Radical cyclization of epoxynitriles mediated by titanocene chloride

Article abstract of DOI:10.1055/s-2004-822901

The reductive radical cyclization of β-, γ-, δ- and ε-epoxynitriles has been achieved using titanocene chloride. The reaction was regioselective and afforded cyclic β-hydroxyketones in good yield. The catalytic version of this radical cyclization is also

Full text of DOI:10.1055/s-2004-822901

LETTER
1011
Radical Cyclization of Epoxynitriles Mediated by Titanocene Chloride
Radical
C
yclizatio
.
n
of
E
poxyni
F
trile
s
Mediate
e
d
by
T
itano
r
cene Ch
n
loride ández-Mateos,* L. Mateos Burón, R. Rabanedo Clemente, Ana I. Ramos Silvo, R. Rubio González
Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Salamanca, Plaza de los Caídos 1-5,
37008 Salamanca, Spain
E-mail: afmateos@usal.es
Received 16 December 2003
the cyano group. However, Cp2TiCl failed in those cy-
clizations. T. Hirao has developed a catalytic version of
this reaction promoted by Cp2TiCl/Me3SiCl/Zn.7
Abstract: The reductive radical cyclization of b-, g-, d- and e-ep-
oxynitriles has been achieved using titanocene chloride. The reac-
tion was regioselective and afforded cyclic b-hydroxyketones in
good yield. The catalytic version of this radical cyclization is also
reported.
To our knowledge, they have not been studies before
relative to the intramolecular reductive coupling of
epoxynitriles.
Key words: radical cyclization, titanocene chloride, epoxynitrile,
cyclobutanone, cycloheptanone
To realize the radical addition to nitriles, we next investi-
gated the reaction of Cp2TiCl,8 generated in situ from
Cp2TiCl2 and Zn in THF at room temperature, with two
series of epoxynitriles with different tethers between the
two functional groups. (Figure 1 and Figure 2) Com-
pounds 2–5 were obtained from 3-methyl-3-buten-1-ol
and 4-methyl-3-penten-1-ol, and compound 1 from hep-
tanaldehyde by standard procedures. This will be de-
scribed elsewhere. The radical reactions were carried out
by slowly adding the reagent to the epoxynitrile.9 The
results, which afforded monocyclic compounds, are
summarized in Figure 1.
Radical additions to polar multiple bonds have been
scarcely explored, and few of them have been exploited in
organic syntheses.1 Radical cyclization onto nitriles is a
slow process; the available kinetic data are restricted to
the 5-exo-intermolecular addition of a radical onto nitrile
to give a cyclic iminyl radical.2
N
N
k = 4.103 (25 °C)
We started our investigation with epoxynitrile 1: instead
of the expected cyclization product, which would be a cy-
clopropanone, we obtained allylic alcohol 1a, with one
carbon less than the starting material. This product must
be generated after homolytic cleavage of the oxirane by b-
fragmentation, with loss of the CN group. The fragmenta-
tion could be either homolytic, or heterolytic via two-elec-
tron reduction of the epoxide. The reaction deserves
further study.
