Thwarting β-hydride elimination: Capture of the alkylpalladium intermediate of an asymmetric intramolecular heck reaction

Article abstract of DOI:10.1002/1521-3773(20010417)40:8<1439::AID-ANIE1439>3.0.CO;2-F

In spite of containing three conformationally accessible β-H atoms, palladacycle 1a is an isolable intermediate in the asymmetric Heck cyclization of 2a. Although 1a is stable in the presence of the hydrotriflate salt of 1,2,2,6,6-pentamethylpiperidine, i

Full text of DOI:10.1002/1521-3773(20010417)40:8<1439::AID-ANIE1439>3.0.CO;2-F

COMMUNICATIONS
suspended in dry DMF (40 mL) in a 100 mL round-bottom flask.
2,2,6,6-Tetramethylpiperidine 1-oxyl (3.57 g, 20.7 mmol) was added
slowly, the flask was sealed with a drying tube, and stirred for 3 h.
Chloromethylated divinylbenzene (1%)/polystyrene (loading
1.07 mmolg 1, 100 ± 200 mesh, 2 g, 2.14 mmol) was added and the
reaction was agitated for three days at room temperature. The resin
was filtered and thoroughly washed with water, water/DMF (1/1),
DMF, THF, CH2Cl2, and MeOH and dried in vacuo. Loading:
0.93 mmolg 1. Chlorine content: 0.07%. b) Oxidation to oxoammo-
nium resin 2 (Method C; Scheme 1). N-Chlorosuccinimide (6 equiv)
was dissolved in CH2Cl2, 4m HCl in dioxane was added (5 equiv).
After 5 min the solution was added to resin 1 (1 equiv) swollen in dry
CH2Cl2. Agitation for 15 min was followed by filtration of the resin
and washing with dry CH2Cl2. Half-life time (t1/2) of the activated form
was about one week when stored in vacuo at 48C. c) Oxidation of
alcohols. Alcohols 3a ± 22a (1 equiv) were dissolved in dry CH2Cl2.
Freshly prepared oxoammonium resin 2 (5 equiv as calculated from
the loading of resin 1) was added and agitated at room temperature for
1 h for the primary alcohols and 2 h for the secondary alcohols. The
resin was filtered and washed with CH2Cl2, the washings were
employed for analysis by GC, using a 25 m  0.32 mm Permabond SE
54 (df ˆ 1.0 m) fused silica capillary. Temperature program: 508C,
of chemically diverse alcohols (Figure 2). The mixture
(1 mgmL per alcohol) was analyzed by GC-FID as well as
1
GC-MS. In the starting mixture all alcohols could be
separated and identified by their mass spectra. Following
treatment with resin 2 for 2 h, GC analysis revealed the
complete disappearance of all of the alcohol precursors. All
but one of the expected aldehyde, ketone, lactone, or dione
products could be separated and identified; 8b and 12b co-
eluted, whereas 16b was not detected at all. The concen-
tration of products with a low-boiling point eluting early in the
GC was reduced, whereas the concentration of the high-
boiling aldehydes and ketones remained stable in the complex
mixture.
In summary, the reported polymer-bound oxoammonium
reagent should be of great value in polymer-supported
transformations in solution, in automated parallel synthesis
operations, and in flow-through reactors in up-scaled produc-
tion processes. Herein we have only considered the preformed
oxoammonium salts as reactive species. The potential of the
TEMPO ± resin should, however, be exploitable as well as in
situ generated oxoammonium salt, obtained by one of the
available regeneration systems (e.g. CuII/O2), in multiple
phases, or by electrochemical means.
1
2 min isotherm, 58Cmin to 2008C. H2 was used as carrier gas (pi ˆ
50 kPa) for FI detection and He for GC-MS in the EI-mode (70 eV).
