The Journal of Organic Chemistry
ARTICLE
Scheme 3. Proposed Reaction Pathway for the Palladium-
(II)-Catalyzed Domino Reaction with Arylboronic Acid 2
mixture was extracted with CHCl3 three times, concentrated, and
purified by flash chromatography (silica, iso-hexane/ethyl acetate/
triethylamine).
2-(1,2-Bis(p-acetylphenyl)ethoxy)-N,N-dimethylethanamine (3n).
1H NMR (400 MHz, CDCl3): δ 7.90 (2H, d, J = 8.5 Hz), 7.81 (2H,
d, J = 8.4 Hz), 7.31 (2H, d, J = 8.3 Hz), 7.18 (2H, d, J = 8.3 Hz), 4.51 (1H,
dd, J = 7.3, 6.0 Hz), 3.44ꢀ3.38 (1H, m) 3.36ꢀ3.29 (1H, m), 3.19 (1H,
dd, J = 13.6, 7.6 Hz), 2.94 (1H, dd, J = 13.7, 5.9 Hz), 2.59 (3H, s), 2.56
(3H, s), 2.52ꢀ2.40 (2H, m), 2.19 (6H, s). 13C NMR (100 MHz,
CDCl3): δ 198.1, 198.0, 147.2, 143.9, 136.9, 135.7, 130.0, 128.8, 128.5,
127.1, 83.3, 67.7, 59.1, 46.0, 44.7, 26.9, 26.8. HRMS (ESIþ): calculated
for C22H28NO3 (M þ Hþ) 354.2069, found 354.2074. Brown colored
oil. (90 mg, 59%) (Method B).
General Experimental Procedure for Domino Heck/Suzuki
Diarylation: Method I. A mixture of 1b0 (80 mg, 0.42 mmol), the
corresponding boronic acid (1.26 mmol), p-benzoquinone (50 mg, 0.46
mmol), Pd(O2CCF3)2 (7 mg, 5 mol %), and 2.5 mL of 1,4-dioxane was
stirred in a open reaction vial and heated at 60 °C using a preheated
metal block for 20 h. The reaction mixture was worked up, and 5h, 5n,
5o, and 5s were isolated as previously described in General Experimental
Procedure for Domino Heck/Suzuki Diarylation: Method B.
2-(1,2,3-Triphenylethoxy)-N,N-dimethylethanamine (5h). 1H NMR
(400 MHz, CDCl3): δ 7.31ꢀ6.93 (15H, m), 4.87 (1H, d, J = 9.0 Hz),
4.14 (1H, d, J = 9.0 Hz), 3.41ꢀ3.28 (2H, m), 2.35 (2H, t, J = 5.8 Hz),
2.04 (6H, s). 13C NMR (100 MHz, CDCl3): δ 142.3, 142.2, 140.9,
129.2, 129.0, 128.3, 128.2, 128.1, 127.9, 127.6, 126.32, 126.31, 85.1, 67.7,
59.3, 59.1, 46.0. HRMS (ESIþ): calculated for C24H28NO (M þ Hþ)
346.2171, found 346.2173. Pink colored oil. (55 mg, 38%) (Method I).
alkene ligand stabilized palladacycle B (L = p-Bq or MA). The
selectivity for the formation of the domino product (3 or 5)
instead of the unsaturated Heck product (4 or 6) is determined
by a very fine balance between a Suzuki-type transmetalation
with 2, furnishing 3 or 5 via intermediate C, and a terminating syn
β-hydride elimination, yielding undesired 4 or 6. When p-Bq (or
MA) is present, the domino product is formed in a reductive
elimination process together with palladium(0). After subse-
quent p-Bq-mediated oxidation of palladium(0) to palladium-
(II), the catalytic cycle may proceed. We speculate that the
selectivity for 3 and 5 using chelating 1a or 1b is a result of the
metal coordination of one of the electron-poor π-bonds of p-Bq
(or MA),47 which inhibits the competing β-elimination
process.48,49 In the case of vinyl ether 1b, the β-phenyl group
disturbs the insertion of the aryl-Pd complex and consequently
increases the reaction time.
’ ASSOCIATED CONTENT
S
Supporting Information. General experimental proce-
b
dure, compound characterization data, and copies of spectra and
chromatograms. This material is available free of charge via the
’ CONCLUSION
’ AUTHOR INFORMATION
We have extended the scope of the chelation-controlled and p-
Bq-mediated palladium(II)-catalyzed domino HeckꢀMizoroki/
SuzukiꢀMiyaura method to be compatible with electron-defi-
cient arylboronic acids for the preparation of 2-(1,2-dia-
rylethoxy)-N,N-dimethylethanamines (3) using the chelating
vinyl ether 1a. The principle of reactivity enhancement by
catalyst presentation has been demonstrated by the direct one-
pot synthesis of 2-(1,1,2-triarylethoxy)-N,N-dimethylethana-
mines (5) from a β-phenyl vinyl ether. The selectivity for the
domino process with the dimethylamino ethyl vinyl ether 1a was
compared with the less impressive outcomes from reactions with
alternative vinyl ethers. Finally, we have further established the
importance of the combined ligand/reoxidant p-Bq by attempt-
ing to replace it with alternative reoxidants and ligands. An
extension to other chelating olefins, targeting stereoselective
aspects of the domino oxidative HeckꢀMizoroki/Suzu-
kiꢀMiyaura reaction promises to be worthwhile.
Corresponding Author
*Phone: þ46-18-4714667. Fax: þ46-18-4714474. E-mail: mat-
’ ACKNOWLEDGMENT
We acknowledge financial support from the Swedish Founda-
tion for Strategic Research and Knut and Alice Wallenberg
Foundation. We also thank Prof. Adolf Gogoll for valuable
NMR discussions and Dr. Luke Odell for linguistic revision of
the manuscript.
’ REFERENCES
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44, 581.
(3) Heck, R. F.; Nolley, J. P. J. J. Org. Chem. 1972, 37, 2320.
(4) Dieck, H. A.; Heck, R. F. J. Org. Chem. 1975, 40, 1083.
(5) Fujiwara, Y.; Moritani, I.; Matsuda, M.; Teranishi, S. Tetrahedron
Lett. 1968, 35, 3863.
(6) Du, X.; Suguro, M.; Hirabayashi, K.; Mori, A. Org. Lett. 2001,
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(7) Jung, C. J.; Mishra, R. K.; Yoon, C. H.; Jung, K. W. Org. Lett.
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’ EXPERIMENTAL SECTION
General Experimental Procedure for Domino Heck/Suzuki
Diarylation: Method B. A mixture of 1a (50 mg, 0.43 mmol), the
corresponding boronic acid (1.30 mmol), p-benzoquinone (52 mg, 0.47
mmol), Pd(O2CCF3)2 (7.2 mg, 5 mol %), and 2.5 mL of 1,4-dioxane was
stirred in an open reaction vial and heated at 60 °C using a preheated
metal block for 2 h. The cold reaction mixture was diluted with 1,4-
dioxane and filtered through Celite. After concentration the reaction
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dx.doi.org/10.1021/jo1018188 |J. Org. Chem. 2011, 76, 2433–2438