Scheme 1 Radical addition to C≡N triple bond
The process, as shown in Scheme 1, is slower than that
corresponding to the 5-hexenyl (2.5 × 105 s–1) or 5-hexy-
nyl radical (1 × 104 s–1).2 Though the 5-exo-cylization is
not reversible, in some cases, e.g. ring strain or formation
of stabilized radical, could be give nitrile translocation.3
We have not found examples of 3-exo- and 4-exo-cycliza-
tions of radical onto nitriles. The 6-exo-4a and 7-exo-
processes4b have been reported scarcely, and often these
reactions fail due to competition from faster 1,5-hydrogen
transfer processes. The 5-exo-radical cyclization onto ni-
trile has been the most studied.4 The examples reported
are based on the creation of the radical from halides or se-
lenides with tributyltin hydride4 or the reductive coupling
of ketonitriles using a one-electron reducing agent.5 Re-
cently, K. Itoh et al.6 have reported the Cp2TiPh mediated
reductive cyclization of cyanoketones in the 5- and 6-exo-
modes to provide an entry to 5- and 6-membered a-hy-
droxycycloalkanones. The reaction was more efficient in
providing bicyclic than monocyclic hydroxyketones; at-
tempts to achieve 7-exo-cyclization failed. Those authors
attributed a key role to the coordination of the Cp2TiPh to
Compound 2 was treated with Cp2TiCl to explore the pos-
sibility of cyclobutanone formation. The hydroxycyclo-
butanone 2a was obtained cleanly in 73% yield. We next
examined the 5-exo- and 6-exo-cyclization of the nitriles
3 and 4. Compounds 3 and 4 afforded the hydroxycyclo-
pentanone 3a and the hydroxycyclohexanone 4a, respec-
tively, in an exclusive way. A catalytic version of the
reaction with titanocene dichloride has been carried out
with epoxynitrile 4, following the conditions reported by
A. Gansäuer et al.,10 which employ a 5% of Cp2TiCl2 as
reagent and collidine hydrochloride as a source of pro-
tons. After 4 days the hydroxyketone 4a was obtained as
the unique product of the reaction, however the conver-
sion was low (37%).11 This result demonstrates a free
radical mechanism. The 7-exo-cyclization was carried out
with epoxynitrile 5, which also afforded a cyclic com-
pound, the hydroxycycloheptanone 5a (45% yield), to-
gether with the acyclic unsaturated hydroxynitrile 5b,
and its reduction product 5c in a 1:2 ratio and 27%
yield. When the reaction was carried out by addition of
SYNLETT 2004, No. 6, pp 1011–1014
0
6.
0
5.
2
0
0
4
Advanced online publication: 01.04.2004
DOI: 10.1055/s-2004-822901; Art ID: G35703ST
© Georg Thieme Verlag Stuttgart · New York

1012
A. Fernández-Mateos et al.
LETTER
[Ti]O
O[Ti]
N
CN
O
( )4
( )4
65%
73%
CN
O
Ti(III)
CN
OH
1
1a
O
Ti(III)
Ti(III)
HO
CN
CN
O
O
O
2a
2
[Ti]O
[Ti]O
N-[Ti]
[Ti]
O
CN
HO
80%
88%
OH
3a
CN
H3O+
3
-H[Ti]
O
[Ti]O
OH
O
HO
+H[Ti]
CN
CN
CN
4a
4
OH
H3O+
O
HO
45%
9%
O
Scheme 2 Reaction mechanism of Cp2TiCl with epoxynitriles
5a
5b
5
CN
Attempts to obtain the desired bicyclo[4.1.0]heptanone
from epoxynitrile 6 with Cp2TiCl were unfruitful. The
only product obtained was the unsaturated cyanoalcohol
6a. It is interesting to note that in this case b-elimination
corresponded to the hydrogen instead of the cyano group,
as we observed for compound 1. The 4-exo-cyclization of
compound 7 was very clean and afforded 7a as a single
diastereoisomer in good yield (89%). Similarly, the
epoxynitrile 8 afforded only cyclized products by the 5-
exo-mode: the hydroxy ketones 8a and 8b (ratio 5:1) in
80% yield.
OH
CN
CN
18%
OH
5c
Figure 1 Cycloalkanones from epoxynitriles
The behaviour of the epoxynitrile 9 against Cp2TiCl,
slightly different from its parent compound, gave the de-
sired bicyclic compound 9a (43%), together with the
cyanoalcohol 9b (36%).14
compound 5 to the Cp2TiCl, the ratio of the products was
inverted (5a 30% and 5b:5c 62%, 1:2).This means that an
excess of Ti(III) promotes the coupling of this species
with the carbon radical instead of the coupling with the
cyano group (Scheme 2).
It should be noted that the cis-fused isomer was the major
compound obtained from 8 and the trans-fused isomer
was the exclusive isomer from 9.
A common aspect for all reactions with titanocene di-
chloride is the regioselectivity in the homolytic cleavage
of the oxirane ring.
Furthermore, the reaction of the e-epoxynitrile 10 did not
give the desired 7-exo reductive cyclization product. In-
stead, the cyanoalcohol 10a was obtained. This result con-
trasts with the result obtained for the acyclic epoxynitrile
5.
In order to broaden the radical cyclization study and to
find synthetic applications for this method, we accom-
plished the cyclization of a series of cyclic epoxynitriles
that might afford interesting bicyclic compounds that
would find use as intermediates in the synthesis of the nat-
ural products.
The present epoxynitrile cyclization is a novel and power-
ful route to b-hydroxycycloalkanones. The synthetic
versatility of this method was demonstrated in the prepa-
ration of bicyclic compounds. Also remarkable is the easy
and high yield synthesis of cyclobutanones and cyclohep-
tanones by this intramolecular radical addition, for which
there are few preparation methods in the literature.
