A. Clerici et al. / Tetrahedron Letters 45 (2004) 1825–1827
1827
m=z 297–295 (M + 1, 40); 296–294 (M, 60); 102 (100).
Treatment of 3 in CHCl3 with water, under vigorous
stirring for 1 h, afforded trans-4-Br-cinnamaldehyde 4a in
the organic layer and di-isopropylamine hydrochloride in
the aqueous phase. 4a: mp ¼ 80 ꢁC (ether); 1H NMR
(CDCl3): d 6.70 (1H, dd, J ¼ 7:9, 15.9 Hz); 7.42 (1H, d,
J ¼ 15:9 Hz); 7.43 (2H, ArH, d, J ¼ 8:8 Hz); 7.58 (2H,
ArH, d, J ¼ 8:8 Hz); 9.71 (1H CHO, d, J ¼ 7:9 Hz). MS
(CI): m=z 213–211 (M + 1, 100).
Since this novel reduction system seems to have general
applicability, its extension is under investigation to both
other amines and other substrates. It remains to be seen
whether this attractive approach is to be successful in
enantioselective and/or catalytic pinacol coupling.
7. Method I: dropwise addition of 2.0 mL of a 1.0 M TiCl4
solution in CH2Cl2 (2.0 mmol) to a well stirred solution of
DIPEA (2.0 mmol) in CH2Cl2 (10 mL), cooled at 0 ꢁC
under N2, afforded an instantaneous violet solution
indicative of TiCl3 formation. After 10 min, 4-Br-benz-
aldehyde (2.0 mmol) dissolved in CH2Cl2 (5 mL) was
added in one portion. After further 30 min at rt, the
reaction was quenched with a semisaturated NH4Cl
solution (10 mL) under vigorous stirring. The mixture
was then extracted with AcOEt6 (3 · 50 mL), the organic
layers washed with water (3 · 5 mL), dried and concen-
Acknowledgements
We wish to thank Prof. F. Minisci for helpful discus-
1
sions, Mr. M. Teti for running H NMR analyses and
MURST (Cofin 2002) for financial support of this work.
References and notes
1. (a) Evans, D. A.; Urpi, F.; Somers, T. C.; Clark, J. S.;
Bilodeau, M. T. J. Am. Chem. Soc. 1990, 112, 8215–8216;
(b) Evans, D. A.; Clark, J. S.; Metternich, R.; Novack, V.
J.; Sheppard, G. S. J. Am. Chem. Soc. 1990, 112, 866–868;
(c) Evans, D. A.; Rieger, D. L.; Bilodeau, M. T.; Urpi, F.
J. Am. Chem. Soc. 1991, 113, 1047–1049; (d) Figueras, S.;
Martin, R.; Romea, P.; Urpi, F.; Vilarrasa, J. Tetrahedron
Lett. 1997, 38, 1637–1640; (e) Crimmins, M. T.; King,
B. W.; Tabet, E. J. Am. Chem. Soc. 1997, 119, 7883–7884;
(f) Adrian, J. J. C.; Barkin, J. L.; Fox, R. J.; Chick, J. E.;
Hunter, A. D.; Nicklow, R. A. J. Org. Chem. 2000, 65,
6264–6267; (g) For a selected review, see: Arya, P.; Qin, H.
Tetrahedron 2000, 56, 917, and references cited therein; (h)
Crimmins, M. T.; King, B. W.; Tabet, E. A.; Chandhardy,
K. J. Org. Chem. 2001, 66, 894–902; (i) Chosh, A. K.;
Kim, J. H. Tetrahedron Lett. 2002, 43, 5621–5624, and
references cited therein.
2. Yoshida, Y.; Hayashi, R.; Sumihara, H.; Tanabe, Y.
Tetrahedron Lett. 1997, 38, 8727–8730, see note 11.
3. We did not observe this redox process when co-ordinating
solvents, such as THF or MeOH, were used instead of
CH2Cl2. With these solvents, the octahedral co-ordinative
valence of the metal ion is saturated, thus hampering
further TiCl4 complexation with DIPEA.
