Fast and regioselective Heck couplings with N-acyl-N-vinylamine derivatives

Article abstract of DOI:10.1021/jo050669u

Highly regioselective Heck couplings of aryl inflates with N-acyl-N-vinylamines lacking an N-alkyl substituent were achieved with reaction times of approximately 1 h in yields ranging from 62 to 98% using 1.5 mol % of Pd₂(dba)₃, 3 mol % of DPPF, and diethylisopropylamine in dioxane. The efficiency of these cross-couplings were studied with several N-vinylamides and an example each of an N-vinylcarbamate and an N-vinylurea. The Heck coupling products easily underwent acidic hydrolysis to the corresponding aryl methyl ketone or in situ hydrogenation in the presence of (Ph ₃P)₃RhCl under a hydrogen atmosphere to provide the N-acyl derivatives of pharmaceutically relevant benzylic amines. The coupling of a vinyl triflate and more interestingly a vinyl tosylate to N-vinyl acetamide was also studied affording a 2-acylamino-1,3-butadiene with the same high regioselectivity in preference for the α-isomer. This result suggests that Heck couplings of electron-rich alkenes with vinyl tosylates also follow a cationic pathway.

Full text of DOI:10.1021/jo050669u

Fast and Regioselective Heck Couplings with N-Acyl-N-vinylamine
Derivatives
Anders Lindhardt Hansen and Troels Skrydstrup*
Department of Chemistry and the Interdisciplinary Nanoscience Center, University of Aarhus,
Langelandsgade 140, 8000 Aarhus C, Denmark
ts@chem.au.dk
Received April 5, 2005
Highly regioselective Heck couplings of aryl triflates with N-acyl-N-vinylamines lacking an N-alkyl
substituent were achieved with reaction times of approximately 1 h in yields ranging from 62 to
98% using 1.5 mol % of Pd2(dba)3, 3 mol % of DPPF, and diethylisopropylamine in dioxane. The
efficiency of these cross-couplings were studied with several N-vinylamides and an example each
of an N-vinylcarbamate and an N-vinylurea. The Heck coupling products easily underwent acidic
hydrolysis to the corresponding aryl methyl ketone or in situ hydrogenation in the presence of
(Ph3P)3RhCl under a hydrogen atmosphere to provide the N-acyl derivatives of pharmaceutically
relevant benzylic amines. The coupling of a vinyl triflate and more interestingly a vinyl tosylate to
N-vinyl acetamide was also studied affording a 2-acylamino-1,3-butadiene with the same high
regioselectivity in preference for the R-isomer. This result suggests that Heck couplings of electron-
rich alkenes with vinyl tosylates also follow a cationic pathway.
Introduction
provide products of â-substitution, while with electron-
rich substituents (vinyl ethers and amides), arylation
generally occurs at the R-position.2 In the latter class,
successful regioselective couplings also necessitate the
use of aryl triflates and a palladium catalyst with
bidentate ligands, ideal conditions for an ionic pathway.3-5
Only a few cyclic and acyclic enamides have hitherto
been examined in this Pd-catalyzed reaction, where all
examples tested represent cases with an alkyl substituent
on the nitrogen.2b,3,4,6 Yet, the products obtained from the
coupling with N-acyl-N-vinylamines lacking an N-alkyl
The palladium(0)-catalyzed coupling between aryl
halides/triflates and olefins, referred to as the Heck
reaction, represents a viable method for carbon-carbon
bond construction.1 The degree of the regioselective
outcome for this important arylation reaction is influ-
enced by a number of factors including the substitution
pattern of the olefin, where alkenes bearing electron-
withdrawing groups (e.g., acrylates, acrolein) selectively
(1) For some relevant reviews, see: (a) Heck, R. F. Palladium
Reagents in Organic Syntheses; Academic Press: Orlando, 1985. (b)
Tsuji, J. Palladium Reagents and Catalysts: Innovation is Organic
Synthesis; Wiley: Chichester, U.K., 1995. (c) Brase, S.; de Meijere, A.
In Metal-Catalyzed Cross-Coupling Reactions; Diederich F., Stang, P.
J., Eds.; Wiley-VCH: New York, 1998; Chapter 3. (c) Link, J. T.;
Overman, L. E. In Metal-Catalyzed Cross-Coupling Reactions; Dieder-
ich F., Stang, P. J., Eds.; Wiley-VCH: New York, 1998; Chapter 6. (d)
Transition Metal Catalyzed Reactions; Davis S. G., Murahashi, S.-I.,
Eds.; Blackwell Science, Oxford, 1999. (e) Beletskaya, I.; Cheprakov,
A. V. Chem. Rev. 2000, 100, 3009. (f) Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., Ed.; John Wiley &
Sons: New York, 2002. (f) Whitcombe, N. J.; Hii, K. K.; Gibson, S. E.
Tetrahedron 2001, 57, 7449. (g) Hegedus, L. S. Transition Metals in
the Synthesis of Complex Organic Molecules, 2nd ed.; University
Science Books: Sausalito, CA, 1999; Chapter 4.6. (h) Beller, M.;
Riermeier, T. H.; Stark, G. In Transition Metals for Organic Synthesis;
Beller, M., Bolm, C., Eds.; Wiley-VCH: Weinheim, Germany, 1998;
Vol. 1, p 208. (i) Crisp, G. T. Chem. Soc. Rev. 1998, 27, 427.
(2) For a few papers on the topic of insertion and regioselectivity,
see: (a) Ozawa, F.; Kubo, A.; Hayashi, T. J. Am. Chem. Soc. 1991,
113, 1417. (b) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2. (c)
Ludwig, M.; Stromberg, S.; Svensson, M.; Akermark, B. Organome-
tallics 1999, 18, 970. (d) Larhed, M.; Hallberg, A. In Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.;
John Wiley & Sons: New York, 2002.
(3) Cabri, W.; Candiani, I.; Bedeschi, A.; Santi, R. J. Org. Chem.
1992, 57, 3558.
(4) For an excellent and historical account on factors controlling
regioselectivity in the Heck reaction with electron-rich alkenes, see:
Mo, J.; Xu, L.; Xiao, J. J. Am. Chem. Soc. 2005, 127, 751.
(5) For an exception to this rule using ionic solvents, see ref 4.
(6) (a) Andappan, M. M. S.; Nilsson, P.; von Schenck, H.; Larhed,
M. J. Org. Chem. 2004, 69, 5212. (b) Vallin, K. S. A.; Zhang, Q.; Larhed,
M.; Curran, D. P.; Hallberg, A. J. Org. Chem. 2003, 68, 6639. (c)
Harrison, P.; Meek, G. Tetrahedron Lett. 2004, 45, 9277.
