Palladium-catalyzed synthesis of N-vinyl pyrroles and indoles

Article abstract of DOI:10.1021/jo051450i

A stereospecific palladium-catalyzed N-vinylation of aza-heterocycles with vinyl inflates is described. Cyclic and acyclic vinyl triflates along with nonnucleophilic azaheterocycles were found to be substrates for this palladium-catalyzed synthesis of N-vinyl pyrrole and indole derivatives.

Full text of DOI:10.1021/jo051450i

cerning the N-vinylation of dialkylamines and azoles are
even more rare as compared to reports of N-vinylation
of amides and carbamates.6,7 A single study on the
palladium-catalyzed coupling of lithiated azoles with
vinyl bromides has been reported.6c Herein we describe
a palladium-catalyzed stereospecific coupling of vinyl
triflates with pyrroles and indoles.
Palladium-Catalyzed Synthesis of N-Vinyl
Pyrroles and Indoles
Mohammad Movassaghi* and Alison E. Ondrus
Department of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139
Recently, Buchwald reported the efficient copper-
catalyzed asymmetric conjugate reduction of a variety of
3-aza-2-enoates (2) to give the corresponding 3-aza-
alkanoates (3, eq 1).7 The necessary 3-aza-2-enoate (2)
substrates were prepared via a copper-catalyzed N-
vinylation of azaheterocycles and lactams with Z-3-
iodoenoates (1).
movassag@mit.edu
Received July 13, 2005
A stereospecific palladium-catalyzed N-vinylation of aza-
heterocycles with vinyl triflates is described. Cyclic and
acyclic vinyl triflates along with nonnucleophilic azahetero-
cycles were found to be substrates for this palladium-
catalyzed synthesis of N-vinyl pyrrole and indole derivatives.
We were particularly interested in the use of this
chemistry for the synthesis of optically active â-azolyl
carboxylic acid building blocks for complex alkaloid
synthesis. However, the reaction conditions for generat-
ing the necessary Z-3-iodoenoates (1), namely treatment
of the corresponding ynoates with sodium iodide in acetic
acid at elevated temperatures (60 f 150 °C),8 were not
compatible with several substrates of interest. Further-
more, a similar direct synthesis of the isomeric E-3-
iodoenoates9 is not available. We envisioned the use of
readily available â-ketoesters as precursors for the ste-
reospecific synthesis of both Z- and E-â-pyrrolyl enoates
4 (Scheme 1). Specifically, we sought a catalytic method
Transition-metal-catalyzed carbon-nitrogen bond for-
mation has become a powerful methodology in organic
synthesis.1 A variety of highly active palladium and
copper catalyst systems have been reported for the
N-arylation of amines, amides, azoles, and carbamates.2,3
However, there exist fewer examples of C-N bond
formation as a method of N-vinylation.1,4,5 Reports con-
(1) (a) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc.
Chem. Res. 1998, 31, 805-818. (b) Hartwig, J. F. Acc. Chem. Res. 1998,
31, 852-860. (c) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046-
2067. (d) Yang, B. H.; Buchwald, S. L. J. Organomet. Chem. 1999, 576,
125-146. (e) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219,
131-209. (f) Hartwig, J. F. In Handbook of Organopalladium Chem-
istry for Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience: New
York, 2002; p 1051.
(2) (a) Wolfe, J. P.; Wagaw, S.; Buchwald, S. L. J. Am. Chem. Soc.
1996, 118, 7215-7216. (b) Driver, M. S.; Hartwig, J. F. J. Am. Chem.
Soc. 1996, 118, 7217-7218. For examples of palladium-catalyzed
N-arylation of azoles, see: (c) Mann, G.; Hartwig, J. F.; Driver, M. S.;
Ferna´ndez-Rivas, C. J. Am. Chem. Soc. 1998, 120, 827-828. (d) Old,
D. W.; Harris, M. C.; Buchwald, S. L. Org. Lett. 2000, 2, 1403-1406.
(e) Watanabe, M.; Nishiyama, M.; Yamamoto, T.; Koie, Y. Tetrahedron
Lett. 2000, 41, 481-483.
