Highly trans-selective intramolecular pinacol coupling of dials catalyzed by bulky Cp2TiPh

Article abstract of DOI:10.1039/a902154j

Cp₂Ti(Ph)Cl in the presence of Me₃SiCl and Zn provides an effective pinacol coupling catalyst for aromatic and aliphatic aldehydes.

Full text of DOI:10.1039/a902154j

Highly trans-selective intramolecular pinacol coupling of dials catalyzed by
bulky Cp2TiPh
Yoshihiko Yamamoto, Reiko Hattori and Kenji Itoh*
Department of Applied Chemistry and Department of Molecular Design and Engineering, Graduate School of
Engineering, Nagoya University, Chikusa, Nagoya 464-8603, Japan. E-mail: itohk@apchem.nagoya-u.ac.jp
Received (in Cambridge, UK) 18th March 1999, Accepted 29th March 1999
Cp2Ti(Ph)Cl in the presence of Me3SiCl and Zn provides an
effective pinacol coupling catalyst for aromatic and aliphatic
aldehydes.
(13%).10 The complete loss of diastereoselectivity demon-
strated the importance of the titanocene catalyst. In addition to
the aromatic aldehyde, less reactive aliphatic aldehyde 1b was
converted into the corresponding diol 2b in good yield, although
its threo-selectivity was lower than 2a. These results demon-
strate that Cp2Ti(Ph)Cl is an efficient catalyst for the pinacol
coupling of both aromatic and aliphatic aldehydes.
Chiral 1,2-diols have found extensive use as asymmetric ligands
for catalytic asymmetric reactions1 and as chiral auxiliaries for
diastereoselective transformation of carbonyl substrates.2 Such
valuable diols are commonly obtained by the resolution of
racemic products prepared from a wide variety of aldehydes via
threo-selective pinacol coupling.3 Pinacol coupling has also
been employed as a key step in the construction of highly
important natural and artificial compounds.3 For these pur-
poses, stoichiometric reactions have so far been employed,
however, catalytic methods are highly desirable as a metal-
atom-economical and practical entry to the above 1,2-diols.
From this point of view, some catalytic methods have been
developed,4 but few of them have been applied to the
intramolecular coupling of dials.4g This is partly because the
intramolecular pinacol coupling of dials is often accompanied
by side reactions such as intramolecular aldol condensation.
With this in mind, we developed the Cp2Ti(Ph)Cl-catalyzed
intramolecular pinacol coupling of dials, which gave cyclic
1,2-diols in moderate to good yields with excellent trans-
selectivity under mild conditions (Scheme 1).
On the basis of the above results, we applied our new
catalytic system to the intramolecular reductive coupling of
dials (Table 1). In the presence of 6 mol% Cp2Ti(Ph)Cl, the acid
sensitive 1,5-dial 3a was reduced at ambient temperature over
38 h to afford the desired diol 4a in 40% yield with excellent
trans-selectivity (trans:cis = 99:1). It is noteworthy that this
high diastereoselectivity is in striking contrast to the cis-
selectivity observed in the known methods using stoichiometric
11
amounts of SmI2 or TiCl3(THF)3–ButOH catalyst.4g In a
similar manner, 10 mol% of the catalyst transformed 1,6-diol 3b
into trans-cyclohexanediol 4b in a higher yield (65%).
Moreover, 1,6-dial 3c having a bulky But group at the 3-position
gave only a single stereoisomer 4c in 52% yield. The relative
Cp2TiCl has received much attention as an excellent single-
electron reductant in organic synthesis.5 In this context, Teuben
et al. have reported the Cp2TiPh-mediated reductive coupling of
benzonitrile leading to benzil,6 and recently we have found that
the same titanium(iii) reagent reacted with g- and d-ketonitriles
to give a-hydroxycycloalkanones as reductive cyclization
products in good yield.7 The importance of the TiIII–Ph s-bond
is obvious from the fact that the parent Cp2TiCl was not
effective for the above two reductive transformations. The
phenyltitanium(iii) reagent was readily prepared in situ via
reduction of Cp2TiCl2 with PriMgCl followed by the addition of
PhMgBr.6,7 The same reactive species may alternatively be
generated by reducing Cp2Ti(Ph)Cl8 with Zn powder.9 Given
this fact, Cp2Ti(Ph)Cl should catalyze pinacol coupling reac-
tions in the presence of a stoichiometric amount of Zn. In fact,
stoichiometric reaction using equimolar amounts of
Cp2Ti(Ph)Cl and Zn promoted the desired reductive coupling of
benzaldehyde 1a to give hydrobenzoin 2a in 99% yield with a
diastereoselectivity of threo:erythoro = 84:16. We carried out
the catalyzed reaction as follows; a THF (5 ml) solution of 1a (3
mmol) and Me3SiCl (1.5 equiv.) was added to a mixture of 3
mol% Cp2Ti(Ph)Cl and Zn (1 equiv.) in THF (20 ml) and the
mixture was stirred for 70 min at ambient temperature. Usual
work-up gave 2a in 88% yield with a diastereomeric ratio of
threo:erythro = 71:29 (Scheme 2). In the absence of the
titanium catalyst, 2a was obtained in only 7% yield (threo:ery-
thro = 50:50) along with the reduced product benzyl alcohol
Scheme 2
Table 1 Intramolecular pinacol coupling of dials 3a–d using Cp2Ti(Ph)Cl–
Zn–Me3SiCla
Catalyst/
mol%
Yieldb
(%)
Dial
t/h
Diol
trans:cisc
a Conditions: Cp2Ti(Ph)Cl, Zn (1 equiv.), Me3SiCl (1.5 equiv), THF (0.05
M), room temp. b Isolated yields. c Ratios determined by 1H NMR analysis
of isolated products.
Scheme 1
Chem. Commun., 1999, 825–826
825