10.1021/jo050669u CCC: $30.25 © 2005 American Chemical Society
Published on Web 06/25/2005
J. Org. Chem. 2005, 70, 5997-6003
5997

Hansen and Skrydstrup
SCHEME 1
SCHEME 2
substituent would provide compounds of potentially
higher synthetic versatility and value. As displayed in
Scheme 1, the Heck coupling between such substrates
not only allows access to R-aryl enamides and aryl
ketones, but the hydrogenation of the alkene product
would lead to an alternative and facile entry to benzylic
amines and N-acyl derivatives thereof, which represent
important constituents of numerous compounds of po-
tential medicinal applications.7,8 In contrast, almost
identical substrates have been demonstrated to undergo
successful intermolecular C-N bond-forming reactions
which represents potentially a major competing reaction
to the desired Heck coupling.9
Herein we describe general reaction conditions for the
preparation of N-acyl-R-arylvinylamines10 in good yields
and short reaction times (e1 h) via the Pd(0)-catalyzed
coupling of N-acyl-N-vinylamines with aryl triflates
without competing amidations. In addition, a protocol for
Heck coupling and in situ hydrogenation is reported for
a facile access to chiral benzylic amides and carbamates.
amines required for this study.11 In the first and nonop-
timized approach, nucleophiles were simply added to
freshly prepared vinyl isocyanate12 providing access to
the corresponding enamides 1-3, including one example
each of a vinyl carbamate and vinyl urea. In an alterna-
tive method, Buchwald’s protocol for the amidation of
vinyl iodides employing a combination of copper iodide,
N,N′-dimethyl ethylenediamine, and vinyl iodide was
adapted (Scheme 2).13,14 Although vinyl iodide was not
examined in this reported work, its coupling with trans-
cinnamide and 2-methoxyacetamide provided the corre-
sponding vinylamides 4 and 5 in 50 and 56% yield,
respectively (see the Supporting Information). Neverthe-
less, higher catalyst loading was required in order for
this coupling reaction to proceed compared to the origi-
nally reported protocol, which may be linked to the low
purity of the commerically obtained vinyl iodide.
Results and Discussion
Two approaches were adapted for the preparation of
the noncommercially available starting N-acyl N-vinyl-
Initial efforts were focused on identifying suitable
reaction conditions for promoting the Heck coupling
between 2-naphthyl triflate and N-vinyl acetamide, as
displayed in Table 1. Particular attention was paid to the
reaction times later, and hence all reactions were first
run over a period of approximately 17 h in accordance
with earlier reports.3,6 Four bidentate ligands (3 mol %)
were tested using Pd2(dba)3 (1.5 mol %) as the palladium-
(0) source and 3 equiv of the popular base dicyclohexyl-
methylamine15 in dioxane (entries 1-4). DPPP, DPPF,
and Dmphen6a,16,17 provided the best yields, which were
(7) During the course of these investigations, Harrison and Meek
(ref 6c) published a short and nonoptimized Heck coupling study with
N-vinylacetamide, with coupling yields ranging from 24 to 69%.
(8) For some recent examples, see: (a) Kessler, A.; Faure, H.; Petrel,
C.; Ruat, M.; Dauban, P.; Dodd, R. H. Bioorg. Med. Chem. Lett. 2004,
14, 3345. (b) Milkiewiez, K. L.; Marsilje, T. H.; Woodworth, R. P., Jr.;
Bifulco, N., Jr.; Hangauer, M. J.; Hangauer, D. G. Bioorg. Med. Chem.
Lett. 2000, 10, 483. (c) Venkatachalam, T. K.; Sudbeck, E. A.; Mao, C.;
Uckun, F. M. Bioorg. Med. Chem. Lett. 2000, 10, 2071. (d) Dankwardt,
S. M.; Martin, R. L.; Chan, C. S.; Van Wart, H. E.; Walker, K. A. M.;
Delaet, N. G.; Robinson, L. A. Bioorg. Med. Chem. Lett. 2001, 11, 2085.
(e) Venkatachalam, T. K.; Qazi, S.; Samuel, P.; Uckun, F. M. Bioorg.
Med. Chem. Lett. 2003, 13, 485. (f) Auberson, Y. P.; Allegeier, H.;
Bischoff, S.; Lingenhoehl, K.; Moretti, R.; Schmutz, M. Bioorg. Med.
Chem. Lett. 2002, 12, 1099. (g) Ashwood, V. A.; Field, M. J.; Horwell,
D. C.; Julien-Larose, C.; Lewthwaite, R. A.; McCleary, S.; Pritchard,
M. C.; Raphy, J.; Singh, L. J. Med. Chem. 2001, 44, 2276. (h) Hanano,
T.; Adachi, K.; Aoki, H.; Morimoto, H.; Naka, Y.; Hisadome, M.;
Fukuda, T.; Sumichika, H. Bioorg. Med. Chem. Lett. 2000, 10, 881.
(9) Yin, J.; Buchwald, S. L. Org. Lett. 2000, 2, 1101.
(10) For other approaches to the synthesis of N-acyl R-arylvinyl-
amines, see: (a) Padwa, A.; Akiba, M.; Cohen, L. A.; MacDonald, G. J.
Tetrahedron Lett. 1981, 22, 2435. (b) Padwa, A.; Akiba, M.; Cohen, L.
A.; MacDonald, G. J. J. Org. Chem. 1983, 48, 695. (c) Burk, M. J.; Casy,
G.; Johnson, N. B. J. Org. Chem. 1998, 63, 6084. (d) van den Berg, M.;
Haak, R. M.; Minnaard, A. J.; De Vries, A. H. M.; Feringa, B. L. Adv.
Synth. Catal. 2002, 344, 1003. (e) Wallace, D. J.; Klauber, D. J.; Chen,
C.-Y.; Volante, R. P. Org. Lett. 2003, 5, 4749.
(11) N-Vinylacetamide is commerically available.
(12) (a) Hart, R. Bull. Soc. Chim. Belg. 1956, 65, 291. (b) Kirby, C.;
Kroto, H. W. J. Mol. Spectrosc. 1978, 70, 216.
(13) Jiang, L.; Job, G. E.; Klapars, A.; Buchwald, S. L. Org. Lett.
2003, 5, 3667.
(14) See the Supporting Information.
(15) For some examples, see: (a) Gu¨rtler, C.; Buchwald, S. L. Chem.
Eur. J. 1999, 5, 3107. (b) Littke, A. F.; Fu, G. C. J. Am. Chem. Soc.
2001, 123, 6989. (c) Hills, I. D.; Fu, G. C. J. Am. Chem. Soc. 2004,
126, 13178.
(16) Andappan, M. M. S.; Nilsson, P.; Larhed, M. Chem. Commun.
