Preparation, thermal stability and carbonyl addition reactions of 2,5-difluorophenyl lithium and 2,5-difluorophenyl grignard

Synlett

Volumn , Issue 9, 2004, Pages 1646-1648

  Scott, Jeremy P ^a   Brewer, Sarah E ^a   Davies, Antony J ^a   Brands, Karel M J ^a  

^a NEUROSCIENCE RESEARCH CENTRE   (United Kingdom)

Author keywords

Addition reactions; Magnesium bromine exchange; Metalations; Organometallic reagents; Thermal stability

Indexed keywords

2,5 DIFLUOROPHENYLLITHIUM; ALDEHYDE; AMINE; BENZENE DERIVATIVE; BROMINE DERIVATIVE; CHLORINE DERIVATIVE; FLUOROBENZENE; KETONE; LITHIUM DERIVATIVE; MAGNESIUM DERIVATIVE; ORGANOLITHIUM COMPOUND; UNCLASSIFIED DRUG;

ARTICLE; CARBONYL ADDITION REACTION; CHEMICAL REACTION; GRIGNARD REACTION; LITHIATION; SYNTHESIS; THERMOSTABILITY;

EID: 3943099915     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2004-825592     Document Type: Article

References (20)

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2. (b) For a recent review, see: Knochel, P.; Dohle, W.; Gommermann, N.; Kneisel, F. F.; Kopp, F.; Korn, T.; Sapountzis, I.; Vu, V. A. Angew. Chem. Int. Ed. 2003, 42, 4302.
3. Leazer, J. L.; Cvetovich, R.; Tsay, F.-R.; Dolling, U.; Vickery, T.; Bachert, D. J. Org. Chem. 2003, 68, 3695.
4. Halogen-magnesium exchange reactions employing organomagnesium ate complexes have been reported: (a) Inoue, A.; Kitagawa, K.; Shinokubo, H.; Oshima, K. J. Org. Chem. 2001, 66, 4333. (b) Mase, T.; Houpis, I. N.; Akao, A.; Dorziotis, I.; Emerson, K.; Hoang, T.; Iida, T.; Itoh, T.; Kamei, K.; Kato, S.; Kato, Y.; Kawasaki, M.; Lang, F.; Lee, J.; Lynch, J.; Maligres, P.; Molina, A.; Nemoto, T.; Okada, S.; Reamer, R.; Song, J. Z.; Tschaen, D.; Wada, T.; Zewge, D.; Volante, R. P.; Reider, P. J.; Tomimoto, K. J. Org. Chem. 2001, 66, 6775.
5. Halogen-magnesium exchange reactions employing organomagnesium ate complexes have been reported: (a) Inoue, A.; Kitagawa, K.; Shinokubo, H.; Oshima, K. J. Org. Chem. 2001, 66, 4333. (b) Mase, T.; Houpis, I. N.; Akao, A.; Dorziotis, I.; Emerson, K.; Hoang, T.; Iida, T.; Itoh, T.; Kamei, K.; Kato, S.; Kato, Y.; Kawasaki, M.; Lang, F.; Lee, J.; Lynch, J.; Maligres, P.; Molina, A.; Nemoto, T.; Okada, S.; Reamer, R.; Song, J. Z.; Tschaen, D.; Wada, T.; Zewge, D.; Volante, R. P.; Reider, P. J.; Tomimoto, K. J. Org. Chem. 2001, 66, 6775.
6. 2 = Ph) by reverse phase HPLC with UV detection at 210 nm on a Zorbax SB Phenyl 250 x 4.6 mm column.
7. (a) ortho-Halophenyl lithiums are well known benzyne precursors at elevated temperatures, see inter alia: Kessar, S. V. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I.; Paquette, L. A., Eds.; Pergamon Press: Oxford, 1991, Vol. 4, Chap. 2.3, 483-515.
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9. For example, Aldrich 2003 catalogue prices: 1-Bromo-2,5-difluorobenzene (24795-2) £648/mol, £3.36/g; 1,4-difluorobenzene (D10220-2) £88/mol, £0.77/g.
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19. 2NO: C, 71.27; H, 6.31; N, 4.62. Found: C, 71.29; H, 6.31; N, 4.63.
20. Addition reactions of organolithium 2 to the carbonyl substrates illustrated, other than 1,4-cyclohexanedione mono-ethylene ketal, have not been evaluated in the absence of TMEDA.