Catalytic Asymmetric Construction of Quaternary α‐Amino Acid Containing Pyrrolidines through 1,3‐Dipolar Cycloaddition of Azomethine Ylides to α‐Aminoacrylates

The first catalytic enantioselective 1,3‐dipolar cycloaddition of azomethine ylides to α‐aminoacrylate catalyzed by a AgOAc/ferrocenyl oxazolinylphosphine (FOXAP) system was developed, which exhibits excellent exo‐ and enantioselectivity (92–99 % ee). This process provides efficient access to useful 4‐aminopyrrolidine‐2,4‐dicarboxylic acid (APDC)‐like compounds containing a unique quaternary α‐amino acid unit.     

Highly Enantioselective Synthesis of α‐Stereogenic Esters through Catalytic Asymmetric Michael Addition of 4‐Oxo‐4‐arylbutenoates

Highly enantioselective Michael addition of 1,3‐dicarbonyl compounds and nitromethane to 4‐oxo‐4‐arylbutenoates catalyzed by N,N′‐dioxide–Sc(OTf)₃ complexes has been developed. Using 0.5–2 mol % catalyst loading, various α‐stereogenic esters were obtained regioselectively with excellent yields (up to 97 %) and enantioselectivities (up to >99 % ee). Moreover, the reaction performed well under nearly solvent‐free conditions. The products with functional groups are ready for further transformation, which showed the potential value of the catalytic approach. According to the experimental results and previous reports, a plausible working model has been proposed to explain the origin of the activation and the asymmetric induction.     

L-Proline Catalyzed Enamination of β-Dicarbonyl Compounds under Solvent-free Conditions

A simple, general and efficient method has been developed for synthesis of various β-enamino ketones and esters by reacting β-dicarbonyl compounds with amines using a catalytic amount of L-proline at room temperature under solvent-free conditions in excellent yields.     

Chemo‐ and Enantioselective Oxidative α‐Azidation of Carbonyl Compounds

We report high‐performance I⁺/H₂O₂ catalysis for the oxidative or decarboxylative oxidative α‐azidation of carbonyl compounds by using sodium azide under biphasic neutral phase‐transfer conditions. To induce higher reactivity especially for the α‐azidation of 1,3‐dicarbonyl compounds, we designed a structurally compact isoindoline‐derived quaternary ammonium iodide catalyst bearing electron‐withdrawing groups. The nonproductive decomposition pathways of I⁺/H₂O₂ catalysis could be suppressed by the use of a catalytic amount of a radical‐trapping agent. This oxidative coupling tolerates a variety of functional groups and could be readily applied to the late‐stage α‐azidation of structurally diverse complex molecules. Moreover, we achieved the enantioselective α‐azidation of 1,3‐dicarbonyl compounds as the first successful example of enantioselective intermolecular oxidative coupling with a chiral hypoiodite catalyst.     

An Enantioselective Assembly of Dihydropyranones through an NHC/LiCl‐Mediated in situ Activation of α,β‐Unsaturated Carboxylic Acids

A straightforward N‐heterocyclic carbene (NHC)/LiCl‐mediated synthesis of dihydropyranones from α,β‐unsaturated carboxylic acids and 1,3‐dicarbonyl compounds was realized through the in situ activation strategy. The key advantages of this protocol include ready availability and high stability of starting materials, good yields, and excellent enantioselectivity.     

A General Proline‐Catalyzed Synthesis of 4,5‐Disubstituted N‐Sulfonyl‐1,2,3‐Triazoles from 1,3‐Dicarbonyl Compounds and Sulfonyl Azide

An efficient proline‐catalyzed synthesis of 4,5‐disubstituted‐N‐sulfonyl‐1,2,3‐triazoles has been accomplished from 1,3‐dicarbonyl compounds and sulfonyl azides. The developed reaction is suitable for various symmetrical and unsymmetrical 1,3‐dicarbonyl compounds, tolerates various functional groups and affords 4,5‐disubstituted‐N‐sulfonyl‐1,2,3‐triazoles in good yield with excellent regioselectivity. Rhodium‐catalyzed denitrogenative functionalization of 4,5‐disubstituted‐N‐sulfonyl‐1,2,3‐triazoles further demonstrates their utility in organic synthesis.     

Microwave‐Assisted Convenient Synthesis of α,β‐Unsaturated Esters and Ketones via Aldol‐Adduct Elimination

Various fluorinated 3‐oxo ester/1,3‐diketones were reacted with carbonyl compounds, in presence of piperidine and under microwave irradiation, to afford (E)‐α,β‐unsaturated esters and ketones in good yields. The systematic study reveals that the reaction proceeded through the formation of aldol adduct. The method provides a new and simple way for C,C bond formations.     