2004, 218.
5998 J. Org. Chem., Vol. 70, No. 15, 2005

Heck Couplings with N-Acyl-N-vinylamine Derivatives
TABLE 1. Optimization of Heck Coupling between
2-Naphthyl Triflate and N-Vinylacetamide Followed by
Acid-Catalyzed Hydrolysis
TABLE 2. Heck Coupling of N-Acyl-N-vinylamines and
Aryl Triflates Followed by Acid-Catalyzed Hydrolysisa
entry
ligand
base
time (h) yielda (%) (R/â ratio)
1
2
3
4
5
6
7
(R)-BINAP Cy2NMe
19
15
17
15
17
17
17
75 (>19:1)
83 (>19:1)
83 (77:23)
84 (>19:1)
23 (>19:1)
76 (>19:1)
90 (>19:1)
DPPP
Dmphen
DPPF
DPPF
DPPF
DPPF
Cy2NMe
Cy2NMe
Cy2NMe
Cs2CO3
TEA
DIPEA
a Isolated yields.
obtained after acid hydrolysis of the acid-labile arylvinyl
product to the corresponding methyl ketone, although in
the latter case the regioselectivity proved poor. Reducing
the number of equivalents of the enamide or base, or
using other polar solvents (DMF, DMA), was less effective
in terms of either the yields or regioselectivity. Further
optimization of the base with DPPF as the ligand showed
that the use of diethylisopropylamine provided the high-
est coupling yield (90%, entry 7).
This two-step coupling protocol was then tested with
a few other aryl triflates and N-acyl-N-vinylamines,
including a vinylurea and vinyl carbamate (Table 2). The
aryl ketones 6-9 were obtained in yields reaching 90%
and greater (entries 1-3 and 5-7) in all but one example.
Only in the case with the vinyl urea (entry 4) was the
reaction mixture complex after the Heck coupling ac-
a All reactions was carried out using 4 equiv of olefin, 1 equiv
of triflate, and 3 equiv of base. b Isolated yields, all selectivities
>19:1 (branched/linear).
1
cording to the H NMR spectrum of the crude reaction
fication step (Table 4). Hence, after completion of the
cross-coupling step, 5 mol % of (PPh3)3RhCl was added
directly to the reaction mixture followed by stirring
overnight under a hydrogen atmosphere. Under these
conditions, the N-acyl benzylic amines were isolated in
yields ranging from 53% to 92% after isolation.18 Harrison
and Meek have already revealed the possibility of per-
forming asymmetric hydrogenations with an N-acyl
R-arylvinylamine implying the adaptability of this ap-
proach to enantiomerically enriched N-acyl benzylic
amines.6c. Whereas the trans-isomer 25 of the vinyl
triflate was prepared using N-phenyltriflimide according
to a known procedure,19 the tosylate furnished a 2.5:1
trans/cis (26/27) isomeric mixture in a yield of 69% upon
treatment of the ketoester with potassium tert-butoxide
and tosyl anydride in acetonitrile. Attempts to prepare
solely the trans-isomer 26 according to the same proce-
dure described for the synthesis of the triflate were not
successful and only led to an approximately 1:1 mixture
of the two double-bond isomers in low yield. Fortunately,
the vinyl tosylates could be separated by column chro-
matography.
mixture. Nevertheless, a 64% yield of the 2-naphthyl
methyl ketone 6 could be obtained after subjection to
aqueous HCl. Many of these ketones are trivial and
comercially available, but this study does serve to prove
the high efficiency of the Heck coupling step.
Although long reaction times were expected for these
Heck couplings as previously reported for other N-
vinylamides (g15 h), analysis of some of these reactions
revealed that completion of the coupling step was reached
within approximately 1 h (Table 2, entries 2, 3, 6, and
7). This is also illustrated in Table 3, where the N-acyl-
R-arylvinylamines are isolated via column chromatogra-
phy. In all cases, only short reaction periods were
required for obtaining the Heck product, even as brief as
15 min as observed for the 3-N,N-dimethylaminophenyl
triflate in entry 9. In general, the yields are good, but
somewhat lower than in the two-step protocol to the aryl
ketones. This discrepancey is most likely due to the
coupling product’s slight acid instability. Nevertheless,
the N-acyl-R-arylvinylamines survived quick column
isolation, and their spectral analyses by 1H and 13C NMR
were run in other solvents than CDCl3. It should also be
noted that in none of these cases did we identify products
from a potentially competing amidation reaction.9
Alternatively, we examined the possibility of subjecting
the Heck coupling product to hydrogenation conditions
with Wilkinson’s catalyst without an intermediate puri-
Subjection of the vinyl triflate 25 and N-vinylacetamide
to the same Heck coupling conditions as described above
provided the 2-acetamido-1,3-butadiene 28 in a coupling
yield of 62% with the expected control of regiochemistry
(18) For an example of an asymmetric version of this hydrogenation
(17) dppp ) 1,3-bis(diphenylphosphino)propane, dppf ) 1,1′-bis-
(diphenylphosphino)ferrocene, (R)-BINAP ) (R)-2,2′-bis(diphenylphos-
phino)-1,1′-binaphthyl, dmphen ) 2,9-dimethyl-1,10-phenanthroline.
step, see ref 6c.
(19) Ohba, M.; Kawase, N.; Fujii, T. J. J. Am. Chem. Soc. 1996, 118,
8250.
J. Org. Chem, Vol. 70, No. 15, 2005 5999

Hansen and Skrydstrup
TABLE 3. Heck Coupling of Enamides and Aryl
Triflatesa
TABLE 4. Heck Coupling N-Acyl-N-vinylamines and
Aryl Triflatesa
a All reactions was carried out using 4 equiv of olefin, 1 equiv
of triflate, and 3 equiv of base. b Isolated yields, all selectivities
>19:1 (branched/linear). c Both double bonds hydrogenated.
SCHEME 3
a All reactions was carried out using 4 equiv of olefin, 1 equiv
of triflate, and 3 equiv of base. b Isolated yields, all selectivities
>19:1 (branched/linear).
in favor of the R-vinylation product (Scheme 2). More
interesting though was the performance of the trans-vinyl
tosylate 26 which upon treatment under identical cou-
pling conditions generated the same butadiene product
with both a comparable reactivity (55% yield) and high
regioselectivity.20 This result not only suggests that vinyl
tosylates are suitable for Heck coupling reactions with
electron-rich alkenes but that a cationic mechanism may
potentially be operating for the tosylates as well. Whether
this successful C-C bond formation can be expanded to
the use of aryl tosylates will certainly be an interesting
route to pursue considering that tosylating reagents are
generally less expensive and more readily accessible than
triflating agents. Nevertheless, more suitable ligands for
the palladium center would undoubtedly be required to
perform the more difficult oxidative addition step.21
Finally, it should be noted that the corresponding cis-
vinyl tosylate 27 displayed no reactivity under the
conditions studied reflecting possible detrimental sterical
interactions under the oxidative addition step.
