Zirconocene dichloride-catalyzed pinacol coupling of aromatic aldehydes and ketones

Article abstract of DOI:10.1080/00397910500522165

The reductive coupling of aromatic aldehydes and ketones has been achieved using a catalytic amount of zirconocene dichloride in the presence of magnesium metal and chlorotrimethylsilane in THF at room temperature to afford the corresponding 1,2-diols in good yields and diastereoselectivity. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910500522165

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Zirconocene Dichloride–Catalyzed Pinacol
Coupling of Aromatic Aldehydes and Ketones
a
a
a
M. Lakshmi Kantam , Khathija Aziz & Pravin R. Likhar
a
Inorganic and Physical Chemistry Division , Indian Institute of Chemical
Technology , Hyderabad, India
Published online: 16 Aug 2006.
To cite this article: M. Lakshmi Kantam , Khathija Aziz & Pravin R. Likhar (2006) Zirconocene
Dichloride–Catalyzed Pinacol Coupling of Aromatic Aldehydes and Ketones, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:10, 1437-1445
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Synthetic Communications , 36: 1437–1445, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500522165
Zirconocene Dichloride–Catalyzed Pinacol
Coupling of Aromatic Aldehydes
and Ketones
M. Lakshmi Kantam, Khathija Aziz, and Pravin R. Likhar
Inorganic and Physical Chemistry Division, Indian Institute of Chemical
Technology, Hyderabad, India
Abstract: The reductive coupling of aromatic aldehydes and ketones has been
achieved using a catalytic amount of zirconocene dichloride in the presence of
magnesium metal and chlorotrimethylsilane in THF at room temperature to afford
the corresponding 1,2-diols in good yields and diastereoselectivity.
Keywords: Carbonyl compounds, pinacol coupling, reductive coupling, zirconocene
dichloride
INTRODUCTION
The reductive coupling of carbonyl compounds is an important methodology
[1]
in organic synthesis that offers direct access to 1,2-diols. The 1,2-diols are
versatile building blocks in biologically active molecules and as the chiral
[
2]
ligands.
factors such as reductants, solvents, and the reaction pH. The classical
The selective pinacol formation critically depends on many
[1]
[3]
[3]
pinacol-coupling reactions use amalgams of sodium, magnesium, or
[5]
aluminium. Since the pioneering contributions by Mukaiyama et al. and
[
4]
[
6]
[7]
McMurry and Fleming, many stoichiometric reagents (Mg/TMSCl,
[
5]
[8]
[9]
TiCl /Zn, TiCl /Li(Hg), CeI2, Yb,
[10]
[11]
[12]
and Sm(Hg) ) have
Nb,
4
4
been developed for this reaction. The introduction of low-valent transition
metals and lanthanoid-based reagents has provided dramatic developments
Received in India October 10, 2005
Address correspondence to M. Lakshmi Kantam, Inorganic and Physical Chemistry
Division, Indian Institute of Chemical Technology, Hyderabad 500007, India.
Fax: þ91-40-27160921; E-mail: mlakshmi@iict.res.in
1
437

1
438
M. L. Kantam, K. Aziz, and P. R. Likhar
[
[
13]
14]
in efficiency and selectivity of inter- or intramolecular pinacol coupling.
Later catalytic versions of pinacol coupling were developed by Gansauer
using a titanocene complex in the presence of Zn/MgBr and Me SiCl
2
3
[
15]
[16]
and by Mori et al.
using InCl /Mg/TMSCl. Recently Shi et al.
3
described the pinacol coupling of carbonyl compounds stoichiometrically
by Rieke nickel and catalytically using NiCl2 with Li or Mg/TMSCl
respectively.
Earlier, pinacol coupling of 2,3-O-isopropylidene-D-glyceraldehyde, ben-
zaldehyde, and acetophenone was reported using a stoichiometric amount of
III
Cp Zr Cl) .
[17]
(
Na/Hg.
The dimer was prepared by the reduction of Cp ZrCl with
2 2
2
2
In continuation of our interest in zirconocene dichloride–catalyzed
organic transformations, we herein report the pinacol coupling of aromatic
aldehydes and ketones using zirconocene dichloride as a catalyst in the
presence of both magnesium metal and chlorotrimethyl silane (TMSCl)
to provide the corresponding 1,2-diols respectively in good yields and
diastereoselectivity (Scheme 1).
RESULTS AND DISCUSSION
The results of the reductive coupling of various carbonyl compounds are
shown in Table 1, and they demonstrate that this catalytic system was
effective for a broad range of substrates including aromatic aldehydes and
aromatic ketones. The property of substituents at the para position showed
no significant effect on this coupling reaction (Table 1, entries 2–5). There
is no reaction without Mg or TMSCl. However, when the reaction time is
prolonged to 25 h, even in the absence of the catalyst, pinacol is obtained in
very low yield albeit without diastereoselectivity. The reductive coupling of
aromatic ketones proceeded smoothly to afford 1,2-diols in moderate yields
with moderate diastereoselectivity (Table 1, entries 6–8) with the use of
10 mol% zirconocene dichloride.
Scheme 1. Ar = C
R ¼ CH , C
6 5 6 5 3 6 5 6 5 3 6 5
H , 4-Cl-C H , 4-OCH -C H , 4-OH-C H , and 4-CH -C H ;
3
6 5
H .