Compound 6 was obtained from commercial 3,7-dimeth-
yl-2,6-octadienenitrile, and compounds 7–10 from a-
cyclocitral12 by standard procedures, to be described else-
where.13
Synlett 2004, No. 6, 1011–1014 © Thieme Stuttgart · New York

LETTER
Radical Cyclization of Epoxynitriles Mediated by Titanocene Chloride
1013
(2) (a) Beckwith, A. L. J.; Hay, B. D. J. Am. Chem. Soc. 1989,
111, 230. (b) Beckwith, A. L. J.; Hay, B. D. J. Am. Chem.
Soc. 1989, 111, 2674. (c) Beckwith, A. L. J. Tetrahedron
1981, 37, 3073.
(3) Bowman, W. R.; Bridge, C. F.; Brookes, P. Tetrahedron
Lett. 2000, 41, 8989; and references cited therein.
(4) (a) Fallis, A. G.; Brinza, I. M. Tetrahedron 1997, 53, 17543.
(b) Curran, D. P.; Liu, W. Synlett 1999, 117.
(5) (a) Corey, E. J.; Pyne, S. G. Tetrahedron Lett. 1983, 24,
28211. (b) Molander, G. A.; Kenny, C. J. Am. Chem. Soc.
1989, 111, 8236. (c) Shono, T.; Kise, N.; Fujimoto, T.;
Tominaga, N.; Morita, H. J. Org. Chem. 1992, 57, 7175.
(6) Yamamoto, Y.; Matsumi, D.; Hattori, R.; Itoh, K. J. Org.
Chem. 1999, 64, 3224.
(7) Zhou, L.; Hirao, T. Tetrahedron 2001, 57, 6927.
(8) (a) RajanBabu, T. V.; Nugent, W. A. J. Am. Chem. Soc.
1994, 116, 986. (b) Nugent, W. A.; RajanBabu, T. V. J. Am.
Chem. Soc. 1988, 110, 8561. (c) Gansäuer, A.; Pierobon,
M.; Bluhm, H. Angew. Chem. Int. Ed. 1998, 37, 101.
(9) General Procedure. A mixture of Cp2TiCl2 (2.2 mmol) and
Zn (3 mmol) in strictly deoxygenated THF (4 mL) was
stirred at r.t. until the red solution turned green. In a separate
flask, the epoxy nitrile (1 mmol) was dissolved in strictly
deoxygenated THF (10 mL). The green Ti(III) solution was
slowly added via cannula to the epoxide solution. After 30
min, an excess of sat. NaH2PO3 was added, and the mixture
was stirred for 20 min. The product was extracted into Et2O
and washed with sat. NaHCO3 and H2O. After removal of the
solvent, the crude product was purified by flash
OH
OH
O
55%
CN
CN
6a
6
O
O
69%
80%
CN
CN
H
7a
7
OH
OH
O
O
O
H
H
8a
8
8b
5 : 1
OH
O
OH
O
CN
79%
CN
CN
H
H
9
9a
9b
chromatography.
4
: 3
(10) (a) Gansäuer, A.; Bluhm, H.; Pierobon, M. J. Am. Chem.
Soc. 1998, 120, 12849. (b) Gansäuer, A.; Bluhm, H. Chem.
Rev. 2000, 100, 2771.
OH
CN
O
(11) Catalytic Radical Reaction. General Procedure. To a
mixture of collidine hydrochloride (2.5 mmol), epoxy nitrile
(1.0 mmol), and Zn (2.0 mmol) in THF (10 mL) was added
titanocene dichloride (0.05 mmol), and the resulting mixture
was stirred at r.t. After addition of Et2O, the mixture was
washed with H2O, 2 N HCl, H2O, sat. aq NaHCO3, and H2O,
and dried. After removal of the solvent, the crude product
was purified by flash chromatography on silica gel.
(12) Geyde, R. N.; Aura, P. C.; Deck, K. Can. J. Chem. 1971, 49,
1764; all compounds synthesized are racemic although, only
one enantiomer is depicted..
(13) The structure of epoxynitriles 6–10, in which the oxiranic
oxygen and the side chain are cis, is based on spectroscopic
data and comparison with the model compound I, whose
structure was determined by X-ray crystallography (Figure
3): Mori, K.; Aki, S.; Kido, M. Liebigs Ann. Chem. 1993, 83.