Conclusion
(20) For examples on the use of vinyl and aryl tosylates in pal-
ladium(0)-catalyzed coupling reactions, as well as oxidative addition
studies, see: (a) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998,
120, 7369. (b) Fu, X.; Zhang, S.; Yin, J.; McAllister, T. L.; Jiang, S. A.;
Tann, C.-H.; Thiruvengadam, T. K.; Zhang, F. Tetrahedron Lett. 2002,
43, 573. (c) Roy, A. H.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125,
8704. (d) Roy, A. H.; Hartwig, J. F. Organometallics 2004, 23, 194. (e)
Klapars, A.; Campos, K. R.; Chen, C.-y.; Volante, R. P. Org. Lett. 2005,
7, 1185.
We have successfully developed standard reaction
conditions for the Heck coupling of non-N-alkylated
N-acyl-N-vinylamines with aryl triflates providing access
to N-acyl-R-arylvinylamines in good yields and with
regioselectivities attaining >19:1. Subsequent acidic hy-
drolysis or in situ hydrogenation with Wilkinson’s cata-
lyst allowed for the preparation of the corresponding
(21) Not unexpectedly, aryl tosylates were not reactive to the
coupling conditions developed.
6000 J. Org. Chem., Vol. 70, No. 15, 2005

Heck Couplings with N-Acyl-N-vinylamine Derivatives
colorless solid: 1H NMR (400 MHz, CD3CN) δ (ppm) 7.92 (bs,
1H), 7.44-7.41 (m, 2H), 7.37-7.34 (m, 2H), 5.59 (bs, 1H), 5.03
(bs, 1H), 2.00 (s, 3H); 13C NMR (100 MHz, CD3CN) δ (ppm)
170.4, 141.8, 137.8, 134.6, 129.3(2C), 128.8(2C), 103.7, 24.1;
HRMS C10H10ONCl [M + Na+] calcd 218.0349, found 218.0355.
methyl ketones and the N-acyl derivative of benzylic
amines. Extrapolation of these Heck reactions to a vinyl
triflate and tosylate proved successful in both cases in
terms of coupling yields and regiocontrol. The latter case
suggests that vinyl tosylates also couple via a cationic
mechanism as demonstrated for aryl and vinyl triflates.
Further work is now ongoing to apply this Heck coupling
reaction with aryl tosylates, in addition to its exploitation
as a key step for the synthesis of natural products with
pharmaceutically interesting activities.
N-(1-Biphenyl-4-ylvinyl)acetamide (14).22 N-Vinylaceta-
mide (50 mg, 0.59 mmol), biphenyl-4-yl triflate (226 mg, 0.881
mmol), DIPEA (0.154 mL, 0.881 mmol), DPPF (9.8 mg, 0.018
mmol), and Pd2(dba)3 (8.0 mg, 0.0088 mmol) were reacted for
1 h. The crude product was purified by flash chromatography
on silica gel using ethyl acetate/CH2Cl2 (1:9) as eluent. This
afforded 101 mg of the title compound (72% yield) as colorless
crystals: 1H NMR (400 MHz, CD3CN) δ (ppm) 7.81 (bs, 1H),
7.71-7.66 (m, 4H), 7.59-7.56 (m, 2H), 7.52-7.47 (m, 2H),
7.43-7.38 (m, 1H), 5.63 (bs, 1H), 5.13 (bs, 1H), 2.07 (s, 3H);
13C NMR (100 MHz, CD3CN + 5% DMSO-d6) δ (ppm) 170.4,
142.5, 141.5, 141.0, 138.3, 129.9(2C), 128.5, 127.8(2C), 127.72-
(2C), 127.54(2C), 103.0, 24.2; HRMS C16H15ON [M + Na+] calcd
260.1051, found 260.1056.
Experimental Section
General Procedure for Heck Coupling. The olefin (4
equiv), aryl triflate (1 equiv), DIPEA (3 equiv), and DPPF (0.03
equiv) were dissolved in dioxane (3 mL). Pd2(dba)3 (0.015 equiv)
was then added, and the sample vial was fitted with a Teflon-
sealed screwcap and removed from the glovebox. The reaction
mixture was heated for the time stated for each product at 85
°C. The reaction was monitored by TLC. Saturated aqueous
NaHCO3 was added, and the aqueous phase was extracted
with ethyl acetate (3 times). The combined organic phases were
dried over MgSO4. After concentration in vacuo, the crude
product were purified by column chromatography.
N-[1-(7-Methoxynaphthalen-2-yl)vinyl]acetamide (15).
N-Vinylacetamide (50 mg, 0.59 mmol), 7-methoxy-2-naphthyl
triflate (270 mg, 0.881 mmol), DIPEA (0.154 mL, 0.881 mmol),
DPPF (9.8 mg, 0.018 mmol), and Pd2(dba)3 (8.0 mg, 0.0088
mmol) were reacted for 1 h 15 min. The crude product was
purified by flash chromatography on silica gel using ethyl
acetate/CH2Cl2/pentane (1:8:1) as eluent. This afforded 106 mg
of the title compound (75% yield) as off-white crystals: mp
139.2-141.0 °C; 1H NMR (400 MHz, CD3CN) δ (ppm) 7.90 (bs,
1H), 7.85 (bs, 1H), 7.79-7.76 (m, 2H), 7.44 (dd, 1H, J ) 8.8,
2.0 Hz), 7.27 (d, 1H, J ) 2.8 Hz), 7.15 (dd, 1H, J ) 8.8, 2.4
N-(1-Naphth-2-ylvinyl)acetamide (10).22 2-Naphthyl tri-
flate (92.4 mg, 0.335 mmol), N-vinylacetamide (123 mg, 1.45
mmol), DIPEA (0.190 mL, 1.09 mmol), DPPF (6.0 mg, 0.011
mmol), and Pd2(dba)3 (4.9 mg, 0.0054 mmol) were reacted for
1 h. The crude product was purified by flash chromatography
on silica gel using ethyl acetate/CH2Cl2 (1:9) as eluent. This
yielded a brown solid which was recrystallized in ethyl acetate/
pentane. This afforded 54 mg of the title compound (77% yield)
as off-white crystals: 1H NMR (400 MHz, CD3CN) δ (ppm) 8.07
(bs, 1H), 7.96 (s, 1H), 7.92-7.86 (m, 3H), 7.61 (dd, 1H, J )
8.8, 2 Hz), 7.55-7.50 (m, 2H), 2.08 (s, 3H); 13C NMR (100 MHz,
CD3CN) δ (ppm) 170.7, 142.6, 136.4, 134.2, 134.1, 129.1, 129.0,
128.5, 127.5, 127.4, 126.0, 125.4, 103.7, 24.2; HRMS C14H13-
ON [M + Na+] calcd 234.0895, found 234.0884.