(3) For examples of copper-catalyzed N-arylation, see: (a) Kiyomori,
A.; Marcoux, J.-F.; Buchwald, S. L. Tetrahedron Lett. 1999, 40, 2657-
2660. (b) Collman, J. P.; Zhong, M. Org. Lett. 2000, 2, 1233-1236. (c)
Gujadhur, R. K.; Bates, C. G.; Venkataraman, D. Org. Lett. 2001, 3,
4315-4317. (d) Klapars, A.; Antilla, J. C.; Huang, X.; Buchwald, S. L.
J. Am. Chem. Soc. 2001, 123, 7727-7729. (e) Klapars, A.; Huang, X.;
Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 7421-7428. (f) Kwong,
F. Y.; Buchwald, S. L. Org. Lett. 2003, 5, 793-796. (g) Ma, D.; Cai, Q.;
Zhang, H. Org. Lett. 2003, 5, 2453-2455. (h) Padwa, A.; Crawford, K.
R.; Rashatasakhon, P.; Rose, M. J. Org. Chem. 2003, 68, 2609-2617.
(i) Antilla, J. C.; Baskin, J. M.; Barder, T. E.; Buchwald, S. L. J. Org.
Chem. 2004, 69, 5578-5587.
(4) For intramolecular palladium-catalyzed N-vinylation of amides,
see: (a) Palomo, C.; Aizpurua, J. M.; Legido, M.; Picard, J. P.;
Dunogues, J.; Constantieux, T. Tetrahedron Lett. 1992, 33, 3903-3906.
(b) Cuevas, J.-c.; Patil, P.; Snieckus, V. Tetrahedron Lett. 1989, 30,
5841-5844. (c) Kozawa, Y.; Mori, M. Tetrahedron Lett. 2002, 43, 111-
114. For recent reports on palladium-catalyzed N-vinylation, see: (d)
Wallace, D. J.; Klauber, D. J.; Chen, C.-y.; Volante, R. P. Org. Lett.
2003, 5, 4749-4752. (e) Klapars, A.; Campos, K. R.; Chen, C.-y.;
Volante, R. P. Org. Lett. 2005, 7, 1185-1188.
(5) For a recent review on the use of copper in cross-coupling
reactions, see: (a) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem.
Rev. 2004, 248, 2337-2364. For amidation of vinyl halides with copper
as the catalyst or promoter, see: (b) Ogawa, T.; Kiji, T.; Hayami, K.;
Suzuki, H. Chem. Lett. 1991, 1443-1446. (c) Shen, R.; Porco, J. A., Jr.
Org. Lett. 2000, 2, 1333-1336. (d) Shen, R.; Lin, C. T.; Porco, J. A., Jr.
J. Am. Chem. Soc. 2002, 124, 5650-5651. (e) Jiang, L.; Job, G. E.;
Klapars, A.; Buchwald, S. L. Org. Lett. 2003, 5, 3667-3669. (f) Han,
C.; Shen, R.; Su, S.; Porco, J. A., Jr. Org. Lett. 2004, 6, 27-30. (g) Pan,
X.; Cai, Q.; Ma, D. Org. Lett. 2004, 6, 1809-1812. (h) Hu, T.; Li, C.
Org. Lett. 2005, 7, 2035-2038. For copper-catalyzed and -promoted
N-alkynylation, respectively, see: (i) Frederick, M. O.; Mulder, J. A.;
Tracey, M. R.; Hsung, R. P.; Huang, J.; Kurtz, K. C. M.; Shen, L.;
Douglas, C. J. J. Am. Chem. Soc. 2003, 125, 2368-2369. (j) Dunetz, J.
R.; Danheiser, R. L. Org. Lett. 2003, 5, 4011-4014. For a copper-
catalyzed C-N bond formation using allenyl halides, see: (k) Trost,
B. M.; Stiles, D. T. Org. Lett. 2005, 7, 2117-2120.
(6) For palladium-catalyzed N-vinylation of amines, see: (a) Bar-
luenga, J.; Ferna´ndez, M. A.; Aznar, F.; Valde´s, C. Chem. Commun.
2002, 2362-2363. (b) Willis, M. C.; Brace, G. N. Tetrahedron Lett.
2002, 43, 9085-9088. For palladium-catalyzed N-vinylation of lithiated
azoles, see: (c) Lebedev, A. Y.; Izmer, V. V.; Kazyul’kin, D. N.;
Beletskaya, I. P.; Voskoboynikov, A. Z. Org. Lett. 2002, 4, 623-626.
