Regioselective Conjugate Addition of Nitriles to α,β‐Unsaturated Imines: Synthesis of Fluorinated Primary Enamines and 2‐Aminopyridine Derivatives

Abstract

The regioselective Michael addition of the carbanion of 2‐phenylacetonitrile (R2 = Ph) and malononitrile (R2 = CN) to fluoroalkylated α,β‐unsaturated imines 1 is described. Fluorinated imines 1 were used as intermediates for the regioselective 1,4‐addition and synthesis of functionalized fluorinated primary enamines 5 and 7, fluorine‐containing trans‐3,4‐dihydro‐2‐aminopyridines 2, and fluorinated 2‐aminopyridines 4 and 8, which were obtained with total atom economy. Derivatives 2 and 8 were also prepared by an intramolecular cyclocondensation reaction of functionalized fluorinated primary enamines 5 and 7, respectively, in the presence of a base (NaH).

Fluoroalkylated α,β-Unsaturated Imines as Synthons for the Preparation of Fluorinated Triazinane-2,4-diones and Dihydropyrimidin-2(1H)-ones

“…We also reported an efficient procedure for the synthesis of electron-poor 1-azadienes derived from α-amino acids or α-aminophosphonates using an aza-Wittig approach, as well as successful normal ADA reactions of α,β-unsaturated N -arylimines, hydrazones, and ADA reaction of α,β-unsaturated sulfinylmines with electron-rich dienophiles and Michael additions (1,4 addition) of α,β-unsaturated N -arylimines. In the development of new fluorinated substrates, we prepared the first stable N-unsubstituted α,β-unsaturated imine Ia (Scheme ) from primary fluorine-substituted enaminophosphonates, , and we used these derivatives for the preparation of vinylogous α-aminonitriles IIIa , β-aminonitriles II I b (X = CN), and β-aminoesters IIIb (X = CO 2 Et), obtained by 1,2-addition of trimethylsilyl cyanide, acetonitrile, or ethyl acetate, while the regioselective Michael addition of α-carbanions derived from carboxylic esters and nitriles to fluorinated imines I may afford functionalized pyridine derivatives IV . , …”

Regiospecific 1,4-Michael Addition of Phenylacetonitrile to 1,5-Diarylpenta-2,4-Dien-1-Ones

“…However, reports of the use of phenylacetonitrile as a Michael donor are scarce. 4,5 In addition, dienones as Michael acceptors can provide carbonyl and alkenyl groups for target molecules. Reports using dienones in the Michael addition have mainly focused on the use of 1,4-dien-3-ones to conduct double Michael addition.…”