HZ), 5.72 (bs, 1H), 5.16 (bs, 1H), 3.90 (s, 3H), 2.07 (s, 3H); 13
C
NMR (100 MHz, CD3CN) δ (ppm) 170.3, 159.2, 142.8, 137.1,
135.5, 130.0, 129.7, 128.7, 125.0 123.1, 120.0, 107.2, 103.2,
56.0, 24.3; HRMS C15H15O2N [M + Na+] calcd 264.1000, found
264.1000.
N-(1-Phenylvinyl)acetamide (16).22 N-Vinylacetamide
(85 mg, 1.0 mmol), phenyl triflate (339 mg, 1.50 mmol), DIPEA
(0.261 mL, 1.50 mmol), DPPF (17 mg, 0.031 mmol), and Pd2-
(dba)3 (14 mg, 0.015 mmol) were reacted for 1 h. The crude
product was purified by flash chromatography on silica gel
using ethyl acetate/CH2Cl2/pentane (1:6:3) as eluent. This
afforded 113 mg of the title compound (70% yield) as a brown
solid: 1H NMR (400 MHz, CD3CN) δ (ppm) 7.805 (bs, 1H),
7.48-7.45 (m, 2H), 7.40-7.35 (m, 3H), 5.65 (bs, 1H), 5.02 (bs,
1H), 2.03 (s, 3H); 13C NMR (100 MHz, CD3CN) δ (ppm) 170.3,
142.8, 139.2, 129.5, 129.4 (2C), 127.2(2C), 102.6, 24.2; HRMS
C10H11ON [M + Na+] calcd 184.0738, found 184.0732.
N-[1-(4-Acetylphenyl)vinyl]acetamide (11).23 N-Vinyl-
acetamide (30 mg, 0.36 mmol), 4-acetylphenyl triflate (194 mg,
0.742 mmol), DIPEA (0.094 mL, 0.54 mmol), DPPF (6.0 mg,
0.011 mmol), and Pd2(dba)3 (5.0 mg, 0.0054 mmol) were reacted
for 105 min. The crude product was purified by flash chroma-
tography on silica gel using ethyl acetate/CH2Cl2 (1:4) as
eluent. This afforded 65 mg of the title compound (89% yield)
as an orange solid: 1H NMR (400 MHz, CD3CN) δ (ppm) 8.03
(bs, 1H), 7.92 (d, 2H, J ) 8.8 Hz), 7.55 (d, 2H, J ) 8.8 Hz),
5.64 (s, 1H), 5.15 (s, 1H), 2.56 (s, 3H), 2.03 (s, 3H); 13C NMR
(100 MHz, CD3CN) δ (ppm) 198.4, 170.4, 143.2, 142.0, 137.8,
129.2(2C), 127.2(2C), 105.1, 27.0, 24.0; HRMS C12H14O2N [M
+ Na+] calcd 226.0844, found 226.0848.
N-(1-Naphthalen-2-yl-vinyl)-2-phenylacetamide (17).
N-Vinyl-2-phenylacetamide (30 mg, 0.19 mmol), 2-naphthyl
triflate (77 mg, 0.28 mmol), DIPEA (0.049 mL, 0.28 mmol),
DPPF (3.1 mg, 0.0056 mmol), and Pd2(dba)3 (2.5 mg, 0.0028
mmol) were reacted for 75 min. The crude product was purified
by flash chromatography on silica gel using ethyl acetate/CH2-
Cl2/pentane (1:2:7) as eluent. This afforded 33 mg of the title
compound (62% yield) as off-white crystals: mp 114.2-115.8
N-[1-(4-Cyanophenyl)vinyl]acetamide (12).23 N-Vinyl-
acetamide (50 mg, 0.56 mmol), 4-cyanophenyl triflate (221 mg,
0.881 mmol), DIPEA (0.154 mL, 0.881 mmol), DPPF (9.8 mg,
0.018 mmol), and Pd2(dba)3 (8.0 mg, 0.0088 mmol) were reacted
for 1 h. The crude product was purified by flash chromatog-
raphy on silica gel using ethyl acetate/pentane (3:2) as eluent.
This afforded 88 mg of the title compound (81% yield) as bright
yellow crystals: 1H NMR (400 MHz, CD3CN) δ (ppm) 7.91 (bs,
1H), 7.66-7.63 (m, 2H), 7.54-7.52 (m, 2H), 5.55 (bs, 1H), 5.10
(bs, 1H), 1.96 (s, 3H); 13C NMR (100 MHz, CD3CN) δ (ppm)
170.4, 143.4, 141.7, 133.2(2C), 127.9(2C), 119.6, 112.4, 106.2,
23.9; HRMS C11H10ON2 [M + Na+] calcd 209.0691, found
209.0694.
1
°C; H NMR (400 MHz, CD3CN) δ (ppm) 7.97 (bs, 1H), 7.89-
7.83 (m, 4H), 7.56 (dd, 1H, J ) 8.8, 1.6 Hz), 7.53-7.50 (m,
2H), 7.34-7.28 (m, 5H), 5.73 (s, 1H), 5.23 (s, 1H), 3.68 (s, 2H);
13C NMR (100 MHz, CD3CN) δ (ppm) 171.1, 142.4, 136.9,
136.3, 134.2, 134,1, 130.4, 129.6, 129.1, 129.0, 128.5, 127.9,
127.6, 127.5, 125.8, 125.3, 104.0, 44.6; HRMS C20H17ON [M +
Na+] calcd 310.1208, found 310.1210.
N-(1-(3-Dimethylaminophenyl)vinyl)acetamide (18).