68%
10
10a
Figure 2 Bicyclic hydroxycycloalkanones from epoxynitriles
Acknowledgment
Financial support for this work from the Ministerio de Ciencia y
Tecnología of Spain (PPQ2002-00290) is gratefully acknowledged.
We also thank the Junta de Castilla y León for the fellowships to
L.M.B. and A.I.R.S., and the Ministerio de Ciencia y Tecnología for
the fellowship to R.R.C.
O
References
SO2Ph
I
(1) (a) Curran, D. P. In Comprehensive Organic Synthesis, Vol.
4; Trost, B. M.; Fleming, I.; Paquette, L. A., Eds.; Pergamon:
Oxford, 1991, Chap. 4.2.5. (b) Giese, B.; Kopping, B.;
Göbel, T.; Thoma, G.; Dickhaut, J.; Kulicke, K. J.; Trach, F.
In Organic Reactions, Vol. 48; Paquette, L. A., Ed.; Wiley:
New York, 1996, 308. (c) Tsang, R.; Fraser-Reid, B. J. Am.
Chem. Soc. 1986, 108, 8102. (d) Chang, S. Y.; Jiaang, W.
T.; Cherng, C. D.; Tang, K. H.; Huang, C. H.; Tsai, Y. M. J.
Org. Chem. 1997, 62, 9089. (e) Curran, D. P.; Diederichsen,
U.; Palovich, M. J. Am. Chem. Soc. 1997, 119, 4797.
(f) Kim, S.; Jon, S. Y. Chem. Commun. 1996, 1335.
(g) Fernández-Mateos, A.; Martín de la Nava, E.; Pascual
Coca, G.; Ramos Silvo, A.; Rubio González, R. Org. Lett.
1999, 1, 607.
Figure 3
(14) (a) The stereochemistry of the bicyclic hydroxyketone 7a
was established by 1H NMR and 13C NMR spectra, H-C
correlations and NOE experiments. The hydroxyketone 8a
was reported by: Fernández-Mateos, A.; Pascual Coca, G.;
Rubio González, R.; Tapia Hernández, C. J. Org. Chem.
1996, 61, 9097; the stereochemistry of hydroxyketone 9a
was determined by 1H NMR and 13C NMR spectra. (b) 2-
Methyl-1-nonen-3-ol (1a): IR (film): 3370, 1653 cm–1. 1H
NMR (CDCl3): d = 0.88 (3 H, t, J = 7.0 Hz), 1.20–1.60 (10
H, m), 1.72 (3 H, s), 4.05 (1 H, t, J = 6.5 Hz), 4.83 (1 H, s),
Synlett 2004, No. 6, 1011–1014 © Thieme Stuttgart · New York

1014
A. Fernández-Mateos et al.
LETTER
4.93 (1 H, s) ppm. 13C NMR (CDCl3): d = 13.98, 17.41,
22.53, 25.49, 29.16, 31.74, 34.95, 75.97, 110.80, 147.67
ppm. MS (EI): m/z (%) = 156 (3) [M+], 113 (11), 99 (11), 94
(12), 86 (18), 71 (100), 55 (20). HRMS (IE): 156.1511 (M+,
C10H20O), calcd 156.1514. 2-Hydroxymethyl-2-methyl-
cyclobutanone (2a): IR (film): 3461, 1775 cm–1. 1H NMR
(CDCl3): d = 1.18 (3 H, s), 1.75 (1 H, m), 2.20 (1 H, m), 2.99
(2 H, m), 3.53 (1 H, d, J = 15.0 Hz), 3.69 (1 H, d, J = 15.0
Hz) ppm. 13C NMR (CDCl3): d = 17.76, 21.25, 43.16, 65.75,
66.00, 215.21 ppm. MS (EI): m/z (%) = 96 (6) [M+ – 16], 85
(7), 69 (44), 57 (100). HRMS (IE): 114.0678 (M+, C6H10O2),
calcd 114.0680.
