Novel, stereoselective tricyclization of a dienyne by titanium aryloxide centers

Article abstract of DOI:10.1039/b209889j

Titanium centers supported by aryloxide ligation mediate the tricyclization of a dienynevia intramolecular insertion of an olefin into the titanium-vinyl bond of a titanacyclopent-2-ene.

Full text of DOI:10.1039/b209889j

Novel, stereoselective tricyclization of a dienyne by titanium aryloxide
centers†
Richard A. Himes, Phillip E. Fanwick and Ian P. Rothwell*
Department of Chemistry, Purdue University, 1393 Brown Building, West Lafayette, IN, 47907-1393, USA.
E-mail: rothwell@purdue.edu; Fax: 765-494-0239; Tel: 765-494-5473
Received (in Cambridge, UK) 10th October 2002, Accepted 14th November 2002
First published as an Advance Article on the web 28th November 2002
Titanium centers supported by aryloxide ligation mediate
the tricyclization of a dienyne via intramolecular insertion of
an olefin into the titanium–vinyl bond of a titanacyclopent-
2-ene.
chlorosilane9 or primary haloalkane.‡ Bicyclization of 1-trime-
thylsilyl-6-hepten-1-yne (2) according to the route in Scheme 1
affords a titanacyclopent-2-ene (3) in 64% yield as a yellow
powder. This compound does not undergo ring expansion in the
presence of excess 1-hexene even at elevated temperatures.
Observed as a byproduct in the synthesis of 6-hepten-1-yne
(1), 1,11-dodecadien-6-yne (4) may be prepared in 40% yield
following the procedure outlined in Scheme 1.§ Aryloxide-
supported titanium centers will react with 4 to form a tricyclic
titanacyclohept-3-ene (5). The 2,6-diphenylphenoxide deriva-
tive (5a) was isolated in greater purity and higher yield (67%) as
an orange solid following recrystallization from hot benzene.
Slow cooling affords crystals suitable for X-ray diffraction
analysis.
Fig. 1 shows the solid-state structure of 5a. Seven-membered
titanacyclic rings are scarce.10 The structure of 5a is the first
reported for a titanacycloheptene.11 The geometry is pseudo-
tetrahedral about the metal center. The bond lengths Ti–C(16),
Ti–C(26), Ti–O(3), and Ti–O(4) are within expected limits,
though the O(3)–Ti–O(4) angle is opened and the C(16)–Ti–
C(26) angle pinched compared to other structurally charac-
terized aryloxide-supported titanacycles.11 The molecule exists
as a single isomer with the titanacyclic ring adopting the cis
conformation.
The metal-mediated bicyclization of enynes has proven to be a
powerful synthetic method.1 Group 4 metal complexes facilitate
the construction of unsymmetrical cyclic compounds via this
methodology2 and promote further functionalization via inser-
tion of carbon monoxide,3 isocyanides,4 and aldehydes.5
However, no report exists of ring expansion via insertion of
olefins by Group 4 metal complexes.
As part of our continuing studies of the formation and
reactivity of titanacyclic compounds supported by aryloxide
ligands we have sought routes to titanacyclopent-2-enes for
comparison with metallocene analogues. During this work we
have discovered the tricyclization of dienynes, a reaction that
appears to proceed via intramolecular insertion of olefin into the
titanium–vinyl bond of an unobserved titanacyclopent-2-ene
intermediate.6,7
Enynes may be synthesized in two steps from dibromoalk-
anes.8 The alkynyl proton may be substituted (Scheme 1) with
silyl or alkyl groups in moderate to high yield via deprotonation
by nBuLi and subsequent quenching with an appropriate
The solid-state structure and stereochemistry are retained in
solution, as confirmed by NMR spectroscopy. In the 1H NMR
spectrum, the product has a distinct upfield resonance (5a: d
20.06 ppm; 5b: d 20.47 ppm) appearing as a sharp doublet. 1H-
1H COSY correlations allow unambiguous assignment of the
upfield peak to the pseudo-equatorial protons on C(16) and
C(26). The protons are coupled (2J = 10.5–10.8 Hz) to the
corresponding axial protons. Fig. 1 demonstrates that the
pseudo-equatorial protons are in position to experience diamag-
netic anisotropy from the phenyl substituents of the aryloxides.
Scheme 1 Reaction pathways
Fig. 1 ORTEP view of 5a. Selected bond distances (Å) and angles (°): Ti–
O(3) 1.821(2), Ti–O(4) 1.815(2), Ti–C(16) 2.067(4), Ti–C(26) 2.073(4),
C(12)–C(22) 1.322(5), O(3)–Ti–O(4) 132.30(11), C(16)–Ti–C(26)
97.41(16), O(3)–Ti–C(16) 104.73(15), O(3)–Ti–C(26) 108.11(14), O(4)–
Ti–C(16) 104.48(13), O(4)–Ti–C(26) 104.51(14).
† Electronic supplementary information (ESI) available: synthesis of
compounds 1–6 and spectroscopic data for 1–3. See http://www.rsc.org/
suppdata/cc/b2/b209889j/
18
CHEM. COMMUN., 2003, 18–19
This journal is © The Royal Society of Chemistry 2003