N-Vinylacetamide (50 mg, 0.59 mmol), (3-dimethylamino)-
phenyl triflate (237 mg, 0.881 mmol), DIPEA (0.154 mL, 0.881
mmol), DPPF (9.8 mg, 0.018 mmol), and Pd2(dba)3 (8.1 mg,
0.0089 mmol) were reacted for 15 min. The crude product was
purified by flash chromatography on silica gel using ethyl
acetate/CH2Cl2 (1:4) as eluent. This afforded 78 mg of the title
compound (65% yield) as a colorless solid: mp 133.0-135.4
°C;1H NMR (400 MHz, CD3CN) δ (ppm) 7.69 (bs, 1H), 7.19 (t,
1H, J ) 8.0 Hz), 6.80-6.72 (m, 3H), 5.68 (bs, 1H), 4.98 (bs,
N-[1-(4-Chlorophenyl)vinyl]acetamide (13).24 N-Vinyl-
acetamide (50 mg, 0.59 mmol), 4-chlorophenyl triflate (230 mg,
0.881 mmol), DIPEA (0.154 mL, 0.881 mmol), DPPF (9.8 mg,
0.018 mmol), and Pd2(dba)3 (8.0 mg, 0.0088 mmol) were reacted
for 1 h. The crude product was purified by flash chromatog-
raphy on silica gel using ethyl acetate/CH2Cl2 (1:9) as eluent.
This afforded 90 mg of the title compound (79% yield) as a
J. Org. Chem, Vol. 70, No. 15, 2005 6001

Hansen and Skrydstrup
1H), 2.94 (s, 6H), 2.03 (s, 3H); 13C NMR (100 MHz, CD3CN) δ
(ppm) 170.3, 151.9, 143.5, 140.2, 130.0, 115.4, 113.7, 111.2,
101.3, 40.8, 24.4; HRMS C10H11ON [M + H+] calcd 205.1341,
found 205.1344.
49.6, 23.1, 22.8; HRMS C10H13ON [M + Na+] calcd 186.0895,
found 186.0888.
N-(1-Naphthalen-2-ylethyl)-2-methoxyacetamide (22).28
2-Naphthyl triflate (100 mg, 0.362 mmol), N-vinyl-2-methoxy-
acetamide (144 mg, 1.45 mmol), DIPEA (0.190 mL, 1.09 mmol),
DPPF (6.0 mg, 0.011 mmol), and Pd2(dba)3 (4.9 mg, 0.0054
mmol) were reacted for 75 min. After transfer of the reaction
mixture, Rh(PPh3)3Cl (16.7 mg, 0.0181 mmol) was added. The
reaction was left overnight. The reaction was not finished, and
the mixture was filtered through a silica plug with ethyl
acetate. After concentration in vacuo, 3 mL of absolute ethanol
and Rh(PPh3)3Cl (16.7 mg, 0.0181 mmol) was added. The
reaction was left overnight under an atmosphere of hydrogen.
The crude product was purified by flash chromatography on
silica gel using ethyl acetate/CH2Cl2 (1:4) as eluent. This
afforded 47 mg of the title compound (53% yield) as an off-
white solid: 1H NMR (400 MHz, CDCl3) δ (ppm) 7.84-7.81
(m, 3H), 7.77 (s, 1H), 7.50-7.44 (m, 3H), 6.82 (bd, 1H, J ) 6
Hz), 5.39-5.32 (m, 1H), 3.95 (d, 1H, J ) 16.0 Hz), 3.89 (d, 1H,
J ) 16.0 Hz), 3.41 (s, 2H), 1.62 (d, 3H, J ) 7.2 Hz); 13C
NMR (100 MHz, CDCl3) δ (ppm) 168.7, 140.4, 133.5, 132.9,
128.7, 128.0, 127.7, 126.4, 126.0, 124.8, 124.7, 72.1, 59.3, 48.2,
21.9; HRMS C15H17O2N [M + Na+] calcd 266.1157, found
266.1163.
General Procedure for Heck Coupling Followed by
Hydrogenation. The olefin (4 equiv), aryl triflate (1 equiv),
DIPEA (3 equiv), and DPPF (0.03 equiv) were dissolved in
dioxane (3 mL). Pd2(dba)3 (0.015 equiv) was then added, and
the sample vial was fitted with a Teflon-sealed screwcap and
removed from the glovebox. The reaction mixture was heated
for the time stated for each product (see the Supporting
Information) at 85 °C. The reaction was monitored by TLC.
After completion of the Heck coupling, the reaction mixture
were transferred to a round-bottomed flask, and 3 mL of dry
ethanol was added. Rh(PPh3)3Cl (0.05 equiv) was added, and
the flask was sealed with a rubber septum. A balloon filled
with H2(g) was connected to the system, and the reaction was
left at 20 °C for the time stated for the individual products.
Saturated aqueous NH4Cl was added, and the aqueous phase
was extracted with ethyl acetate (3 times). The combined
organic phases were dried over MgSO4. After concentration
in vacuo, the crude products were purified by column chro-
matography.
N-(1-Naphthalen-2-ylethyl)acetamide (19).25 2-Naphthyl
triflate (100 mg, 0.362 mmol), N-vinylacetamide (123 mg, 1.45
mmol), DIPEA (0.190 mL, 1.09 mmol), DPPF (6.0 mg, 0.011
mmol), and Pd2(dba)3 (4.9 mg, 0.0054 mmol) were reacted for
45 min. After transfer of the reaction mixture, Rh(PPh3)3Cl
(16.7 mg, 0.0181 mmol) was added. The reaction time was 3
h. The crude product was purified by flash chromatography
on silica gel using ethyl acetate/CH2Cl2 (1:1) as eluent. This
afforded 71 mg of the title compound (92% yield) as a colorless
oil. Yield corrected for contamination with minor amounts of
triphenylphosphine oxide: 1H NMR (400 MHz, CDCl3) δ (ppm)
7.72-7.69 (m, 3H), 7.64 (bs, 1H), 7.38-7.32 (m, 3H), 5.93 (bd,
1H, J ) 5.6 Hz), 5.23-5.15 (m, 1H) 1.89 (s, 3H), 1.47 (d, 3H,
J ) 6.8); 13C NMR (100 MHz, CDCl3) δ (ppm) 169.3, 140.7,
133.4, 132.8, 128.6, 128.0, 127.7, 126.3, 126.0, 124.9, 124.7,
49.0, 23.6, 21.8; HRMS C14H15ON [M + Na+] calcd 236.1051,
found 236.1079.
N-[1-(4-Acetylphenyl)ethyl]acetamide (20).26 4-Acetylphe-
nyl triflate (102 mg, 0.381 mmol), N-vinylacetamide (123 mg,
1.45 mmol), DIPEA (0.190 mL, 1.09 mmol), DPPF (6.0 mg,
0.011 mmol), and Pd2(dba)3 (4.9 mg, 0.0054 mmol) were reacted
for 60 min. After transfer of the reaction mixture, Rh(PPh3)3-
Cl (16.7 mg, 0.0181 mmol) was added. The reaction time was
6 h. The crude product was purified by flash chromatography
on silica gel using ethyl acetate/CH2Cl2 (1:1) as eluent. This
afforded 67 mg of the title compound (90% yield) as an off-
white solid. Yield corrected for contamination with minor
amounts of triphenylphosphine oxide: 1H NMR (400 MHz,
CDCl3) δ (ppm) 7.92 (d, 2H, J ) 8.4 Hz), 7.39 (d, 2H, J ) 8.4
Hz), 5.84 (bd, 1H, J ) 6 Hz), 5.19-5.12 (m, 1H), 2.58 (s, 3H),
2.00 (s, 3H), 1.49 (d, 3H, J ) 6.8 Hz); 13C NMR (100 MHz,
CDCl3) δ (ppm) 197.8, 169.4, 148.8, 136.3, 128.9(2C), 126.4-
(2C), 48.8, 26.8, 23.5, 21.9; HRMS C12H15O2N [M + Na+] calcd
228.1000, found 228.0994.
