In the presence of sodium carbonate, the [4+3] cycloadditions of α‐halogeno hydrazones with nitrones were performed efficiently, and affording 2,3,4,7‐tetrahydro‐1,2,4,5‐oxatriazepines in moderate to high yields.
A catalytic enantioselective synthesis of α‐arylaminocyclobutanones from racemic α‐hydroxycyclobutanone and a selection of N‐alkylanilines has been established, via a tandem condensation/keto‐enol tautomerization process reminiscent of the Amadori and Heyns rearrangements.
A novel synthetic method to access fused indolin‐3‐ones with a tetrasubstituted carbon stereocenter has been developed via NHC‐catalyzed umpolung formal [3+3] cycloaddtion of enals with isatogens. This methodology could be also applied for the quick construction of the 6‐5‐5 tricyclic pyrrolo[1,2‐a]indole skeleton which is frequently found as a core structure of many indole alkaloids.
Visible light irradiation of N‐bromosuccinimide serves as an effective means to convert methyl 2‐(azidomethyl)‐3‐arylpropenoates and 2‐(azidomethyl)‐3‐arylacrylonitriles to the corresponding iminyl radicals via α‐hydrogen abstraction and subsequent extrusion of dinitrogen. Thus formed iminyl radicals then undergo intramolecular ortho attack on the aryl ring, affording methyl quinoline‐3‐carboxylates and quinoline‐3‐carbonitriles respectively.
α‐Substituted β‐acetyl amides could undergo C C bond cleavage to form α‐keto amides when treated with copper(II) chloride (CuCl2) and boron trifluoride diethyl etherate (BF3⋅OEt2) under an oxygen atmosphere. The yield can be increased by the addition of tert‐butyl hydroperoxide which alone can also effect the reaction. The reaction provides a new protocol for the synthesis of α‐keto amides.
A new type of phosphonium phase‐transfer catalyst prepared from easily available chiral amino acids was evaluated in a model reaction between oxindole and methyl vinyl ketone, and the catalyst derived from isoleucine was found to be the best. Michael additions of 3‐monosubstituted oxindoles to methyl vinyl ketone, acrolein or propargyl aldehyde proceeded smoothly to afford 3,3‐disubstituted oxindoles in good to excellent yields with moderate to excellent ees.
An unprecedented organocatalytic enantioselective cascade Michael/hemiketalization/retro‐aldol reaction of 2‐[(E)‐2‐nitrovinyl]phenols and 2,4‐dioxo‐4‐arylbutanoates is described. With a bifunctional squaramide catalyst incorporating (1R,2R)‐1,2‐diphenylethane‐1,2‐diamine, the reactions afford products in 75–99% yields with 80–98% ee. This process provides an enantioselective pathway for the synthesis of chiral α‐keto esters, precursors of 3‐arylproline derivatives, δ‐amino α‐keto acids or cyclic α‐keto lactams.
The first enantioselective Friedel–Crafts alkylation of indoles and pyrroles with 3‐hydroxy‐3‐indolyloxindoles to access two novel types of 3,3‐diaryloxindoles catalyzed by chiral imidodiphosphoric acids has been reported. A range of quaternary carbon centered 3,3‐diaryloxindoles were synthesized in high yield (up to >99%) with excellent enantioselectivity (up to 98% ee) at low catalyst loadings (as low as 0.5 mol%). The Friedel–Crafts reaction between indoles and 3‐hydroxy‐3‐indolyloxindoles is amenable to gram scale syntheses.
The asymmetric aldol reaction of 3‐acetyl‐2H‐chromen‐2‐ones and isatins has been realized by using a bifunctional quinidine‐derived urea as the catalyst. The corresponding 3‐hydroxyoxindole derivatives containing a 2H‐chromen‐2‐one moiety were obtained in good yields and high enantioselectivities. When (Z)‐ethyl 2‐benzylideneacetoacetate was used as the substrate, a mixture of two diastereomers (both Z and E) was obtained due to isomerization of the double bond under the reaction conditions.
A new copper‐mediated synthesis of α‐sulfonylethanone oximes from styrenes, sodium arylsulfinates and tert‐butyl nitrite (t‐BuONO; TBN) is presented. This intermolecular three‐component method enables the one‐step formation of C N and C S bonds under mild conditions, and represents a new, straightforward approach to α‐sulfonylethanone oximes.
The highly catalytic asymmetric α‐hydroxylation of β‐indanone esters and β‐indanone amides using peroxide as the oxidant was realized with a new C‐2′ substituted Cinchona alkaloid derivatives. The two enantiomers of α‐hydroxy‐β‐indanone esters could be obtained by simply changing the oxidant. This protocol allows a convenient access to the corresponding α‐hydroxy‐β‐indanone esters and α‐hydroxy‐β‐indanone amides with up to 99% yield and 98% ee.
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).
We have developed and optimized an enantioselective Michael reaction of malononitrile with β,β‐disubstituted nitroalkenes. This reaction was catalyzed by a cinchona alkaloid derived thiourea catalyst, producing products of high yields (up to 98 %) and stereoselectivities (up to 93 % ee). One of the adducts was used as an intermediate for the synthesis of dihydropyrrole derivative bearing a synthetically valuable quaternary chiral center.
The catalytic asymmetric [4+2] annulations of isatins with but‐3‐yn‐2‐one catalyzed by the Cinchona alkaloids‐derived oragnocatalyst (DHQD)2PHAL have been developed in the presence of 3.0 equivalents of D ‐diethyl tartrate in the mixed solvent (diphenyl ether/diethyl ether=1/1) or a slightly modified one, affording the corresponding substituted spiro[indoline‐3,2′‐pyran]‐2,4′(3′H)‐diones in good to excellent yields with high enantioselectivities under mild conditions.
The efficient simultaneous activation of cyclohexenones or simple alkyl acyclic enones and 2‐hydroxynitrostyrenes was realized by using a prolinol thioether catalyst. Thus, a highly chemo‐, diastereo‐ and enantioselective synthesis of functionalized tetrahydroxanthenones and chromanes with up to three contiguous stereocenters was developed.
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 novel method has been developed for the synthesis of 3‐pyrrolines from β‐ketopropargylamines via a 5‐endo‐dig carbocyclization. This transformation involves a silver‐catalyzed Conia‐ene type reaction tolerating broad substrate scope with good to excellent yields. Furthermore, this methodology has been extended for the construction of 2‐substituted pyrroles under base‐mediated conditions.
