Interestingly, increasing the addition temperature to 220 uC led to
the exclusive formation of 4. Addition of 1 at higher temperatures
(0 uC to rt) decreased the yield of 4. The exclusive formation of 4
similarly took place in the absence of an additional Lewis acid, the
yield of 4 being the same with or without BF3?OEt2. These results
clearly indicate that ligand exchange occurs partially (250 to
230 uC) or completely (220 uC) in the reaction conditions. The
relative instability of the intermediate complex B could explain the
decrease of the yield at temperatures higher than 0 uC.
The spontaneous elimination in the hydrolytic workup conditions
afforded the cyclopentenone derivatives 6a–d in good yields. Both
aromatic and aliphatic nitriles were successfully employed for
this transformation. Finally, the same procedure could be applied
with esters. Thus, the reaction of myrcene with ethyl acetate
afforded 3-(4-methyl-3-pentenyl)-1-methyl-3-cyclopenten-1-ol in
59% yield.13
In conclusion, we have reported the first example of a titanium-
mediated reaction of 1,3-dienes with one-carbon components,
leading to cyclopentene derivatives. The simplicity of the procedure
as well as the readily available reagents and starting materials are
noteworthy. Further studies on titanium-mediated [4 + 1] assembly
reactions are currently underway.
The reaction pathway depicted in Scheme 2 opens the way for
the assembly of 5-membered carbocyclic rings through titanium-
mediated [4 + 1] addition reactions. When applying the optimised
conditions below, the reaction of nitriles with 1,3-dienes proceeded
smoothly to afford the corresponding 3-cyclopentenyl amines in
good yields. Table 1 summarises the results employing different
Christophe Laroche, Philippe Bertus* and Jan Szymoniak*
UMR 6519 - Re´actions Se´lectives et Applications, CNRS - Universite´ de
Reims Champagne-Ardenne, BP 1039, 51687 REIMS Cedex 2, France.
E-mail: philippe.bertus@univ-reims.fr; jan.szymoniak@univ-reims.fr;
Fax: +33 326 913 166; Tel: +33 326 913 244
i
nitriles and dienes, together with PrMgCl and Ti(OiPr)4. Both
aliphatic and aromatic nitriles coupled with isoprene (entries 1–3
and 4, 5 respectively). The reaction even took place with the
sterically hindered 1-adamantanecarbonitrile (entry 3) and an
a,b-unsaturated nitrile (entry 6). A bromine atom can be present in
the substrate and is tolerated by the reaction conditions (entry 5).
The use of other 2-substituted and 2,3-substituted dienes was also
successful (entries 7–9).12
Notes and references
{ Representative procedure, preparation of 3-methyl-1-nonyl-3-cyclopen-
tenylamine (entry 2, Table 1): To a solution of Ti(OiPr)4 (0.33mL,
1.1 mmol) and isoprene (0.2 mL, 2 mmol) in Et2O (5 mL) a solution of
iPrMgCl (1.1 mL, 2 M in Et2O) was added under argon at 278 uC. The
mixture was warmed for ca. 2 h up to 220 uC, during which period the
solution became green. At this temperature, decanenitrile (0.19 mL,
1 mmol) was added. After the resulting dark red mixture was allowed to
warm to rt and stirred for 1 h, 1 N HCl (ca. 3 mL) and ether (ca. 15 mL)
were added. NaOH (10% aq, ca. 10 mL) was added and the mixture was
extracted with ether. The combined ether layers were dried (MgSO4),
filtered, and concentrated under reduced pressure. The residue was
purified by flash chromatography on silica gel (Et2O : Et3N 98 : 2) to
afford 188 mg (84%) of the title product as a colourless oil; IR n/cm21
3355, 2924, 1591, 1466; 1H-NMR (250 MHz; CDCl3) d 0.85 (t, J 5 6.8 Hz,
3H), 1.20–1.35 (m, 18H), 1.70 (s, 3H), 1.97–2.12 (m, 2H), 2.30–2.46 (m,
2H), 5.25 (s, 1H); 13C-NMR (63 MHz; CDCl3) d 14.5, 17.3, 23.1, 25.3,
29.7, 30.0, 30.1, 30.7, 32.3, 43.6, 48.6, 52.5, 61.4, 122.7, 138.8; MS (70 eV)
The reaction with nitriles is not limited to the preparation of
3-cyclopentenyl amines. It also offers a new access to 3-substituted
2-cyclopentenones (Scheme 3). With 2-trimethylsilyloxybutadiene
the reaction took place using the previously established conditions,
leading to the corresponding silyloxycyclopentenyl amines 5a–d.
