Metalation of iminium ions formed in the reaction of tertiary amines with TiCl4

Article abstract of DOI:10.1021/ol990745d

(equation presented) TiCl₄ reacts with trialkylamines at 0-25°C to give iminium ions that on metalation followed by reaction with diaryl ketones, produce α,β-unsaturated aldehydes.

Full text of DOI:10.1021/ol990745d

ORGANIC
LETTERS
1999
Vol. 1, No. 6
857-859
Metalation of Iminium Ions Formed in
the Reaction of Tertiary Amines with
TiCl4
Pandi Bharathi and Mariappan Periasamy*
School of Chemistry, UniVersity of Hyderabad, Central UniVersity P. O.,
Hyderabad-500 046, India
mpsc@uohyd.ernet.in
Received June 17, 1999
ABSTRACT
TiCl4 reacts with trialkylamines at 0−25 °C to give iminium ions that on metalation followed by reaction with diaryl ketones, produce r,â-
unsaturated aldehydes.
The TiCl4/R3N reagent system has been extensively used in
the preparation of titanium enolates for application in aldol
reactions.1 Also, it has been used for the oxidative coupling
of phenylacetic acid esters and amides to obtain the corre-
sponding 2,3-diphenylsuccinic acid derivatives.2
the results are summarized in Table 1.4 The symmetric diaryl
ketones, 1-4 and 7, produced the corresponding R,â-
unsaturated aldehydes in good yields. The unsymmetric
ketone, 4-methylbenzophenone (6), gave a 1:1 mixture of E
Previously, we examined the use of the TiCl4/Et3N reagent
system for the oxidative coupling of aryl methyl ketimines
to 2,5-diarylpyrroles3a and for the direct metalation of
1-alkynes.3b Herein, we report that the reaction of trialkyl-
amines with TiCl4 gives iminium ions which undergo
metalation followed by reaction with diaryl ketones to
produce the corresponding R,â-unsaturated aldehydes (eq 1).
(2) (a) Matsumara, Y.; Nishimura, M.; Hiu, H.; Watanabe, M.; Kise, N.
J. Org. Chem. 1996, 61, 2809.
(3) (a) Periasamy, M.; Srinivas, G.; Bharathi, P. J. Org. Chem. 1999,
64, 4204. (b) Bharathi, P.; Periasamy, M. Unpublished results.
(4) Representative Procedure for the Reaction of Diaryl Ketones. In
DCM (25 mL), benzophenone (0.456 g, 2.5 mmol) and TiCl4 (2.2 mL of
1:1 solution of TiCl4/CH2Cl2, 10 mmol) were taken at 0 °C under N2. The
Et3N (1.4 mL, 10 mmol) was added to this solution and stirred for 0.5 h at
0 °C. It was stirred further at 25 °C for 8 h. A saturated NH4Cl solution
(20 mL) was added and stirred for 0.5 h. The organic layer was separated,
and the aqueous layer was extracted with CH2Cl2 (2 × 25 mL). The
combined organic extract was washed with brine solution (10 mL) and dried
over anhydrous MgSO4. The solvent was removed and the residue was
chromatographed on a silica gel column. The unreacted ketone was eluted
using 2:98 EtOAc/hexane mixture. The aldehyde 1a, 3,3-diphenyl-2-
propenal, was separated using 4:98 EtOAc/hexane mixture as eluent (0.374
g, 72%). Procedure for the Reaction of Benzaldehyde. In DCM (25 mL),
TiCl4 (2.2 mL of 1:1 solution of TiCl4/CH2Cl2, 10 mmol) was taken, and
the Et3N (1.4 mL, 10 mmol) was added at -78 °C under N2. The contents
stirred at -78 °C for 1 h. Benzaldehyde (1.02 mL, 10 mmol) was added at
-78 °C. The contents were brought to 25 °C in 1 h and stirred further for
2 h. A saturated NH4Cl (20 mL) solution was added and stirred for 0.5 h.
The organic layer was separated, and the aqueous layer was extracted with
CH2Cl2 (2 × 25 mL). The combined organic extract was washed with brine
solution (10 mL) and dried over anhydrous MgSO4. The solvent was
removed, and the residue was chromatographed on a silica gel column.
The unreacted benzaldehyde was eluted using 2:98 EtOAc/hexane mixture.
The cinnamaldehyde was separated using 4:98 EtOAc/hexane mixture as
eluent (0.607 g, 46%).
This transformation was examined with various aromatic
ketones and benzaldehyde. It was found to be general, and
(1) (a) Harrison, C. R. Tetrahedron Lett. 1987, 4135. (b) Evans, D. A.;
Clark, J. S.; Matternich, R.; Novack, V. J.; Sheppard, G. S. J. Am. Chem.
Soc. 1990, 112, 866. (c) Evans, D. A.; Rieger, D. L.; Bilodeau, M. T.;
Urpi, F. J. Am. Chem. Soc. 1991, 113, 1047. (d) Crimmins, M. T.; King,
B. W.; Tabet, E. A. J. Am. Chem. Soc. 1997, 119, 7883. (e) Yoshida, Y.;
Hayashi, R.; Sumihara, H.; Tanabe, Y. Tetrahedron Lett. 1997, 8727 and
references therein.
10.1021/ol990745d CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/31/1999

