Cascade Cyclizations and Couplings Involving Nickel Enolates

Article abstract of DOI:10.1021/ja037423w

A new strategy for effecting cascade cyclization processes using nickel enolates has been developed. Nickel enolates may be cleanly generated by the oxidative cyclization of an enal and alkyne with Ni(O), and the resulting enolate may be functionalized by a variety of alkylation processes. Partially and fully intramolecular versions of the process allow the rapid synthesis of complex polycyclics from simple achiral, acyclic precursors.

Full text of DOI:10.1021/ja037423w

Published on Web 10/08/2003
Cascade Cyclizations and Couplings Involving Nickel
Enolates
Gireesh M. Mahandru, Andy R. L. Skauge, Sanjoy K. Chowdhury,
Kande K. D. Amarasinghe, Mary Jane Heeg,† and John Montgomery*
Contribution from the Department of Chemistry, Wayne State UniVersity,
Detroit, Michigan 48202-3489
Received July 21, 2003; E-mail: jwm@chem.wayne.edu
Abstract: A new strategy for effecting cascade cyclization processes using nickel enolates has been
developed. Nickel enolates may be cleanly generated by the oxidative cyclization of an enal and alkyne
with Ni(0), and the resulting enolate may be functionalized by a variety of alkylation processes. Partially
and fully intramolecular versions of the process allow the rapid synthesis of complex polycyclics from simple
achiral, acyclic precursors.
Introduction
jugate addition entries to transition metal enolates have allowed
notable progress toward this goal,4 we envisioned that polyun-
Cascade metal-catalyzed cyclization processes have emerged
as enormously useful methods for assembling complex poly-
cyclic molecules from simple polyunsaturated precursors.1 The
iterative migratory insertion of various unsaturated groups into
a reactive metal-carbon bond is often an important theme, and
processes of this type may be coupled with carbonylation,
transmetalation, and reductive elimination in well-timed se-
quences typically controlled by selective placement of reactive
groups within a cyclization precursor.2 Palladium-catalyzed
methods involving the insertion of alkynes and 1,1-disubstituted
alkenes, typically termed Heck cyclizations, have been very
widely explored because the insertions proceed efficiently and
involve σ-alkyl species that are not prone to reaction termination
by â-hydride elimination.1,2
Transition metal enolates have been well documented in many
contexts, and their modes of reactivity are diverse.3 Their
preparation typically involves carbonyl enolization followed by
addition to a metal electrophile,3 addition of metal anions to
R-halocarbonyls,3a conjugate additions or reductions of R,â-
unsaturated carbonyls,4 and isomerization of allylic alcohols.5
Simple electrophilic alkylations and aldol additions,3a,g,4 aryla-
tions and alkenylations,6 and â-hydride elimination7 are among
the many reactivity trends that are often seen for transition metal
enolates. The diverse reactivity of transition metal enolates, if
coupled with the complexity generation allowed by cascade
cyclizations, would provide a powerful new strategy for complex
molecule construction. Although conjugate reduction and con-
saturated precursors could potentially provide access to very
complex processes that involve the formation and alkylation of
transition metal enolates as only two of numerous individual
steps in elaborate metal-promoted polycyclizations. Herein, we
describe our results toward this general goal.
Results and Discussion
Our interest in the chemistry of nickel enolates stems from
our recent work in the development of nickel-catalyzed cy-
(3) (a) Burkhardt, E. R.; Bergman, R. G.; Heathcock, C. H. Organometallics
1990, 9, 30 and references therein. (b) Doney, J. J.; Bergman, R. G.;
Heathcock, C. H. J. Am. Chem. Soc. 1985, 107, 3724. (c) Burkhardt, E.
R.; Doney, J. J.; Bergman, R. G.; Heathcock, C. H. J. Am. Chem. Soc.
1987, 109, 2022. (d) Heathcock, C. H.; Doney, J. J.; Bergman, R. G. Pure
Appl. Chem. 1985, 57, 1789. (e) Slough, G. A.; Bergman, R. G.; Heathcock,
C. H. J. Am. Chem. Soc. 1989, 111, 938. (f) Hartwig, J. F.; Andersen, R.
A.; Bergman, R. G. J. Am. Chem. Soc. 1990, 112, 5670. (g) Campora, J.;
Maya, C. M.; Palma, P.; Carmona, E.; Gutie´rrez-Puebla, E.; Ruiz, C. J.