Table 1 Preparation of 3-cyclopentenylamines{
R1
R2
R3
Yield (%)a,b
?
m/z 223 (M , 15), 208 (13), 194 (6), 154 (48), 124 (84), 96 (100); Analysis
calculated for C15H29N?HCl (%): C, 69.33; H, 11.64; N, 5.39; found C,
69.14; H, 11.69; N, 5.29.
Entry
1
2
3
4
5
6
7
8
9
a
Me
Me
Me
Me
Me
Me
H
H
H
H
H
H
H
H
Me
CH2Ph
nC9H19
1-Adamantyl
Ph
61
84
79
74
66
45
77
79
63c
1 (a) M. Beller and C. Bolm, Transition metals for organic synthesis,
Wiley-VCH, Weinheim, 2004; (b) I. Ojima, M. Tzamarioudaki,
Z. Li and R. J. Donovan, Chem. Rev., 1996, 96, 635–662; (c)
M. Lautens, W. Klute and W. Tam, Chem. Rev., 1996, 96,
49–92.
2 (a) S. E. Gibson, S. E. Lewis and N. Mainolfi, J. Organomet. Chem.,
2004, 689, 3873–3890 and references therein; (b) M. E. Welker, Chem.
Rev., 1992, 92, 97–112; (c) S. Yamago and E. Nakamura, Org. React.,
2002, 61, 1–217; (d) H. L. Stokes, L. Ni, J. A. Belot and M. E. Welker,
J. Organomet. Chem., 1995, 487, 95–104.
3 (a) J. Barluenga, S. Lope´z and J. Flo´rez, Angew. Chem., Int. Ed., 2003,
42, 231–233; (b) S. V. Gagnier and R. C. Larock, J. Am. Chem. Soc.,
2003, 125, 4804–4807; (c) E. Negishi, S. Ma, J. Amanfu, C. Cope´ret,
J. A. Miller and J. M. Tour, J. Am. Chem. Soc., 1996, 118, 5919–5931;
(d) M. A. Sierra, B. Soderberg, P. A. Lander and L. S. Hegedus,
Organometallics, 1993, 12, 3769–3771; (e) M. Franck-Neumann,
E. L. Michelotti, R. Simler and J.-M. Vernier, Tetrahedron Lett.,
1992, 33, 7361–7364; (f) B. E. Eaton and B. Rollman, J. Am. Chem.
Soc., 1992, 114, 6245–6246 and references therein.
3-BrC6H4
CHLCH–Ph
nC9H19
(CH2)2–CHLCMe2
Ph
Me
nC9H19
nC9H19
All reactions were performed under Ar with 1.1 eq of Ti(OiPr)4,
i
2 equiv. of diene and 2.2 equiv. of PrMgBr unless otherwise stated.
b
c
Isolated yields. Reaction performed with two-fold amount of
reagents.
4 (a) G. Erker, G. Kehr and R. Fro¨hlich, Adv. Organomet. Chem., 2004,
51, 109–162; (b) G. Erker, G. Kehr and R. Fro¨hlich, J. Organomet.
Chem., 2004, 689, 4305–4318; (c) A. Nakamura and A. Mashima,
J. Organomet. Chem., 2004, 689, 4552–4563.
5 In contrast, a number of insertion reactions have been performed
starting from isomeric D2-zirconacyclopentenes, leading to both open-
chain and cyclic final products, see: E. Negishi and S. Huo, in Titanium
Scheme 3
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Chem. Commun., 2005, 3030–3032 | 3031