(7) Rainka, M. P.; Aye, Y.; Buchwald, S. L. Proc. Natl. Acad. Sci.
U.S.A. 2004, 101, 5821-5823.
(8) For the synthesis of Z-â-iodoenoates, see: Piers, E.; Wong, T.;
Coish, P. D.; Rogers, C. Can. J. Chem. 1994, 72, 1816-1819.
(9) For synthesis of E-â-iodoenoates via an iododestannylation step,
see: (a) Thibonnet, J.; Launay, V.; Abarbri, M.; Ducheˆne, A.; Parrain,
J.-L. Tetrahedron Lett. 1998, 39, 4277-4280. (b) Maguire, R. J.; Munt,
S. P.; Thomas, E. J. J. Chem. Soc., Perkin Trans. 1 1998, 2853-2863.
(c) Dieter, R. K.; Lu, K. J. Org. Chem. 2002, 67, 847-855. For
isomerization of Z-â-iodoenoates, see: (d) Ohba, M.; Kawase, N.; Fujii,
T. J. Am. Chem. Soc. 1996, 118, 8250-8257. (e) Dudley, G. B.; Takaki,
K. S.; Cha, D. D.; Danheiser, R. L. Org. Lett. 2000, 2, 3407-3410.
10.1021/jo051450i CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/20/2005
8638
J. Org. Chem. 2005, 70, 8638-8641

SCHEME 1. Stereospecific Synthesis of â-Pyrrolyl
Enoates
found to minimize the formation of both the â-ketoester
and the ynoate byproducts.14,15 Attempted palladium-
catalyzed coupling of preformed pyrrolyllithium with
vinyl triflate 5b gave predominantly (∼80%) the undes-
ired elimination product 9b (eq 2).6c Furthermore, when
N-tributylstannylpyrrole16 was used in place of pyrrole
(7a) for the synthesis of N-vinyl pyrrole 4ba, in the
absence of anhydrous potassium phosphate, the product
mixture contained as much as 50% C-coupled product
8ba (eq 2).17 Interestingly, this undesired C-coupled
byproduct was not observed using pyrrole (7a) with the
optimal conditions described above.
Considering the synthetic utility of N-vinyl pyrroles
and indoles and encouraged by these early results, we
sought to explore the generality of this catalytic N-
vinylation reaction (Table 1). Representative vinyl tri-
flates18 and azaheterocycles used as substrates in these
studies are shown in Chart 1.
for the stereospecific N-vinylation of pyrroles with con-
figurationally defined vinyl triflates.10
Initial experiments on the coupling of pyrrole (7a) and
vinyl triflates 5a,b (eq 2) revealed that copper-based
catalyst systems were not effective, typically returning
the unreacted triflates. However, the combination of
palladium dibenzylideneacetone (Pd2(dba)3) and 2-di-
cyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl
(XPhos)11,12 provided a highly active catalyst system for
the efficient and selective synthesis of the desired N-vinyl
pyrroles. Under optimal conditions, the coupling of the
vinyl triflate 5a (1 equiv) with pyrrole (7a, 1.5 equiv)
using Pd2dba3 (5 mol %), XPhos (10 mol %) as ligand in
the presence of anhydrous potassium phosphate (1.40
equiv) in toluene at 60 °C proceeded to give the desired
Z-â-pyrrolyl enoate 4aa with complete stereospecificity
in 84% yield after 3.5 h (Table 1, entry 1). Under identical
conditions, the coupling of the more sensitive dimethoxy-
acetal containing vinyl triflate 5b afforded the corre-
sponding N-vinyl pyrrole 4ba (eq 2) in 79% isolated
yield.13
The coupling of Z-vinyl triflate 5a with the less
nucleophilic acyl pyrrole 7b at 60 °C affords the desired
product 4ab in 70% yield after 7 h (Table 1, entry 2). An
enhancement in the rate of this coupling reaction was
noted using dioxane as a cosolvent, affording N-vinyl
pyrrole derivative 4ab in 91% isolated yield after 1 h at
60 °C (Table 1, entry 3). Alternatively, increasing the
reaction temperature to 80 °C gave 4ab in 81% yield after
complete consumption of starting material (Table 1, entry
4). The coupling of Z-vinyl triflate 5a with the more
sterically hindered tetrahydroindolone 7c was found to
be more difficult as compared to the acyl pyrrole 7b
(Table 1, compare entries 2 and 5). The use of toluene-
dioxane solvent mixture and higher reaction tempera-
tures slightly increased the yield of this coupling reaction
to afford 4ac in 50% isolated yield (Table 1, entry 7). The
coupling of the cyanoindole 7e, the least reactive azole
examined in this study, with Z-vinyl triflate 5a gave only
24% yield of the N-vinyl azaheterocycle 4ae after 48 h
(Table 1, entry 8). Both the use of toluene-dioxane
solvent mixture and higher reaction temperatures were
found to increase the formation of the ynoate 9a (eq 2)
without a net increase in the yield of the coupled product
4ae (Table 1, entries 9 and 10).15,19
To highlight the stereospecificity of this transforma-
tion, we examined the coupling between E-vinyl triflate
5c and various azaheterocycles (Table 1, entries 11-17).
