Metal‐Mediated [2+3] Cycloaddition of Nitrones to Palladium‐Bound Isonitriles

[2+3] Cycloadditions! The metal‐mediated [2+3] cycloaddition of acyclic [^?O⁺N(R²)?(H)R³] and nonaromatic cyclic nitrones [^?O⁺N^a?CHCH₂CH₂C^bMe₂(N^a? C^b)] to palladium‐bound isonitriles cis‐[PdCl₂(C?NR)₂] proceeds under mild conditions to furnish novel heterocyclic carbene complexes, which then undergo N? O bond rupture to give imino complexes and free isocyanates (see scheme).

     

Ln[N(SiMe3)2]3‐Catalyzed Cross‐Diinsertion of CN/CC into an NH Bond: Facile Synthesis of 1,2,4‐Trisubstituted Imidazoles from Propargylamines and Nitriles

A lanthanide‐catalyzed sequential insertion of C?N and C?C into an N?H bond is presented. The convenient reaction, which proceeds under mild conditions, is an efficient method for preparing 1,2,4‐trisubstituted imidazoles directly from readily available propargylamines and nitriles.     

Heteroannulation of Arynes with α‐Amino Imides: Synthesis of 2,2‐Disubstituted Indolin‐3‐ones and Application to the Enantioselective Total Synthesis of (+)‐Hinckdentine A

A novel heteroannulation reaction between α‐amino imides and in situ generated arynes has been developed for the synthesis of 2,2‐disubstituted indolin‐3‐ones. An enantioselective total synthesis of the marine alkaloid (+)‐hinckdentine A was subsequently accomplished using this reaction as a key step. A catalytic enantioselective Michael addition of an α‐aryl‐α‐isocyanoacetate to phenyl vinyl selenone was employed for the construction of the enantioenriched α‐quaternary α‐amino ester.     

De Novo Synthesis of Imidazoles by Visible‐Light‐Induced Photocatalytic Aerobic Oxidation/[3+2] Cycloaddition/Aromatization Cascade

A visible‐light‐induced photocatalytic aerobic oxidation/[3+2] cycloaddition/aromatization cascade between secondary amines and isocyanides has been successfully developed. The reaction provides a general and efficient access to diversely substituted imidazoles and imidazo[1,5‐a]quinoxalin‐4(5 H)‐ones in good yields under mild conditions.     

Construction of Spirocyclic Oxindoles through Regio‐ and Stereoselective [3+2] or [3+2]/[4+2] Cascade Reaction of α,β‐Unsaturated Imines with 3‐Isothiocyanato Oxindole

On the basis of asymmetric regioselective [3+2] or [3+2]/[4+2] cascade reaction of 3‐isothiocyanato oxindoles with C=C and C=N bonds of α,β‐unsaturated methanesulfonamides, diversified S‐containing heterocyclic spirooxindole derivatives could be obtained in high yields along with good to excellent diastereo‐ and enantioselectivities under mild conditions in the presence of cinchona alkaloid‐derived organocatalysts.     

Donor/Acceptor‐Stabilized 1‐Silaketene: Reversible [2+2] Cycloaddition with Pyridine and Evolution by an Olefin Metathesis Reaction

The reaction of silacyclopropylidene 1 with benzaldehyde generates a 1‐silaketene complex 2 by a formal atomic silicon insertion into the C=O bond of the aldehyde. The highly reactive 1‐silaketene 2 undergoes a reversible [2+2] cycloaddition with pyridine to give sila‐β‐lactam 3 . Of particular interest, in the presence of 4‐dimethylaminopyridine (DMAP), 1‐silaketene complex 2 evolves through an intramolecular olefin metathesis reaction, generating a new 1‐silaketene complex 8 and cis‐stilbene. Theoretical studies suggest that the reaction proceeds through the formation of a transient silacyclobutanone, a four‐membered‐ring intermediate, similar to that proposed by Chauvin and co‐workers for the transition‐metal‐based olefin metathesis.     

Gold‐Catalyzed [2+2+1] Cycloaddition of 1,6‐Diyne Carbonates and Esters with Aldehydes to 4‐(Cyclohexa‐1,3‐dienyl)‐1,3‐dioxolanes

A synthetic method to stereoselectively prepare 4‐(cyclohexa‐1,3‐dienyl)‐1,3‐dioxolanes in good to excellent yields by gold(I)‐catalyzed [2+2+1] cycloaddition of 1,6‐diyne carbonates and esters with aldehydes is described. The cascade process involves 1,2‐acyloxy migration followed by cyclopropenation and cycloreversion. This leads to an unprecedented [2+2+1] cycloaddition of the resulting alkenylgold carbenoid species, examples of which are extremely rare, with two aldehyde molecules at catalyst loadings as low as 1 mol %. The usefulness of this cycloisomerization chemistry was further demonstrated by the transformation of one example to the corresponding phenol.     

