492
Published on the web April 16, 2011
Iron-catalyzed Pinacol Coupling of Aryl Ketones with a Phenyltitanium Reagent:
A New Type of Catalytic Reaction
Tamio Hayashi* and Keigo Sasaki
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502
(Received February 28, 2011; CL-110165; E-mail: thayashi@kuchem.kyoto-u.ac.jp)
A reaction of aryl ketones with phenyltitanium triisoprop-
Table 1. Pinacol coupling of acetophenone (1a) with [PhTi(Oi-
Pr)3] in the presence of transition-metal catalystsa
oxide ([PhTi(Oi-Pr)3]) in the presence of [Fe(acac)3] as a catalyst
(1 mol %) gave the corresponding pinacols in high yields. The
catalytic cycle of this process involves an iron-catalyzed
disproportionation of [PhTi(Oi-Pr)3] into biphenyl and a low-
valent titanium species.
O
catalyst (1 mol%) 1M HCl(aq)
+ [PhTi(Oi-Pr)3]
Ph
Me
THF, 20 °C, 3 h
1a
OH
HO
OH
+
+
Ph Ph
Ph
Ph
Me
Me
Me
Ph Ph
Since iron is one of the most abundant metals on earth and
consequently is one of the most inexpensive and environ-
mentally friendly, there have recently been extensive studies on
the use of iron salts and complexes as catalysts for organic
transformations.1 During the course of our studies on iron-
catalyzed carbon-carbon bond forming reactions,2 we found that
a new type of iron-catalyzed transformation takes place for the
reaction of aryl ketones with phenyltitanium triisopropoxide3-5
([PhTi(Oi-Pr)3]), which gives high yields of the pinacol coupling
products.
2a
3
4a
Yield/%b Yield/%b Recovered/%b
Entry Catalyst
2ac
4a
1a
1d
2d
3e
4f
5
[Fe(acac)3]
none
[Fe(acac)3]
[Fe(acac)3]
FeCl3
81 (80)
19
64
17
32
25
17
38
53
51
50
<1
36
<1
<1
<1
<1
3
43
40
43
0
83 (80)
63
75 (73)
6
7
8
9
[Co(acac)3]
[Ni(acac)2]
[Ru(acac)3]
[Rh(acac)3]
[Pd(acac)2]
83
36
4
4
3
Table 1 demonstrates the unique catalysis by iron salt to
promote pinacol coupling. Thus, to a solution of [Fe(acac)3]
(0.01 mmol, 1 mol %) in THF (2.0 mL) were added a solution of
[PhTi(Oi-Pr)3], which was generated in a separate flask from
[ClTi(Oi-Pr)3] (1.5 mmol) and PhLi in cyclohexane/Et2O
(1.6 mmol), and acetophenone (1a, 1.0 mmol) successively,
and the mixture was stirred at 20 °C for 3 h. Acidic hydrolysis
with 1 M HCl followed by silica gel chromatography gave
0.40 mmol (80% yield) of pinacol coupling product, 2,3-
diphenylbutane-2,3-diol (2a, dl/meso = 8/2), together with
0.485 mmol (97% based on 1a) of biphenyl (3) and 0.19 mmol
(19%) of 1,1-diphenylethanol (4a) (Entry 1). In the absence of
[Fe(acac)3], the pinacol 2a or biphenyl (3) was not formed under
otherwise the same conditions. Instead, the reaction gave 64%
yield of alcohol 4a which should result from nucleophilic attack
of the phenyltitanium reagent on ketone 1a (Entry 2). Thus, the
present pinacol coupling is clearly demonstrated to be catalyzed
by the small amount of [Fe(acac)3]. The yield of pinacol 2a was
slightly enhanced by increasing the amount of [Fe(acac)3]
catalyst to 5 mol % (Entry 3). The use of isolated [PhTi(Oi-Pr)3]
in place of the in situ generated phenyltitanium also gave
pinacol 2a albeit in a little lower yield (Entry 4). The pinacol
coupling was also observed with FeCl3 as a catalyst (Entry 5).
Of other metal complexes examined, [Co(acac)3] was catalyti-
cally as active as [Fe(acac)3] to give a high yield of 2a (Entry 6).
[Ni(acac)2] also catalyzed the present pinacol coupling although
its activity is lower than that of [Fe(acac)3] or [Co(acac)3]
(Entry 7). Ruthenium, rhodium, or palladium acac complex did
not catalyze the pinacol coupling (Entries 8, 9, and 10).
10
aThe reaction was carried out with 1a (1.0 mmol), [PhTi(Oi-
Pr)3] (1.5 mmol, generated from [ClTi(Oi-Pr)3] and PhLi),
catalyst (0.01 mmol, 1 mol %) in THF at 20 °C for 3 h. De-
termined by 1H NMR. The numbers in parentheses are isolated
yield. cThe ratio of dl/meso 2a is 8/2 for all the Entries 1 and
3-10. dThe yields of biphenyl (3) are 97% and <2% for Entries
1 and 2, respectively. eThe reaction with 5 mol % of [Fe(acac)3].
fThe reaction with isolated [PhTi(Oi-Pr)3].
b
Some organometallic reagents such as Grignard reagents have
also been used to reduce titanium(IV) complexes for the pinacol
coupling. For example, “[Ti(Oi-Pr)3]” generated by treatment of
[Ti(Oi-Pr)4] with EtMgBr is reported to be an effective reagent
for the coupling of aromatic aldehydes and ketones.8 It is
interesting that [PhTi(Oi-Pr)3], which is a stable titanium(IV)
complex, promotes the pinacol coupling in the presence of an
iron catalyst in our system. The formation of biphenyl (3)
observed in the iron-catalyzed pinacol coupling suggests that
[PhTi(Oi-Pr)3] undergoes disproportionation in the presence of
an iron catalyst to give biphenyl (3) and a low-valent titanium
species, most likely “[Ti(Oi-Pr)3],” which will bring about the
pinacol coupling of ketones (Scheme 1).
The reaction pathway proposed in Scheme 1 is supported
in part by control experiments shown in Scheme 2. Thus, to a
solution of [PhTi(Oi-Pr)3] (1.0 mmol) in THF, [Fe(acac)3]
(0.10 mmol) was added at 20 °C, and the mixture was stirred
at the same temperature for 10 min. Acidic hydrolysis of the
reaction mixture gave 0.29 mmol (58% yield) of biphenyl (3),
It has been well-documented that trivalent titanium species,
generated by reduction of tetravalent titanium complexes with
magnesium or zinc metal, function as one-electron reducing
reagents of carbonyl compounds to lead to pinacol coupling.6,7
Chem. Lett. 2011, 40, 492-494
© 2011 The Chemical Society of Japan
Hayashi, Tamio