The cis conformation is also confirmed by the appearance in the
13C NMR spectrum of two sets of aryloxide peaks, including
two well resolved resonances for the ipso Ti–O–C carbons of
the inequivalent phenoxides.
thermal catalysis. Investigations into further reactivity and all
aspects of the chemistry discussed herein are currently under-
way.
Reactive titanium centers are also supplied by precursor
titanacycles such as 8 (Scheme 2). The presence of substrate (4)
induces retrocyclization of 8 to release 1,7-octadiene. Clean
formation of 5b follows. This reaction may be monitored by 1H
NMR. Conversion to 5b occurs rapidly at 100 °C, slowly at
room temperature, but at no point can intermediates be
observed. We hypothesize a mechanism involving intermediate
formation of titanacyclopent-2-ene (9) followed by rapid
intramolecular insertion of olefin into the titanium–vinyl bond
(Scheme 2).
Formation of 9 has some precedent. Negishi et al. have
reported the in situ synthesis of a zirconacyclopent-2-ene (10)
from 1,10-undecadien-5-yne.3 Insertion of olefin does not occur
due to the strain of the resulting fused cyclobutane, the
electronics of the cyclopentadienyl zirconium center, or a
combination of these factors. The reactivity of 10 toward free
olefins was not investigated.
Notes and references
‡ Attempts to synthesize an organometallic compound by reaction of 1 with
titanium–aryloxide centers failed. Other researchers have reported difficulty
in the cyclization reaction of terminal enynes.2,3 Our system gives a
trisubstituted (1-pentenyl)benzene arising from cyclotrimerization as the
only isolable product.
§
Selected spectroscopic data. For 4: 1H NMR (C6D6): d 5.73–5.60 (m,
2 H), 5.02–4.91 (m, 4 H), 2.08–2.01 (m, 8 H), 1.46 (quin, 4 H); 13C (CDCl3):
d138.24, 115.14, 80.25, 33.04, 28.57, 18.51. HRMS calcd. for C12H17 [M 2
H]: 161.1330, found: 161.1325. For 5a: 1H NMR (C6D6): d 7.47–6.89
(aromatics), 2.84 (dd, 2 H), 2.01–1.85 (m, 4H), 1.58 (t, J = 12 Hz, 2H),
1.50–1.31 (m, 6H), 1.29–1.21 (m, 4H), 0.86–0.82 (m, 4H), 20.062 (d, J =
10.5 Hz, 2H); 13C NMR (C6D6): d 160.23, 159.78 (Ti–O–C); 137.17,
1
103.13 (TiCH2), 43.52, 38.71, 31.90, 24.52. For 5b: H NMR (C6D6): d
7.39–6.85 (aromatics), 2.85 (dd, 2 H), 2.06–1.82 (m, 4H), 1.50 (t, 2H),
1.46–1.32 (m, 6H), 1.22 (m, 4H), 0.87 (m, 4H), 20.47 (d, J = 10.8 Hz, 2H);
13C NMR (C6D6): d 160.77 (Ti–O–C; 2 nearly overlapping peaks), 142.46,
104.64 (TiCH2), 43.76, 38.83, 32.02, 24.51. For 6: 1H NMR (C6D6): d
2.67–2.63 (m, 2 H), 2.14–2.10 (m, 4 H), 1.74–1.57 (m), 1.39–1.35 (m), 1.06
(d, J = 6.9 Hz, 6 H), 0.92–0.89 (m). HRMS calcd. for C12H20: 164.1565.
Found: 164.1558.
Why this mechanism precludes formation of the trans isomer
cannot currently be explained. Preference for the cis conforma-
tion may arise from the steric demands of the aryloxide ligands.
To test this theory, experiments are being conducted with less
sterically hindered metal centers.
¯
Crystal data for 5a: TiC48H44O2, M = 700.78, triclinic, space group P1
(no. 2), a = 11.9946(4), b = 11.7706(4), c = 13.7377(6) Å, a =
73.1412(15), b = 77.5151(14), g = 84.8318(15)°, V = 1811.51(18) Å3, Dc
= 1.285 g cm23, Z = 2, T = 150 K. Of the 8326 unique reflections
Simple reactivity of 5 has been investigated. Hydrolysis of
the metallacycle yields a novel cyclopentylidene-cyclopentane
6 (Scheme 1). It may be isolated by exposure of a C6D6 solution
of 5 to ambient atmosphere followed by preparative-scale TLC.
Only one isomer is isolated. Compound 5 also displays thermal
reactivity. The metallacycle is unstable at high temperatures