One‐pot synthesis of tetrahydroindeno[1,2‐b]pyrrolo‐3‐carboxylates derivatives

Tetrahydroindeno [1,2‐b]pyrrole‐3‐carboxylate were synthesized in a one‐pot procedure by the reaction of 1,3‐dicarbonyl and activated carbonyl compounds such as benzyl or ninhydrin in ethanol/water in the presence of ammonium acetate. J. Heterocyclic Chem., (2011).     

Synthesis of α‐Stereogenic Amides and Ketones by Enantioselective Conjugate Addition of 1,4‐Dicarbonyl But‐2‐enes

Constructing α‐stereogenic amides and ketones : The highly regioselective and enantioselective conjugate addition of 1,3‐dicarbonyl compounds to 1,4‐dicarbonyl but‐2‐enes has been developed with the chiral bicyclic guanidine as catalyst (ee values up to 97 %; see scheme).

     

Synthesis of Functionalized Pyrazoles via 1,3‐Dipolar Cycloaddition of α‐Diazo‐β‐ketophosphonates,Sufones and Esters with Electron‐Deficient Alkenes

1,3‐Dipolar cycloaddition of diazo compounds with olefinic substrates is a promising atom‐economic strategy for the construction of functionalized pyrazoles. Over the last few years, our group has been engaged in the synthesis of phosphonyl/sulfonylpyrazoles and pyrazole esters by employing Bestmann‐Ohira Reagent (BOR) and its sulfur and ester analogs as 1,3‐dipole precursors with various dipolarophiles. This account describes the novel synthetic methods developed in our laboratory, in the perspective of closely related work by others, for the synthesis of phosphonyl/sulfonylpyrazoles, pyrazole esters and the total synthesis of Withasomnine, a natural product, by using 1,3‐dipolar cycloaddition as the key step.     

A New Four‐Component Reaction for the Synthesis of Spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles]

A new four‐component synthesis of spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles] and spiro[acenaphthylene‐1(2H),4′‐[4H‐indeno[1,2‐b]pyridines] by the reaction of indane‐1,3‐dione, 1,3‐dicarbonyl compounds, isatins (=1H‐indole‐2,3‐diones) or acenaphthylene‐1,2‐dione, and AcONH₄ in refluxing toluene in the presence of a catalytic amount of pyridine is reported.     

Reaction of cyclic imidates with α,β‐unsaturated esters: Synthesis of new pyrrolo[2,1‐b]‐1,3‐oxazine and pyrido[2,1‐b]‐1,3‐oxazine derivatives

The cycloaddition reaction of cyclic imidates, 2‐benzyl‐5,6‐dihydro‐4H‐1,3‐oxazines 1a , 1b , 1c , 1d , 1e , 1f , with dimethyl acetylenedicarboxylate 2 , trimethyl ethylenetricarboxylate 4 , or dimethyl 2‐(methoxymethylene)malonate 6 afforded new fused heterocyclic compounds, such as methyl (6‐oxo‐3,4‐dihydro‐2H‐pyrrolo[2,1‐b]‐1,3‐oxazin‐7‐ylidene)acetates 3a , 3b , 3c , 3d , 3e , 3f (71–79%), dimethyl 2‐(6‐oxo‐3,4,6,7‐tetrahydro‐2H‐pyrrolo[2,1‐b]‐1,3‐oxazin‐7‐yl)malonates 5b , 5c , 5d , 5e , 5f (43–71%), or methyl 6‐oxo‐3,4‐dihydro‐2H,6H‐pyrido[2,1‐b]‐1,3‐oxazine‐7‐carboxylates 7a , 7b , 7c , 7d , 7e , 7f (32–59%), respectively. In these reactions, 1a , 1b , 1c , 1d , 1e , 1f (cyclic imidates, iminoethers) functioned as their N,C‐tautomers (enaminoethers) 2 to α,β‐unsaturated esters 2 , 4, and 6 to give annulation products 3 , 5 , and 7 following to the elimination of methanol, respectively. J. Heterocyclic Chem., (2011).     

Oxidative esterification of methylarenes and 1,3‐dicarbonyls catalysed by copper chloride immobilized on magnetic nanoparticles

Superparamagnetic CuCl nanoparticles were prepared and identified as an effective heterogeneous catalyst for the tandem transformation of methylarenes and 1,3‐dicarbonyl compounds into the corresponding enole esters by the use of tert ‐butyl hydroperoxide as an external oxidant. The catalyst can be removed from the reaction medium simply by use of an external magnet. As a consequence, various derivatives of enol esters were synthesized in moderate to good yields.     

