has previously studied these complexes in the conjugate
allylation reactions of N-acylpyrroles and alkylidene
malononitriles.9 We envision that by utilizing this umpo-
lung reactivity of a propargylpalladium complex we could
build molecular complexity through a cascade process.
Reactions would initate through nucleophilic attack of the
propargylpalladium complex on a conjugate acceptor and
subsequently utilize the resultant carbon nucleophile and
allene functionalities.10 However, the reaction selectivity
would be complicated by equilibration of propargyl- and
allenylpalladium complexes that may occur under these
reaction conditions (Scheme 1).11 Therefore, successful
development of the reaction would require identification
of catalysts that would be able to control the relative
reactivity of these intermediates.
protodepalladation would generate cyclopentene product
3 (steps d and e).3e,16ꢀ20
Scheme 1. Proposed Annulation Reactiona
A working model of a catalytic cycle for cyclopentene
synthesis from allenylboronic ester and alkylidene cyano
esters is outlined in Scheme 1. In analogy to our earlier
work, we proposed that allenylboronic ester 2 would be a
suitable precursor for formation of the requisite organo-
palladium complexes in situ.12 Transmetalation of allenyl-
boronic acid pinacol ester with a Pd(II) catalyst would
proceed through an SE20 mechanism to provide propar-
gylpalladium complex 4 (step a). While equilibration of 4
to provide allenylpalladium complex 5 could occur (step
b),13 we hypothesized that the relative reactivities of com-
plexes 4 and 5 could be modulated by ligand tuning
which would allow for the acceleration of one pathway
over the alternatives. Conjugate attack of 4 on the electro-
phile would produce allene 6 (step c).14 Alternatively,
intermediate 6 could arise from migratory insertion of
allenylpalladium complex 5 with the electrophile.15 Final-
ly, endo carbopalladation of the pendant allene and
a (a) Transmetalation; (b) isomerization; (c) allenylation of electro-
phile; (d) carbopalladation; (e) protodepalladation.
During our initial evaluation of reaction conditions we
identified several ligands that promoted formation of
cyclopentene 3 (Table 1). Mono- and bidentate phosphines
provided low conversion (entries 1 and 2). A phosphite
ligand provided a mixture of cyclized products presumably
resulting from reaction of both allenyl- and propargylpal-
ladium complexes 4 and 5, as well aslinear products arising
from the interruption of the catalytic cycle (entry 3). We
found that ligation of the palladium catalyst by a mono-
dentate phosphoramidite promoted the selective forma-
tion of cyclopentene 3a in the highest yields (entries
4ꢀ5).21,22 These data support our initial hypothesis that
ligand tuning can be used toinfluencethe relativereactivity
of complexes 4 and 5.23 Notably, with phosphoramidite
ligands, acyclic products (8a and 9a) were not formed and
(8) Zanoni, G.; Pontiroli, A.; Marchetti, A.; Vidari, G. Eur. J. Org.
Chem. 2007, 3599.
(9) (a) Shaghafi, M. B.; Kohn, B. L.; Jarvo, E. R. Org. Lett. 2008, 10,
4743. (b) Waetzig, J. D.; Swift, E. C.; Jarvo, E. R. Tetrahedron 2009, 65,
3197. (c) Barczak, N. T.; Grote, R. E.; Jarvo, E. R. Organometallics
2007, 27, 4863.
(10) A related transformation, enantioselective silver-catalyzed pro-
pargylation reaction of imines, has been developed in our laboratories:
Wisniewska, H. M.; Jarvo, E. R. Chem. Sci. 2011, 2, 807.
(11) Examples of reactions involving allenyl- and propargylpalla-
dium complexes: (a) Elsevier, C. J.; Kleijn, H.; Boersma, J.; Vermeer, P.
Organometallics 1986, 5, 716. (b) Ogoshi, S.; Fukunishi, Y.; Tsutsumi,
K.; Kurosawa, H. J. Chem. Soc., Chem. Commun. 1995, 2485. (c)
Ogoshi, S.; Nishida, T.; Fukunishi, Y.; Tustusmi, K.; Kurosawa, H.
