Moisés Gulías

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.

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.

Rhodium‐Catalyzed (5+1) Annulations Between 2‐Alkenylphenols and Allenes: A Practical Entry to 2,2‐Disubstituted 2H‐Chromenes

Readily available alkenylphenols react with allenes under rhodium catalysis to provide valuable 2,2-disubstituted 2H-chromenes. The whole process, which involves the cleavage of one C-H bond of the alkenyl moiety and the participation of the allene as a one-carbon cycloaddition partner, can be considered a simple, versatile, and atom-economical (5+1) heteroannulation. The reaction tolerates a broad range of substituents both in the alkenylphenol and in the allene, and most probably proceeds through a mechanism involving a rhodium-catalyzed C-C coupling followed by two sequential pericyclic processes.

Nickel‐Catalyzed [3+2+2] Cycloadditions between Alkynylidenecyclopropanes and Activated Alkenes

Owing to the simultaneous presence of a coordinating double bond and a strained carbocycle, methyleneand alkylidenecyclopropanes (ACPs) undergo a number of interesting metal-assisted transformations. In this context, over the last few years, we have developed a variety of [3+n] palladium-catalyzed intramolecular cycloadditions of alkylidenecyclopropanes (such as 1), which provide practical entries to a variety of interesting bicycles (2 and 3, Scheme 1a). Very recently, we also showed that the introduction of an additional two-carbon partner into the system makes it possible to accomplish intramolecular [3+2+2] annulation reactions that lead to cycloheptanecontaining tricycles of type 4. In related studies, Evans and co-workers have elegantly demonstrated the possibility of using rhodium catalysts to induce intermolecular [3+2+2] processes (!3’, Scheme 1a). All of these reactions take place with cleavage of the distal bond of the ACP (C2 C3), and most probably proceed through the formation of 2alkylidene metallacyclobutane intermediates of type A, resulting from a distal insertion of the metal in the ACP (Scheme 1a). On the other hand, it has been shown that nickel complexes can promote alternative [3+2] and [3+2+2] annulations of ACPs, which involve the cleavage of a

Development of transition-metal-catalyzed cycloaddition reactions leading to polycarbocyclic systems*

We present a compilation of methodologies developed in our laboratories to assemble polycyclic structures containing small- and medium-sized cycles, relying on the use of transition-metal-catalyzed (TMC) cycloadditions. First, we discuss the use of alkylidenecyclopropanes (ACPs) as 3C-atom partners, in particular in their Pd-catalyzed (3 + 2) cycloadditions with alkynes, alkenes, and allenes, reactions that lead to cyclopentane-containing polycyclic products in excellent yields. Then, we present the expansion of this chemistry to a (4 + 3) annulation with conjugated dienes, and to inter- and intramolecular (3 + 2 + 2) cycloadditions using external alkenes as additional 2C-π-systems. These reactions allow the preparation of different types of polycyclic structures containing cycloheptene rings, the topology of the products depending on the use of Pd or Ni catalysts. Finally, we include our more recent discoveries on the development of (4 + 3) and (4 + 2) intramolecular cyclo-additions of allenes and dienes, promoted by Pt and Au catalysts, and discuss mechanistic insights supported by experimental and density functional theory (DFT) calculations. An enantioselective version of the (4 + 2) cycloaddition with phosphoramidite Au(I) catalysts is also presented.

Rhodium‐Catalyzed Intramolecular [3+2+2] Cycloadditions between Alkylidenecyclopropanes, Alkynes, and Alkenes

A Rh-catalyzed intramolecular [3+2+2] cycloaddition is reported. The cycloaddition affords synthetically relevant 5,7,5-fused tricyclic systems of type 2 from readily available dienyne precursors. The transformation takes place with moderate or good yields, high diastereoselectivity, and total chemoselectivity.

Concise, Enantioselective, and Versatile Synthesis of (−)‐Englerin A Based on a Platinum‐Catalyzed [4C+3C] Cycloaddition of Allenedienes

A practical synthesis of (-)-englerinu2005A was accomplished in 17u2005steps and 11u2009% global yield from commercially available achiral precursors. The key step consists of a platinum-catalyzed [4C+3C] allenediene cycloaddition that directly delivers the trans-fused guaiane skeleton with complete diastereoselectivity. The high enantioselectivity (99u2009%u2005ee) stems from an asymmetric ruthenium-catalyzed transfer hydrogenation of a readily assembled diene-ynone. The synthesis also features a highly stereoselective oxygenation, and a late-stage cuprate alkylation that enables the preparation of previously inaccessible structural analogues.

Iridium(I)-Catalyzed Intramolecular Hydrocarbonation of Alkenes: Efficient Access to Cyclic Systems Bearing Quaternary Stereocenters

A catalytic, versatile and atom-economical C-H functionalization process that provides a wide variety of cyclic systems featuring methyl-substituted quaternary stereocenters is described. The method relies on the use of a cationic IrI -bisphosphine catalyst, which promotes a carboxamide-assisted activation of an olefinic C(sp2 )-H bond followed by exo-cyclization to a tethered 1,1-disubstituted alkene. The extension of the method to aromatic and heteroaromatic C-H bonds, as well as developments on an enantioselective variant, are also described.

5.13 (4+3) Cycloadditions

Seven-membered rings form the basic skeleton of many relevant polycyclic products, and therefore there is a great interest in the development of practical and rapid strategies for their assembly. Among the different constructive strategies, (4+3) cycloadditions represent a particularly useful alternative because of the ready availability of four-carbon partners (dienes) and three-atom precursors. Many developments in the area, in particular those involving the use of oxyallyl cations as three-atom components, were achieved in the 1970s and 80s, and are collected in the first edition of Comprehensive Organic Synthesis in 1991. However, many other relevant advances, including new (4+3) cycloaddition tactics, have been reported since then. This chapter covers and discusses these advances from both a mechanistic and synthetic perspective. The different cycloaddition strategies have been organized on the basis of similar mechanistic features and/or common hypothetical intermediates. A section discussing ‘formal’ (4+3) annulations that involve sequential processes occurring via well-defined and even stable organic intermediates have also been included. Finally, a number of synthetic applications are also collected, so that the reader can perceive the current synthetic potential of the technology.

Rhodium(III)‐Catalyzed Annulation of 2‐Alkenyl Anilides with Alkynes through C−H Activation: Direct Access to 2‐Substituted Indolines

A RhIII complex featuring an electron-deficient η5 -cyclopentadienyl ligand catalyzed an unusual annulation between alkynes and 2-alkenyl anilides to form synthetically appealing 2-substituted indolines. Formally, the process can be viewed as an allylic amination with concomitant hydrocarbonation of the alkyne. Mechanistic experiments indicate that this transformation involves an unusual rhodium migration with a concomitant 1,5-H shift.