In every case, the palladium-catalyzed stereospecific
C-N bond formation proceeded to afford the desired
Two commonly observed side products in these cou-
pling reactions were the â-ketoesters 6a,b and the
ynoates 9a,b (eq 2). Potassium phosphate tribasic was
most effective as the base additive compared to potassium
phosphate dibasic, cesium carbonate, triethylamine, and
1,8-diazabicyclo[5.4.0]undec-7-ene; the latter gave pre-
dominantly the undesired ynoate byproduct. The use of
rigorously dried anhydrous potassium phosphate was
(14) Best results were obtained by further drying commercially
available anhydrous potassium phosphate (160 °C, 0.1 Torr, 12 h) and
handling it under inert atmosphere.
(15) For a discussion on the competitive elimination reaction to give
ynoates in studies concerning the palladium-catalyzed C-O and C-S
bond formation, see: Rossi, R.; Bellina, F.; Mannina, L. Tetrahedron
1997, 53, 1025-1044.
(16) For the synthesis of N-(tributylstannyl)pyrrole, see: William-
son, B. L.; Stang, P. J. Synlett 1992, 199-200.
(10) For reviews on the preparation and use of vinyl triflates, see:
(a) Ritter, K. Synthesis 1993, 735-762. (b) Baraznenok, I. L.; Nena-
jdenko, V. G.; Balenkova, E. S. Tetrahedron 2000, 56, 3077-3119. Also,
see: (c) Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 33, 6299-
6302.
(11) Use of XPhos gave superior results as compared to tri-(o-tolyl)-
phosphine, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), and
2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (SPhos).
(12) (a) Tomori, H.; Fox, J. M.; Buchwald, S. L. J. Org. Chem. 2000,
65, 5334-5341. (b) XPhos is commercially available.
(13) In the absence of palladium catalyst, none of the coupling
products were observed.
(17) For use of dialkylaminotributystannanes in N-arylation reac-
tions, see: (a) Kosugi, M.; Mameyama, M.; Migita, T. Chem. Lett. 1983,
927-928. (b) Paul, F.; Patt, J.; Hartwig, J. F. J. Am. Chem. Soc. 1994,
116, 5969-5970. (c) Guram, A. S.; Buchwald, S. L. J. Am. Chem. Soc.
1994, 116, 7901-7902.
(18) See Supporting Information for details.
(19) For a discussion on the competitive loss of triflates via nucleo-
philic attack at the sulfur center during N-arylation of amines with
electron-deficient aryl triflates, see: (a) Wolfe, J. P.; Buchwald, S. L.
J. Org. Chem. 1997, 62, 1264-1267. (b) Louie, J.; Driver, M. S.;
Hamann, B. C.; Hartwig, J. F. J. Org. Chem. 1997, 62, 1268-1273.
J. Org. Chem, Vol. 70, No. 21, 2005 8639

TABLE 1. Palladium Catalyzed N-Vinylation of Azaheterocycles with Vinyl Triflates
a Reaction temperature in degrees Celsius; reaction time in hours. b Solvent: A ) toluene, B ) toluene-1,4-dioxane (3:1). c Isolated
yield after purification. d Remaining vinyl triflate: entry 5, 38%; entry 7, 13%; entry 8, 65%; entry 25, 25%. e Complete consumption of
5a; the ynoate 9a constitutes the mass balance. f Complete conversion to product 4cb (>90% yield) prior to chromatographic purification.
g Ethyl 2-oxo-cyclopentanecarboxylate was formed (∼50%).