Purities are reported in Table 1. Exemplified yields for 10 mg alcohol,
after reaction for 1 h, washing with CH2Cl2 (4 Â 3 mL), and evapo-
ration of the solvent at room temperature: 9b: 8.9 mg, 90%; 10b:
8.7 mg, 88%; 20b: 9.2 mg, 91%. The identity of the isolated products
was confirmed by NMR analysis (250 MHz, CDCl3).
Received: October 4, 2000
[25] D. H. Hunter, D. H. R. Barton, W. J. Motherwell, Tetrahedron Lett.
1984, 25, 603 ± 606.
Revised: January 26, 2001 [Z15900]
[26] Y. Nakatami, K. Kawashima, Synthesis 1978, 147 ± 148.
[1] S. W. Kaldor, M. G. Siegel, Curr. Opin. Chem. Biol. 1997, 1, 101 ± 106.
[2] D. L. Flynn, R. V. Devraj, W. Naing, J. J. Parlow, J. J. Weidner, S. L.
Yang, Med. Chem. Res. 1998, 8, 219 ± 243.
[3] S. V. Ley, I. R. Baxendale, R. M. Bream, P. S. Jackson, A. G. Leach,
D. A. Longbottom, M. Nesi, J. S. Scott, R. I. Storer, S. J. Taylor, J.
Chem. Soc. Perkin Trans. 1 2000, 23, 3815 ± 4195.
[4] S. J. Shuttleworth, S. M. Allin, P. K. Sharma, Synthesis 1997, 1217 ±
1239.
[5] S. J. Shuttleworth, S. M. Allin, R. D. Wilson, D. Nasturica, Synthesis
2000, 1035 ± 1074.
[6] Combinatorial ChemistryÐSynthesis, Analysis, Screening (Ed.: G.
Jung), Wiley-VCH, Weinheim, 1999.
[7] Combinatorial Peptide and Nonpeptide Libraries (Ed.: G. Jung),
VCH, Weinheim, 1996.
[8] J. Rademann, J. Smerdka, G. Jung, P. Grosche, D. Schmid, Angew.
Chem. 2001, 113, 390 ± 393; Angew. Chem. Int. Ed. 2001, 39, 381 ± 385.
[9] Comprehensive Organic Synthesis, Vol. 1 and 2 (Ed.: B. M. Trost),
Pergamon, Oxford, 1991.
[10] A. J. Mancuso, D. Swern, Synthesis 1981, 165 ± 185.
[11] D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4156 ± 4158.
[12] E. J. Corey, J. W. Suggs, Tetrahedron Lett. 1975, 2647 ± 2650.
[13] A. I. Meyers, K. Higashiyama, J. Org. Chem. 1987, 52, 4592 ± 4597.
[14] A. Akelah, D. C. Sherrington, Chem. Rev. 1981, 81, 557 ± 587.
[15] G. Gardillo, M. Orena, S. Sandri, Tetrahedron Lett. 1976, 17, 3985 ±
3988.
[16] B. Hinzen, S. V. Ley, J. Chem. Soc. Perkin Trans. 1 1997, 1907 ± 1910.
[17] M. Caldarelli, J. Habermann, S. V. Ley, J. Chem. Soc. Perkin Trans. 1
1999, 107 ± 110.
Thwarting b-Hydride Elimination: Capture of
the Alkylpalladium Intermediate of an
Asymmetric Intramolecular Heck Reaction**
Martin Oestreich, Philip R. Dennison,
Jeremy J. Kodanko, and Larry E. Overman*
Dedicated to Professor Dieter Hoppe
on the occasion of his 60th birthday
The asymmetric intramolecular Heck reaction[1, 2] has
proven to be one of the most efficient methods for enantio-
selective construction of quaternary carbon centers.[3] We
[*] Prof. Dr. L. E. Overman, Dr. M. Oestreich, Dr. P. R. Dennison,[‡]
J. J. Kodanko
Department of Chemistry
University of California, Irvine
516 Rowland Hall, Irvine, CA 92697-2025 (USA)
Fax : (‡1)949-824-3866
E-mail: leoverma@uci.edu
[18] P. L. Anelli, C. Biffi, F. Montanari, S. Quici, J. Org. Chem. 1987, 52,
2559 ± 2562.
