Stereochemistry of the Kulinkovich cyclopropanation of nitriles

Journal of Organic Chemistry

Volumn 74, Issue 15, 2009, Pages 5528-5532

  Astashko, Dmitry ^a   Hyung, Goo Lee ^a   Bobrov, Denis N ^a   Cha, Jin K ^a  

^a WAYNE STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMICAL EQUATIONS; CHEMICAL PROBES; CYCLOPROPANATION; HOMOALLYLIC ALCOHOL; INTRAMOLECULAR CYCLOPROPANATION; INVERSION OF CONFIGURATION; TERTIARY AMIDES;

AMIDES; CHEMICAL REACTIONS; CYANIDES; DEUTERIUM; LABELS; PROPANE; STEREOCHEMISTRY;

OLEFINS;

ALCOHOL DERIVATIVE; ALKENE; AMIDE; CYCLOPROPANE; HOMOALLYLIC ALCOHOL DERIVATIVE; NITRILE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; CYCLOPROPANATION; KULINKOVICH CYCLOPROPANATION; STEREOCHEMISTRY;

ALKENES; CYCLIZATION; CYCLOPROPANES; MOLECULAR STRUCTURE; NITRILES; STEREOISOMERISM;

EID: 68049110503     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo900823h     Document Type: Article

References (30)

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4. (c) Kulinkovich, O. G. Russ. Chem. Bull., Int. Ed. 2004, 53, 1065.
5. Amides: (a) Chaplinski, V.; de Meijere, A. Angew. Chem., Int. Ed. Engl. 1996, 35, 413.
6. (b) Lee, J.; Cha, J. K. J. Org. Chem. 1997, 62, 1584.
7. Compare (c) Masalov, N.; Feng, W.; Cha, J. K. Org. Lett. 2004, 6, 2365.
8. Carbonates: Lee, J.; Kim, Y. G.; Bae, J. G.; Cha, J. K. J. Org. Chem. 1996, 61, 4878.
9. Nitriles: (a) Bertus, P.; Szymoniak, J. Chem. Commun. 2001, 1792.
10. (b) Bertus, P.; Szymoniak, J. J. Org. Chem. 2002, 67, 3965.
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22. 3 (1 equiv) and the cyclohexyl Grignard reagent (2 equiv) was also found to be satisfactory but did not offer an advantage over the present procedure (except for 7). (b) In the case of tertiary alcohol 7, however, the pre-formation of the mixed titanate by the action of MeTi(O-i-Pr)3 was required for the successful cyclopropanation. (c) Several cyclopropylamine products underwent slow decomposition during chromatography, which precluded isolation of pure minor isomers for full characterization. (d) The uncyclized ketones were isolated in 20-38% and 13% yields from cyclopropanation of 6 and 7, respectively, but are not shown in Scheme 2 for convenience.
23. trans for comparison.
24. 5 This conspicuous difference between cyclohexyl and cyclopentyl Grignard reagents supports the intermediacy of D and can be rationalized in terms of different relative rates for ring closure versus olefin exchange.
25. Isolation of uncyclized ketones (e.g., 10) is consistent with the regiochemistry of intermediate G.
26. 9c
27. (a) These putative intermediates in Scheme 4 have eluded isolation for full characterization. For a computational study on the related Kulinkovich cyclopropanation of esters, see: Wu, Y.-D.; Yu, Z.-X. J. Am. Chem. Soc. 2001, 123, 5777.
28. (b) The reactivity of the Kulinkovich reagent is conceptually related to that of the Negishi reagent: Negishi, E.; Huo, S. In Titanium and Zirconium in Organic Synthesis; Marek, I., Ed.; Wiley-VCH: Weinheim, 2002; pp 1-49.
29. See also : Buchwald, S. L.; Watson, B. T.; Wannamaker, M. W.; Dewan, J. C. J. Am. Chem. Soc. 1989, 111, 4486.
30. (a) The atypical dichotomy is indicative of a small difference in activation energy between two modes of the final cyclization step: complexation between the titanium metal and the imine functional group predisposes to retention of configuration; on the other hand, inversion of configuration is favored on grounds of steric effects. (b) It is interesting to note that an idealized W-shaped transition state is unattainable for the bicyclic titanate B, which might help reinforce ring closure with retention of configuration.