(1-Naphthalen-2-ylethyl)carbamic Acid Propyl Ester
(23). 2-Naphthyl triflate (100 mg, 0.362 mmol), vinylcarbamic
acid propyl ester (94 mg, 0.72 mmol), DIPEA (0.095 mL, 0.54
mmol), DPPF (6.0 mg, 0.011 mmol), and Pd2(dba)3 (4.9 mg,
0.0054 mmol) were reacted for 1 h. After transfer of the
reaction mixture, Rh(PPh3)3Cl (16.7 mg, 0.0181 mmol) was
added. The reaction was left overnight. The crude product was
purified by flash chromatography on silica gel using ethyl
acetate/CH2Cl2/pentane (1:6:13) as eluent. This afforded 80 mg
of the title compound (86% yield) as a clear oil. 1H NMR (400
MHz, CDCl3) δ (ppm) 7.83-7.80 (m, 3H), 7.75 (s, 1H), 7.48-
7.43 (m, 3H), 5.05-4.94 (m, 2H), 4.92-3-90 (m, 2H), 1.68-
1.55 (m, 5H), 0.921 (t, 3H, J ) 7.4 Hz); 13C NMR (100 MHz,
CDCl3) δ (ppm) 156.2, 141.4, 133.7, 133.0, 128.6, 128.0, 127.8,
126.3, 125.9, 124.6, 124.5, 66.73, 51.0, 22.6, 22.5, 10.3; HRMS
C16H19O2N [M + Na+] calcd 280.1313, found 280.1314.
N-(1-Naphthalen-2-ylethyl)-3-phenylpropionamide (24).
2-Naphthyl triflate (50 mg, 0.18 mmol), N-vinyl-trans-cinna-
mide (63 mg, 0.36 mmol), DIPEA (0.047 mL, 0.27 mmol), DPPF
(3.0 mg, 0.054 mmol), and Pd2(dba)3 (2.5 mg, 0.0027 mmol)
were reacted for 1 h. After transfer of the reaction mixture,
Rh(PPh3)3Cl (8.3 mg, 0.0090 mmol) was added. The reaction
was left overnight. The crude product was purified by flash
chromatography on silica gel using ethyl acetate/CH2Cl2/
pentane (1:6:3) as eluent. This afforded 37 mg of the title
compound (68% yield) as a colorless solid: mp 109.9-112.0
1
°C; H NMR (400 MHz, CD3CN) δ (ppm) 7.86-7.81 (m, 3H),
7.71 (s, 1H) 7.51-7.45 (m, 2H), 7.39 (dd, 1H, J ) 8.4, 1.6 Hz),
7.27-7.16 (m, 5H), 6.84 (bd, 1H, J ) 5.6 Hz), 5.15-5.08 (m,
1H), 2.89 (t, 2H, J ) 7.2 Hz), 2.48 (t, 2H, J ) 7.6 Hz), 1.43 (d,
3H, J ) 7.2 Hz); 13C NMR (100 MHz, CD3CN) δ (ppm) 172.0,
143.2, 142.5, 134.3, 133.5, 129.4, 129.3, 129.0, 128.7, 128.5,
127.1, 127.0, 126.7, 125.9, 125.0, 49.6, 38.4, 32.3, 22.5; HRMS
C21H21ON [M + Na+] calcd 326.1521, found 326.1521.
N-(1-Phenylethyl)acetamide (21).27 N-Vinylacetamide
(85 mg, 1.0 mmol), phenyl triflate (339 mg, 1.50 mmol), DIPEA
(0.261 mL, 1.50 mmol), DPPF (17 mg, 0.031 mmol), and Pd2-
(dba)3 (14 mg, 0.015 mmol) were reacted for 1 h. After transfer
of the reaction mixture, Rh(PPh3)3Cl (23.0 mg, 0.05 mmol) was
added. The reaction was left overnight. The crude product was
purified by flash chromatography on silica gel using ethyl
acetate/CH2Cl2 (1:1) as eluent. This afforded 149 mg of the
title compound (77% yield) as a light brown solid. Yield
corrected for contamination with minor amounts of triph-
enylphosphine oxide: 1H NMR (400 MHz, CD3CN) δ (ppm)
7.35-7.30 (m, 3H), 7.25-7.21 (m, 2H), 6.81 (bs, 1H), 4.98-
4.90 (m, 1H), 1.87 (s, 3H), 1.38 (d, 3H, J ) 7.2 Hz); 13C NMR
(100 MHz, CD3CN) δ (ppm) 169.8, 145.9, 129.4, 127.8, 126.9,
(E)-3-[[(Trifluoromethyl)sulfonyl]oxy]-2-butenoic Acid
Ethyl Ester (25).19 Ethyl acetoacetate (0.253 mL, 3 mmol) in
DMF (2 mL) was added dropwise to a mixture of sodium
hydride (72 mg, 3.0 mmol) in DMF (2 mL). The reaction
mixture was stirred for 10 min at 20 °C. N-Phenyltrifluo-
romethanesulfonimide (1.07 g, 3.00 mmol) was added, and the
reaction was allowed to stir for an additional 3 h. The crude
mixture was diluted with 60 mL of ether, and the organic
phase was washed with saturated aqueous NH4Cl, H2O, and
brine. The organic phase was dried over MgSO4. After con-
centration in vacuo, the crude product was purified by flash
chromatography on silica gel using CH2Cl2/pentane (1:4) as
eluent. This afforded 252 mg of the title compound (48% yield)
as a colorless oil: 1H NMR (400 MHz, CDCl3) δ (ppm) 5.94 (s,
6002 J. Org. Chem., Vol. 70, No. 15, 2005

Heck Couplings with N-Acyl-N-vinylamine Derivatives
1H), 4.21 (q, 2H, J ) 7.2 Hz), 2.50 (s, 3H), 1.29 (t, 3H, J ) 7.2
Hz); 13C NMR (100 MHz, CDCl3) δ (ppm) 164.3, 162.1, 118.9
(q, 1C, J ) 318.3 Hz), 113.5, 61.3, 18.5, 14.2.
