A Novel Efficient Three-Component One-Pot Synthesis of 1,3-Diazabicyclo[3.1.0]hex-3-ene System under Microwave Irradiation

Abstract

Bridgehead aziridines 3 were synthesized in high yields and excellent diastereocontrol by a three-component reaction of an aldehyde, phenacyl chloride and ammonium acetate in acetic acid using microwave irradiation.

Structure Investigation of Bridgehead Aziridine: Synthesis, Theoretical, and Crystallographic Study of 2,4,6‐Triphenyl‐1,3‐diazabicyclo[3.1.0]hex‐3‐ene

“…4. In agreement with the stereoselectivity of the reaction [12], compound 3 (denoted by 3 (2R,5S,6R) in Fig. 4) appears to be the most stable of the diastereoisomers.…”

“…In the present paper, we report a straightforward procedure for the diastereoselective synthesis of the 1,3-diazabicyclo[3.1.0]hex-3-ene system [10]. This is based on a one-pot multi-component mechanism [11] involving a-halogeno ketones such as 1 and aldehydes such as 2 in the presence of AcOH/AcONH 4 [12] (Scheme). We carried out a study of the structural characteristics of the new derivative 2,4,6-triphenyl-1,3-diazabicyclo[3.1.0]hex-3-ene (3) by using the X-ray diffraction technique.…”

Small Heterocycles in Multicomponent Reactions

“…Photolysis of small ring heterocycles has been explored in the hopes of uncovering mechanistic insight into excited state rearrangements, development of photochromic materials, as well as for synthetic approaches to aromatic heterocycles. Among these systems, the synthesis of fused 1,3-diazabicyclo[3.1.0]­hex-3-ene has remained a challenge due to the perceived requirement of preparing N H-aziridine ketones as starting materials and the reversibility of imidazoline formation under the reaction conditions. ,− An MCR approach to this scaffold was developed using microwave heating of ammonium acetate, phenacyl chloride ( 347 ), and a benzaldehyde derivative ( 348 ) in the presence of acid and molecular sieves to generate 349 as a racemic single exo-diastereomer, as confirmed by 2D-NMR and X-ray crystallography (Scheme ) Aliphatic aldehydes containing α-hydrogens did not give the desired products, though pivalaldehyde did produce 349 in reduced yield.…”

Ammonium Acetate

“…The method provides an easy route to bridgehead aziridines, which are potential drug precursors. 10 (E) Ammonium acetate has been utilized to prepare medicinally important enantiopure substituted imidazoles through a cyclocondensation reaction of 1,2-aminoalcohol with an aldehyde, a 1,2-dicarbonyl compound, and NH 4 OAc. A study using different ammonia sources in this method established that NH 4 OAc is superior to other sources like aqueous NH 3 and NH 4 Cl in its efficiency and in the stereoselectivity of the reaction.…”

“…4 In some cases ammonium acetate shows excellent catalytic activity. 5 Literature reveals that it has been extensively used in the synthesis of N-heterocyclic compounds (pyridines, [6][7][8] pyridopyrimidines, 9 aziridines, 10 imidazoles, 11 benzoxazines 12 ), many of which exhibit pharmacological activity or act as drug precursors. Moreover, it finds application in modern techniques of analytical chemistry 13a and molecular biology (purification and precipitation of DNA, 13b protein crystallization 13c ).…”