E-enoate. Acyl pyrrole 7b, tetrahydroindolone (7c), indole
(7d), and 3-cyanoindole (7e) were successfully coupled
with E-vinyl triflate 5c to give the corresponding N-vinyl
azaheterocycle in 60, 73, 74, and 74% yield, respectively
(Table 1, entries 12, 14, 15, and 16). Interestingly, the
E-vinyl triflate 5c demonstrated an enhanced rate of
coupling relative to that of the Z-vinyl triflate 5a in all
cases examined. Additionally, the coupling reactions
employing E-vinyl triflate 5c exhibited a much slower
rate of ynoate formation as compared to those using
Z-vinyl triflate 5a. Where possible, the use of 1,4-dioxane
as a cosolvent and higher reaction temperatures for a
8640 J. Org. Chem., Vol. 70, No. 21, 2005

CHART 1
found to be substrates for this palladium-catalyzed
synthesis of N-vinyl pyrrole and indole derivatives.
Successful use of nonnucleophilic azaheterocycles in this
coupling reaction is noteworthy. The ready availability
of both E- and Z-vinyl triflates,23 in conjunction with the
herein described chemistry, offers an attractive method
for the synthesis of N-vinyl azaheterocycles.
Experimental Section
Representative Experimental Procedure. Z-3-Pyrrol-1-
yl-but-2-enoic Acid Ethyl Ester (4aa, Table 1, Entry 1).
Toluene (1.90 mL) was added to an argon-purged sample of Pd2-
(dba)3 (17.5 mg, 19.1 µmol, 0.05 equiv), XPhos (18.2 mg, 38.1
µmol, 0.10 equiv), and rigorously anhydrous K3PO4 (113 mg, 534
µmol, 1.40 equiv) in a flame-dried flask. Pyrrole (7a, 40.0 µL,
572 µmol, 1.50 equiv) was then added, and the deep red mixture
was heated to 60 °C. After 30 min, triflate 5a24 (100 mg, 381
µmol, 1 equiv) was added via syringe, producing a color change
to forest green within approximately 10 min and then to brown
within an additional 1 h. After 3.5 h, TLC analysis indicated
that the reaction was complete, whereupon the mixture was
allowed to cool to 23 °C, was diluted with EtOAc (10 mL), and
was vacuum filtered through a plug of Celite (diameter 2.5 cm,
height 2.5 cm). The Celite plug and flask were rinsed with an
additional 15-mL portion of EtOAc, and the combined organic
filtrates were washed with water (7.5 mL) and brine (7.5 mL),
dried over anhydrous sodium sulfate, filtered, and concentrated
under reduced pressure to give a deep brown residue. Purifica-
tion of the crude material by flash column chromatography (silica
gel: diameter 3.0 cm, height 22 cm; 60% EtOAc/hexanes)
afforded the vinyl pyrrole 4aa (57.1 mg, 84%) as a yellow oil.
1H NMR (500 MHz, CDCl3, 20 °C): 6.90 (app t, J ) 2.2 Hz, 2H),
6.23 (app t, J ) 2.2 Hz, 2H), 5.52 (q, J ) 1.2 Hz, 1H), 4.10 (q, J
) 7.1 Hz, 2H), 2.26 (d, J ) 1.3 Hz, 3H), 1.20 (t, J ) 7.1 Hz, 3H).
13C NMR (125.7 MHz, CDCl3, 20 °C): 165.2, 147.7, 121.4, 110.1,
107.6, 60.5, 24.5, 14.4. FTIR (neat): 2982 (w, C-H), 1718 (s,
CdO), 1641 (s, CdC), 1481, 1182, 1051. HRMS-ESI (m/z): calcd
for C10H13NO2Na [M + Na]+: 202.0838, found: 202.0839.
