Organocatalyzed highly stereoselective 1,4‐thia‐Michael addition of mercaptans to linear 2,4‐dienones and 2‐en‐4‐ynones was developed using Cinchona alkaloid‐based squaramides. Application of only 0.5–1 mol % loading afforded products in up to 98:2 e.r. and above 99:1 after a single recrystallization. The adducts of allyl mercaptan can be conveniently further transformed to new chiral 2‐substituted 2,5‐dihydrothiophenes by ring‐closing metathesis.
A highly efficient and enantioselective inverse electron‐demand hetero‐Diels–Alder reaction of in situ generated 1,2‐diaza‐1,3‐dienes with enol ethers has been developed with the use of a chiral copper/bisoxazoline complex as the catalyst. The reaction exhibits high enantioselectivity (up to 90% ee) and provides a robust and powerful method to synthesize a variety of structurally diverse and densely substituted chiral pyridazine derivatives in good to excellent yields.
A phosphane‐catalyzed [3+3] annulation of azomethine imines with ynones has been developed. Under mild reaction conditions, the reaction proceeds smoothly to afford tricyclic dinitrogen‐fused heterocyclic compounds in moderate to excellent yields with moderate to excellent stereoselectivies. Using a chiral phosphine as the catalyst, the reaction could work to give the cycloadduct in moderate yield with moderate enantioselectivity.
A novel and efficient domino process has been developed for the synthesis of 1,4‐benzoxazepine derivatives from a range of readily accessible N‐tosylaziridines, 2‐iodophenols and isocyanides. This process involves the aziridine ring‐opening reaction with 2‐iodophenol, followed by a palladium‐catalyzed isocyanide‐insertion reaction. This regioselective and high‐yielding transformation could be extended to its application for the synthesis of natural products and biologically interesting heterocycles.
A series of 1,2‐ and 1,4‐dihydroquinolines has been successfully prepared. The Pd‐catalyzed intramolecular N‐arylation of Z‐enamines, formally prepared by the Horner–Wadsworth–Emmons olefination, proceeded efficiently to furnish the cyclized products. Depending on the cyclization conditions, substituted 1,4‐dihydroquinolines and further isomerized 1,2‐dihydroquinolines were independently obtained in high yields with an excellent control of isomerization of the double bond.
A novel copper‐catalyzed oxidative alkylation of α‐amino carbonyl compounds with ethers has been established for the selective synthesis of α‐etherized α‐amino carbonyl compounds. This oxidative alkylation is achieved by dual C(sp3) H bond oxidative cross‐coupling, and its scope is expanded to α‐amino ketones, α‐amino esters and α‐amino amides.
A practical and environmentally friendly strategy for generating alkoxycarbonyl radicals from readily available carbazates under metal‐free conditions has been developed. In the presence of tetrabutylammonium iodide and tert‐butyl hydroperoxide, 2‐isocyanobiphenyls smoothly underwent radical alkoxycarbonylation with carbazates to afford phenanthridine‐6‐carboxylates.
Highly regio‐ and diastereoselective 1,2‐addition of organolithium reagents to chiral fluoroalkyl α,β‐unsaturated N‐tert‐butanesulfinyl ketimines was developed, providing a general and efficient method for the asymmetric synthesis of structurally diverse α‐tertiary fluoroalkyl allylic amines in high yields and with excellent diastereoselectivities (dr up to>99:1). The synthetic application of the method was demonstrated by the rapid and convenient preparation of challenging α‐fluoroalkyl α‐amino acids with α‐tetrasubstituted carbon.
A practical, nickel‐catalyzed Kumada‐type double cross‐coupling reaction of gem‐difluoroalkenes with 1,4‐ or 1,5‐di‐Grignard reagents was developed. The reaction proceeded efficiently at room temperature and a variety of cyclization products, arylmethylenecyclopentanes and arylmethylenecyclohexanes, were obtained in high to excellent yields, respectively.
By using Cinchona‐derived chiral phosphines as catalytic ligands, enantioenriched cis‐3a,8a‐hexahydropyrrolo[2,3‐b]indoles (ent‐HPIs), which are core scaffolds in a large array of biologically active natural products, can be convergently assembled under mild conditions through the silver(I)‐catalyzed asymmetric domino reaction of readily available isocyanoacetates and 2‐(2‐aminophenyl)acrylates. Various functionalities can be tolerated in the reaction, affording enantioenriched HPIs in high overall yields and good enantioselectivities (up to 92% ees).
An enantioselective protonation by means of chiral scandium complex‐catalyzed aza‐Michael reaction was realized. A series of α‐aryl‐substituted vinyl ketones reacted with pyrazoles smoothly, affording the corresponding enantiomerically enriched pyrazole derivatives with excellent results (up to 99% yield, 94% ee). Water and hydrogen chloride were found to accelerate the protonation process.
A new enantioselective synthetic method for the synthesis of α,α‐dialkylmalonates with a quaternary carbon center was developed via α‐alkylation of prochiral malonates by phase‐transfer catalysis (PTC). Asymmetric α‐alkylation of benzylideneamino tert‐butyl α‐methylmalonates under phase‐transfer catalytic conditions in the presence of (S,S)‐3,4,5‐trifluorophenyl‐NAS bromide afforded the corresponding α,α‐dialkylmalonates in high yields (up to 97%) with excellent enantioselectivities (up to 98% ee). The products were then selectively hydrolyzed to chiral malonic monoacids under basic, acidic, or catalytic hydrogenation conditions.
A spiro‐pyrrolidine‐catalyzed tandem aza‐1,4‐addition/hemi‐acetalization reaction was developed with excellent enantioselectivity (12 examples of ≥99% ee), and several substrates proceeded with higher ee (up to 10% increase) compared with the literature data. Particularly, an interesting and unusual aza‐1,6‐/oxa‐1,4‐addition for some substrates was also observed.
The direct α‐Csp2 H functionalization and thiomethylation of α‐oxoketene dithioacetals (DTAs) has been accomplished with dimethyl sulfoxide (DMSO) in the presence of iodine and a copper(I) salt for the first time. A prerequisite is the in situ iodination of the α‐Csp2 atom of dithioacetals that could offer other reaction channels. The operationally simple one‐pot protocol includes region‐defined consecutive iodination and sulfenylation of the challenging α‐Csp2 H bond of dithioacetals employing cheap and readily available reagents. DMSO here plays a dual role as thiomethyl source and solvent.
A novel phosphine‐promoted intramolecular cyclization of dicyclopropenones 1 has been described in this contribution. A variety of 2,3‐dihydro‐1H‐indene‐4,6‐diol derivatives 2 and hexahydropentalen‐2‐one derivatives 3 were obtained selectively in moderate to good yields under mild conditions through different phosphine‐promoted reactions.
A quinine‐derived thiourea catalysed the enantioselective addition of 4‐substituted pyrazolones to isatin‐derived ketimines, providing a variety of aminooxindole‐pyrazolone adducts containing congested vicinal tetrasubstituted stereocentres with excellent outcomes (up to 98% yield, >20:1 dr and 98% ee).