a
Table 1. Reductive coupling of aromatic carbonyl compounds catalyzed by zirconocene dichloride/Mg
b
Yield (%)
c
Entry
Substrate
Time (h)
Product
dl/meso
1
2
70
62
72/28
2
8
96/04
3
4
5
3
2
73
52
87
85/15
73/27
70/30
1.5
(continued)

Table 1. Continued
b
Yield (%)
c
Entry
Substrate
Time (h)
Product
dl/meso
d
6
7
6
66
48/52
d
50
8
5
83/17
d
68
8
—
a
Reaction conditions are exemplified in the general reaction procedure.
Isolated yields obtained after chromatography.
b
c
1
Ratio determined by H NMR.
d
2
Ketone (4 mmol), Mg (8 mmol), TMSCl (16 mmol), catalyst (10 mol%), and THF (20 ml), rt, N atmosphere.

Zirconocene Dichloride–Catalyzed Pinacol Coupling
1441
Furthermore, when zinc was added as a reductant under similar conditions
the yields were improved but the diastereoselectivity pattern was changed
(Table 2).
In summary, we have developed a Cp ZrCl /Mg/TMSCl system for the
2
2
reductive coupling of aromatic aldehydes and ketones at room temperature to
afford the corresponding 1,2-diols in good yields and with diastereoselectivity.
EXPERIMENTAL
All aromatic substituted/unsubstituted aldehydes, all aromatic substituted/
unsubstituted ketones, and NaCp were purchased from Aldrich or Fluka and
used without further purification. ZrCl was supplied by NFC, Hyderabad.
4
Mg turnings, zinc metal, chlorotrimethyl silane (TMSCl), NaHCO , and
3
Na SO were purchased from s.d.fine-chem Ltd., India. ACME silica gel
4
2
(60–200 mesh) was used for column chromatography. All the other solvents
and chemicals were obtained from commercial sources and purified using
standard methods.
Preparation of Zirconocene Dichloride
The catalyst zirconocene dichloride was synthesized following the reported
[
18]
literature procedure. A suspension of zirconium tetrachloride (11.6 g,
.05 mol) was prepared using dry THF (10 ml) under nitrogen atmosphere,
0
and the sodium cyclopentadienide 2.0 M in THF (50 ml, 0.1 mol) was added
dropwise to it over a period of 20 min. Then the mixture was allowed to
stirr for 4 h. The reaction mixture was concentrated by rotavapor, and the
solid obtained was subjected to Soxhlet extraction with chloroform,
saturated with HCl gas, for 6 h. The chloroform extract was concentrated to
ca. 10 ml and crystallized at 2308C (dry ice/acetone) to get the pure
catalyst (9.1 g, 62% yield).
General Procedure for the Reductive Coupling Reaction
of Benzaldehyde
In a typical run, benzaldehyde (0.5 ml, 5 mmol) was added to a mixture of
magnesium turnings (0.480 g, 20 mmol), TMSCl (2.5 ml, 20 mmol),
Cp ZrCl (2.7 mol%), and THF (20 ml) in a round-bottomed flask and
2
2
stirred under nitrogen atmosphere at room temperature. After completion of
the reaction (TLC analysis), diethyl ether and aqueous HCl were added to
the resulting mixture. The organic layer was separated, washed with
saturated NaHCO3 solution, dried over Na SO , and concentrated. The
2
4
residue was purified by column chromatography on silica gel (60–120,

a
Table 2. Reductive coupling of aromatic carbonyl compounds catalyzed by zirconocene dichloride using Zn as reductant
b
Yield (%)
c
Entry
Substrate
Time (h)
Product
dl/meso
67/33
1
2
96
2
3
4
4
3
2
71
76
88
50/50
33/67
78/22

5
6
1.5
96
81
50/50
91/9
6
7
8
82
28/72
a
Reaction conditions: Aldehyde/ketone (5 mmol), Zn (20 mmol), TMSCl (20 mmol), catalyst (2.7 mol%), and THF solvent (20 ml), rt, N2
atmosphere.
b
Isolated yields obtained after column chromatography.
c 1
Ratio determined by H NMR.

1
444
M. L. Kantam, K. Aziz, and P. R. Likhar
eluted with hexane/ethyl acetate) to give 1,2-diphenyl-1,2-ethanediol 2a
(
370mg, 70% yield, dl/meso ¼ 72/28) and benzyl alcohol (Table 1, entry 1).
1
H NMR (CDCl ) d: 2.88 (2H, s, br), 4.59 [4.72] (2H, s), 6.9–7.2 (10H, m).
3
þ
The values in the brackets are of the meso-isomer. EIMS (m/z) 180 (M -34),
179 (100), 73 (12.5).
ACKNOWLEDGMENTS
Khathija Aziz thanks the Council of Scientific and Industrial Research, India,
for the award of a senior research fellowship.
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