Asymmetric Synthesis of Multifunctionalized 2,3-Benzodiazepines by a One-Pot N-heterocyclic Carbene/Chiral Palladium Sequential Catalysis

Abstract

We report the first example of the construction of chiral 2,3-benzodiazepine compounds which are of biologic and pharmaceutical relevance by asymmetric catalysis. Catalyzed by a thiazolium-derived carbene and a palladium-chiral bidentate phosphine complex in sequence, one-pot reaction between 1-(2-(2-nitrovinyl)­aryl)­allyl esters 1 with azodicarboxylates 2 took place efficiently at ambient temperature to produce 4-nitro-1-vinyl-1H-2,3-benzodiazepine-2,3-dicarboxylates 5 in good to excellent yields with an enantiomeric ratio of up to 95:5.

Recent advances in Pd-catalyzed asymmetric cyclization reactions

“…In 2020, Cheng and co-workers reported the construction of chiral 2,3-benzodiazepine compounds catalyzed by a thiazolium-derived carbene and a palladium-chiral bidentate phosphine complex in a cascade nucleophilic addition and intramolecular N -allylation reaction involving the use of 1-(2-(2-nitrovinyl)aryl)allyl esters 36 and azodicarboxylates 37 as reaction partners (Scheme 9). 27 The substrate scope was wide since various aryl- and heterocyclic aryl-substituted allyl acetate analogues were well-tolerated. It should be pointed out that the reaction of 1-(3-(2-nitrovinyl)thiophen-2-yl)allyl acetate with azodicarboxylates did not yield the expected product because of the poisoning effect of thiophene imposed on the palladium catalyst.…”

Combined Power of Organo‐ and Transition Metal Catalysis in Organic Synthesis

“…2,3‐Benzodiazepine and hydrogenated 2,3‐benzodiazepines constitute the core skeletons of many biologically active compounds. Recently, Cheng and co‐workers demonstrated a NHC/Pd sequential catalytic method for the asymmetric synthesis of a multi functionalized 1 H ‐2,3‐benzodiazepines 146 by reacting 1‐(2‐(2‐nitrovinyl)phenyl)allyl acetates 144 and azodicarboxylates 145 [118] . In this one‐pot multicatalytic cascade process, initially, the NHC precursor was added, followed by the chiral Pd catalyst, to the reaction mixtures 144 and 145 .…”

Recent Advances in Cooperative N-Heterocyclic Carbene Catalysis

“…The palladium-catalyzed allylic substitutions are applied to the enantioselective NHC catalysis [15][16][17][18][19][20]. The cooperative catalysis was achieved by using chiral NHC catalyst and palladium catalyst (Figure 1) [15][16][17].…”