Synthesis of 1,2-Dihydropyrimidine-2-carboxylates via Regioselective Addition of Rhodium(II) Carbenoids to 2H-Azirine-2-carbaldimines.

An efficient two-step procedure "imine formation/azirine-carbenoid coupling" has been developed for the preparation of 1,2-dihydropyrimidines from azirine-2-carbaldehydes, primary amines, and diazo carbonyl compounds under Rh(II) catalysis. The formation of 1,2-dihydropyrimidines involves 100% regioselective addition of the rhodium carbenoid to endocyclic nitrogen atom of the 2H-azirine-2-carbaldimine. According to the DFT calculations the reaction proceeds via dissociation of the metal-bound complex of the azirinium ylide to metal-free azirinium ylide, ring-opening of the latter to give a 1,5-diazahexa-1,3,5-triene, followed by 1,6-cyclization. The 1,2-dihydropyrimidines with two different electron-withdrawing substituents at the C2 position can undergo in solution inversion of configuration of the stereogenic center at C2 via "the N1-C2 bond cleavage/rotation around the N-C single bond/1,6-cyclization" sequence.

Pseudopericyclic 1,5- versus Pericyclic 1,4- and 1,6-Electrocyclization in Electron-Poor 4-Aryl-2-azabuta-1,3-dienes: Indole Synthesis from 2H-Azirines and Diazo Compounds.

Transformations of 2-azabuta-1,3-dienes, formed in Rh2(OAc)4-catalyzed reactions of diazo carbonyl compounds with 2H-azirines, dramatically depend on the nature of substituents. 4,4-Diphenyl-2-azabuta-1,3-dienes with two electron-acceptor substituents at C(1) undergo thermal 1,5-cyclization to give indoles in good yields. The increase in electron-withdrawing ability of C(1)-substituents facilitates the reaction that proceeds via pseudopericyclic 1,5-electrocyclization of 2-azabutadiene into 7aH-indolium ylide followed by prototropic shift. 3,4-Diphenyl-2-azabuta-1,3-dienes, resulting from reaction of 2,3-diphenyl-2H-azirine and diazo compounds, do not produce indoles via 1,5-cyclization due to the trans-configuration of the 4-Ph-group and the nitrogen, but undergo 1,4-cyclization to 2,3-dihydroazetes. 1,6-Cyclization into 2H-1,4-oxazines with participation of the oxygen of ester or amide group at C(1) of corresponding 2-azabuta-1,3-dienes does not take place due to kinetic and thermodynamic reasons. Instead of this, 1,6-electrocyclization with participation of phenyl substituent at C(4) of the 2-azabuta-1,3-dienes, providing isoquinoline derivatives, can occur at elevated temperatures. The DFT-calculations (mPWB1K/6-31+G(d,p)) confirm the dependence of 2-azabuta-1,3-diene transformation type on the nature of substituents.