Chemistry Letters 2000
839
coupling of an aldehyde. Then, it was revealed that pinacols
were obtained within 6 hours in high yields with high diastereo-
selectivities when 2 or 3 molar amounts of copper to
titanium(IV) iodide were used (entries 4–6). On the other hand,
when a combination of titanium(IV) bromide and copper was
used, the reaction proceeded slowly and the yield of pinacol
was rather low (entries 10,11), though the corresponding pinacol
was obtained in high yield when 3-phenylpropionaldehyde was
treated with titanium(II) bromide and copper for a longer time
(18 hours, entry 12).
obtained at all. Concerning the pinacol coupling reaction of
pivalaldehyde by using other metals, niobium,12 samarium13
and cerium14 proceeded to give the corresponding pinacol in
fairly good yield with high diastereoselectivity. However,
yields of the corresponding pinacols decreased when α-mono-
and α-di-substituted aliphatic aldehydes were treated with the
above metallic compounds.
As for the reaction mechanism, the reductive coupling pro-
ceeded by a similar manner as mentioned in the case of using
titanium(II) bromide and copper reducing system shown in the
previous communication.5
Thus, an efficient method was established for the pinacol
coupling reaction of aromatic and α-mono-, di-, tri-substituted
aliphatic aldehydes by using a combination of titanium(IV)
iodide and copper in a mixed solvent of dichloromethane and
pivalonitrile affording the corresponding pinacols in good to
high yields and dl-diastereoselectivities.
This work was supported by Grant-in-Aids for Scientific
Research from the Ministry of Education, Science, Sports and
Culture.
References and Notes
1
For a review, see: a) G. M. Robertson, in “Comprehensive
Organic Synthesis,” ed. by B. M. Trost and I. Fleming, Pergamon
Press, Oxford (1991), Vol. 3, p 563. b) T. Wirth, Angew. Chem.,
Int. Ed. Engl., 35, 61 (1996). c) A. Fürstner and B Bogdanovic,
Angew. Chem., Int. Ed. Engl., 35, 2442 (1996).
a) A. Clerici, L. Clerici, and O. Porta, Tetrahedron Lett., 37, 3035
(1996). b) T. A. Lipski, M. A. Hilfiker, and S. G. Nelson, J. Org.
Chem., 62, 4566 (1997).
2
3
4
5
6
T. Mukaiyama, A. Kagayama, and I. Shiina, Chem. Lett., 1998,
1107.
S. Matsubara, Y. Hashimoto, T. Okano, and K. Utimoto, Synlett,
1999, 1411.
T. Mukaiyama, A. Kagayama, and K. Igarashi, Chem. Lett., 2000,
336.
G. Brauer, “Handbook of Preparative Inorganic Chemistry,” ed.
By G. Brauer, Academic Press, New York (1965), Vol. 2. p 1185.
S. P. Narula and H. K. Sharma, Inorg. Synth., 24, 181 (1985).
Postulated low valent titanium iodide mediated reducting coupling
of carbonyl compounds affording the corresponding olefins was
reported by S. Talukdar, S. K. Nayak, and A. Banerji, J. Org.
Chem., 63, 4925 (1998).
Copper powder was purchased from Soekawa Chemical Co., Ltd.
and used as received. Other metals were dried under vacuum at
100 °C.
7
8
Based on these results, reductive coupling reactions of var-
ious aromatic and aliphatic aldehydes using low valent titanium
iodide reducing system were tried (summarized in Table 2).
Aromatic and α,β-unsaturated aldehydes were converted to the
corresponding pinacols at –23 °C in good to high yields and
diastereoselectivities along with small amounts of 1,3-di-
oxolanes (entries 1–4). When aliphatic aldehydes were used as
substrates, the reductive coupling proceeded at the temperature
ranging from 0 °C to room temperature to give the corresponding
pinacols in good to high yields and diastereoselectivities
(entries 5–10). Concerning vanadium complex catalyzed pinacol
coupling reaction, Hirao and co-workers suggested that the
diastereoselection was affected by the bulkiness of the α-posi-
tion of aldehydes.11 In the case of using a combination of tita-
nium(IV) iodide and copper, it is interesting to note that the
coupling proceeded smoothly to give pinacols in good to high
yields and diastereoselectivities, irrespective of the number of
substitutuents at α-position of aliphatic aldehydes. Different
from the above results, when a bulky α-tri-substituted aliphatic
aldehyde, e.g. pivalaldehyde, was treated with a combination of
titanium(II) bromide and copper, the coupling product was not
9
10 The typical reaction procedure for the pinacol coupling of 3-
phenylpropionaldehyde: To a reddish brown suspension of titani-
um(IV) iodide (0.65 mmol) and copper powder (1.3 mmol) in
dichloromethane (2.5 ml) was added pivalonitrile (2.6 mmol)
under argon atmosphere. The color was changed to dark brown
and the mixture was stirred for additional 30 minutes at room tem-
perature. Resulted CuI or CuI2 suspended dark brown solution
was cooled to 0 °C and a solution of 3-phenylpropionaldehyde
(0.5 mmol) in dichloromethane (1.5 ml) was added. The reaction
mixture was stirred for 6 hours, and then the work up was done as
shown in Ref. 3. The crude product was purified by TLC to afford
the desired pinacol and co-product (80% and 11%, respectively).
11 T. Hirao, M. Asahara, Y. Muguruma, and A. Ogawa, J. Org.
Chem., 63, 2812 (1998).
12 J. Szymoniak, J. Besançon, and C Moïse, Tetrahedron, 50, 2841
(1994).
13 T. B. Christensen, D. Riber, K. Daasbjerg, and T Skrydstrup,
Chem. Commun., 1999, 2051.
14 U. Groth and M. Jeske, Angew. Chem., Int. Ed. Engl., 39, 574
(2000).