species that on metalation followed by reaction with diaryl
ketone would give the product as shown in Scheme 1. There
is precedence for such processes in the Pd(II)6 and Hg(II)7
chemistry.
Table 1. Reaction of Diaryl Ketone/Aldehyde with TiCl4/Et3N
Scheme 1
We have also examined this transformation using other
tertiary amines (Scheme 2). Whereas the Et3N gave good
Scheme 2
a The products were identified by 1H,13C-NMR and mass spectral data.8
b The yields are based on the ketone/aldehyde used.
and Z isomers. However, the ferrocenyl phenyl ketone (5)
gave only one isomer. In the case of flourenone (4), the
McMurry coupling product 9,9′-bifluorene (4%) was also
isolated. The benzaldehyde yielded cinnamaldehyde in
addition to some unidentified polar compounds.
In 1955, it was reported that the reaction of TiCl4 with
N(CH3)3 leads to “(CH3)2NCH2Cl” and TiCl3.5 Accordingly,
this transformation may be explained by the tentative
mechanistic pathway involving iminium ion intermediate as
outlined in Scheme 1. The reaction of TiCl4 with trialkyl-
amine may proceed with the initial formation of an amine-
TiCl4 complex. Elimination of â-hydrogen from the amine
moiety of this complex would produce the iminium ion
yields of the aldehydes, other amines produced the aldehydes
in low yields. However, the reaction of tributylamine is
interesting since there is further dehydrogenation. Presum-
ably, the initially formed iminium ion undergoes metalation
(6) (a) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G.
Principle and application of organotransition metal chemistry; University
Science Books: Mill Valley, 1987; p 725. (b) McCrindle, R.; Ferguson,
G.; Arsenault, G. J.; McAlees, A. J.; Stephenson, D. K. J. Chem. Res. (S)
1984, 360.
(7) Leonard, N. J.; Hay, A. S.; Fulmer, R. W.; Gash, V. W. J. Am. Chem.
Soc. 1955, 77, 439.
(5) Antler, W., Lambengayer, A. W. J. Am Chem. Soc. 1955, 77, 5250.
858
Org. Lett., Vol. 1, No. 6, 1999

