N-heterocyclic carbene catalyzed switchable reactions of enals with azoalkenes: formal [4 + 3] and [4 + 1] annulations for the synthesis of 1,2-diazepines and pyrazoles

Chang Guo; Basudev Sahoo; Constantin G Daniliuc; Frank Glorius

doi:10.1021/ja510737n

N-heterocyclic carbene catalyzed switchable reactions of enals with azoalkenes: formal [4 + 3] and [4 + 1] annulations for the synthesis of 1,2-diazepines and pyrazoles

J Am Chem Soc. 2014 Dec 17;136(50):17402-5. doi: 10.1021/ja510737n. Epub 2014 Dec 3.

Authors

Chang Guo¹, Basudev Sahoo, Constantin G Daniliuc, Frank Glorius

Affiliation

¹ Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster , Corrensstraße 40, 48149 Münster, Germany.

PMID: 25418586
DOI: 10.1021/ja510737n

Abstract

A regio- and enantioselective formal [4 + 3] annulation reaction between enals and in situ formed azoalkenes has been achieved. A diverse set of 1,2-diazepine derivatives were synthesized in good yields with excellent enantioselectivities (often 99% ee). Alternatively, modifying the standard NHC catalyst switched the reactivity toward a formal [4 + 1] annulation to afford functionalized pyrazoles. The electronic and steric properties of the N-heterocyclic carbene organocatalyst play a vital role in controlling the reaction pathway (homoenolate vs acyl-anion reactivity of enal), allowing selective access to diverse 1,2-diazepine and pyrazole derivatives from identical substrates.