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Volumn 71, Issue 7, 2006, Pages 2706-2714

Role of the gem-difluoro moiety in the tandem ring-closing metathesis-olefin isomerization: Regioselective preparation of unsaturated lactams

Author keywords

[No Author keywords available]

Indexed keywords

CATALYSTS; CHEMICAL REACTIONS; ISOMERIZATION; ISOMERS; SOLVENTS; SYNTHESIS (CHEMICAL);

EID: 33645544948     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo0525635     Document Type: Article
Times cited : (93)

References (59)
  • 4
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    • Wiley-VCH Verlag Gmbh and Co. KGaA: Weinheim
    • Grubbs, R. H. In Handbook of Metathesis; Wiley-VCH Verlag Gmbh and Co. KGaA: Weinheim, 2003; Vols. 1-3.
    • (2003) Handbook of Metathesis , vol.1-3
    • Grubbs, R.H.1
  • 6
    • 29044439970 scopus 로고    scopus 로고
    • During the preparation of this manuscript Grubbs and co-workers published a paper that describes a method for the suppression of undesired isomerization side reactions that are sometimes associated with olefin metathesis: Hong, S. H.; Sanders, D. P.; Lee, C. W.; Grubbs, R. H. J. Am. Chem. Soc. 2005, 127, 17160-17161.
    • (2005) J. Am. Chem. Soc. , vol.127 , pp. 17160-17161
    • Hong, S.H.1    Sanders, D.P.2    Lee, C.W.3    Grubbs, R.H.4
  • 10
    • 0037451439 scopus 로고    scopus 로고
    • For a recent revision of nonmetathetic reactions mediated by Grubbs' catalysts, see: Alcaide, B.; Almendros, P. Chem. Eur. J. 2003, 9, 1258-1262.
    • (2003) Chem. Eur. J. , vol.9 , pp. 1258-1262
    • Alcaide, B.1    Almendros, P.2
  • 11
    • 33645546853 scopus 로고    scopus 로고
    • note
    • For the deprotection of allylic amines through isomerization reactions with Grubbs' catalysts, see:
  • 13
    • 15444375617 scopus 로고    scopus 로고
    • (b) Alcaide, B.; Benito, P.; Alonso, J. M.; Luna, A. Synthesis 2005, 668-672. For the Kharasch addition of chloroform across olefins mediated by ruthenium catalysts, see:
    • (2005) Synthesis , pp. 668-672
    • Alcaide, B.1    Benito, P.2    Alonso, J.M.3    Luna, A.4
  • 21
    • 15444363138 scopus 로고    scopus 로고
    • For a recent example of the application of the RCM-isomerization protocol, see: Bressy, C.; Menant, C.; Piva, O. Synlett 2005, 577-582.
    • (2005) Synlett , pp. 577-582
    • Bressy, C.1    Menant, C.2    Piva, O.3
  • 22
    • 33645539859 scopus 로고    scopus 로고
    • note
    • Snapper and co-workers described one example of the preparation of a tosyl enamide by means of his RCM-isomerization protocol (see ref 11a).
  • 42
    • 33645546175 scopus 로고    scopus 로고
    • note
    • See Supporting Information for experimental details.
  • 43
    • 33645535704 scopus 로고    scopus 로고
    • note
    • The different behavior of toluene as solvent had already been observed by Fürstner in some RCM processes. He hypothesized that competing interactions between the mesityl group and aromatic solvents might reduce the stabilizing effect of the intramolecular π-π stacking with the benzylidene substituent; as a result, the catalyst would have more conformational freedom and therefore could display a different reactivity. See ref 6.
  • 44
    • 33645545193 scopus 로고    scopus 로고
    • note
    • Double bond isomerization prior to the RCM has been observed in several reports. See ref 10.
  • 45
    • 33645542772 scopus 로고    scopus 로고
    • note
    • The preparation of nonfluorinated analogues to 6 has been described through a tandem isomerization-RCM of enynes, the inverse process of that described here. See ref 10d.
  • 46
    • 19544380068 scopus 로고    scopus 로고
    • The synthesis of nonfluorinated cyclic enamides via copper-catalyzed intramolecular vinylation of amides was described very recently. However, this method does not afford rings with more than seven members, and it is greatly affected by the basicity of the substituent on the nitrogen atom. Our method thus circumvents the problems of this approach. See: Hu. T.; Li, C. Org. Lett. 2005, 7, 2035-2038.
    • (2005) Org. Lett. , vol.7 , pp. 2035-2038
    • Hu, T.1    Li, C.2
  • 48
    • 0034733140 scopus 로고    scopus 로고
    • Ru-hydride species are known to catalyze olefin isomerization: (a) Wakamatsu, H.; Nishida, M.; Adachi, N.; Mori, M. J. Org. Chem 2000, 65, 3966-3970 and references therein.
    • (2000) J. Org. Chem , vol.65 , pp. 3966-3970
    • Wakamatsu, H.1    Nishida, M.2    Adachi, N.3    Mori, M.4
  • 50
    • 33645553250 scopus 로고    scopus 로고
    • note
    • A theoretical study of the mechanism of these reactions is currently underway in our laboratory and will be published in due course.
  • 51
    • 33645553538 scopus 로고    scopus 로고
    • note
    • 2-allyl grouping to undergo isomerization processes: (Diagram presented)
  • 52
    • 33645555012 scopus 로고    scopus 로고
    • note
    • In this case, δ-lactam 14 would arise from the result of a double isomerization in the nonfluorinated precursor 22. In contrast, no six-membered lactam was detected in the case of fluorinated derivatives, which indicates that the double bond isomerization catalyzed by ruthenium catalyst 2 does not take place on the difluoroolefinic chain.
  • 54
    • 15044355873 scopus 로고    scopus 로고
    • 4 must be used as additive in this case because of the presence of a free amine group], pyrrol 41 was the only product isolated, arising from the aromatization of the isomerized product in the workup procedure. The same results were obtained when we started from the 2,5-dihydropyrrol 42 previously synthesized by RCM in a two-step sequence as described by Yang et al. See: Yang, Q.; Xiao, W.-J.; Yu, Z. Org. Lett. 2005, 7, 871 -874. It is assumed that the basicity of the nitrogen atom plays an important role in the nature of the final product. The presence of an electron-withdrawing group in the nitrogen atom prevents the dehydrogenation step towards the corresponding pyrrole.
    • (2005) Org. Lett. , vol.7 , pp. 871-874
    • Yang, Q.1    Xiao, W.-J.2    Yu, Z.3
  • 55
    • 33645550302 scopus 로고    scopus 로고
    • note
    • 11b only 30% of the isomerization product 6a was observed even after continuous heating of the reaction flask for 1 week.
  • 58
    • 33645547337 scopus 로고    scopus 로고
    • note
    • Similar results were also obtained in a two-step sequence in which the initially formed, nonisomerired metathesis product was treated with catalyst 2 in refluxing toluene: (Diagram presented)


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