shorter reaction time afforded more efficient palladium-
catalyzed N-vinylation.20 An initial short incubation of
the reaction components at 60 °C followed by warming
to higher temperatures provided the best results.21
The palladium-catalyzed N-vinylation reactions with
cyclic vinyl triflates 5d and 5e were found to be slower
than those of the vinyl triflates 5a and 5c. However, the
greater thermal stability and the absence of the compet-
ing base-induced triflate elimination allowed the use of
higher reaction temperatures with these substrates. The
coupling of azaheterocycles 7b, 7c, and 7e with triflate
5d gave the corresponding N-vinyl products in 70, 62,
and 17% yield, respectively (Table 1, entries 18, 20, and
22). In the latter case a significant quantity (∼50%) of
ethyl 2-oxo-cyclopentanecarboxylate was isolated, sug-
gesting a competitive sulfonyl transfer reaction.19 The
coupling of the vinyl triflate 5e with the acyl pyrrole 7b
proceeded efficiently at 110 °C to give the N-vinyl pyrrole
4eb in 91% yield (Table 1, entry 24). Neither of the less
reactive azaheterocycles 7c nor 7e gave appreciable
amounts of the corresponding coupling products with
vinyl triflate 5e.
The coupling of vinyl triflate 5f with acyl pyrrole 7b
afforded the desired N-vinyl azole 4fb in 72% yield (Table
1, entry 26), demonstrating the possible extension of this
chemistry to unactivated vinyl triflates. However, the
longer reaction time and the higher reaction temperature
needed for the synthesis of product 4fb should be noted.
The reduction of the steric bulk of the vinyl triflate and
the presence of the electron-withdrawing ester each have
a beneficial effect on the rate of the coupling reaction.
The relative rate of coupling for the vinyl triflates
discussed here was found to be: 5c > 5a > 5d > 5e > 5f
(Chart 1). Similarly, the azaheterocycles used in this
study may be ranked from most reactive to the least
reactive: 7a > 7b > 7d > 7c > 7e (Chart 1). While the
deprotonation of the heterocycle is facilitated by the
presence of an electron-withdrawing substituent, these
less nucleophilic heterocycles exhibit a slower overall rate
of coupling. Hence, undesired reactions including triflate
elimination and sulfonyl transfer reactions may compete
when very nonnucleophilic azaheterocycles are used as
substrates.22
Acknowledgment. M.M. is a Dale F. and Betty Ann
Frey Damon Runyon Scholar supported by the Damon
Runyon Cancer Research Foundation (DRS-39-04). M.M.
is a Firmenich Assistant Professor of Chemistry. A.E.O.
acknowledges a Robert T. Haslam Presidential Gradu-
ate Fellowship. We thank Mr. Matthew P. Rainka and
Professor Stephen L. Buchwald for helpful discussions.
We thank Mr. Robert W. Sindelar for early contributions
to this study. We acknowledge generous financial sup-
port by the donors of the American Chemical Society
Petroleum Research Fund (40631G1), MIT, Amgen Inc.,
and NIH-NIGMS (GM074825).
Supporting Information Available: Complete experi-
1
mental procedures, spectroscopic data, and copies of H and
13C NMR spectra for all products. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO051450I
(22) Consistent with this observation, no coupling product was
observed using 2-formylpyrrole in conjunction with vinyl triflates 5a,
5c, and 5e. Formation of unreactive (azaheterocyclic)n-palladium
complexes due to higher concentration of the aza-anion may also be
in part responsible for the observed lower reactivity of acidic azahet-
erocycles; see ref 2c.
In conclusion, a catalytic method for the stereospecific
N-vinylation of azaheterocycles using vinyl triflates was
described. Both cyclic and acyclic vinyl triflates were
(20) For a discussion on the rate of reductive elimination and C-N
bond formation in N-arylation of azaheterocycles, see ref 2c.
(21) The immediate heating of the starting reaction components to
temperatures above 60 °C is not recommended. In the case of triflate
5a, omission of this incubation time resulted in a noticeable decrease
in the efficiency of the coupling reaction.
(23) The ease of stereospecific synthesis of fully substituted vinyl
triflates as compared to the corresponding vinyl iodides is noteworthy;
see refs 8-10.
(24) For the general procedure used to prepare the vinyl triflate 5a,
see: Kim, H.-O.; Ogbu, C. O.; Nelson, S.; Kahn, M. Synlett 1998, 1059-
1060.
J. Org. Chem, Vol. 70, No. 21, 2005 8641