Experimental and theoretical insights regarding the cycloaddition reaction of carbohydrate-based 1,2-diaza-1,3-butadienes and acrylonitrile. A model case for the behavior of chiral azoalkenes and unsymmetric olefins

Martín Avalos, Reyes Babiano, Pedro Cintas, Fernando R. Clemente, Ruth Gordillo, José L. Jiménez, Juan C. Palacios

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A series of carbohydrate-based tetrahydropyridazines are prepared by the hetero-Diels-Alder reaction of the chiral 1,2-diaza-1,3-butadienes 1 and 2 with acrylonitrile. Reactions are regiospecific, and the observed diastereoselection is consistent with a preferred attack to the Re face of the heterodiene unit, as the chiral sugar placed at C4 does largely protect the opposite Si face. The stereochemistry of the major cycloadduct 4 has been firmly established by an X-ray crystallographic study that, in addition, reveals a conformation placing the cyano group in axial orientation. Cycloadducts such as 9 and 11, in which the axial cyano group and the carbohydrate moiety exhibit a cis relationship, undergo a facile E2 elimination that relieves the steric congestion. A detailed computational study is reported to provide better insight into the factors that influence this asymmetric cycloaddition. A DFT study (B3LYP/6-31G*) on a reduced model does correctly predict the regiochemistry observed experimentally, while the facial diastereoselection is modeled at a semiempirical (PM3) level on the parent reagents, thereby accounting for the steric factor provided by the chiral substituent. The calculations also indicate that the axial orientation of the cyano group can be rationalized in terms of a stabilizing anomeric effect.

Original languageEnglish (US)
Pages (from-to)2241-2251
Number of pages11
JournalJournal of Organic Chemistry
Issue number7
Publication statusPublished - Apr 5 2002


ASJC Scopus subject areas

  • Organic Chemistry

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