‡
[ ] NMR analyses
[**] This research was supported by the National Institutes of Health
(grant GM-12389). M.O. thanks the Deutsche Forschungsgemein-
schaft (DFG) for an Emmy Noether fellowship (Oe 249/1-1). NMR
and mass spectra were determined at the University of California,
Irvine with instruments purchased with the assistance of the NSF and
NIH shared instrumentation programs. We are grateful to Dr.
Joseph W. Ziller and Dr. John Greaves for their assistance with
X-ray structure and mass spectrometric analyses.
[19] P. L. Anelli, S. Banfi, F. Montanari, S. Quici, J. Org. Chem. 1989, 54,
2970 ± 2972.
[20] G. Sourkouni-Argirusi, A. Kirschning, Org. Lett. 2000, 2, 3781 ± 3784.
[21] C. Bolm, T. Pey, Chem. Commun. 1999, 1795 ± 1796.
[22] A. E. J. de Nooy, A. C. Besemer, H. van Bekkum, Synthesis 1996,
1153 ± 1174.
[23] M. F. Semmelhack, C. R. Schmid, D. A. Cortes, Tetrahedron Lett.
1986, 27, 1119 ± 1122.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
[24] Experimental details: a) Preparation of TEMPO resin 1. Sodium
hydride (1.28 g, stabilized with paraffin oil, 60%, 32.1 mmol) was
Angew. Chem. Int. Ed. 2001, 40, No. 8
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4008-1439 $ 17.50+.50/0
1439

COMMUNICATIONS
have been engaged for some time in the development of
catalytic asymmetric Heck cyclizations, with particular focus
on enantioselective synthesis of oxindoles containing quater-
nary stereocenters.[4] Chiral oxindoles of this type have
numerous applications in synthesis and are key intermediates
in our approach to the synthesis of pyrrolidinoindoline
alkaloids,[5] having recently been employed in enantioselec-
tive total syntheses of monomeric[6] and dimeric[7] members of
this large family of natural products.
One focus of our current efforts is the enantioselective total
synthesis of a tetrameric member of the polypyrrolidinoindo-
line alkaloid family, quadrigemine C (1),[8] which is proposed
to have a meso bis(pyrrolidinoindoline) core decorated with
two pyrrolidinoindolines of identical absolute configuration.
This uncommon stereochemistry led us to consider a con-
vergent dimerization strategy for synthesis of 1 (Scheme 1).
Bn
R
Bn
N
N
a
b
O
O
R
O
OPG
Li
7: R = OMe, PG = Ac (59%)
8: R = H, PG = Tf (74%)
6
O
O
SnBu3
c–e for 9
c for 10
Bn
O
N
N
H
Bn
O
OPG
O
O
N
R
O
O
N
H
R
OTf
I
13
9: R = OMe, PG = Ac (71%)
10: R = H, PG = Tf (72%)
11: R = OMe (50%)
12: R = H (55%)
Scheme 2. a) 1) lithium acetylide, THF, 6, 788C to 258C, 5 h, 2) AcCl
or PhNTf2, THF, 258C to RT, 12 h; b) Bu3SnH, [Pd(PPh3)4], THF (BHT-
inhibited), 08C to RT; c) [Pd2(dba)3] ´ CHCl3, P(2-furyl)3, CuI, NMP, RT,
12 h; d) K2CO3, THF/MeOH (1:1), RT, 2 h; e) PhNTf2, Cs2CO3, DMF, RT,
12 h. Ac ˆ acetyl, BHTˆ 2,6-di-tert-butyl-4-methylphenol, Bn ˆ benzyl,
dba ˆ trans,trans-dibenzylideneacetone, DMF ˆ N,N-dimethylformamide,
NMP ˆ 1-methyl-2-pyrrolidinone, PG ˆ protective group, Tf ˆ trifluoro-
methanesulfonyl.
