Transition-metal Catalyzed Stereospecific Ring-opening Reactions Or Cycloadditions Of Vinyl Aziridines

Chiral N-heterocycles,tryptamine and romatic ethylamine scaffolds are abundant in many biologically active natural products and pharmaceuticals.Therefore,the discovery of efficient synthetic methodologies to access these compounds continues to attract the attention of organic chemists.Vinyl aziridines are increasingly being exploited as versatile building blocks in organic synthesis because of the ring strain associated with the three-membered ring and the carbon-carbon multiple bond,which can participate in reactions and stabilize charges and radicals formed.Therefore,we choose vinyl aziridines to serve as activated synthons for synthesis of enantioenriched N-heterocycles by cycloaddition or tryptamine and romatic ethylamine scaffolds by ring-opening reaction with indoles or naphthols through chirality transfer strategy.The research contents mainly include the following six parts:1.Rhodium(Ⅰ)-catalyzed intermolecular[3+2]and[5+2]cycloaddition of vinyl aziridines with alkynesA product-switchable rhodium-catalyzed intermolecular cycloaddition of vinylaziridines and general alkynes has been developed and enables the efficient and divergent synthesis of two types of aza-heterocycles,2,3-dihydropyroles and 2,5-dihydroazepines from identical starting materials through[3+2]and[5+2]cycloadditions respectively.Notably,the chirality of vinylaziridines can be efficiently transferred to the[3+2]cycloadducts.2.Rhodium(I)-catalyzed intermolecular[3+2]cycloaddition of vinyl azirndines with allenesWe have demonstrated a regiodivergent approach to 3-or 2-methylene-pyrrolidines by the rhodium-catalyzed intermolecular stereospecific[3+2]cycloadditions of vinyl aziridines and either N-alleneamines or general allenes.This method delivers valuable chiral pyrrolidines with broad substrate scope,and high diastereoselectivity and enantioselectivity by a chirality-transfer strategy 2-Methylene-pyrrolidines were obtained as the major products by the cycloadditions of vinyl aziridines with the distal C=C bond of general allenes,whereas,cycloaddition with the distal C=C bond of general allenes are rare3.Rhodium(Ⅰ)-catalyzed intermolecular[3+2]cycloaddition of vinyl aziridines with oxime ethersA highly efficient and stereoselective synthesis of enantioenriched imidazolidines by rhodium-catalyzed intermolecular[3+2]cycloaddition reaction of chiral vinyl aziridines and oxime ethers has been successfully developed.Notably,both aldoximes and ketoximes are suitable substrates to afford the corresponding chiral imidazolidines in high yields with good stereoselectivity.This method delivers valuable chiral imidazolidines with broad substrate scope,and high diastereoselectivity and enantioselectivity by a chirality-transfer strategy4.Iridium(Ⅰ)-catalyzed domino-ring-opening cyclization of vinyl aziridines withβ-ketocarbonylsThe first iridium-catalyzed domino ring-opening cyclizations of vinylaziridines with β-ketocarbonyls has been achieved.Switchable synthesis of functionalized 2-methylene-pyrrolidines and 2-pyrrolines were realized by substrate control.The salient features of this reaction include high atom-economy,mild conditions,general substrate scope,and easy further transformations of the products5.Rhodium(Ⅰ)-catalyzed stereospecific nucleophilic ring-opening reaction of vinyl aziridines with indolesThe highly efficient and stereospecific synthesis of the enantioenriched versatile building blocks-namely,β-vinyltryptamines by rhodium-catalyzed nucleophilic ring-opening reaction of vinylaziridines and indoles is presented.To demonstrate the synthetic utility of our method,up to 11 natural product and pharmaceutically relevant chiral indole scaffolds were synthesized in highly efficient reaction sequences Furthermore,two novel asymmetric routes to the formal total synthesis of a potent constrained analogue of MS-245 and a neuronal nitric oxide synthase and 5-HT1B/1D receptor inhibitor are realized6.Rhodium(Ⅰ)-catalyzed stereospecific nucleophilic ring-opening reaction of vinyl aziridines with naphthols or phenolswe have demonstrated that hydroxyarenes can serve as a C-nucleophiles rather than O-nucleophiles in rhodium-catalyzed regioselective ring-opening reactions of vinylaziridines.The reaction provides an efficient,straightforward,and atomeconomic route to functionalized 2-arylethylamines in an enantioselective manner by a chirality-transfer strategy7.Design,Synthesis of N-Me-YanPhos and Application in Palladium-Catalyzed Enantioselective Fluoroarylation of gem-DifluoroalkenesThe first example of highly enantioselective fluoroarylation of gem-difluoroalkenes with aryl halides is presented by using a new chiral sulfinamide phosphine(Sadphos)type ligand(N-Me-YanPhos).N-Me-YanPhos can be easily synthesized on a gram scale from readily available starting materials in 3 steps Salient feautures of this work including readily available starting materials,good yields,high enantioselectivities as well as broad substrate scope make this approach very practical and attractive.Notably,asymmetric synthesis of a biologically active molecule analogue 4er is also reported.