Am. Chem. Soc. 2003, 125, 1482. (h) Fujii, A.; Hagiwara, E.; Sodeoka, M.
J. Am. Chem. Soc. 1999, 121, 5450. (i) Ito, Y.; Nakatsuka, M.; Kise, N.;
Saegusa, T. Tetrahedron Lett. 1980, 21, 2873. (j) Balegroune, F.; Grandjean,
D.; Lakkis, D.; Matt, D. J. Chem. Soc., Chem. Commun. 1992, 1084. (k)
Murahashi, T.; Kurosawa, H. J. Organomet. Chem. 1999, 574, 142. (l)
Albe´niz, A. C.; Catalina, N. M.; Espinet, P.; Redo´n, R. Organometallics
1999, 18, 5571. (m) Zuideveld, M. A.; Kamer, P. C. J.; van Leeuwen, P.
W. N. M.; Klusener, P. A. A.; Stil, H. A.; Roobeek, C. F. J. Am. Chem.
Soc. 1998, 120, 7977. (n) Pagenkopf, B. L.; Kru¨ger, J.; Stojanovic, A.;
Carreira, E. M. Angew. Chem., Int. Ed. 1998, 37, 3124.
(4) (a) Zhao, C.-X.; Duffey, M. O.; Taylor, S. J.; Morken, J. P. Org. Lett.
2001, 3, 1829. (b) Taylor, S. J.; Duffey, M. O.; Morken, J. P. J. Am. Chem.
Soc. 2000, 122, 4528. (c) Taylor, S. J.; Morken, J. P. J. Am. Chem. Soc.
1999, 121, 12202. (d) Yoshida, K.; Ogasawara, M.; Hayashi, T. J. Am.
Chem. Soc. 2002, 124, 10984. (e) Hayashi, T.; Takahashi, M.; Takaya, Y.;
Ogasawara, M. J. Am. Chem. Soc. 2002, 124, 5052. (f) Lipshutz, B. H.;
Papa, P. Angew. Chem., Int. Ed. 2002, 41, 4580. (g) Huddleston, R. R.;
Krische, M. J. Synlett 2003, 12. (h) Cauble, D. F.; Gipson, J. D.; Krische,
M. J. J. Am. Chem. Soc. 2003, 125, 1110. (i) Wang, L.-C.; Jang, H.-Y.;
Roh, Y.; Lynch, V.; Schultz, A. J.; Wang, X.; Krische, M. J. J. Am. Chem.
Soc. 2002, 124, 9448. (j) Jang, H.-Y.; Huddleston, R. R.; Krische, M. J. J.
Am. Chem. Soc. 2002, 124, 15156. (k) Huddleston, R. R.; Krische, M. J.
Org. Lett. 2003, 5, 1143.
† To whom corresondence regarding X-ray crystallographic determina-
tions should be addressed.
(1) (a) Link, J. T. In Organic Reactions; Overman, L. E., Ed.; Wiley: New
York, 2002; Vol. 60, p 157. (b) Poli, G.; Giambastiani, G.; Heumann, A.
Tetrahedron 2000, 56, 5959.
(2) (a) Trost, B. M.; Shi, Y. J. Am. Chem. Soc. 1993, 115, 9421. (b) Overman,
L. E. Pure Appl. Chem. 1994, 66, 1423. (c) Sugihara, T.; Coperet, C.;
Owczarczyk, Z.; Harring, L. S.; Negishi, E. J. Am. Chem. Soc. 1994, 116,
7923. (d) Negishi, E. Pure Appl. Chem. 1992, 64, 323. (e) Brown, S.;
Clarkson, S.; Grigg, R.; Thomas, W. A.; Sridharan, V.; Wilson, D. M.
Tetrahedron 2001, 57, 1347.
(5) (a) Motherwell, W. B.; Sandham, D. A. Tetrahedron Lett. 1992, 33, 6187.
(b) Uma, R.; Cre´visy, C.; Gre´e, R. Chem. ReV. 2003, 103, 27.
(6) (a) Culkin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003, 36, 234. (b) Moradi,
W. A.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123, 7996. (c) Sole´, D.;
Diaba, F.; Bonjoch, J. J. Org. Chem. 2003, 68, 5746.
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J. AM. CHEM. SOC. 2003, 125, 13481-13485
13481

A R T I C L E S
Mahandru et al.