Metal‐Free Oxidative Radical Addition of Carbonyl Compounds to α,α‐Diaryl Allylic Alcohols: Synthesis of Highly Functionalized Ketones

A metal‐free direct alkylation of simple carbonyl compounds (ketones, esters, and amides) with α,α‐diaryl allylic alcohols is described. The protocol provides facile access to highly functionalized dicarbonyl ketones by a radical addition/1,2‐aryl migration cascade. The regioselectivity of the reaction was precisely controlled by the nature of the carbonyl compound.     

Intramolecular Cooperative CC Bond Cleavage Reaction of 1,3‐Dicarbonyl Compounds with 2‐Iodoanilines to Give o‐(N‐Acylamino)aryl Ketones and Multisubstituted Indoles

A copper‐catalyzed C?C bond cleavage reaction of 1,3‐dicarbonyl compounds with 2‐iodoanilines was developed. In this process, the ortho effect played an important role in the reactivity and a new reaction pathway that involved a (2‐aminophenyl)‐bis‐(1,3‐dicarbonyl) copper species was clearly observed by a time‐course HRMS analysis of the reaction mixture. Unlike the previous reports, both the nucleophilic and electrophilic parts of the 1,3‐dicarbonyl compound were coupled with 2‐iodoaniline by C?C bond cleavage to form o‐(N‐acylamino)aryl ketones, which could be efficiently converted into multisubstituted indoles.     

Palladium‐Catalyzed Oxidative C≡C Triple Bond Cleavage of 2‐Alkynyl Carbonyl Compounds Toward 1,2‐Dicarbonyl Compounds†

A new, general palladium‐catalyzed oxidative strategy for the cleavage of the C≡C triple bond is presented. By employing PdCl₂, CuBr₂, TEMPO and air as the catalytic system and H₂O as the carbonyl oxygen atom source, a wide range of 2‐alkynyl carbonyl compounds, including 1,3‐disubstituted prop‐2‐yn‐1‐ones, propiolamides and propiolates, lost an alkynyl carbon to access various 1,2‐dicarbonyl compounds, e.g., 1,2‐diones, 2‐keto amides and 2‐keto esters, through Wacker oxidation, intramolecular cyclization and C—C bond cleavage cascades.     

Efficient one pot preparation of variously substituted thieno [2,3‐b] thiophene

An efficient one pot access to variously substituted thieno[2,3‐b]thiophene is described. The title compounds were obtained from 1,3‐dicarbonyl or equivalent compounds, carbon disulfide and halomethyl derivatives in good to high yields and fully characterized.     

Cascade Mn‐Mediated γ‐Alkylation/oxa‐Michael Addition of Enones with 1,3‐Dicarbonyls

A radical‐based strategy for regioselective γ‐C?C bond formation/oxa‐conjugate addition, forming the tetrahydrobenzofuran core common to many bioactive natural products is described. The technique utilizes readily available enone derivatives and 1,3‐dicarbonyl compounds as coupling partners in an oxidative formal [3+2] cycloaddition mediated by Mn^III. The transformation delivers polycyclic products in good yields and proceeds with complete regiocontrol and excellent stereoselectivity. Sterically encumbered substrates are notably well‐tolerated and bond formation occurs readily to form neopentyl and all‐carbon quaternary centers in good yields. Several stereo‐ and chemoselective transformations of the products are described.     

N‐Heterocyclic Carbene Catalyzed Synthesis of δ‐Sultones via α,β‐Unsaturated Sulfonyl Azolium Intermediates

A limited array of reactive intermediates have enabled a wealth of discoveries in N‐heterocyclic carbene organocatalysis. In this study, the viability of α,β‐unsaturated sulfonyl azoliums as double electrophiles in new reactions is examined. Specifically, the (3+3) annulation of such species with the trimethylsilyl enol ethers of various 1,3‐dicarbonyl compounds has been developed. This reaction provides access to a range of novel unsaturated δ‐sultones (18 examples) in good yields (40–88 %) under mild reaction conditions. Mechanistic studies and the development of an enantioselective variant (55 % yield, 73:27 e.r.) support the intermediacy of an α,β‐unsaturated sulfonyl azolium species.     

Synthesis of Pyrrolidines and Pyrrolizidines with α‐Pseudoquaternary Centers by Copper‐Catalyzed Condensation of α‐Diazodicarbonyl Compounds and Aryl γ‐Lactams

N‐aryl γ‐lactams react intermolecularly with acceptor–acceptor diazo reagents, usually dicarbonyl compounds, in a copper‐catalyzed process to yield functionalized pyrrolidines with α‐pseudoquaternary centers. As 1,2‐acyl or ‐phosphoryl migration is preferred, single regioisomers are obtained. Furthermore, in the presence of a Lewis acid, subsequent Friedel–Crafts reactions yield tricyclic pyrrolizidines in excellent yields (90–96 %) and diastereoselectivities (up to >20:1).