We gratefully acknowledge financial support (09750947 and
09305059) from the Ministry of Education, Science Sports and
Culture, Japan.
Notes and references
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2 H.-J. Altenbach, Chiral Cyclic Acetals in Synthesis, in Organic
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Krohn and H.-U. Reissig, Wiley, Weinheim, 1991, p. 19.
3 For recent review of pinacol coupling, see: R. G. Dushin, in
Comprehensive Organometallic Chemistry II, ed. L. S. Hegedus,
Pergamon, Oxford, 1995, vol. 12, p. 1071; G. M. Robertson, in
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York, 1991, vol. 3, p. 563; A. Fu¨rstner and B. Bogdanovic, Angew.
Chem., Int. Ed. Engl., 1996, 35, 2443.
4 Samarium-catalyzed reactions: (a) E. Le´onard, E. Dunach and J.
Pe´richon, J. Chem. Soc., Chem. Commun., 1989, 276; (b) R. Nomura, T.
Matsuno and T. Endo, J. Am. Chem. Soc., 1996, 118, 11666. Titanium-
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Gansa¨uer, Synlett, 1997, 363; (e) A. Gansa¨uer and D. Bauer, J. Org.
Chem., 1998, 63, 2070; (f) T. Hirao, B. Hatano, M. Asahara, Y.
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Fig. 1 Mechanism of stereoselection.
configurations of all three stereogenic centers in 4c were
completely controlled. The stereochemistry of 4c was deter-
mined by comparison of its spectral data with those previously
reported.12 In the 1H NMR spectrum, the methyne protons a to
the hydroxy groups have no Hax–Hax or Hax–Heq coupling with
coupling constants over 10 Hz, indicating that both are
constrained to occupy the equatorial positions. Among the four
isomers, 4c is the only one having no axial methyne proton a to
the hydroxy groups, as shown in Fig. 1. In addition, the 13C
NMR spectrum of 4c and its melting point are in good
agreement with reported data.12
These results clearly indicate that the bulky TiIV fragment
surrounded by two cyclopentadienyl and one phenyl ligands
cannot coordinate to the other carbonyl terminus, and cycliza-
tion must proceed via diradical intermediates such as 5, in which
two bulky Cp2(Ph)TiO moieties occupy axial positions in order
to reduce steric repulsion (Fig. 1). This is in contrast to the
intramolecular coupling of 3b promoted by SmI2 affording cis-
products via chelated intermediates such as 6.11
6 E. J. M. de Boer and J. H. Teuben, J. Organomet. Chem., 1977, 140, 41;
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In addition to the aliphatic dials, a biphenylic dial 3d was
converted into a tricyclic diol 4d13 in good yield (70%) with
high trans-selectivity (trans:cis = 91:9).
In conclusion, we have demonstrated that Cp2Ti(Ph)Cl is an
effective pinacol coupling catalyst for both aromatic and
aliphatic aldehydes in the presence of Me3SiCl and Zn. The
catalytic intramolecular pinacol coupling of dials afforded
cyclic trans-1,2-diols with excellent trans-selectivities of
trans:cis = > 90:10, indicative of non-chelation intermediates
being involved in the present reductive cyclization. These
results are in striking contrast to reported cis-selective
methods.
9 T. Chivers and E. D. Ibrahim, J. Organomet. Chem., 1972, 46, 313.
10 For the reductive coupling of benzaldehyde with Zn, see: J.-H. So,
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13 D. A. Lewis and R. N. Armstrong, Biochemistry, 1983, 22, 6297.
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Chem. Commun., 1999, 825–826