Tandem alkylation-defluorination reaction: Synthesis of 2-(N-alkyl-N-aryl)amino-3,3-difluoropropenoates from 2-(N-aryl)imino-3,3,3-trifluoropropanoates

Tetrahedron Letters

Volumn 37, Issue 12, 1996, Pages 2045-2048

  Uneyama, Kenji ^a   Yan, Fengyang ^a   Hirama, Susumu ^a   Katagiri, Toshimasa ^a  

^a OKAYAMA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ORGANOFLUORINE DERIVATIVE; PROPIONIC ACID DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS; TECHNIQUE;

EID: 0029971231     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00214-6     Document Type: Article

References (29)

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2. (b) Kobayashi, Y.; Kumadaki, I.; Taguchi, T. "Fluorine Pharmacology" pp 241-247. Hirokawa Publishing Co.: Tokyo (1993).
3. References cited in "Recent Development of Mono and Difluorination": Uneyama, K. J. Synth. Org. Chem. Jpn. 1993, 51, 232.
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19. Compounds 1a, c-h were prepared by Pokatalyzed carboxylation of the imidoyl iodides as previously reported: Watanabe, H.; Hashizume, Y.; Uneyama, K. Tetrahedron Lett. 1992, 33, 4333.
20. A typical defluorination of 1a: To a solution of imino ester 1a (55 mg, 0.20 mmol) in toluene (1 ml) at room temperature was added diethylzinc (1.00 M in hexane, 0.22 ml, 0.22 mmol) under argon. After being stirred for 30 seconds, the reaction was immediately quenched by addition of water and the organic layer was extracted with ethyl acetate . Usual workup followed by purification by silica gel column gave 2a (50.2 mg, 88 % yield).
21. Butyl, methyl, and phenyl lithiums attack to the imino carbon of 1, see ref. 9.
22. 3) δ 63.92 (t, J = 21 Hz, 1F).
23. 1,4-Addition of Grignard reagent to 2-trifluoromethylacrylate produces 2-alkyl-3,3-difluoroacrylate, see ref. 8(i).
24. Several studies have shown abnormal 1,4-addtion of nudeophile at heteroatom (N or O) in the reaction of organometallic reagents with 1,2-diketones, 1,2-dimines, 1,2-ketimines. One of the present authors had reported production of both α-ethylbenzoin (usual 1,2-addition product) and benzoin ethyl ether or ethylbenzoate (abnormal 1,4-oxygen addition product) in the reaction of 'EtMgBr' with benzil: (a) Maruyama, K.; Katagiri, T. J. Am. Chem. Soc. 1986, 108, 6263.
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29. A similar selective nucleophilic 1,4-addtion at oxygen of ortho-quinone in the reaction of dialkyl zinc had reported: Eistert, B.; Klein, L. Chem. Ber. 1968, 101, 900.