Highly Stereoselective [4+2] and [3+2] Spiroannulations of 2‐(2‐Oxoindolin‐3‐ylidene)acetic Esters Catalyzed by Bifunctional Thioureas

A new Michael–Michael cascade reaction between 2‐(2‐oxoindolin‐3‐ylidene)acetic esters 1 and nitroenoates 2 , catalyzed by bifunctional thioureas, is investigated. The combination of the two Michael reactions results in a novel and facile [4+2] or [3+2] spiroannulation process, which is characterized by the following features: 1) two carbon–carbon bonds and four stereocenters, including a quaternary spiro carbon, are formed under mild conditions; 2) an unprecedented and stereochemically defined substitution pattern on the spirocarbocyclic unit is obtained; 3) the double‐bond configuration of the donor–acceptor nitroenoate 2 determines the absolute configuration of the spiro center, whereas the remaining stereocenters are formed under control of the catalyst. The effect on the final stereochemical outcome of structural variations of each starting material, catalyst, and experimental conditions is analyzed in detail. In particular, the use of specifically designed chiral nitroenoates enables diverse polyfunctional spirocyclohexane derivatives containing six consecutive stereogenic centers to be constructed. To our knowledge, this is the first asymmetric organocatalytic strategy enabling both five‐ and six‐membered β‐nitro spirocarbocyclic oxindoles.     

NHC/Nickel(II)‐Catalyzed [3+2] Cross‐Dimerization of Unactivated Olefins and Methylenecyclopropanes

Cross‐dimerization of a methylenecyclopropane ( 1 ) and an unactivated alkene ( 2 ) with typical hydroalkenylation reactivity was observed for the first time by using a [NHC‐Ni(allyl)]BAr^F catalyst (NHC=N‐heterocyclic carbene). Results show that the C?C cleavage of 1 did not involve a Ni⁰ oxidative addition, which was crucial in former systems. Thus the method reported here emerges as a complementary method for attaining highly chemo‐ and regioselective synthesis of methylenecyclopentanes ( 3 ) with broad scope. An efficient NHC/Ni^II‐catalyzed rearrangement of 1 leads to the convergent synthesis of 3 in the presence of 2 .     

Catalytic Divergent [3+3]‐ and [3+2]‐Cycloaddition by Discrimination Between Diazo Compounds

Highly selective divergent cycloaddition reactions of enoldiazo compounds and α‐diazocarboximides catalyzed by copper(I) or dirhodium(II) have been developed. With tetrakis(acetonitrile)copper(I) tetrafluoroborate as the catalyst epoxypyrrolo[1,2‐a]azepine derivatives were prepared in good yields and excellent diastereoselectivities through the first reported [3+3]‐cycloaddition of a carbonyl ylide. Use of Rh₂(pfb)₄ or Rh₂(esp)₂ directs the reactants to regioselective [3+2]‐cycloaddition generating cyclopenta[2,3]pyrrolo[2,1‐b]oxazoles with good yields and excellent diastereoselectivities.     

Silver‐Catalyzed Isocyanide–Isocyanide [3+2] Cross‐Cycloaddition Involving 1,2‐Group Migration: Efficient Synthesis of Trisubstituted lmidazoles

Imidazole ring is an important five‐membered aromatic heterocycle that is widely present in natural products and synthetic molecules. The isocyanide–isocyanide [3+2] cross‐cycloaddition reaction constitutes a straightforward method to access imidazoles starting from the easily available chemicals. So far, only three successive reports are known and all lead to the formation of 1,4‐disubstituted imidazoles. Here, we report the first isocyanide–isocyanide [3+2] cross‐cycloaddition reaction allowing for the formation of 1,4,5‐trisubstituted imidazoles under silver catalysis. An unexpected 1,2‐migration of sulfonyl, alkoxycaybonyl, and carbamoyl groups took place during the cyclization process that is responsible for the formation of trisubstituted imidazoles. This report displayed a mechanistically novel synthetic method toward a variety of imidazole derivatives, which are otherwise difficult to access by conventional methods.     

Stereoselective [4+2]‐Cycloaddition with Chiral Alkenylboranes

A method for the stereoselective [4+2]‐cycloaddition of alkenylboranes and dienes is presented. This transformation was accomplished through the introduction of a new strategy that involves the use of chiral N‐protonated alkenyl oxazaborolidines as dieneophiles. The reaction leads to the formation of products that can be readily derivatized to more complex structural motifs through stereospecific transformations of the C?B bond such as oxidation and homologation. Detailed computation evaluation of the reaction has uncovered a surprising role of the counterion on stereoselectivity.     

Dearomatization of 3‐Nitroindoles by a Phosphine‐Catalyzed Enantioselective [3+2] Annulation Reaction

The dearomatization of 3‐nitroindoles through a chiral‐phosphine‐mediated [3+2] annulation reaction is described. This method makes use of readily available 3‐nitroindoles as an aromatic feedstock and rapidly delivers a wide range of cyclopentaindoline alkaloid scaffolds in a highly enantioselective manner. Notably, phosphine‐triggered cyclization has not been utilized previously in a dearomatization process.