Angewandte
Chemie
DOI: 10.1002/anie.200802520
Synthetic Methods
Divergent Titanium-Mediated Allylations with Modulation by Nickel
or Palladium**
Araceli G. Campaæa, Btissam Bazdi, Noelia Fuentes, Rafael Robles, Juan M. Cuerva,*
J. Enrique Oltra,* Susana Porcel, and Antonio M. Echavarren*
Titanocene(III)-mediated radical processes are important
À
tools for the formation of C C bonds under mild conditions,
and are compatible with many functional groups.[1,2] More-
over, titanium(III) complexes can be used substoichiometri-
cally,[3] which has allowed the development of enantioselec-
tive versions of these reactions.[4]
A serious limitation of these radical processes, however,
derives from the fact that titanium(III)-mediated radical
generation requires reactive substrates, such as allylic halides,
which are often cumbersome in introduction and manipula-
tion. Allylic carbonates and carboxylates, in contrast, are
easily prepared and handled but are inert against titanocene-
(III) complexes. Nevertheless, it is known that nickel and
palladium complexes can readily activate allylic carbonates
and carboxylates I (Scheme 1) to form h3-allylmetal com-
plexes (II). On the basis of these results, we deemed that the
combination of palladium or nickel derivatives with
titanocene(III) complexes would facilitate the development
of novel allylation processes using accessible allyl carbonates
or carboxylates.
In the case of palladium catalysis, it is known that the
Oppolzer-type cyclization of organometallic species (II, M =
Scheme 1. Mechanism for palladium-catalyzed,titanocene-mediated
allylation of carbonyl compounds and nickel-catalyzed,titanocene-
Pd, Scheme 1) to cyclic derivatives (VI) is relatively slow at
mediated carbocylization of allylic carboxylates. [M]=transition metal
room temperature.[5] Thus, reduction of II by a single-
catalyst; Cp=cyclopentadienyl; E+ =electrophilic reagent (e.g. alde-
hyde).R=OEt,Me,or Ph.
electron-transfer reagent, such as [Cp2TiCl],[6] could lead to
the allylic radical III, which might be eventually trapped by a
second [Cp2TiCl]species to give an allylic titanium(IV)
complex IV. Finally, nucleophilic attack of the organometallic
derivative IV on an aldehyde or other electrophilic reagent
would provide the corresponding allylation product V.
On the other hand, nickel-catalyzed carbocyclizations, via
intermediates such as II (M = Ni, Scheme 1) to cyclic
derivatives VI, are relatively fast at room temperature.[7]
Once formed, VI might be reduced by [Cp2TiCl]to a primary
radical VII, which could be trapped by a second [Cp2TiCl]
species to give an alkyl titanium(IV) complex VIII. Hydrol-
ysis of the organometallic derivative VIII would yield carbo-
cycles IX. Thus, we anticipated that the use of palladium or
nickel catalysts could modulate titanium(III) to drive allyla-
tion reactions with allyl carboxylates by two different path-
ways, either through intermolecular coupling with electro-
philic reagents or to give carbocyclic derivatives by an
intramolecular allylation.
To check our hypothesis, we chose allylic carbonate E-1 as
a model allylation reagent. Thus, reaction of decanal with
carbonate E-1 and an excess of [Cp2TiCl](2.0 equiv), [8] in the
presence of PdCl2 (20 mol%) and triphenylphosphine,[9] gave
the expected coupling product 2 as a single stereoisomer in
76% yield (Scheme 2).[10] In contrast, when carbonate E-1
was treated with an excess of [Cp2TiCl](2.0 equiv) in the
presence of [NiCl2(PPh3)2](20 mol%), a mixture of carbo-
cycles 3 and 4 (4:1 ratio) was obtained in almost quantitative
[*] A. G. Campaæa,B. Bazdi,N. Fuentes,Dr. R. Robles,Dr. J. M. Cuerva,
Prof. J. E. Oltra
Department of Organic Chemistry,Faculty of Sciences
University of Granada
18071 Granada (Spain)
E-mail: jmcuerva@ugr.es
S. Porcel,Prof. A. M. Echavarren
Institute of Chemical Research of Catalonia (ICIQ)
Av. Països Catalans 16,43007 Tarragona (Spain)
Fax: (+34)977-920-225
E-mail: aechavarren@iciq.es
[**] We thank the “Junta de Andalucía” (research group FQM339),the
Spanish MEC (projects CTQ2005-08402/BQU,CTQ2007-60745/
BQU,Consolider Ingenio 2010,and predoctoral fellowship to
A.G.C),the UAM (predoctoral fellowship to S.P.),and the ICIQ
Foundation for financial support.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2008, 47, 7515 –7519
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7515