Titanium alkoxide complex of functionalized conjugated dienes. A versatile bis-anionic template for stereoselective construction of carbon frameworks

Article abstract of DOI:10.1021/ja0341844

1,3-Butadiene-2-carboxylates were treated with a titanium(II) alkoxide reagent, Ti(O-i-Pr)₄/2i-PrMgCl, to generate diene-titanium alkoxide complexes, the presence of which was verified by hydrolysis and deuteriolysis to give the corresponding monoolefins or their bis-deuterated counterpart. These diene complexes underwent successive addition to an aldehyde (as the first electrophile) and iodine (as the second one) in a highly regio- and stereoselective manner to give the corresponding iodo alcohol. Optically active 1,3-butadiene-2-carboxylates afforded the same adducts of high asymmetric induction. Besides these electron-deficient dienes, electron-rich 2-siloxy-1,3-butadienes also participated in the formation of the titanium complex, which led to the preparation of functionalized enol silyl ethers through regio- and stereoselective coupling with carbonyl compounds and hydrolytic workup. Copyright

Full text of DOI:10.1021/ja0341844

Published on Web 04/26/2003
Titanium Alkoxide Complex of Functionalized Conjugated Dienes. A Versatile
Bis-anionic Template for Stereoselective Construction of Carbon Frameworks
Hirokazu Urabe,*,† Kazuhisa Mitsui,† Shinya Ohta,† and Fumie Sato*,‡
Departments of Biological Information and Biomolecular Engineering, Graduate School of Bioscience and
Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku,
Yokohama, Kanagawa 226-8501, Japan
Received January 15, 2003; E-mail: hurabe@bio.titech.ac.jp; fsato@bio.titech.ac.jp
Conjugated diene-group 4 metal (Ti or Zr) complexes, hereby
depicted as the form of ∆3-metalacyclopentene B representative of
the other possible structures A and C (Figure 1), have been
Figure 1. Conjugated diene-metal complexes A-C and ∆2-metalacyclo-
pentene D (M ) metal).
generated from the corresponding dienes and a low-valent metal
species.1-3 While isomeric ∆2-metalacyclopentenes D have found
broad and intensive use in organic synthesis,2,4 such applications
of the ∆3-isomer B are so far much less explored.5 We report herein
the generation and reactions of functionalized diene-titanium
alkoxide complexes, where the functional groups play a pivotal
role in the realization of unique synthetic transformations.
Functionalized conjugated diene 2, readily prepared by the
titanium-mediated coupling of acetylenes,6 was treated with a
titanium(II) alkoxide reagent, Ti(O-i-Pr)4/2i-PrMgCl (1),2,7 at -50
°C to generate titanacyclopentene 3, the presence of which was
verified by the production of monoolefin 4 (as a single E-isomer)
or its deuterated counterpart 4-d2 (with almost complete deuterium
incorporation, ds ) diastereoselectivity) after hydrolysis or deuter-
iolysis (Scheme 1). Titanacycle 3 underwent the addition to
aldehydes in a highly regio- and stereoselective manner to give
adducts 6-9 involving a quaternary carbon center8 and an (E)-
olefin after hydroytic workup. The shown relative stereochemistry
of representative 7a was unambiguously determined by derivati-
zation.9 The Me3Si group in the products could be desilylated in
subsequent transformations (see Scheme 2), or the Me2PhSi group
in 7b was converted to a hydroxy group by the Tamao-Fleming
oxidation10 to give 11 (Scheme 1).9
Scheme 1. Construction of Multistereogenic Centers on the
Template of ∆3-Titanacyclopentene
Scheme 2. Asymmetric Induction to Multiple Centers via the
Chiral Template
More importantly, iodinolysis of oxatitanacycles 5 gave iodides
10 as a 95:5 mixture of two isomers, which must reflect the diaster-
eoselectivity of the step of aldehyde addition (93:7) rather than
that of the iodination step. Thus, the iodination itself proceeded
with nearly complete stereoselectiVity to create three stereogenic
centers in one pot! The shown stereochemistry of 10a was verified
by derivatization.9,11
Switching the tert-butyl ester of 2 to a chiral auxiliary would
lead to asymmetric construction of multiple stereocenters (Scheme
2). Of several chiral substrates examined,9 diene 126,12 derived from
(-)-8-phenylmenthol was found to be the most satisfactory one.
The titanacycle from 12 reacted with an aldehyde to give adduct
13 with high asymmetric induction as well as diastereoselectivity.
The absolute configuration of 13 was confirmed by derivatization.9
Removal of the chiral auxiliary with Dibal (to 15), followed by
desilylation with a base,13 gave pure stereodefined diol 16. Alter-
natively, the stereoselective iodinolysis of the intermediate oxati-
tanacycle as described in Scheme 1 created three consecutive chiral
centers to give optically active iodo alcohol 14, which was isolated
as a single isomer.
regioselective addition of titanacycle 18 to an aldehyde was again
viable, the diastereoselectivity between the alcoholic and quaternary
carbons of the products 20 (i.e., 1,2-ds) considerably decreased as
compared to that of the open-chain products in Scheme 1. On the
other hand, the stereocontrol of the incoming aldehyde by the lactam
substituent R ()i-Pr) was virtually perfect to give 20b with very
high 1,3-ds as shown in Scheme 3.9
While other functionalized dienes 21 and 226 in Figure 2
generated diene complexes as well,9 nonfunctionalized 23 and 24,6
having an alkyl chain in place of the carbonyl group of 2 or 17,
did not form the complexes. Besides these dienes, the exposure of
2-siloxybutadienes 2514 to 1 generated the desired diene-titanium
The titanacycle formation is also valid to cyclic dienes such as
17,6 giving monoolefins 19 after hydrolysis (Scheme 3). While the
† Department of Biological Information.
‡ Department of Biomolecular Engineering.
9
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J. AM. CHEM. SOC. 2003, 125, 6074-6075
10.1021/ja0341844 CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Supporting Information Available: Experimental procedures,
structural determination and physical properties of products, and
proposed reaction paths (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
References
Figure 2.
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d1 in the Supporting Information).
alkoxide complexes 26 in good yields, as evidenced by their
hydrolysis affording monoolefins 27 (Scheme 4). Elimination of
the siloxy group from the titanacycle 26 (to (allenylmethyl)titanium
species 28) was not observed.15 On the contrary, the coupling of
26 with carbonyl compounds followed by hydrolysis proceeded in
a highly regio- and stereoselective manner to give stereodefined
functionalized enol silyl ethers 29 and 30, which are otherwise
difficult to obtain.14
In conclusion, functionalized conjugated diene-titanium alkoxide
complexes provide versatile templates for organic synthesis, where
the functional group promotes the complex formation, controls
regio- and stereoselectivities of the subsequent reactions, and
imparts a chiral element to the template. Further applications of
these complexes will be reported in due course.
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Acknowledgment. We thank the Japan Society for the Promo-
tion of Science and Kurata Foundation (to H.U.) for financial
support.
(15) Cf.: Chinkov, N.; Majumdar, S.; Marek, I. J. Am. Chem. Soc. 2002, 124,
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