2-Hydroxymethyl-2-methyl-cyclopentanone (3a): IR
(film): 3445, 1732 cm–1. 1H NMR (CDCl3): d = 0.98 (3 H, s),
1.60–2.40 (6 H, m), 3.42 (1 H, d, J = 10.9 Hz), 3.58 (1 H, d,
J = 10.9 Hz) ppm. 13C NMR (CDCl3): d = 18.74, 19.20,
33.05, 38.29, 50.24, 66.91, 224.31 ppm. MS (EI): m/z = 128
(9) [M+], 110 (9), 97 (9), 82 (27), 69(89), 57 (100). HRMS
(IE): 128.0836 (M+, C7H12O2), calcd 128.0837.
2-Hydroxymethyl-2-methyl-cyclohexanone (4a): IR
(film): 3443, 1703 cm–1. 1H NMR (CDCl3): d = 1.11 (3 H, s),
1.50–2.00 (6 H, m), 2.24 (1 H, dt, J1 = 4.2 Hz, J2 = 14.0 Hz),
2.46 (1 H, ddd, J1 = 6.0 Hz, J2 = 12.5 Hz, J3 = 14.2 Hz), 3.47
(2 H, dd, J1 = 12.0 Hz, J2 = 17.0 Hz) ppm. 13C NMR
(CDCl3): d = 20.12, 20.69, 27.19, 35.50, 38.89, 50.10, 68.85,
217.88 ppm. MS (EI): m/z (%) = 124 (27) [M+ – 18], 112
(36), 97 (18), 82 (100), 69 (50), 55 (97). HRMS (IE):
142.1001 (M+, C8H14O2), calcd 142.0994.
43.83, 70.30, 112.96, 118.58, 142.31 ppm. MS (EI): m/z (%)
= 165 (2) [M+], 150 (98), 134 (10), 107 (11), 97 (12), 85 (16),
69 (100). HRMS (IE): 165.1152 (M+, C10H15NO), calcd
165.1154.
(1SR,5RS,6SR)-5-Hydroxy-2,2,6-trimethyl-bicyclo
[4,2,0]octan-7-one (7a): Mp 91–94 °C. IR (film): 3482,
1769 cm–1. 1H NMR (CDCl3): d = 0.92 (3 H, s), 1.00 (3 H,
s), 1.18 (3 H, s), 1.22 (1 H, m), 1.62 (1 H, m), 1.78 (3 H, m),
2.68 (1 H, dd, J1 = 9.0 Hz, J2 = 16.4 Hz), 3.06 (1 H, dd,
J1 = 10.6 Hz, J2 = 16.4 Hz), 3.83 (1 H, br s) ppm. 13C NMR
(CDCl3): d = 20.94, 26.70, 27.86, 28.93, 29.39, 29.49, 43.23,
47.71, 64.59, 69.99, 212.04 ppm. MS (EI): m/z (%) = 182 (2)
[M+], 167 (15), 140 (8), 122 (69), 107(60), 84 (100), 69(31).
HRMS (IE): 182.1302 (M+, C11H18O2), calcd 182.1307.
(3aSR,7RS,7aRS)-7-Hydroxy-4,4,7a-trimethyl-
octahydro-inden-1-one (8b): IR (film): 3479, 1738 cm–1.
1H NMR (CDCl3): d = 0.94 (3 H, s), 0.96 (3 H, s), 1.05 (3 H,
s), 2.35 (2 H, m), 3.69 (1 H, dd, J1 = 4.8 Hz, J2 = 11.1 Hz)
ppm. 13C NMR (CDCl3): d = 10.32, 19.26, 21.49, 26.48,
31.39, 31.90, 39.22, 51.47, 52.27, 76.63, 222.89 ppm. MS
(EI): m/z (%) = 196 (12) [M+], 181 (14), 140 (53), 123 (15),
97 (100), 81 (22), 69(15), 55 (24). HRMS (IE): 196.1460
(M+, C12H20O2), calcd 196.1463.
(4aSR,8RS,8aRS) 8-Hydroxy-5,5,8a-trimethyl-
octahydro-naphthalen-1-one (9a): IR (film): 3567, 1694
cm–1. 1H NMR (CDCl3): d = 0.89 (3 H, s), 0.94 (3 H, s), 1.20
(3 H, s), 1.20–1.80 (7 H, m), 2.00–2.20 (2 H, m), 2.54 (2 H,
m), 3.86 (1 H, m) ppm. 13C NMR (CDCl3): d = 13.29, 20.67,
22.08, 25.25, 25.68, 32.70, 34.05, 37.71, 39.58, 52.12,
54.19, 73.40, 218.09 ppm. MS (EI): m/z (%) = 210 (7) [M+],
192 (20), 185 (5), 167 (5), 154 (16), 136 (11), 121 (8), 111
(100), 95 (11), 81 (16), 69 (20), 55 (52). HRMS (IE):
210.3124 (M+, C13H22O2), calcd 210.3126.
