Exploration of five membered cyclic sulfamidate imines as nucleophiles in various organic transformations

Abstract

This thesis presents for the first time use of five membered cyclic sulfamidate imines as powerful nucleophiles. 5-alkylidene/alkyl-substituted cyclic sulfamidate imines/aza-heterocyclic scaffolds have been prepared by utilizing this unique reactivity of five membered cyclic sulfamidate imines in an efficient, cost-effective and eco-friendly manner. To begin with a general introduction of the synthetic application of five membered cyclic sulfamidate imines which exclusively focused on the nucleophilic addition or hydrogenation to the azomethine functionality of the titled compounds. The next chapter illustrates a very simple, mild and robust method for the synthesis of exclusively Z-trisubstituted 5-alkylidene cyclic sulfamidate imines in good to excellent yields via a condensation reaction of 4-aryl-5H-1,2,3-oxathiazole-2,2- dioxides with several aryl/alkyl-substituted aldehydes using 10 mol% of L-proline as a cheap, nontoxic and naturally available organocatalyst in DMF at room temperature. In addition, the syntheses of 5-alkyl substituted cyclic sulfamidate imines, trans-β-amino-α-azido/triazole and 2-hydroxy-4-triazole-5-phenylpyrrolidine derivatives have been achieved from corresponding 5-alkylidene cyclic sulfamidate imines through our developed method. The third chapter describes a stereoselective synthesis of functionalized spiro- sulfamidate imine fused δ-lactone scaffold via a one-pot three-component sequential reaction between 4-aryl-5H-1,2,3-oxathiazole-2,2-dioxides, trans-β-aryl/alkyl- substituted acroleins and paraformaldehyde in CH2Cl2 at room temperature in the presence of commercially available L-proline and DBU as the organocatalysts. Moreover, highly enantioselective synthesis of the above title compounds were achieved by using (S)-(-)-α,α-diphenyl-2-pyrrolidinemethanol trimethylsilyl ether as a catalyst instead of L-proline. Furthermore, the obtained Michael adduct was converted into the synthetically valuable intermediate β-amino-α-azido derivative through some efficient steps. XX Chapter four demonstrates an unprecedented synthesis of pharmacologicallynteresting 4,6-diarylpicolinates in high to excellent yields via a domino reaction of cyclic sulfamidate imines with Morita-Baylis-Hillman acetates of nitroolefins/nitrodienes in the presence of DABCO as an organic base at 55 °C. Furthermore, the biologically interesting imidazo[1,2-a]pyridine (alpidem derivative) has been prepared in high chemical yield through a unique procedure. In chapter five, a facile, green, metal-free new one-pot synthetic strategy has been developed for the easy access to a wide array of functionalized pyridines having an ester, a nitrile or an acetyl group at the C-3 position in good to excellent yields via a domino SN2/elimination/6π-aza-electrocyclization/aromatization reaction of several 4-aryl/hetero-aryl-substituted 5-membered cyclic sulfamidate imines with a broad range of MBH acetates of acrylate/acrylonitrile/MVK in 2-MeTHF promoted by DABCO as an organobase under an O2 atmosphere. Finally, a potential PDE10A inhibitor14 triazolopyridine derivative was prepared in 81% yield from 4,6-diphenyl nicotinonitrile using some reported method. This sixth chapter unfolds a novel L-proline catalyzed Michael reaction between 4- aryl/ heteroaryl-substituted cyclic sulfamidate imines and a range of β-styryl/aryl- substituted acroleins at room temperature, where resultant Michael adducts subsequently undergo in situ elimination/ cyclization/aromatization under the influence of DABCO as an organobase to generate an important class of 2-aryl-4- (E)-styrylpyridines/2,4-diarylpyridines in good to high yields. Interestingly, commercially available 2-arylisonicotinic acids as useful intermediates for the synthesis of highly active CypA inhibitors were prepared by the oxidation of alkene double bonds 2-aryl-4-styrylpyridines using KMnO4 as a strong oxidizing agent. The final chapter of the thesis focuses on the future prospect of the developments as reported in this thesis, many effective methods can be designed for the development of various heterocyclic scaffolds involving cyclic sulfamidate imines as powerful nucleophiles taking several readily available starting materials.