(75–100 °C) over long periods. 5a appears to disproportionate
into tetraphenoxy titanium and unknown organic products.
However, both derivatives of 5 undergo catalysis in the
2
collected (5 5 q 5 28°) with Mo-Ka (l = 0.71073 Å), the 8313 with Fo
> 2.0 s(Fo2) were used in the final least-squares refinement to yield R =
0.085 and RW = 0.179. CCDC 197519. See http://www.rsc.org/suppdata/
cc/b2/b209889j/ for crystallographic data in CIF or other electronic
format
1 See the following, and references therein: (a) E.-i. Negishi, in
Comprehensive Organic Synthesis,, ed. B. M. Trost, Pergamon, Oxford,
1991,vol. 5, p., 1163; (b) B. M. Trost, Angew. Chem., Int. Ed. Engl.,
1995, 34, 259; (c) N. E. Schore, Chem. Rev., 1988, 88, 1081–1119.
2 See, for example: (a) S. L. Buchwald and R. B. Nielsen, Chem. Rev.,
1988, 88, 1047; (b) R. D. Broene and S. L. Buchwald, Science, 1993,
261, 1696; (c) T. V. RajanBabu, W. A. Nugent, D. F. Taber and P. J.
Fagan, J. Am. Chem. Soc., 1988, 110, 7128; (d) E.-i. Negishi, S. J.
Holmes, J. M. Tour and J. A. Miller, J. Am. Chem. Soc., 1985, 107,
2568; (e) F. Sato, H. Urabe and S. Okamoto, Chem. Rev., 2000, 100,
2835; (f) H. Urabe, T. Hata and F. Sato, Tetrahedron Lett., 1995, 36,
4261–4264.
3 E.-i. Negishi, S. J. Holmes, J. M. Tour, J. A. Miller, F. E. Cederbaum,
D. R. Swanson and T. Takahashi, J. Am. Chem. Soc., 1989, 111,
3336.
4 S. C. Berk, R. B. Grossman and S. L. Buchwald, J. Am. Chem. Soc.,
1994, 116, 8593.
1
presence of excess dienyne. H NMR studies show 5 converts
several equivalents of 4 into organic products. We believe the
main product to be 7, which forms via b-H abstraction and
elimination. However, GC/MS identifies at least five additional
C12 and C24 catalytic products. Further elucidation of this
reaction will be communicated in due course.
In conclusion, we have synthesized a novel aryloxide-
supported titanacyclohept-3-ene via tricyclization of a dienyne.
We believe this transformation proceeds through an unprece-
dented insertion of olefin into the titanium–vinyl bond of a
titanacyclopent-2-ene. In addition, the tricyclized organome-
tallic product shows interesting reactivity and synthetic useful-
ness in forming novel organic molecules by hydrolysis and
5 H. Urabo and F. Sato, J. Org. Chem., 1996, 61, 6756.
6 For insertion of olefins into titanacyclopent-3-ene, see: (a) J. E. Hill, P.
E. Fanwick and I. P Rothwell, Organometallics, 1991, 10, 3428; (b) J.
E. Hill, G. J. Balaich, P. E. Fanwick and I. P. Rothwell, Organome-
tallics, 1993, 12, 2911; (c) G. J. Balaich, J. E. Hill, S. A. Waratuke, P.
E. Fanwick and I. P. Rothwell, Organometallics, 1995, 54, 14265.
7 For insertions of olefins into titanacyclopenta-2,4-dienes, see: E. S.
Johnson, G. J. Balaich and I. P. Rothwell, J. Am. Chem. Soc., 1997, 119,
7685.
8 (a) Synthesis of w-bromo-1-enes: G. A. Kraus and K. Landgrebe,
Synthesis, 1984, 885; (b) Synthesis of w-ene-1-yne: W. Novis Smith and
O. F. Beumel, Synthesis, 1974, 441.
9 M. Shipman, H. R. Thorpe and I. R. Clemens, Tetrahedron, 1998, 54,
14265.
10 Titanacycloheptanes formed by reaction of dilithio- or bis-Grignard
reagent with Cp2TiCl2 have been reported : L. M. Engelhardt, Wing-Por
Leung, R. I. Papasergio, C. L. Raston, P. Twiss and A. H. White, J.
Chem. Soc., Dalton Trans., 1987, 2347.
11 Hetero-titanacycloheptanes have been synthesized. See: M. G. Thorn, J.
E. Hill, S. A. Waratuke, E. S. Johnson, P. E. Fanwick and I. P. Rothwell,
J. Am. Chem. Soc., 1997, 119, 8630.
Scheme 2 Intramolecular insertion of olefin to give tricyclized product.
CHEM. COMMUN., 2003, 18–19
19