(q, 2H, J ) 7.1 Hz), 2.44 (s, 3H), 2.10 (s, 3H), 1.19 (t, 3H, J )
7.2 Hz); 13C NMR (100 MHz, CDCl3) δ (ppm) 163.0, 156.3,
145.5, 133.6, 129.8(2C), 128.5(2C), 110.9, 60.4, 21.8, 21.7, 14.2;
HRMS C13H16O5S [M + Na+] calcd 307.0616, found 307.0626.
(E)-Ethyl-4-acetamido-3-methyl-2,4-pentadienoate (28)
from Tosylate Coupling. Ethyl (E)-3-(p-toluenesulfonoxy)-
2-butenoate (150 mg, 0.53 mmol), N-vinylacetamide (0.040 mL,
0.35 mmol), DIPEA (69 mg, 0.53 mmol), DPPF (5.8 mg, 0.011
mmol), and Pd2(dba)3 (4.8 mg, 0.0053 mmol) were heated to
85 °C for 5 h. The crude reaction mixture was concentrated
directly onto silica gel and purified by flash chromatography
on silica gel using ethyl acetate/CH2Cl2 (1:4) as eluent. This
afforded 38 mg of the title compound (55% yield) as an off-
white amorphous solid: 1H NMR (400 MHz, CD3CN) δ (ppm)
7.63 (bs, 1H), 5.93 (bs, 1H), 5.42 (bs, 1H), 5.17 (bs, 1H), 4.11
(q, 2H, J ) 7.2 Hz), 2.21 (s, 3H), 1.95 (s, 3H), 1.22 (t, 3H, J )
7.0 Hz); 13C NMR (100 MHz, CD3CN) 170.0, 167.5, 152.2,
144.0, 117.4, 108.5, 60.8, 23.8, 16.1, 14.6; HRMS C10H15O3N
[M + Na+] calcd 220.0950, found 220.0956.
(E)-Ethyl-4-acetamido-3-methyl-2,4-pentadienoate (28)
from Triflate Coupling. (E)-3-[[(Trifluoromethyl)sulfonyl]-
oxy]-2-butenoic acid ethyl ester (150 mg, 0.57 mmol), N-
vinylacetamide (41 mg, 0.48 mmol), DIPEA (124, 0.72 mmol),
DPPF (7.9 mg, 0.014 mmol), and Pd2(dba)3 (6.5 mg, 0.0072
mmol) were heated to 85 °C for 3 h. The crude reaction mixture
was concentrated directly onto silica gel and purified by flash
chromatography on silica gel using ethyl acetate/CH2Cl2 (1:4)
as eluent. This afforded 59 mg of the title compound (62%
yield) as a off-white solid.
Ethyl (E)-3-(p-Toluenesulfonoxy)-2-butenoate (26).29
Ethyl acetoacetate (0.324 mL, 2.56 mmol) in acetonitrile (5
mL) was added dropwise to a mixture of potassium tert-
butoxide (0.315 g, 2.81 mmol) in acetonitrile (15 mL) at 20
°C. The reaction mixture was stirred for 30 min. Tosyl
anhydride (1.00 g, 3.07 mmol) was added, and the reaction
mixture was stirred for an additional 16 h. The reaction
mixture was concentrated in vacuo, and 20 mL of water was
added, after which the aqueous phase was extracted with ether
(3 times). The combined organic phases were dried over
MgSO4. After concentration in vacuo, the crude product was
purified by flash chromatography on silica gel using ethyl
acetate/CH2Cl2/pentane (1:4:15) as eluent. The E- and Z-
isomers was separated on the column. This afforded 358 mg
of the title compound (49% yield) and 144 mg (20% yield) of
the Z-isomer as colorless oils: 1H NMR (400 MHz, CDCl3) δ
(ppm) 7.81 (d, 2H, J ) 8.4 Hz), 7.36 (d, 2H, J ) 8.4 Hz), 5.70
(s, 1H), 4.13 (q, 2H, J ) 7.2 Hz), 2.46 (s, 3H), 2.26 (s, 3H),
1.25 (t, 3H, J ) 7.1 Hz); 13C NMR (100 MHz, CDCl3) δ (ppm)
165.5, 162.4, 145.9, 133.1, 130.1(2C), 128.3(2C), 111.1, 60.6,
21.8, 18.7, 14.2; HRMS C13H16O5S [M + Na+] calcd 307.0616,
found 307.0616.
Z-Isomer (27):30 1H NMR (400 MHz, CDCl3) δ (ppm) 7.89
(d, 2H, J ) 8.4 Hz), 7.35 (d, 2H, J ) 8.4 Hz), 5.48 (s, 1H), 4.04
(22) Zhu, G.; Zhang, X. J. Org. Chem. 1998, 63, 25, 9590.
(23) Harrison, P.; Meek, G. Tetrahedron Lett. 2004, 45, 50, 9277.
(24) Berg, M.; Haak, R. M.; Minnaard, A. J.; Vries, A. H. M. de;
Vries, J. G. de; Feringa, B. L. Adv. Synth. Catal. 344, 9, 2002, 1003.
(25) Reetz, M. T.; Mehler, G.; Meiswinkel, A. Tetrahedron: Asym-
metry 2004, 15, 14, 2165.
Acknowledgment. We are indebted to the Danish
National Science Research Council and the University
of Aarhus for generous financial support.
(26) Hanano, Y.; Adachi, K.; Aoki, Y.; Morimoto, H.; Naka, Y.;
Hisadome, M.; Fukuda, T.; Sumichika, H. Bioorg. Med. Chem. Lett.
2000, 10, 9, 881.
Supporting Information Available: Experimental pro-
cedures for (a) the synthesis of the N-acyl-N-vinylamines and
(b) the Heck coupling reactions followed by acidic hydrolysis.
1H NMR and 13C NMR spectra for the N-acyl-N-vinylamines
and coupling products. This material is available free of charge
via the Internet at http://pubs.acs.org.
(27) Lopez-Serrano, P.; Jongejan, J. A.; Rantwijk, F. van.; Sheldon,
R. A. Tetrahedron: Asymmetry. 2001, 12, 2, 219.
(28) Youshko, M. I.; Rantwijk, van F.; Sheldon, R. A. Tetrahedron:
Asymmetry 2001, 12, 23, 3267.
(29) Nakaminami, G. Bull. Chem. Soc. Jpn. 1962, 35, 1629.
(30) Jalander, L.; Mattinen, J.; Oksanene, L.; Rosling, A. Synth.
Commun. 1990, 20, 6, 881.
JO050669U
J. Org. Chem, Vol. 70, No. 15, 2005 6003