J . Org. Chem. 2001, 66, 3865-3870
3865
Dia ster eoselective In ter - a n d In tr a m olecu la r P in a col Cou p lin g of
Ald eh yd es P r om oted by Mon om er ic Tita n ocen e(III) Com p lex
Cp 2TiP h
Yoshihiko Yamamoto,† Reiko Hattori,† Takeyuki Miwa,† Yu-ichiro Nakagai,†
Takateru Kubota,‡ Chiyo Yamamoto,‡ Yoshio Okamoto,‡ and Kenji Itoh*,†
Department of Molecular Design and Engineering, and Department of Applied Chemistry, Graduate
School of Engineering, Nagoya University, Chikusa, Nagoya 464-8603, J apan
Itohk@apchem.nagoya-u.ac.jp
Received December 26, 2000
A monomeric titanocene(III) derivative, Cp2TiPh, effectively promoted the pinacol coupling of both
an aromatic aldehyde, benzaldehyde, and an aliphatic aldehyde, 3-phenylpropionaldehyde. The
same reactive complex was successfully generated by a catalytic amount of a precursor, Cp2Ti-
(Ph)Cl, and its stoichiometric amount of Zn. The Cp2TiPh-catalyzed pinacol coupling of benzaldehyde
derivatives and aliphatic aldehydes afforded the corresponding 1,2-diols in high yields with moderate
to good threo-selectivity. On the other hand, Cp2TiPh-catalyzed pinacol cyclization of dials gave
cyclic 1,2-diols with excellent diastereoselectivity. The extension of this protocol to chiral dials
demonstrated that the phenyltitanium complex catalytically transmitted an axial chirality or a
central chirality of the starting dials to the central chirality of the resultant 1,2-diols.
In tr od u ction
view. Although many catalytic methods have recently
been developed,5-8 few of them provided a satisfactory
yield and a diastereoselectivity for a wide range of
aldehydes. With this in mind, we investigated the
catalyzed inter- and intramolecular pinacol couplings
using Cp2TiPh.9
The reductive couplings of carbonyl compounds have
found extensive use in organic synthesis.1 In particular,
a threo-selective pinacol coupling has received much
attention because enatiomerically pure threo-diols can be
used for asymmetric syntheses.23 In addition, the pinacol
coupling has been employed as a key step in the synthe-
ses of natural products and pharmaceuticals.4 For these
purposes, stoichiometric reactions have so far been used,
however, catalytic methods are highly desirable from
both an atom-economical and environmental points of
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* To whom correspondence should be addressed. Fax: +81-52-789-
3205.
† Department of Molecular Design and Enginerring, and Depart-
ment of Applied Chemistry.
‡ Department of Applied Chemistry.
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10.1021/jo001781p CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/03/2001