Rh od iu m -Ca ta lyzed Ta n d em Cycliza tion : F or m a tion of
1H-In d en es a n d 1-Alk ylid en ein d a n s fr om Ar ylbor on a te Ester s in
Aqu eou s Med ia
Mark Lautens* and Tzvetelina Marquardt
Davenport Chemical Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street,
Toronto, Ontario M5S 3H6, Canada
mlautens@chem.utoronto.ca
Received February 16, 2004
Arylboronate esters bearing a pendant Michael-type acceptor olefin or acetylene linkage undergo
transmetalation with a rhodium-based catalytic complex to generate a functionalized organorhodium
intermediate which can cyclize onto nonterminal acetylenes in good to excellent yields. The catalytic
system involves the use of electron-rich, sterically bulky ligands as tri-tert-butylphosphonium
tetrafluoroborate stabilizing the organorhodium intermediates and reduces the incidence of
protodeboronation in aqueous media.
In tr od u ction
In recent years, carbon-carbon bond formation using
transition-metal catalysts in water has gained popularity
as an attractive strategy in organic synthesis for the
efficient construction of complex organic molecules.1 As
an alternative to the palladium-catalyzed cross-couplings,
rhodium-catalyzed reactions of boronic acids with acti-
vated alkenes in aqueous media have been developed as
very efficient methods for the formation of carbon-carbon
bonds. Significant contributions include the seminal
studies by Miyaura and Hayashi,2 who demonstrated
highly enantioselective conjugate addition of arylboronic
acids to aldehydes and enones, respectively. An important
aspect of these reactions was that water was necessary
as a cosolvent (or additive) to promote the coupling
process through the generation of a catalytically active
hydroxorhodium(I) intermediate.3
F IGURE 1.
1). As the study pointed to reactivity differences between
rhodium and palladium in intermolecular couplings, it
was of interest to determine how intramolecular pro-
cesses would fare. The majority of methodologies reported
using rhodium catalysis focus on intermolecular pro-
cesses with the metal mediating the formation of only
one carbon-carbon bond.
Recently, we demonstrated our first studies on the
intramolecular tandem carbocyclization process with
arylboronate esters bearing a pendant Michael-acceptor
double bond and strained olefins as coupling partners,
utilizing a water-soluble rhodium catalyst system with
t-Bu-amphos-Cl 3 as a ligand (Figure 1).7
Inspired by the good results for obtaining the indan
systems, our investigations were then focused on ap-
plications of alkynes as coupling partners as this would
significantly broaden the general applicability of the
rhodium-catalyzed tandem cyclization reaction and would
generate products that could undergo further transfor-
mations providing access to biologically active com-
pounds. For example, the products synthesized by the
present coupling methodology might be easily subjected
Recently, we reported the rhodium-catalyzed reaction
of various arylboronic acids to aromatic or heteroaromatic
alkenes4 or alkynes using the water-soluble ligands
TPPDS 15 or the pyridine-substituted ligand 26 (Figure
(1) For rewiews of organic synthesis in water, see: (a) Grieco, P. A.
Organic Synthesis in Water; Blackie Academic and Professional:
London, 1998. (b) Cornils, B.; Herrmann, W. A. Aqueous-Phase
Organometallic Chemistry: Concepts and Applications; Wiley-VCH:
Weinheim, 1998. (c) Li, C. J .; Chan, T. H. Organic Reactions in Aqueous
Media; Wiley-Interscience: New York, 1997. (d) Horva´th, I. T.; J oo´,
F. Aqueous Organometallic Chemistry and Catalysis; Kluwer Aca-
demic: Dordrecht, The Niederlands, 1995. (e) Li, C. J . Chem. Rev. 1993,
93, 2023. (f) Li, C. J .; Chan, T. H. Tetrahedron 1999, 93, 2023. (g) For
a general review on rhodium-catalyzed carbon-carbon bond-forming
reactions of organometallic compounds, see: Fagnou, K.; Lautens, M.
Chem Rev. 2003, 103, 169.
(2) For addition to enones: (a) Sakai, M.; Hayashi, H.; Miyaura, N.
Organometallics 1997, 16, 4229. (b) Takaya, Y.; Ogasawara, M.;
Hayashi, T.; Sakai, M.; Miyaura, N. J . Am. Chem. Soc. 1998, 120, 5579.
(c) For a review, see: Hayashi, T. Synlett 2001, 879.
(3) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J . Am.
Chem. Soc. 2002, 124, 5052.
(5) Other examples for reactions using TPPDS, see: (a) Thorpe, T.;
Brown, S. M.; Crosby, J .; Fitzjohn, S.; Muxworthy, J . P.; Williams, J .
M. J . Tetrahedron Lett. 2000, 41, 4503. (b) Chen, H.; Li, Y.; Chen, J .;
Cheng, P.; Li, X. Catal. Today 2002, 74, 131.
(6) (a) Lautens, M.; Yoshida, M.Org. Lett. 2002, 4, 123. (b) Lautens,
M.; Yoshida, M. J . Org. Chem. 2003, 68, 762. (c) Recently, Hayashi
has reported a similar addition of alkynes: Hayashi, T.; Inoue, K.;
Taniguchi, N.; Ogasawara, M. J . Am. Chem. Soc. 2001, 123, 9918.
(7) Lautens, M.; Mancuso, J . Org. Lett. 2002, 4, 2105.
(4) (a) Lautens, M.; Roy, A.; Fukuoka, K.; Fagnou, K.; Mart´ın-
Matute, B. J . Am. Chem. Soc. 2001, 123, 5358.
10.1021/jo049722p CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/11/2004
J . Org. Chem. 2004, 69, 4607-4614
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