A highly dl-stereoselective pinacolization of aromatic aldehydes mediated by TiCl4-Zn

Article abstract of DOI:10.1039/a909032k

Reduction of TiCl₄(THF)₄ with Zn in CH₂Cl₂ gave a green solution, which was found to promote the reductive coupling of aromatic aldehydes to yield 1,2-diols with high threo selectivity.

Full text of DOI:10.1039/a909032k

A highly dl-stereoselective pinacolization of aromatic aldehydes mediated by
TiCl –Zn
4
Tingyou Li, Wei Cui, Jigang Liu, Jianzhang Zhao and Zongmu Wang*
College of Life Science, Jilin University, Changchun, 130023, P.R. China. E-mail: liwei@mail.jlu.edu.cn
Received (in Cambridge, UK) 15th November 1999, Accepted 2nd December 1999
Reduction of TiCl
4
(THF)
4
with Zn in CH
2
Cl
2
gave a green
was selected as the solvent, with THF as a ligand and a mole
ratio of TiCl to Zn of 2+1, better results were obtained.
A typical procedure is as follows: THF (11.7 mmol) was
added dropwise to a solution of TiCl (3.65 mmol) in 10 ml of
CH Cl under an atmosphere of argon at room temperature. To
solution, which was found to promote the reductive coupling
of aromatic aldehydes to yield 1,2-diols with high threo
selectivity.
4
4
2
2
The pinacol coupling reaction, which allows the generation of
this solution Zn (1.82 mmol) was added in one portion. The
color of the solution changed to green immediately. After
1,2-diols in one step, is a powerful synthetic reaction, and
therefore has been recognized as one of the most significant C–
C bond forming processes in synthetic organic chemistry.1 In
addition, threo-1,2-diols have, after resolution, frequently been
utilized as auxiliaries in asymmetric synthesis.3 Although a
number of methods have been developed for the reductive
stirring for 3 min benzaldehyde (3.65 mmol) in 3 ml of CH
was added in one portion. After 30 min of stirring, the reaction
was quenched with 15 ml of 10% K CO and extracted with
EtOAc followed by chromatography to give 0.22 g of
hydrobenzoin (57%, 94+1 dl+meso).
2 2
Cl
,2
2
3
4–6
coupling of carbonyl compounds, selective pinacolization to
When the reduction time was less than 20 min, acceptable
yields and high dl selectivities were obtained. However, when
the reduction time was greater than 1 h, the color of solution
changes from green to black, and no product was obtained.
threo-diols has only been found with stannylene precursors,7
‘
4 2
active titanium(III) reagents’ prepared from TiCl /BuLi in Et O
8
i
9
10
at 278 °C, TiCl
4
/Bu
2
Te in DME, TiCl
TiCl) , a binuclear complex, can be easily
and used in stiochiometric or catalytic
3 2 2
/CH Cl solution or
11,12
14
(
Cp
2
TiCl)
2
.
(Cp
2
2
According to the reports of Piotr Sobota and Kirrsten
prepared from Cp
2
TiCl
2
Foling,15 we assume that the TiCl
4
(THF)
2
was first reduced to
; ZnCl can then
] and form ionized
(THF) ]. We think the binuclear complex
] is the active compound which reduces
the benzaldehyde to pinacol with high dl-selectivity, exactly as
amounts in the pinacol coupling reaction. Many of these
reagents are expensive and/or air sensitive.
[Ti
2
(m-Cl)
2
Cl
4
(THF)
4
] by Zn in CH
(m-Cl) Cl
2
Cl
2
2
abstract chlorine from [Ti
[TiCl (THF)
2
2
4
(THF)
4
+
2
Here we report the TiCl
aromatic aldehydes in anhydrous solvent at room temperature.
By the choice of an appropriate mole ratio of TiCl and Zn and
an appropriate coordinating additive such as TMEDA, TiCl-Zn
and TiCl –Zn–TMEDA reduce benzaldehyde and other actived
4
–Zn promoted reductive coupling of
2
4
·ZnCl
(THF)
4
3
[Ti (m-Cl) Cl
2
2
4
4
(Cp
[TiCl
2
TiCl)
2
has
·ZnCl
3
high
dl-selectivity.
The
(THF) ] has no activity to benzaldehyde.
and suppress
], a coordinating ad-
ionized
+
2
4
2
(THF)
4
aromatic aldehydes to the corresponding pinacols in good yields
and, what is more important, the coupling is highly dl
selective.
It is noteworthy that the reagents used are readily available,
inexpensive and stable to air oxidation, and the method is easier
and more convenient compared with those so far reported. Thus,
we produced ‘actived titanium’ and reduced aldehydes in one
pot in only a short time.
In order to lower the Lewis activity of the ZnCl
ionization of the [Ti (m-Cl) Cl (THF)
2
2
2
4
4
ditive, especially Lewis bases such as Py and TMEDA, is added.
When the reduction was carried out in the presence of 1.5 equiv.
of TMEDA as an additive the yield improved to 76% and only
the dl-isomer was obtained.
Under the optimised conditions, a variety of symmetrical
1,2-diols were synthesized in good yields and excellent
selectivity, and could be obtained diastereomerically pure after
In 1973, Mukaiyama13 reported that TiCl
–Zn reduced
aromatic aldehydes or ketones to produce the corresponding
,2-diols in high yield, but the stereoselectivity was not
reported. At the outset of the study, we used THF as solvent,
with an aldehyde to TiCl to Zn ratio of 1+1.5+3, and obtained
the hydrobenzoin with a dl+meso ratio of 3+1. When CH Cl
4
1
Table 2 Reductive coupling of aldehyes under optimised conditions
4
2
2
4
Table 1 Coupling of benzaldehyde mediated by TiCl –Zn
Chem. Commun., 2000, 139–140
This journal is © The Royal Society of Chemistry 2000
139

Notes and references
1
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2
3
B. Schmidt and D. Seebach, Angew. Chem., Int. Ed. Engl., 1991, 30,
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4
Fig. 1
1
5
6
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1
976, 42, 260.
a single recrystallization. Functional groups, such as halide and
cyano groups, are tolerated. Aromatic aldehydes bearing an
electron-donating group showed lower reactivity, for example,
p-anisaldehyde afforded no significant conversion via TLC
observation.
Mechanistically it seems reasonable to assume that the active
species is a binuclear titanium complex binding both ketyl
radicals, in which the Ar groups are arranged anti to each other
to minimized steric interaction. When the binuclear titanium
complex is coordinated with TMEDA, the sterically crowded
environment drastically improved the pinacol diastereoselectiv-
ities (Fig. 1).
7 C. Grugel, W. P. Neumann and J. Seifert, Tetrahedron Lett., 1978,
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8
9
H. G. Raubenheimer and D. Seebach, Chimia, 1986, 40, 12.
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Communication a909032k
140
Chem. Commun., 2000, 139–140