Studies On The Tandem Reactions Via The N-Sulfonyl Allenamide Intermediates

As a research hotspot, Construction of heterocycles and carbocycles via tandem reaction is widely used for the synthesis of drug molecules and natural products. In the thesis, preparation of stable allenamides (an effective and versatile building block) and construction of heterocycles and carbocycles by the development of allenamides’ reaction has been reviewed. We have constructed several complex skeletons from propargylic alcohols and sulfonamides, mostly via N-sulfonyl allenamide intermediate. The details are summarized as following:1) Synthesis of indenesAn efficient method to generate N-sulfonyl allenamide intermediate, which could be captured by electrophiles was developed. In this process, a facile and efficient three-component domino reaction involving propargylic alcohol, sulfonamide, NIS was investigated. Highly substituted2-iodoindenes were generated from readily accessible and simple starting materials via this synthetic strategy. Consequently,three δ-bonds were efficiently constructed in this one-pot reaction, including C-C, C-N, and C-I δ-bonds. The possibility of derivatization by cross-coupling reaction was provided by the products containing C-I δ-bond.2) Synthesis of spiro compoundsAn efficient method to generate spiro compounds via Lewis acid catalyzed intramolecular reaction of2-(3-hydroxyprop-l-yn-l-yl) benzenesulfonamide was developed. The reaction was mild and easily operated, α,β-Unsaturated carbonyl compound is postulated to be the key intermediate for the tandem transformation.3) Synthesis of dihydropyrazolesAn efficient strategy to synthesize4-methylene-4,5-dihydro-1H-pyrazoles was developed via a BF3·Et2O catalyzed domino reaction of propargylic alcohols and N-sulfonylhydrazones. The reaction was mild and easily operated. The starting material was easily prepared and a wide range of substrates could apply to the tandem reaction leading to the formation of different4,5-dihydropyrazoles. A tentative mechanism was postulated, and N-sulfonyl allenamide intermediate is postulated to be the key intermediate, which was formed by trapping the in situ generating allenic carbocation with N-sulfonylhydrazone. More significantly,3,3-diarylacrylonitriles, which might be served for potential utility in cancer chemotherapy, could be efficiently obtained from the synthesized4-methylene-4,5-dihydro-1H-pyrazoles via N-N bond cleavage in excellent yields.4) Synthesis of dihydroisoxazolesAn efficient methodology to synthesize2,5-Dihydroisoxazoles,4-iodo-2,5-dihydroisoxazoles and4-bromo-2,5-dihydroisoxazoles was provided from propargyl alcohols and TsNHOH using Yb(OTf)3, iodine and the combination of NBS and Yb(OTf)3, respectively. N-sulfonyl allenamide is postulated to be the key intermediate for these tandem transformations, which was formed by trapping the in situ generating allenic carbocation with TsNHOH. Moreover, the resulting4-iodo-2,5-dihydroisoxazoles could be elaborated by Pd-catalyzed carbonylation to generate4-methoxycarbonyl-4,5-dihydroisoxazoles.