H
N
Me
N
Me
Bn
N
H
H
N
H
N
Me
N
Bn
N
H
H
O
O
When triflate 11 was cyclized under conditions optimized in
our earlier model study (40 mol% Pd(OAc)2, 60 mol% (R)-
BINAP, 1,2,2,6,6-pentamethylpiperidine (PMP), THF, 808C,
4 h),[10] two products were formed in an 85:15 ratio and 82%
overall yield (Scheme 3). Only minor amounts of the expected
Heck product 14 were isolated; the major product was 15, a
compound resulting from a b-methoxide, rather than b-
hydride elimination. The structure of 15 was unambiguously
secured by X-ray crystallography.[15] The quaternary carbon
centers of both oxindoles 14 and 15 were formed in high
N
H
N
N
Me
Bn
N
H
N
H
N
N
Me
H
Bn
Me
1: quadrigemine C
2
O
X
O
O
N
H
N
H
OMe
Bn
N
O
N
O
OTf
Bn
OMe
3: X = CO
4: X = CH2
5
O
O
O
Scheme 1. Retrosynthetic analysis of quadrigemine C (1).
Pd(OAc)2, (R)-BINAP
THF, 80 ˚C, 4 h
N
H
Bn
N
We envisioned dihydroisoindigo intermediate 2, having both
outer pyrrolidinoindoline units installed, a suitable substrate
for our dialkylation method of constructing the vicinal
stereogenic quaternary carbon centers of the central six
rings.[9] Intermediate 2 should be accessible by aldol con-
densation of an isatin (3, X ˆ CO) and a cognate oxindole (4,
X ˆ CH2) followed by reduction. Enantioenriched isatin 3 and
oxindole 4 in turn would derive from asymmetric Heck
cyclization of triflate 5.[10] Herein we report highly enantio-
selective Heck reactions of substrates of type 5 and the
isolation of a s-alkylpalladium intermediate having stereo-
electronically accessible b-hydrogen atoms of this Heck
sequence.[11]
O
OTf
N
(82%)
OMe
O
11
O
O
O
O
O
N
N
+
H
H
OMe
O
O
N
N
Bn
Bn
14 (er = 98:2)
15 (er >99:1)
:
15
85
Cyclization precursors 11 and 12 were each prepared from
3-benzyl-3H-benzooxazol-2-one (6)[12] in short routes analo-
gous to those previously described (Scheme 2).[10] Stille
coupling[13] of vinylstannane 9 or 10 with ketal-protected
7-iodoisatin 13[14] and further functional group manipulation
provided 11 and 12.
PPh2
PPh2
(R)-BINAP =
=
P
P
Scheme 3. Asymmetric Heck reaction of 11.
1433-7851/01/4008-1440 $ 17.50+.50/0 Angew. Chem. Int. Ed. 2001, 40, No. 8
1440
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001

COMMUNICATIONS
enantiomeric ratios (erˆ 98:2 and >99:1, respectively).[16]
O-Tosylation of the protected isatin fragment and X-ray
analysis of the resulting O-tosylimidate derivative established
the absolute configuration of 15.[15, 17]
a-carbon has a diagnostic chemical shift of d ˆ 43.7 in the
13C NMR spectrum, which compares well with literature
precedent for sp3-hybridized alkylpalladium compounds.[19]
1
The 31P NMR spectrum with H decoupling shows two sets
In an attempt to access 15 from a simpler precursor, we
investigated the Heck cyclization of (Z)-butenanilide 12
(Scheme 4). To our surprise, the asymmetric Heck reaction
of signals in a ratio of 95:5, which we assign as two epimeric
palladacycles 16 and epi-16, indicating high stereoselection in
forming the oxindole quaternary carbon center.[18b]
To provide further evidence for the structure of 16, a pure
sample of this product was heated in THF at 808C for 4 h in
the presence of an excess of PMP, 2,6-di-tert-butylpyridine
(TBP), or PMP hydrotriflate. Palladium complex 16 proved to
be stable under these conditions, suffering only minor
decomposition. In dramatic contrast, addition of an equimolar
amount of the stronger acid, TBP hydrotriflate[20] to the bright
yellow solution of 16 and THF at room temperature occa-
sioned an instantaneous color change from yellow to red,
indicating the generation of a Pd0 ± BINAP complex. After
this solution had been heated at 808C for 4 h, the product of b-
hydride elimination 15 was isolated in 48% yield (erˆ 95:5).
