929, 763. 1H
NMR (300 MHz; CDCl3) d (ppm): 0.92 (m, 3H), 2.0 (m, 2H), 2.6 (m,
3H), 4.4 (m, 1H) (duplicated signal: 5.5 (m)), 7.1–7.3 (m, 5H), 8.1 (s,
1H) (duplicated signal: 8.3 (s)). 13C NMR (75.4 MHz, CDCl3) d: 10.7,
10.9, 21.7, 23.0, 25.5, 29.4, 54.9, 63.0, 127.0, 127.5, 127.8, 128.4,
128.6, 129.7, 138.5, 162.7, 163.0. MS m/z (relative intensity) EI:
177 (M+, 18), 176 (M+À1, 28), 148 (100), 121 (69), 107 (22), 91
1-Methylphenanthrimidazole (4g)
Mp 192–194 °C [Lit.26 196 °C]. IR (KBr)
m
/cmÀ1 = 3051, 2953,
2852, 1633, 1612, 1529, 1456, 1377, 1079, 1018, 750, 722. 1H
NMR (300 MHz; CDCl3) d (ppm): 4.25 (s, 3H), 7.5–7.7 (m, 4H),
7.82 (s, 1H), 8.3 (d, J = 9.6 Hz, 1H), 8.62 (d, J = 9.6 Hz, 2H), 8.74 (d,

1838
F. Barba et al. / Tetrahedron Letters 54 (2013) 1835–1838
J = 9.6 Hz, 1H). 13C NMR (75.4 MHz, CDCl3) d: 35.7, 120.7, 122.4,
123.1, 123.5, 124.4, 125.1, 125.4, 125.7, 126.7, 127.4, 128.0,
129.1, 132.6, 142.1. MS m/z (relative intensity) EI: 232 (M+, 100),
217 (6), 204 (14), 190 (24), 177 (8), 163 (7), 88 (5).
References and notes
1. Leuckart, R. Ber. Dtsch. Chem. Ges. 1885, 18, 2341–2344.
2. Advanced Organic Chemistry; Smith, M. B., March, J., Eds., 5th ed.; John Wiley
and Sons, 2001. p 1188.
3. Kobayashi, K.; Nagato, S.; Kawakita, M.; Morikawa, O.; Konishi, H. Chem. Lett.
1995, 575–576.
4,5-Diphenyloxazole (3h)
4. Chen, B.-C.; Bednarz, M. S.; Zhao, R.; Sundeen, J. E.; Chen, P.; Shen, Z.;
Skoumbourdis, A. P.; Barrish, J. C. Tetrahedron Lett. 2000, 41, 5453–5456.
5. Kobayashi, S.; Nishio, K. J. Org. Chem. 1994, 59, 6620–6628.
6. Kobayashi, S.; Yasuda, M.; Hachiya, I. Chem. Lett. 1996, 407–408.
7. Downie, I. M.; Earle, M. J.; Heaney, H.; Shuhaibar, K. F. Tetrahedron 1993, 49,
4015–4034.
Mp 40 °C [Lit.27 42–43 °C]. MS m/z (relative intensity) EI: 221
(M+, 85), 193 (71), 165 (100). CI: 262 (M++41, 3), 250 (M++29,
25), 222 (M++1, 100)
8. Awachie, P. I.; Agwada, V. C. Tetrahedron 1990, 46, 1899–1910.
9. Brewer; Alice, R.E. In Name Reactions for Functional Group Transformations, Li,
J.J.; Corey, E.J., Eds. John Wiley and Sons Inc.; 2007, pp 451–455.
10. Dallinger, D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563–2591.
11. Cechova, L.; Jansa, P.; Dracinsky, M.; Holy, A.; Janeba, K. Tetrahedron 2011, 67,
866–871.
1-Methyl-4,5-diphenyl-1H-imidazole (4h)
Mp 159–161 °C [Lit.28 162–164 °C]. IR (KBr)
2924, 1638, 1600, 1507, 1445, 1194, 1068, 951, 772, 701.
m
/cmÀ1 = 3038,
12. Loupy, A.; Monteux, D.; Petit, A.; Aizpurua, J. M.; Dominguez, E.; Palomo, C.
Tetrahedron Lett. 1996, 45, 8177–8180.