Scheme 1
Scheme 2
clizations of alkynyl enones and organozincs.8 For example,
when enone substrate 1 is treated with Ni(COD)2 in the presence
of dimethylzinc, product 3 is cleanly produced (Scheme 1).9
We speculated that metallacycle 2, which possesses a nickel
enolate motif, was a likely intermediate in this transformation.
To study the mechanism of this process, we attempted to inde-
pendently prepare the proposed metallacycle simply by treating
enone 1 with a stoichiometric quantity of Ni(COD)2/PPh3 (1:2)
in the absence of dimethylzinc. However, this catalytic system
led to the quantitative dimerization of the alkynyl enone to afford
product 4 as a single isomer (Scheme 1).10
Table 1
Recognizing that metallacycle 2 could potentially serve as a
common intermediate leading to either alkylative cyclization
product 3 or dimer 4 depending on the reaction conditions, we
reasoned that stabilization of metallacycle 2 with a bidentate
ligand would suppress uptake of a second equivalent of enone
and allow isolation of the reactive metallacycle. This expectation
was indeed correct, and treatment of alkynyl enal 5 with
stoichiometric Ni(COD)2/tmeda (1:1) cleanly afforded the
structurally well-defined Ni(II) enolate 6 as the major product
after recrystallization (Scheme 2).11 Both solid-state and solution
characterization data were fully consistent with the η1 O-enolate
structure for metallacycle 6.11
Although the preparation of analytically pure metallacycle 6
required careful recrystallization, we were interested in examin-
ing the reactivity of the crude metallacycle which was easily
prepared in solution. Thus, after treatment of alkynyl enal 5
with Ni(COD)2/tmeda for 1 h at room temperature, the resulting
red solution was quenched with either methanol or dilute
aqueous acid. Surprisingly, this one-pot procedure directly
afforded bicyclooctenol 7 in 82% yield (eq 1).12 This process
formally constitutes a reductive [3+2] cycloaddition with
excellent control of stereochemistry. Although many examples
of [3+2] cycloadditions have appeared,13 most examples require
specialized substrate classes that cannot be carried through
1
2
entry
n
X
R
R
% yield
1
2
3
4
5
6
7
8
9
1
1
2
1
1
1
1
1
1
1
1
1
CH2
CH2
CH2
CH2
CH2
O
CH2
CH2
CH2
CH2
CH2
CH2
H
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
9a (82)a
CH3
Ph
COCH3
SiMe3
Ph
9b (72)a
9a′ (40), 11a (18)a
9c (15)a
9d (55)b
9e (78)a
Ph
Ph
9f (71)b
10a (53)a
10b (52)a
11b (27)a
9g (61)b
CH3
H
SiMe3
SiMe3
10
11
12
10c (61)a
a Aqueous workup. b Methanol workup.
routine synthetic sequences and that are sometimes difficult to
install into complex molecules. Thus, the participation of an
easily installed R,â-unsaturated carbonyl as a three-carbon group
that participates in a [3+2] cycloaddition is particularly attrac-
tive.
(8) (a) Montgomery, J. Acc. Chem. Res. 2000, 33, 467. (b) Montgomery, J.;
Amarasinghe, K. K. D.; Chowdhury, S. K.; Oblinger, E.; Seo, J.; Savchenko,
A. V. Pure Appl. Chem. 2002, 74, 129. (c) For related intermolecular
processes, see: Ikeda, S. Acc. Chem. Res. 2000, 33, 511.
(9) Montgomery, J.; Oblinger, E.; Savchenko, A. V. J. Am. Chem. Soc. 1997,
119, 4911.
(10) Seo, J.; Chui, H. M. P.; Heeg, M. J.; Montgomery, J. J. Am. Chem. Soc.
1999, 121, 476.
The scope of the process is illustrated by the following
examples (Table 1). Enals are the most efficient participants in
the reaction (entries 1-6), although aromatic enones are also
satisfactory participants (7-12). With aromatic enones, the
workup conditions are critical. For instance, in the cyclization
(11) Amarasinghe, K. K. D.; Chowdhury, S. K.; Heeg, M. J.; Montgomery, J.
Organometallics 2001, 20, 370.
(12) Chowdhury, S. K.; Amarasinghe, K. K. D.; Heeg, M. J.; Montgomery, J.