As suggested by this observation, replacing PMP with TBP in
Heck reactions of 11 and 12 had a profound effect on the
product distribution. Carrying out these reactions in the
presence of TBP provided conventional Heck products
arising from b-hydride elimination (11 !14 and 12 !15,
Scheme 5) in good yield (Scheme 5), in contrast to related
cyclizations employing PMP as a base (Scheme 3 and 4).[21]
Based on these observations, we propose that the reaction
pathway of the Heck reactions of 11 and 12 is governed by the
acidity of the conjugate acid of the trifluoromethanesulfonic
acid scavenger employed. Although direct estimates do not
exist for THF as solvent, TBP hydrotriflate should be a
stronger acid than PMP hydrotriflate by about 7 pKa
units.[22, 23] When the Heck cyclizations are carried out in the
_
Scheme 4. Asymmetric Heck reaction of 12. P P ˆ (R)-BINAP.
of 12 under identical conditions provided only traces of 15,
together with unreacted starting material and uncharacterized
by-products. When 12 was cyclized in the presence of
100 mol% Pd(OAc)2 and 150 mol% (R)-BINAP, substantial
amounts (ꢀ35 ± 55% based on 12) of a stable, palladium-
containing compound 16 were isolated after workup and flash
chromatography.
Careful mass spectrometric analysis and NMR studies
support the structure depicted for 16 [C27H22N2O4Pd ´ (R)-
BINAP] in Scheme 4. In particular, a 31P ± 1H correlation
proves the existence of the relevant fragment of palladacycle
16: both phosphorus atoms, Pcis and Ptrans, couple with the
hydrogen atoms attached to Ca and Cb; the individual coupling
constants were resolved by decoupling experiments.[18a] The
Scheme 5. Postulated mechanism for the formation of 14 and 15.
Angew. Chem. Int. Ed. 2001, 40, No. 8
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4008-1441 $ 17.50+.50/0
1441

COMMUNICATIONS
high yields and high enantiomeric ratios: K. Hatanaka, J. J. Kodanko,
M. Oestreich, L. E. Overman, L. A. Pfeiffer, J. W. Ziller, unpublished
results.
presence of the strong base PMP, palladacycles 16 and 19 are
generated. Although 16 and 19 possess three and two b-
hydrogen atoms, respectively, these intermediates do not
undergo b-hydride elimination since a tightly bound ligand
(BINAP or the conjugate base of the protected isatin) would
have to dissociate to generate a vacant coordination site.[24, 25]
Therefore, palladacycle 16 is stable, while 19 undergoes b-
methoxide elimination to generate 15.[26] In contrast, when the
Heck reactions are carried out in the presence of the weaker
base TBP, TBP hydrotriflate is acidic enough to shift the
equilibrium from the palladacyclic intermediates toward the
cationic palladium(ii) species 17 and 18, which undergo facile
b-hydride elimination to generate conventional Heck prod-
ucts 14 and 15.
[11] For other examples of s-alkylpalladium(ii) complexes containing
conformationally free b-hydrogen atoms, see: a) R. Arnek, K.
Zetterberg, Organometallics 1987, 6, 1230 ± 1235; b) L. Zhang, K.
Zetterberg, Organometallics 1991, 10, 3806 ± 3813.
[12] H. Ucar, K. Vanderpoorten, S. Cacciaguerra, S. Spampinato, J. P.
