Catalytic Deoxygenative Cyclopropanation of 1,2-Dicarbonyl or Monocarbonyl Compounds via Molybdenum Catalysis

The cyclopropanation of alkenes through the transition-metal-catalyzed decomposition of diazo compounds is a powerful and straightforward strategy to produce cyclopropanes. Nevertheless, the appeal of further application of this strategy is tempered by the potentially explosive nature of the diazo substrates. Therefore, it is highly desirable to develop sustainable and operationally safe surrogates for diazo compounds. In this synpacts article, we discuss recent advances on the cyclopropane syntheses through the catalytic cyclopropanation of alkenes and metal-carbenes generated in-situ from non-diazo precursors, as well as highlight our recent progress on the unprecedented molybdenum-catalyzed deoxygenative cyclopropanation reaction of 1,2-dicarbonyl or monocarbonyl compounds.

Electrocyclizations of Conjugated Azapolyenes Produced in Reactions of Azaheterocycles with Metal Carbenes

Conjugated azapolyenes (azabuta-1,3-dienes, aza-/diaza-/oxaza-/oxadiazahexa-1,3,5-trienes) are highly reactive in electrocyclization reactions, which makes them convenient precursors for the synthesis of a wide range of four-, five-, and six-membered nitrogen heterocycles that are of relevance for medicinal chemistry. Ring opening reactions of 2H-azirines and azoles containing an N–N or N–O bond, initiated by a transition metal carbene, have become increasingly important in recent years, since they easily allow the generation of azapolyenes with different numbers of double bonds and heteroatoms in various positions. This review summarizes the literature, published mainly in the last decade, on the synthetic and mechanistic aspects of electrocyclizations of azapolyenes generated by the carbene method.

Assembling Complex Structures through Cascade and Cycloaddition Processes via Non-Acceptor Gold or Rhodium Carbenes

The ability of highly energetic metal-carbene intermediates to engage in complex cascade or formal-cycloaddition processes is one of the most powerful tools for building intricate molecular architectures in a straightforward manner. Among this type of organometallic intermediates, non-acceptor metal carbenes are particularly challenging to access and, therefore, have experienced a slower development. In this regard, our group has exploited the use of electrophilic gold(I) complexes to selectively activate certain classes of substrates and generate this type of intermediates. Thus, very different type of molecules, such as enynes or 7-substituted cyclohepatrienes, lead to the formation of carbenes under gold(I) catalysis. Related rhodium(II) carbenes can also be generated from cyclohepatrienes. In this account, we aim to summarize our efforts towards the in-situ generation of these highly versatile organometallic species, and the study of their reactivity through formal cycloadditions or complex cascade reactions.

Exporting metal-carbene chemistry to live mammalian cells: Cop-per-catalyzed intracellular synthesis of quinoxalines enabled by N-H carbene insertions

Harnessing the power of transition metal catalysis in biological settings, and especially inside living cells, can open a world of new opportunities in chemical and cell biology, as well as in biomedicine. Yet, advancing in this endeavor requires to address major chal-lenges associated to biocompatibility, transport and bioorthogonality issues, as well as the stability of the catalyst in these aqueous, crowded environments. This is especially relevant in reactions that involve the formation of organometallic intermediates that are considered labile, such as metal carbenes. Here, we demonstrate the viability of perform-ing catalytic metal carbene intermolecular transfer reactions inside live mammalian cells. In particular, we show that copper (II) catalysts can promote the intracellular an-nulation of alpha-keto diazocarbenes with ortho-amino arylamines, in a process that is initiated by the insertion of the carbene into the N-H bond of the substrate. The poten-tial of this transformation is underscored by the intracellular synthesis of a product that alters mitochondrial functions, and by demonstrating cell selective biological re-sponses using targeted copper catalysts. Considering the wide reactivity spectrum of metal carbenes, this work opens the door for significantly expanding the repertoire of reactions that can be performed in live environments and for unveiling new biological applications.

CpxM(III)-Catalyzed Enantioselective C–H Functionalization through Migratory Insertion of Metal-Carbenes/Nitrenes

CpxM(III)-catalyzed enantioselective C−H functionalization reactions have progressed rapidly using either chiral cyclopentadienyl ligands or appropriate chiral carboxylic acids. In this context, highly reactive carbene and nitrene precursors can be served...

Copper-catalyzed asymmetric cyclization of alkenyl diynes: method development and new mechanistic insights

Metal carbenes have proven to be one of the most important and useful intermediates in organic synthesis, but catalytic asymmetric reactions involving metal carbenes are still scarce and remain a...