Synthesis and Antiproliferative Activity of 3-[(R-Hydrazono)Methyl]Cyclobutane-1,1,2,2-Tetracarbonitriles and 3-[(2-R-Hydrazono)Methyl]-6-Methylcyclohex-4-Ene-1,1,2,2-Tetracarbonitriles

Redirecting a Diels–Alder Reaction toward (2 + 2)-Cycloaddition

“…The resulting cyclobutanes (six examples, 56−82% yields) contain an easily modifiable 28 hydrazone fragment, and some of them were found to inhibit leukemia cell growth at nanomolar concentrations. 27 Here we explore the origin of this unexpected regioselectivity and show how Diels−Alder reaction can be redirected toward (2 + 2)cycloaddition.…”

“…Recently, Mar’yasov et al have discovered that the hydrazone cation-stabilizing group also favors (2 + 2)-cycloaddition in reactions with tetracyanoethylene (TCNE) despite the presence of two conjugated double bonds easily adopting s-cis conformation. The resulting cyclobutanes (six examples, 56–82% yields) contain an easily modifiable hydrazone fragment, and some of them were found to inhibit leukemia cell growth at nanomolar concentrations . Here we explore the origin of this unexpected regioselectivity and show how Diels–Alder reaction can be redirected toward (2 + 2)-cycloaddition.…”