4,5-Di(furan-2-yl)oxazole (3i)
13. Mastagli, P.; de Bievre-Gallin, G. Compt. Rend. 1947, 224, 1290–1292.
14. Saidi, O.; Bamforf, M. J.; Blacker, A. J.; Lynch, J.; Marsden, S. P.; Plucinski, P.;
Watson, R. J.; Williams, J. M. J. Tetrahedron Lett. 2010, 51, 5804–5806.
15. Rahman, M.; Kundu, D.; Hajra, A.; Majee, A. Tetrahedron Lett. 2010, 51, 2896–
2899.
16. Nouira, I.; Kostakis, I. K.; Dubouilh, C.; Chosson, E.; Iannelli, M.; Besson, T.
Tetrahedron Lett. 2008, 49, 7033–7036.
17. El-Nagar, G. A.; Mohammad, A. M.; El-Deab, M. S.; El-Anadovli, B. E. J.
Electrochem. Soc. 2012, 159, F249–254.
18. Ito, K.; Oba, H.; Sekiya, M. Bull. Chem. Soc. Jpn. 1976, 49, 2485–2490.
19. Leonard, N. J.; Sauers, R. R. J. Am. Chem. Soc. 1957, 79, 6210–6214.
20. Staple, E.; Wagner, E. C. J. Org. Chem. 1949, 14, 559–578.
21. Lukasiewicz, A. Tetrahedron 1963, 19, 1789–1799.
IR (KBr) m
/cmÀ1 = 3136, 1613, 1458, 1315, 1121, 1011, 739. 1H
NMR (300 MHz; CDCl3) d (ppm): 6.5–6.6 (m, 2H), 7.0–7.1 (m,
2H), 7.5–7.6 (m, 2H), 7.9 (s, 1H). 13C NMR (75.4 MHz, CDCl3) d:
109.3, 110.0, 111.6, 111.8, 125.5, 132.6, 142.6, 146.4, 149.4,
149.5. MS m/z (relative intensity) EI: 201 (M+, 100), 173 (15), 145
(11), 117 (29), 89 (21), 63 (11). Anal. Calcd for C11H7NO3: C,
65.67; H, 3.48; N, 6.97. Found: C, 65.91; H, 3.90; N, 6.68.
4,5-Di(furan-2-yl)-1-methyl-1H-imidazole (4i)
22. Lukes, R.; Jizbar, J. Chem. Listy pro Vedu a Prumysp 1953, 47, 1366–1372.
23. Gajda, T.; Koziara, A.; Zawadzki, S.; Zwierzak, A. Synthesis 1979, 549–552.
24. Katritzky, A. R.; Yao, G.; Lan, X. J. Org. Chem. 1993, 58, 2086–2093.
25. Katritzky, A. R. J. Org. Chem. 2003, 68, 9093–9099.
Mp 73 °C [Lit.29 74–76 °C]. IR (KBr) /cmÀ1 = 3119, 1605, 1457,
m
1259, 1012, 886, 736. 1H NMR (300 MHz; CDCl3) d (ppm): 3.6 (s,
3H), 6.33 (s, 1H), 6.49 (bs, 2H), 6.64 (s, 1H), 7.32 (s, 1H), 7.46 (s,
1H), 7.5 (s, 1H). 13C NMR (75.4 MHz, CDCl3) d: 33.1, 106.3, 111.0,
111.2, 111.9, 138.8, 141.4, 143.1, 149.2. MS m/z (relative intensity)
EI: 214 (M+, 100), 185 (32), 171 (15), 157 (23), 130 (9), 116 (14),
103 (3), 89 (10), 63 (6).
26. Jaffe, G. M.; Day, A. R. J. Org. Chem. 1943, 8, 43–51.
27. Davies, J. R.; Kane, P. D.; Moody, Ch. J. Tetrahedron 2004, 60, 3967–3977.
28. Bellina, F.; Cauteruccio, S.; DiFiore, A.; Rossi, R. Eur. J. Org. Chem. 2008, 5436–
5445.
29. Cawkill, E. J. Chem. Soc., Perkin Trans. 1 1980, 244–248.
Acknowledgments
This study was financed by the Spanish Ministry of Science and
Education supporting the I3 Program to B. Batanero.