J. Organomet. Chem. 2001, 620, 190. (d) Ma, S.; Zhang, A. J. Org. Chem.
2002, 67, 2287. (e) Moriya, T.; Miyaura, N.; Suzuki, A. Synlett 1994, 149.
(f) Miyabe, H.; Yousuke, Y.; Naito, T.; Takemoto, Y. J. Org. Chem.
2004, 69, 1415. (g) Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K.
J. Am. Chem. Soc. 2008, 130, 5048. (h) Tsuji, J.; Watanabe, H.; Minami,
I.; Shimizu, I. J. Am. Chem. Soc. 1985, 107, 2196.
(17) Cyclization of allenyl malonates in the presence of vinylbro-
mides proceeds through an alternative mechanism: Ahmar, M.; Cazes,
B.; Gore, J. Tetrahedron Lett. 1985, 26, 3795.
(18) For endo carbocyclizations of β-dicarbonyls with pendant al-
ꢀ ꢁ
ꢀ
kynes, see: (a) Denes, F.; Perez-Luna, A.; Chemla, F. Chem. Rev. 2010,
110, 2366. (b) McDonald, F. E.; Olson, T. C. Tetrahedron Lett. 1997, 38,
7691.
(19) To confirm that t-butanol is indeed the source of the proton in
the product, the annulation reaction was performed using deutero-tert-
butanol. Deuterium was incorporated into the cyclopentene ring solely
at the C4 position and in 75% incorporation. See Supporting Informa-
tion for details.
(20) A similar mechanism could be proposed for the cycloaddition
reported by Yamamoto and co-workers, see ref 5.
(21) Synthesis of ligand L1: Bartels, B.; Garcia-Yebra, C.; Rominger,
F.; Helmchen, G. Eur. J. Inorg. Chem. 2002, 10, 2569.
(12) Boronic ester 2 is commercially available or may be prepared
according to: Tonogaki, K.; Itami, K.; Yoshida, J. J. Am. Chem. Soc.
2006, 128, 1464.
(22) The following control experiments were performed: in the
absence of base, PdCl2(PhCN)2, ligand, or PdCl2(PhCN)2 and ligand
the reaction does not give product. Replacing PdCl2(PhCN)2, with
Pd2(dba)3 provided only 8% yield, consistent with a mechanism that
avoids Pd(0) intermediates.
(23) An alternative mechanism involving scrambling of allenylboro-
nic acid pinacol ester to propargylboronic acid pinacol ester followed by
Lewis acid catalysis is possible, however, unlikely. Scrambling of the
allenylboronic ester is not observed by 1H NMR under the reaction
conditions. Rather, allenylboronic acid pinacol ester decomposes to
provide allene (C3H4). See Supporting Information1 for details.
(24) Alternative bases (K3PO4, K2CO3, Cs2CO3, LiOt-Bu, KOt-Bu)
were also examined. Only alkoxide bases gave desired product while all
other bases gave product in <10% yield.
(13) Allenylpalladium complex 4 would likely be the more stable
isomer, see refs 11aꢀ11c.
(14) Examples of SE20 attack of allenylmetal complexes on aldehydes:
(a) Haruta, R.; Ishiguro, M.; Ikeda, N.; Yamamoto, H. J. Am. Chem.
Soc. 1982, 104, 7667. (b) Corey, E. J.; Yu, C.-M.; Lee, D.-H. J. Am.
Chem. Soc. 1990, 112, 878. (c) Marshall, J. A.; Yu, R. H.; Perkins, J. F.
J. Org. Chem. 1995, 60, 5550.
(15) For a review of the Heck reaction, see ref 2a, Chapter 3.2.
(16) Related cyclization reactions to form heterocycles: (a) Ma, S.
Acc. Chem. Res. 2003, 36, 701. (b) Prasad, J. S.; Liebeskind, L. S.
Tetrahedron Lett. 1988, 29, 4257.
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