J. Am. Chem. Soc. 2000, 122, 6775.
(13) (a) Welker, M. E. Chem. ReV. 1992, 92, 97. (b) Pearson, W. H. Pure Appl.
Chem. 2002, 74, 1339. (c) Trost, B. M.; Grese, T. A.; Chan, D. M. T. J.
Am. Chem. Soc. 1991, 113, 7350.
9
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Cascade Cyclizations Involving Nickel Enolates
A R T I C L E S
Scheme 3
Table 2
of a phenyl enone, product 9f is generated in 71% yield if the
reaction is quenched with methanol (entry 7). However,
quenching with dilute acid leads to rearranged product 10a
derived from acid-catalyzed 1,3-transposition of the hydroxyl
unit (entry 8). The products derived from enal cyclizations
(entries 1-6) were less prone to rearrangement, and either
aqueous or methanol workup was satisfactory for obtaining
unrearranged products. Regarding substitution on the alkyne,
aromatic (entries 1,3,6-8), aliphatic (entries 2,9), and silyl
(entries 5,11,12) groups were tolerated in good yield. However,
terminal alkynes (entry 10) and alkynoates (entry 4) were poor
substrates. In the case of the terminal alkyne cyclization,
monocyclic product 11b was obtained (entry 10). A heteroatom
was tolerated in the tether chain in good yield (entry 6), and
six-membered cyclizations were also possible (entry 3).
We suggest that the mechanism of this novel process likely
involves a selective monoprotonation of the nickel enolate of 6
upon workup while leaving the vinyl nickel unit intact (Scheme
3). Once the selective monoprotonation occurs to generate
intermediate 12, a rapid insertion of the vinylic Ni-C bond
into the coordinated carbonyl would afford nickel alkoxide 13.14
Further protonation of the Ni-O bond of this alkoxide would
then afford the observed product. It is important to note that a
single diastereomer was obtained in each of the cyclizations
described in Table 1. The reversibility of each of the steps
proposed in the mechanism outlined is unclear, although the
conversion of intermediate 12 into nickel alkoxide 13 is likely
irreversible. Thus, either the kinetic selectivity of binding to
the two prochiral faces of the carbonyl in 12 or the kinetic
selectivity for the carbonyl insertion from rapidly equilibrating
diastereomers of 12 is likely responsible for governing the
reaction diastereoselectivity. As depicted in Scheme 3, if each
mechanistic step proceeds with conservation of the overall
skeletal conformation, there is a direct correlation of metalla-
cycle conformation with observed reaction diastereoselectivity.
Although we have little insight into the accuracy of this model,
it has nonetheless served as an excellent predictor of stereo-
chemistry when examining new substrate classes (vide infra).
Upon developing this working model for the reaction mech-
anism, it became apparent that much chemistry of the nickel
enolate motif beyond simple protonations could potentially be
developed. Using the structurally established metallacycle 6 as
a test case, we examined a variety of tandem processes involving
enolate alkylation (Table 2).15 Upon in situ generation of
metallacycle 6 followed by treatment with reactive electrophiles,
functionalized bicyclooctenols 14 were again obtained, with
incorporation of the electrophilic unit at the expected position.
Alkylations with methyl iodide, allyl iodide, and benzyl iodide
proceeded efficiently to produce single diastereomers of the
(15) For other examples of the addition of electrophiles to metallacycles, see:
(a) Benn, R.; Bu¨ssemeier, B.; Holle, S.; Jolly, P. W.; Mynott, R.;
Tkatchenko, I.; Wilke, G. J. Organomet. Chem. 1985, 279, 63. (b) Suzuki,
K.; Urabe, H.; Sato, F. J. Am. Chem. Soc. 1996, 118, 8729. (c) Urabe, H.;
Suzuki, K. Sato, F. J. Am. Chem. Soc. 1997, 119, 10014. (d) Takimoto,
M.; Kawamura, M.; Mori, M. Org. Lett. 2003, 5, 2599. (e) Terao, J.; Oda,
A.; Ikumi, A.; Nakamura, A.; Kuniyasu, H.; Kambe, N. Angew. Chem.,
Int. Ed. 2003, 42, 3412. (f) Hartwig, J. F.; Bergman, R. G.; Andersen, R.
A. Organometallics 1991, 10, 3326. (g) Hoover, J. F.; Stryker, J. M.
Organometallics 1989, 8, 2973.