followed by elimination of “HTiCl3” to give the conjugated
iminium ion A which on further reactions produces the
corresponding aldehyde (Scheme 3). Similar results were also
realized with some N-alkyl piperidine derivatives (Scheme
2).
Scheme 3
We have also observed that the reaction of TiCl4 with
tribenzylamine gives dibenzylamine (22%) and benzaldehyde
(8) 1a: 13C NMR (δ ppm) 193.02, 161.91, 139.77, 136.79, 130.68,
130.43, 129.40, 128.62, 128.36, 127.37; 1H NMR (δ ppm) 6.6 (d, 1H),
7.2-7.6 (m, 10H), 9.5 (d, 1H); M+ (e/m) 208. 2a: 13C NMR (δ ppm) 192.41,
159.18, 137.81, 136.94, 136.02, 134.66, 131.93, 129.80, 129.05, 128.88,
127.76; 1H NMR (δ ppm) 6.6 (d, 1H), 7.25-7.6 (m, 8H), 9.55(d, 1H); M+
(e/m) 277. 3a: 13C NMR (δ ppm) 193.30, 162.25, 140.84, 139.51, 137.20,
1
134.05, 130.78, 129.33, 128.98, 128.69, 126.53, 21.28; H NMR (δ ppm)
2.35 (s, 3H), 2.45 (s, 3H), 6.65 (d, 1H), 7.2-7.4 (m, 8H), 9.6 (d, 1H). 4a:
13C NMR (δ ppm) 190.08, 151.12, 142.68, 141.08, 138.50, 135.00, 131.48,
131.38, 127.94, 127.59, 122.93, 122.30, 120.47, 120.12; 1H NMR (δ ppm);
6.8 (d, 1H), 7.2-7.4 (m, 8H), 10.8 (d, 1H); M+ (e/m) 206. 5a: 13C NMR
(δ ppm) 192.56, 165.28, 136.52, 129.38, 128.72, 128.02, 124.24, 81.99,
71.63, 70.23, 69.01; 1H NMR (δ ppm) 4.28-4.5 (m, 9H), 6.5 (d, 2H), 7.25-
7.55 (m, 5H), 9.35 (d, 1H); M+ (e/m) 316. 6a: 13C NMR (δ ppm) 193.33,
162.29, 162.13, 140.99, 140.06, 139.68, 136.90, 133.85, 130.84-126.59,
1
21.35; H NMR (δ ppm) 2.39 (s, 3H), 2.44 (s, 3H), 6.57 (d, 1H), 6.61 (d,
(18%) under these conditions. This observation further
illustrates the formation of iminium ion intermediates.
1H), 7.20-7.46 (m, 18H). 7a: 13C NMR (δ ppm) 192.42, 166.70, 166.01,
161.70, 161.02, 159.47, 135.77, 132.58, 132.41, 131.28, 130.64, 130.46,
129.83, 129.67, 127.41, 116.00, 115.85, 115.57, 115.42, 114.84, 114.29,
In conclusion, the iminium ions and the corresponding
novel metalated iminium species reported here have good
potential for further synthetic applications.
1
114.28; H NMR (δ ppm) 6.5 (d, 1H), 7-7.4 (m, 8H), 9.45 (d, 1H); M+
(e/m) 244. 8a: 13C NMR (δ ppm) 193.55, 152.65, 134.05, 131.23, 129.09,
128.51; 1H NMR (δ ppm) 6.7 (d, 1H), 6.8 (d, 1H), 7.3-7.7 (m, 5H), 9.75,
(d, 1H). 9a: 13C NMR (δ ppm) 194.12, 159.33, 140.87, 138.90, 135.30,
131.17, 129.61, 128.92, 128.66, 128.26, 128.11, 14.26 (data of DEPT
experiments correspond to the structure); 1H NMR (δ ppm) 2.0 (s, 3H),
7.2-7.5 (m, 10H), 9.6 (s, 1H); M+ (e/m) 222. 10a: 13C NMR (δ ppm)
193.70, 153.07, 149.62, 140.85, 138.37. 132.50, 130.37, 129.24, 128.66,
128.50, 128.28, 125.27 (data of DEPT experiments correspond to the
structure); 1H NMR (δ ppm) 6.25 (d, 1H), 6.35 (d, 1H), 6.95 (d, 1H), 7.2-
7.65 (m, 11H), 9.48 (d, 1H); M+ (e/m) 234. 11a: 13C NMR (δ ppm) 194.35,
153.77, 151.94, 141.82, 141.08, 130.63, 129.83, 129.17, 128.15, 127.87,
Acknowledgment. We are grateful to the UGC (New
Delhi) for financial support. We are also thankful to the UGC
for support under Special Assistance Program.
Supporting Information Available: 13C NMR spectra
of compounds 1a-12a and IH NMR spectra of compounds
1a, 5a, 6a, and 9a-12a. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
17.04; H NMR (δ ppm) 2.0 (s, 3H), 6.35 (d, 1H), 6.45 (d, 1H), 9.55 (d,
1H 1H), 7.2-7.6 (m, 10H), 9.55 (s, 1H); M+ (e/m) 248. 12a: 13C NMR (δ
ppm) 194.52, 152.49, 151.50, 141.96, 141.08, 136.89, 130.48, 129.11,
128.95, 128.27, 128.17, 127.75, 23.43, 14.08 (data of DEPT experiments
correspond to the structure);1H NMR (δ ppm) 1.2 (t, 3H), 2.45 (q, 2H), 6.4
(d, 1H), 6.35 (d, 1H) 7.2-7.5 (m, 10H), 9.5 (s, 1H); M+ (e/m) 262.
OL990745D
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