Stables, P. Depovere, M. Isa, B. Masereel, J. Delarge, J. H. Poupaert, J.
Med. Chem. 1998, 41, 1138 ± 1145.
[13] a) V. Farina, B. Krishnan, J. Am. Chem. Soc. 1991, 113, 9585 ± 9595;
b) V. Farina, S. Kapadia, B. Krishnan, C. Wang, L. S. Liebeskind, J.
Org. Chem. 1994, 59, 5905 ± 5911.
[14] The carbonyl group of the isatin was protected as a ketal to prevent
side reactions caused by the high electrophilicity of this group. For the
synthesis of isatin ketals, see: M. Rajopadhye, F. D. Popp, J. Med.
Chem. 1988, 31, 1001 ± 1005.
[15] Crystallographic data (excluding structure factors) for the structures
reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no.
CCDC-155109 (15) and CCDC-155110 (O-tosyl derivate of 15).
Copies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: (‡44)1223-
336-033; e-mail: deposit@ccdc.cam.ac.uk).
[16] HPLC analysis using a Daicel Chiralcel OD-H column (hexane/
iPrOH 90:10) provided baseline resolution of enantiomers.
[17] Thus far attempts to chemically correlate 14 and 15 have failed. As a
result, the absolute configuration of 14 is assigned on the basis of its
similar HPLC characteristics on a chiral stationary phase to 15,[16] and
by analogy to our earlier model studies.[10]
[18] a) The full set of data is provided in the Supporting Information and
copies of NMR specta are available from the authors. b) The 31P NMR
spectrum with 1H decoupling with signals being assigned is depicted in
the Supporting Information.
[19] G. R. Hoel, R. A. Stockland, G. K. Anderson, F. T. Ladipo, J.
Braddock-Wilking, N. P. Rath, J. C. Mareque-Rivas, Organometallics
1998, 17, 1155 ± 1165.
In summary, an asymmetric Heck reaction has been
successfully employed for the enantioselective construction
(er> 99:1) of the quaternary stereocenter of an advanced
intermediate en route to quadrigemine C (1). The unusual
outcome of the Pd0 ± BINAP-catalyzed cyclization of 11 is
rationalized by the intermediacy of palladacycle 19, which
preferentially suffers b-methoxide elimination. The corre-
sponding palladacyclic intermediate 16 lacking a methoxy
group on the b-carbon atom is a stable compound. Pallada-
cycle 16 is a rare example of a stable s-alkylpalladium
complex that has b-hydrogen atoms residing on a freely
rotating b-carbon atom.[11] To the best of our knowledge, this
is the first example of the isolation of an intermediate of this
type in a Heck reaction.
Received: January 8, 2001 [Z16380]
[20] A colorless salt, see: G. A. Crispino, R. Breslow, J. Org. Chem. 1992,
57, 1849 ± 1855.
[21] Reactions in the presence of TBP were not completed within 4 h.
After 4 h, 11 gave 14 in 40% yield (40 mol% catalyst loading) and 12
provided 15 in 75% yield (100 mol% catalyst loading).
[1] For recent reviews of the Heck reaction, see: a) I. P. Beletskaya, A. V.
Cheprakov, Chem. Rev. 2000, 100, 3009 ± 3066; b) A. de Meijere, F. E.
Meyer in Metal-Catalyzed Cross-Coupling Reactions (Eds.: F. Die-
derich, P. J. Stang), Wiley-VCH, Weinheim, 1998, Chap. 3; c) J. T.
Link, L. E. Overman in Metal-Catalyzed Cross-Coupling Reactions
(Eds.: F. Diederich, P. J. Stang), Wiley-VCH, Weinheim, 1998,
Chap. 6.
[2] For recent reviews of asymmetric Heck reactions, see: a) Y. Donde,
L. E. Overman in Catalytic Asymmetric Synthesis (Ed.: I. Ojima),
2nd ed., Wiley, New York, 2000, Chap. 8G; b) M. Shibasaki in
Advances in Metal-Organic Chemistry (Ed.: L. S. Liebeskind), JAI,
Greenwich, 1996, pp. 119 ± 151.