(1RS,5RS)-4-(5-Hydroxy-2,2,6-trimethyl-cyclohexyl)-
butyronitrile (9b): IR (film): 3447, 2247 cm–1. 1H NMR
(CDCl3): d = 0.85 (3 H, s), 0.89 (3 H, s), 0.90 (3 H, d, J = 7.4
Hz), 1.10–1.60 (10 H, m), 2.35 (2 H, t, J = 6.2 Hz), 3.67 (1
H, m) ppm. 13C NMR (CDCl3): d = 8.67, 17.44, 23.33, 24.28
(2 C), 26.04, 26.96, 31.45 (2 C), 33.12, 35.62, 47.49, 73.74,
119.55 ppm. MS (EI): m/z (%) = 209(23) [M+], 159 (17), 136
(17), 125 (18), 110 (24), 97 (31), 81(32), 69 (57), 55 (100).
HRMS (IE): 209.1780 (M+, C13H23NO), calcd 209.1779.
(1RS,5RS) 5-(5-Hydroxy-2,2,6-trimethyl-cyclohexyl)-
pentanonitrile (10a): IR (film): 3432, 2247 cm–1. 1H NMR
(CDCl3): d = 0.81 (3 H, s), 0.83 (3 H, s), 0.85 (3 H, d, J = 7.4
Hz), 1.10–1.70 (11 H, m), 2.04 (1 H, m), 2.32 (2 H, t, J = 7.0
Hz), 3.63 (1 H, br s) ppm. MS (EI): m/z (%) = 205(45) [M+]
149 (95), 123 (47), 95 (36), 81 (100). HRMS (IE): 223.1931
(M+, C14H25NO), calcd 223.1936.
2-Hydroxymethyl-2-methyl-cycloheptanone (5a): IR
(film): 3447, 1694 cm–1. 1H NMR (CDCl3): d = 1.14 (3 H, s),
1.40–1.80 (8 H, m), 2.43 (1 H, m), 2.63 (1 H, m), 3.37 (1 H,
d, J = 11.0 Hz), 3.71 (1 H, d, J = 11.0 Hz) ppm. 13C NMR
(CDCl3): d = 21.20, 24.70, 26.21, 30.55, 34.96, 41.10, 51.98,
69.54, 219.68 ppm. MS (EI): m/z (%) = 156 (5) [M+], 138
(36), 126 (11), 109 (14), 95 (23), 81 (24), 69(79), 56 (100).
HRMS (IE): 156.1154 (M+, C9H16O2), calcd 156.1150.
7-Hydroxymethyl-7-heptenenitrile (5b) and 8-hydroxy-
7-methyl-octanenitrile (5c): IR (film): 3432, 2926, 2861,
2247, 1715, 1653, 1464, 1427, 1375 cm–1. 1H NMR
(CDCl3): d 0.89 (3 H, d, J = 6.7 Hz), 1.00–2.10 (20 H, m),
2.34 (4 H, br s), 3.39 (1 H, dd, J1 = 6.4 Hz, J2 = 10.4 Hz),
3.46 (1 H, dd, J1 = 6 Hz, J2 = 10.4 Hz), 4.84 (1 H, s), 5.01
(1 H, s) ppm. 13C NMR (CDCl3): d = 16.45, 17.01 (2 C),
25.13, 25.22, 26.05, 26.76, 28.26, 28.84, 32.47, 32.71,
35.52, 65.64, 68.00, 109.53, 119.67, 119.74, 148.42 ppm.
(1SR,5RS)-2,2-Dimethyl-5-hydroxy-6-methylen-
cyclohexanecarbonitrile (6a): IR (film): 3435, 2241 cm–1.
1H NMR (CDCl3): d = 1.00 (3 H, s), 1.17 (3 H, s), 1.40–1.80
(4 H, m), 3.48 (1 H, s), 4.40 (1 H, m), 5.23 (2 H, s) ppm.
13C NMR (CDCl3): d = 21.78, 29.06, 29.56, 32.91, 35.58,
Synlett 2004, No. 6, 1011–1014 © Thieme Stuttgart · New York