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Volumn 72, Issue 17, 2007, Pages 6464-6472

Investigations on the Suzuki-Miyaura and Negishi couplings with alkenyl phosphates: Application to the synthesis of 1,1-disubstituted alkenes

Author keywords

[No Author keywords available]

Indexed keywords

CARBOXYLIC ACIDS; CATALYST ACTIVITY; DERIVATIVES; PHOSPHATES; SYNTHESIS (CHEMICAL);

EID: 34547943706     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo070912k     Document Type: Article
Times cited : (87)

References (128)
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    • For a discussion on the low reactivity of aryl chlorides in cross-coupling reactions, see: a
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    • 1-Alkyl-1-aryl alkenes: (e) Bernstein, P. R.; Aharony, D.; Albert, J. S.; Andisik, D.; Barthlow, H. G.; Bialecki, R.; Davenport, T.; Dedinas, R. F.; Dembofsky, B. T.; Koether, G.; Kosmider, B. J.; Kirkland, K.; Ohnmacht, C. J.; Potts, W.; Rumsey, W. L.; Shen, L.; Shenvi, A.; Sherwood, S.; Stollman, D.; Russel, K. Bioorg. Med. Chem. Lett. 2001, 11, 2769.
    • 1-Alkyl-1-aryl alkenes: (e) Bernstein, P. R.; Aharony, D.; Albert, J. S.; Andisik, D.; Barthlow, H. G.; Bialecki, R.; Davenport, T.; Dedinas, R. F.; Dembofsky, B. T.; Koether, G.; Kosmider, B. J.; Kirkland, K.; Ohnmacht, C. J.; Potts, W.; Rumsey, W. L.; Shen, L.; Shenvi, A.; Sherwood, S.; Stollman, D.; Russel, K. Bioorg. Med. Chem. Lett. 2001, 11, 2769.
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    • 1,1′-Dialkyl alkener: (g) Takahashi, Y.; Inaba, N.; Kuwahara, S.; Kuki, W. Biosci. Biotechnol. Biochem. 2003, 67, 195.
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    • One reviewer pointed out the possibility of a mechanism involving a Ni-catalyzed hydroarylation of the corresponding alkyne with the aryl boronic acid Shirakawa, E, Takahashi, G, Tsuchimoto, T, Kawakami, Y. Chem. Commun. 2001, 2688, Although plausible, this mechanism would require that the vinyl phosphate undergo elimination with formation of the alkyne. Heating the same vinyl phosphate with potassium phosphate in THF at 75°C for 24 h did not lead to the formation of 3,3-dimethyl-1-phenylbutyne. In addition, formation of the requisite aryl nickel hydride species for the hydroarylation step requires the presence of water in the reaction media. Further investigations on the mechanism behind this isomerization are being conducted and will be reported in due time
    • One reviewer pointed out the possibility of a mechanism involving a Ni-catalyzed hydroarylation of the corresponding alkyne with the aryl boronic acid (Shirakawa, E.; Takahashi, G.; Tsuchimoto, T.; Kawakami, Y. Chem. Commun. 2001, 2688). Although plausible, this mechanism would require that the vinyl phosphate undergo elimination with formation of the alkyne. Heating the same vinyl phosphate with potassium phosphate in THF at 75°C for 24 h did not lead to the formation of 3,3-dimethyl-1-phenylbutyne. In addition, formation of the requisite aryl nickel hydride species for the hydroarylation step requires the presence of water in the reaction media. Further investigations on the mechanism behind this isomerization are being conducted and will be reported in due time.
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    • For reviews and general literature on the Negishi reaction, see: a, Knochel, P, Jones, P, Eds, Oxford: New York
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    • During the formation of the organozinc reagent, ≥1 equiv of LiCl is formed. See ref 4a
    • During the formation of the organozinc reagent, ≥1 equiv of LiCl is formed. See ref 4a.
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    • The presence of excess LiCl may augment the concentration of a more reactive anionic Pd(0) complex in equilibrium with its neutral species. See: (a) Cacchi, S.; Morera, E.; Ortar, G. Tetrahedron Lett. 1984, 21, 2271.
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    • Palladium-catalyzed dimerizations of alkynes are known but since the presence of o-tolyl zinc chloride would result in deprotonation of the alkyne formed in situ, it is believed that 52 is formed by a different mechanism. See: (a) Yang, C.; Nolan, S. P. J. Org. Chem. 2002, 67, 591.
    • Palladium-catalyzed dimerizations of alkynes are known but since the presence of o-tolyl zinc chloride would result in deprotonation of the alkyne formed in situ, it is believed that 52 is formed by a different mechanism. See: (a) Yang, C.; Nolan, S. P. J. Org. Chem. 2002, 67, 591.
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    • The fact that (adamantylethynyl)zinc(II) chloride transmetalates faster than o-tolyl zinc chloride was confirmed by increasing the steric bulk on the organozinc reagent to the m-xylene derivative, resulting in sole formation of the byproduct 52.
    • The fact that (adamantylethynyl)zinc(II) chloride transmetalates faster than o-tolyl zinc chloride was confirmed by increasing the steric bulk on the organozinc reagent to the m-xylene derivative, resulting in sole formation of the byproduct 52.


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