José L. Mascareñas

Gold-Catalyzed [4C+2C] Cycloadditions of Allenedienes, including an Enantioselective Version with New Phosphoramidite-Based Catalysts: Mechanistic Aspects of the Divergence between [4C+3C] and [4C+2C] Pathways

Gold(I) complexes featuring electron acceptor ligands such as phosphites and phosphoramidites catalyze the [4C+2C] intramolecular cycloaddition of allenedienes. The reaction is chemo- and stereoselective, and provides trans-fused bicyclic cycloadducts in good yields. Moreover, using novel chiral phosphoramidite-based gold catalysts it is possible to perform the reaction with excellent enantioselectivity. Experimental and theoretical data dismiss a cationic mechanism involving intermediate II and suggest that the formation of the [4C+2C] cycloadducts might arise from a 1,2-alkyl migration (ring contraction) in a cycloheptenyl Au-carbene intermediate (IV), itself arising from a [4C+3C] concerted cycloaddition of the allenediene. Therefore, these [4C+2C] allenediene cycloadditions and the previously reported [4C+3C] counterparts most likely share such cycloaddition step, differing in the final 1,2-migration step.

Allenes as Three‐Carbon Units in Catalytic Cycloadditions: New Opportunities with Transition‐Metal Catalysts

Allenes are very versatile synthetic units that are used in many types of catalytic cycloaddition reactions. Most examples reported so far involve their use as 2C-atom components, whereas their participations as 3C-atom components have been much less frequent. In this concept article, we present an overview of this latter strategy, emphasizing on those more recent contributions involving the use of Pt(II) and Au(I) catalysts, which have uncovered new opportunities in this area.

Straightforward assembly of benzoxepines by means of a rhodium(III)-catalyzed C-H functionalization of o-vinylphenols.

Readily available o-vinylphenols undergo a formal (5 + 2) cycloaddition to alkynes when treated with catalytic amounts of [Cp*RhCl2]2 and Cu(OAc)2. The reaction, which involves the cleavage of the terminal C-H bond of the alkenyl moiety, generates highly valuable benzoxepine skeletons in a practical, versatile, and atom-economical manner. Using carbon monoxide instead of an alkyne as reaction partner leads to coumarin products which formally result from a (5 + 1) cycloaddition.

Metal-Catalyzed Annulations through Activation and Cleavage of C−H Bonds

The exponential increase in the number of catalytic transformations that involve a metal-promoted activation of hitherto considered inert C-H bonds is promoting a fundamental change in the field of synthetic chemistry. Although most reactions involving C-H activations consist of simple functionalizations or additions, recent years have witnessed an upsurge in related transformations that can be formally considered as cycloaddition processes. These transformations are particularly appealing from a synthetic perspective because they allow the conversion of readily available substrates into highly valuable cyclic products in a rapid and sustainable manner. In many cases, these annulations involve the formation of metallacyclic intermediates that resemble those proposed for standard metal-catalyzed cycloadditions of unsaturated precursors.

Recent developments in gold-catalyzed cycloaddition reactions

Summary In the last years there have been extraordinary advances in the development of gold-catalyzed cycloaddition processes. In this review we will summarize some of the most remarkable examples, and present the mechanistic rational underlying the transformations.

Axially chiral triazoloisoquinolin-3-ylidene ligands in gold(I)-catalyzed asymmetric intermolecular (4 + 2) cycloadditions of allenamides and dienes.

The first highly enantioselective intermolecular (4 + 2) cycloaddition between allenes and dienes is reported. The reaction provides good yields of optically active cyclohexenes featuring diverse substitution patterns and up to three stereocenters. Key to the success of the process is the use of newly designed axially chiral N-heterocyclic carbene-gold catalysts.

Rhodium(III)-catalyzed dearomatizing (3 + 2) annulation of 2-alkenylphenols and alkynes.

Appropriately substituted 2-alkenylphenols undergo a mild formal [3C+2C] cycloaddition with alkynes when treated with a Rh(III) catalyst and an oxidant. The reaction, which involves the cleavage of the terminal C–H bond of the alkenyl moiety and the dearomatization of the phenol ring, provides a versatile and efficient approach to highly appealing spirocyclic skeletons and occurs with high selectivity.

Gold-Catalyzed [4C+3C] Intramolecular Cycloaddition of Allenedienes: Synthetic Potential and Mechanistic Implications

Efficient at room temperature: The Au complex generated in situ from [(IPr)AuCl] and AgSbF(6) promotes the [4C+3C] intramolecular cycloaddition of allenes and dienes at room temperature, and in a particularly efficient and versatile manner. A DFT study on dimethylallenyl precursors agreed with the formation and cycloaddition of a metal-allyl cation intermediate, and points to the 1,2-hydride shift as the key rate-limiting step.

[4+2] and [4+3] catalytic cycloadditions of allenes

This feature review describes the development of catalytic [4+2] and [4+3] cycloadditions of allenes, as efficient and practical methodologies for assembling six and seven-membered cyclic systems. The different methodologies have been classified depending on the type of key reactive intermediate that was proposed in the catalytic cycle.

Rhodium(III)-catalyzed intramolecular annulations involving amide-directed C–H activations: synthetic scope and mechanistic studies

Alkyne tethered benzamides undergo rhodium(III)-catalyzed intramolecular annulations to give tricyclic isoquinoline derivatives in good yields. DFT calculations suggest that the reaction mechanism involves a migratory insertion of the alkyne into the rhodium–nitrogen bond of the rhodacycle intermediate that results from the initial C–H activation. This contrasts with the pathway proposed for intermolecular cases, which considers an insertion into the rhodium–carbon instead of the rhodium–nitrogen bond. The annulation is also effective with acrylamides; and, while anilides fail to participate in the process, naphthylamides do undergo the intramolecular annulation, albeit the chemoselectivity is different than for the intermolecular reactions.