(14) (a) Quan, L. G.; Lamrani, M.; Yamamoto, Y. J. Am. Chem. Soc. 2000,
122, 4827. (b) Jin, H.; Uenishi, J.; Christ, W. J.; Kishi, Y. J. Am. Chem.
Soc. 1986, 108, 5644. (c) Takai, K.; Tagashira, M.; Kuroda, T.; Oshima,
K.; Utimoto, K.; Nozaki, H. J. Am. Chem. Soc. 1986, 108, 6048.
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A R T I C L E S
Mahandru et al.
Scheme 4
Scheme 5
Scheme 6
bicyclooctenols that bear three contiguous stereocenters (entries
1-3). Aldol reactions were also very efficient (entries 4 and
5). Quenching metallacycle 6 with benzaldehyde or formalde-
hyde afforded the expected aldol adducts in excellent yield as
single diastereomers. The benzaldehyde-trapping example (entry
4) provides a particularly good illustration of the potential for
rapid complexity generation by this process, because a simple
acyclic achiral precursor is converted into a bicyclic product
with four contiguous stereocenters and a synthetically versatile
1,3-diol unit in a single synthetic operation. Metallacycle 6
underwent efficient acylations, as demonstrated by quenching
with benzoyl chloride to afford a â-hydroxy ketone (entry 6).
This central metallacycle also participated in a Michael reaction
with acrolein to generate a tricyclic lactol as a mixture of two
diastereomers that were epimeric at the lactol center (entry 7).
Again considering the mechanistic model presented above,
metallacycle 6 likely undergoes exo-selective alkylation to afford
intermediate 15, followed by rapid insertion of the carbonyl to
afford nickel alkoxide 16 (Scheme 4). Protonation of this
alkoxide upon workup would afford the observed products, with
all stereocenters being selectively generated (and correctly
predicted) from the initial metallacycle conformation. At this
point, we have little insight into the basis for the highly selective
anti aldol reaction which presumably proceeds via an open
transition state. The reactions described in Table 2 may be
classified as alkylative [3+2] cycloadditions with the electro-
phile being incorporated at the central carbon of the three-carbon
enone-derived unit.
The generality and scope of enolate alkylations within a
metallacycle framework encouraged us to pursue the synthesis
of more elaborate structures. To examine the participation of
trisubstituted alkenes that would afford tricyclic products with
a quaternary center, precursor 17 was prepared (Scheme 5).16
Enal 17 was treated with Ni(COD)2/tmeda (1:1) in THF for 2
h at room temperature, and the resulting mixture was quenched
with methanol. Despite the additional steric demands of this
substrate, the cyclization proceeded efficiently to produce
triquinane 20 as a single diastereomer in 71% yield. In analogy
to the mechanistic proposal described above, the reaction likely
proceeds by oxidative cyclization to afford metallacycle 18.
Enolate protonation upon workup with methanol, followed by
carbonyl insertion, would afford nickel alkoxide 19. Further
protonation of 19 would then afford the observed diastereomer
of 20. An aldol addition of enolate 18 to formaldehyde was
also attempted, and diol 21 was obtained in 46% yield as a
single diastereomer.
Fully intramolecular variants of the metallacycle formation/
enolate alkylation cascade provide access to even more highly
functionalized polycycles from acyclic precursors. To examine
the feasibility of a complex cyclization of this type, cyclization
precursors were synthesized with the enal, alkyne, and aliphatic
aldehyde all tethered within a single compound. For instance,
dialdehyde 22 was prepared by conventional procedures,16 and
treatment with Ni(COD)2/tmeda, followed by aqueous workup,
afforded spirocycle 25 in 49% yield as a single diastereomer
(Scheme 6). In analogy to the intermolecular variants described
above, the mechanism likely involves chemoselective oxidative
cyclization of the enal and alkyne units to afford metallacycle
23. Diastereoselective intramolecular aldol addition via an open
transition state would afford nickel bis-alkoxide 24, and aqueous
workup would provide the observed product 25.