1
trated in vacuo. H NMR analysis of the crude mixture,
added with an internal standard, afforded the yields and
dl/meso ratio of 2a (and/or 5a) given in Table 1 (entries 1–
3). The combined aqueous layers were brought to a
pHꢀ8–9 by addition of a 10% NaOH solution and then
extracted with AcOEt (3 · 50 mL). Upon usual workup,
trans-4-Br-cinnamaldehyde 4a was recovered (1H NMR
purity P 95%) in the isolated yields reported in Table 1.
Method II: dropwise addition of 2.0 mL of a 1.0 M TiCl4
solution in CH2Cl2 (2.0 mmol) to a well stirred solution of
1a (2.0 mmol) in CH2Cl2 (10 mL), cooled at 0 ꢁC under N2,
afforded a yellow slurry precipitate indicative of 1a-TiCl4
complexation. After 10 min, DIPEA (2.0 mmol) was added
dropwise (5 min) with a syringe affording a homogeneous
green solution, and stirring was continued for additional
30 min at room temperature. Workup as above. Method
III: to a well stirred solution of 1a (2.0 mmol) and DIPEA
(4.0 mmol) in CH2Cl2 (10 mL), cooled at 0 ꢁC under N2,
2.0 mL of a 1.0 M solution of TiCl4 solution in CH2Cl2
(2.0 mmol) were added. The resulting green solution was
then stirred for additional 30 min at room temperature.
Workup as above. 2a (dl): mp 176 ꢁC;8 1H NMR (CDCl3):
d 4.59 (2H, s); 6.96 (4H, ArH, d, J ¼ 8:4 Hz); 7.36 (4H,
ArH, d, J ¼ 8:4 Hz). 2a (meso): mp 137 ꢁC;8 1H NMR
(CDCl3): d 4.80 (2H, s); 7.03 (4H, ArH, d, J ¼ 8:4 Hz);
7.40 (4H, ArH, d, J ¼ 8:4 Hz). 5a: mp 79–82 ꢁC; 1H NMR
(CDCl3): d 2.0 (1H, OH, s, D2O exchanged); 4.65 (2H,
CH2, s); 7.24 (2H, ArH, d, J ¼ 8:2 Hz); 7.48 (2H, ArH, d,
J ¼ 8:2 Hz).
4. The violet color sometimes observed was erroneously
considered indicative of enolate formation.1f
5. Enamines without hydrogen on the nitrogen, as F, are
normally stable: March, J. Advanced Organic Chemistry;
John Wiley: New York, 1985; pp 69–70 and references
cited therein.
6. When the reaction mixture is extracted with AcOEt,
iminium salt 3 remains in the aqueous layer, but if the
extraction is performed with CH2Cl2, 3 is partially
isolated. Recrystallization from CH2Cl2/AcOEt afforded
8. Clerici, A.; Clerici, L.; Porta, O. Tetrahedron Lett. 1996,
37, 3035–3038.
9. Aromatic ketones undergo reductive dimerization only in
TiCl3/NaOH aqueous solution, owing to the increased
reducing power of Ti(III) in basic medium. (a) Clerici, A.;
Porta, O. J. Org. Chem. 1985, 50, 76–81; (b) Clerici, A.;
Pastori, N.; Porta, O. Eur J. Org. Chem. 2002, 3326–3335.
10. (a) Clerici, A.; Porta, O. J. Org. Chem. 1982, 47, 2852–2856;
(b) Clerici, A.; Porta, O. J. Org. Chem. 1985, 50, 76–82.
1
white needles: mp 218–20 ꢁC (dec); H NMR (CDCl3): d
1.49 (6H, d, J ¼ 6:5 Hz); 1.64 (6H, d, J ¼ 6:5 Hz); 4.22
(1H, septuplet, J ¼ 6:5 Hz); 4.98 (1H, septuplet, J ¼
6:5 Hz); 7.55 (2H, ArH, d, J ¼ 8:3 Hz); 7.58 (1H, dd,
J ¼ 10:5, 14.8 Hz); 7.75 (2H, ArH, d, J ¼ 8:3 Hz); 8.91
(1H, d, J ¼ 14:8 Hz); 9.99 (1H, d, J ¼ 10:5 Hz). MS (CI):