Three-Component Approach to Pyridine-Stabilized Ketenimines for the Synthesis of Diverse Heterocycles

Abstract

Ketenimines are versatile synthetic intermediates capable of performing novel transformations in organic synthesis. They are normally generated in situ due to their inherent instability and high level of reactivity. Herein, we report pyridine-stabilized ketenimine zwitterionic salts, which are prepared through click chemistry from readily accessible alkynes and sulfonyl azides. To demonstrate their synonymous reactivity to ketenimines, these salts have been utilized in a cascade sequence to access highly functionalized quinolines including the core structures of an antiprotozoal agent and the potent topoisomerase inhibitor Tas-103.

On the Use of Differential Scanning Calorimetry for Thermal Hazard Assessment of New Chemistry: Avoiding Explosive Mistakes

“…Selected examples that didnts pecify the use of HP crucibles include studies on gem-diiodomethyl carbonyl compounds such as 1 (Figure 5a), [21] pyridine-stabilised ketenimine salts, [22] such as 2 (Figure 5b)a nd N-tosyl-4chlorobenzenesulfonimidoyl fluoride [23] (SulfoxFluor,F igure 5c). In each case,t hese are presented as alternatives to more common reagents (cf diazo compounds,k etenimines, and nonaflyl fluoride or other fluoride sources,respectively), demonstrating more desirable properties and DSC is used to support an improved stability or hazard profile for the new reagents.H owever,f eatures of the DSC plots that were included suggest to us that evaporation or loss of gaseous decomposition products has affected the results:t ypically am inor exotherm that develops into am uch larger endotherm as the temperature increases,obscuring any exothermic decomposition.…”

On the use of differential scanning calorimetry for thermal hazard assessment of new chemistry: Avoiding explosive mistakes

“…Moreover, of those that did specify, all but one used a sealed HP crucible made from unreactive gold or tantalum-lined steel, stainless steel or a glass ampoule. In contrast, the crucible type was only specified in 41% of articles in this dataset from other journals (Figure 2c Selected examples that didn't specify the use of HP crucibles include studies on gem-diiodomethyl carbonyl compounds such as 1 (Figure 5a), [20] pyridine-stabilised ketenimine salts, [21] such as 2 (Figure 5b) and N-tosyl-4chlorobenzenesulfonimidoyl fluoride [22] (SulfoxFluor, Figure 5c). In each case, these are presented as alternatives to more common reagents (cf diazo compounds, ketenimines, and nonaflyl fluoride or other fluoride sources respectively), demonstrating more desirable properties and DSC is used to support an improved stability or hazard profile for the new reagents.…”

Copper-Catalyzed One-Pot Synthesis of N-Sulfonyl Amidines from Sulfonyl Hydrazine, Terminal Alkynes and Sulfonyl Azides

“…The most efficient method is the Cu-catalyzed multicomponent reaction of terminal alkynes, sulfonyl azides and amines, which has been applied to synthesize numerous oxygen-containing and nitrogen-containing heterocyclic compounds [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. The ketenimine intermediate generated by Cu-catalyzed alkynes and sulfonyl azides [ 31 , 32 , 33 ] could take a nucleophilic addition reaction with most amines, as show in Scheme 1 , including aliphatic primary amines [ 34 , 35 , 36 ], aliphatic secondary amines [ 37 , 38 ], aliphatic tertiary amines [ 39 , 40 ], quaternary amine salts [ 41 ], imines [ 27 ], nitrogenous heterocyclic compounds [ 42 , 43 , 44 , 45 ], urea derivatives [ 46 ], oximes [ 47 ], sulfoximines [ 48 ] and enyl amine [ 49 , 50 ]. However, to our knowledge, there are few previous works that used the weak nucleophile sulfonyl hydrazines for this method.…”