In a similar fashion, dialdehyde 26 was treated with Ni-
(COD)2/tmeda followed by methanol workup to afford product
29 as a single diastereomer in 61% isolated yield (two-step yield
from the diol, Scheme 7). Chemoselective oxidative cyclization
in this instance would afford metallacycle 27, followed by
intramolecular aldol addition to afford nickel bis-alkoxide 28,
which produces compound 29 upon workup. The production
of compounds 25 and 29 illustrates the potential for truly
complex polycyclizations that rely upon the transient generation
and alkylation of a transition metal enolate. It is significant to
note that this novel procedure allows completely selective aldol
(16) See Supporting Information for complete experimental details.
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13484 J. AM. CHEM. SOC. VOL. 125, NO. 44, 2003

Cascade Cyclizations Involving Nickel Enolates
A R T I C L E S
Scheme 7
Ni(COD)2 while substantially lowering the cost. As an added
advantage, glovebox manipulations were avoided because
Ni(acac)2 is completely air stable. In two test cases involving
allylation and formaldehyde aldol addition to the metallacycle
derived from aldehyde 5, yields of Ni(acac)2/DIBAL-H-
promoted reactions were only slightly lower than those of
Ni(COD)2-promoted reactions (Scheme 8).
Conclusions
The oxidative cyclization of enals or enones and alkynes with
Ni(0) provides a novel class of well-defined late transition metal
enolates. These nickel enolates exist as the η1 oxygen bound
tautomer, and they undergo alkylations with a broad range of
electrophiles including alkyl halides, aldehydes, enals, and acyl
chlorides. A cascade cyclization process that involves the
generation and alkylation of nickel enolates has been developed,
and the overall transfomation provides access to novel reductive
or alkylative [3+2] cycloadditions. The cascade process may
be accessed in either a partially or a fully intramolecular sense,
and a noteworthy feature is the opportunity to carry out selective
aldol reactions between nonequivalent aldehydes.17 The produc-
tion of compounds 25 and 29 (Schemes 6 and 7) via the fully
intramolecular version illustrates the potential for truly complex
polycyclizations that rely upon the transient generation and
alkylation of a transition metal enolate. In contrast to “poly-
Heck cyclizations” which often involve the iterative incorpora-
tion of several alkenes or alkynes in essentially identical fashion,
the fully intramolecular polycyclizations described herein
involve fundamentally different chemical operations at each
stage of the cascade process. For instance, the production of
compounds 25 and 29 involves an oxidative cyclization of a
Ni(0) bis π-complex, intramolecular aldol addition, insertion
of an alkenyl nickel species into an aldehyde, and ultimately
protonation of a nickel bis-alkoxide. The differential reactivities
of the various nickel-carbon and nickel-oxygen bonds gener-
ated during this cascade sequence are critical to the overall
chemoselectivity of the process. We anticipate that the develop-
ments described herein will suggest future directions for the
involvement of transition metal enolates in cascade processes.
Scheme 8
couplings of nonequivalent aldehydes17 in both the inter- (Table
2, Scheme 5) and the intramolecular (Schemes 6 and 7) sense.
A drawback of these cascade, nickel enolate-mediated cy-
clizations is the requirement for stoichiometric nickel. Numerous
attempts to devise efficient catalytic processes were unsuccess-
ful. Zn° dust was an obvious choice, but efficient turnover rates
were not observed with this additive. Nucleophilic reducing
agents such as silanes and organozincs were not tolerated due
to chemoselectivity issues. We previously reported the nucleo-
philic participation of reducing agents of this type in simpler
coupling processes,8 and these reagents resulted in premature
termination of the desired cascade cyclization event. Given the
complexities associated with attempts to devise an efficient
catalytic process, we examined the use of inexpensive Ni(II)
precursors for the stoichiometric transformation. Following
Mackenzie’s preparation for generation of Ni(COD)2 from
Ni(acac)2,18 we examined cascade reactions with the species
generated by in situ reduction of Ni(acac)2 with DIBAL-H in
the presence of cyclooctadiene. This modified procedure af-
forded results very similar to those obtained with stoichiometric
Acknowledgment. We acknowledge support for this research
from NSF grant CHE-0093048.
Supporting Information Available: Full experimental details,
1
copies of H NMR spectra of all new compounds, and copies
of X-ray crystallographic data (PDF and CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
(17) (a) Northrup, A. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124,
6798. (b) Denmark, S. E.; Ghosh, S. K. Angew. Chem., Int. Ed. 2001, 40,
4759.
(18) Krysan, D. J.; Mackenzie, P. B. J. Org. Chem. 1990, 55, 4229.
JA037423W
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