Hetero-Diels-Alder reactions of homochiral 1,2-diaza-1,3-butadienes with diethyl azodicarboxylate under microwave irradiation. Theoretical rationale of the stereochemical outcome
M. Avalos et al., Hetero-Diels-Alder reactions of homochiral 1,2-diaza-1,3-butadienes with diethyl azodicarboxylate under microwave irradiation. Theoretical rationale of the stereochemical outcome, J ORG CHEM, 64(17), 1999, pp. 6297-6305
The stereoselective normal electron demand Dials-Alder reactions of chiral
1,2-diaza-1,3-butadienes, derived from acyclic carbohydrates having differe
nt configurations (1-6), with diethyl azodicarboxylate (DEAD) are disclosed
. Reactions proceed slowly in benzene solution at room temperature, but are
greatly accelerated by microwave irradiation to form the corresponding fun
ctionalized 1,2,3,6-tetrahydro-1,2,3,4-tetrazines (7-18) in good yields. Th
e observed stereoselectivity is markedly dependent on the relative stereoch
emistry at C-1',2'. Thus, 1,2-diazoalkenes derived from per-O-acylated suga
rs having three configuration at C-1',2' give tetrazines with a high facial
selectivity, whereas those having erythro configuration at C-1',2' afford
products in lower diastereomeric ratios. The facial diastereoselection has
been rationalized by a PM3 computational study. These results prove that in
the transition structures (TSs) the reacting azoalkene exhibits formal neg
ative charges at C-3 and N-2, the former being of greater magnitude, while
the heterodienophile displays a partial positive charge at the substituent
attached to the nitrogen atom. Accordingly, a stabilizing electrostatic int
eraction will only occur in TSs involving an endo orientation of the azodic
arboxylate in its approach to the azadiene, a fact consistent with the expe
rimental observations.