[22] The pKa values for the conjugate acids of PMP (pKa (50% aqueous
ethanol) ˆ 9.54[23a] and pKa (acetonitrile) ˆ 18.7[23b]) and TBP (pKa
(50% aqueous ethanol) ˆ 2.70[23a] and pKa (acetonitrile) ˆ 11.8[23c]
)
have been measured in aqueous ethanol and estimated in acetonitrile;
DpKa is about 7 pKa units in both solvents.
[23] a) J. C. Day, J. Am. Chem. Soc. 1981, 103, 7355 ± 7357; b) M.
Dworniczak, K. T. Leffek, Can. J. Chem. 1990, 68, 1657 ± 1661; c) C.
Schlesener, C. Amatore, J. K. Kochi, J. Am. Chem. Soc. 1984, 106,
7472 ± 7482.
[24] For a review of b-hydride elimination of s-alkyl transition metal
complexes, see: J. Cross in The Chemistry of the Metal ± Carbon Bond,
Vol. 2 (Eds.: F. R. Hartley, S. Patai), Wiley, New York, 1985, Chap. 8.
[25] The six-membered palladacycle ring likely also contributes to the
stability of 19.[11, 24]
[26] For syn as well as anti b-alkoxide eliminations terminating intra-
molecular Heck reactions, see: a) J.-F. Nguefack, V. Bolitt, D. Sinou, J.
Chem. Soc. Chem. Commun. 1995, 1893 ± 1894; b) K. Bedjeguelal, L.
Joseph, V. Bolitt, D. Sinou, Tetrahedron Lett. 1999, 40, 87 ± 90.
[3] Recent reviews of asymmetric synthesis of quaternary centers: a) E. J.
Corey, A. Guzman-Perez, Angew. Chem. 1998, 110, 402 ± 415; Angew.
Chem. Int. Ed. 1998, 37, 388 ± 401; b) K. Fuji, Chem. Rev. 1993, 93,
2037 ± 2066.
[4] a) A. Ashimori, B. Bachand, L. E. Overman, D. J. Poon, J. Am. Chem.
Soc. 1998, 120, 6477 ± 6487; b) A. Ashimori, B. Bachand, M. A. Calter,
S. P. Govek, L. E. Overman, J. Am. Chem. Soc. 1998, 120, 6488 ± 6499.
[5] U. Anthoni, C. Christophersen, P. H. Nielsen in Alkaloids: Chemical
and Biological Perspectives, Vol. 13 (Ed.: W. S. Pelletier), Pergamon,
New York, 1999, pp. 163 ± 236, and references therein.
[6] Total syntheses of physostigmine and physovenine: T. Matsuura, L. E.
Overman, D. J. Poon, J. Am. Chem. Soc. 1998, 120, 6500 ± 6503.
[7] Total syntheses of the chimonanthines: L. E. Overman, D. V. Paone,
B. A. Stearns, J. Am. Chem. Soc. 1999, 121, 7702 ± 7703.
Â
Â
[8] F. Gueritte-Voegelein, T. Sevenet, J. Pusset, M. T. Adeline, B. Gillet,
Â
J. C. Beloeil, D. Guenard, P. Potier, J. Nat. Prod. 1992, 55, 923 ± 930.
[9] a) L. E. Overman, J. F. Larrow, B. A. Stearns, J. M. Vance, Angew.
Chem. 2000, 112, 219 ± 221; Angew. Chem. Int. Ed. 2000, 39, 213 ± 215;
b) S. B. Hoyt, L. E. Overman, Org. Lett. 2000, 2, 3241 ± 3244.
[10] We have recently demonstrated in a model study that (Z)-a-aryl-a,b-
unsaturated o-triflatoanilides smoothly undergo Heck cyclization in
1442
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4008-1442 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 8