Luis A. López

Pyridine Activation via Copper(I)-Catalyzed Annulation toward Indolizines

The copper(I)-catalyzed regioselective [3 + 2] cyclization of pyridines toward alkenyldiazoacetates leading to functionalized indolizine derivatives is reported. A broad range of pyridine derivatives (including quinoline and isoquinoline) is compatible with this cyclization reaction. The process represents the first successful example of metal-catalyzed cyclization of a π-deficient heterocyclic system with alkenyldiazo compounds.

Cu(I)-catalyzed regioselective synthesis of polysubstituted furans from propargylic esters via postulated (2-furyl)carbene complexes.

Polysubstituted furan derivatives are regioselective obtained from (bis-alkynyl)methyl carboxylates in the presence of catalytic amounts of copper(I) salts. This multistep process is consistent with the intermediacy of a copper(I) (2-furyl)carbene complex which is intercepted by suitable trapping reagents.

1,4-Cycloaddition of 1,3-diazabutadienes with enamines: an efficient route to the pyrimidine ring

Abstract [4+2] Cycloaddition reactions of 2-trimethylsilyloxy- and 2-trimethylsilylthio-1,3-diazabutadienes with enamines leading to pyrimidone derivatives are described.

Discrimination of Diazo Compounds Toward Carbenoids: Copper(I)‐Catalyzed Synthesis of Substituted Cyclobutenes

In the last few years the role of diazo compounds in organic synthesis, particularly in cyclization reactions via metal carbenoids (metal: ruthenium, copper, rhodium, etc.) has been prominent. By taking advantage of the ease with which these metal carbenes collapse into the corresponding symmetrical alkenes (homocoupling), we and others have been able to access nonsymmetrical alkenes by the selective heterocoupling of diazoacetate esters with copper(I) and ruthenium(II) carbene complexes [Eq. (1)]. Interestingly, the metal-catalyzed selective cross-coupling reaction between two different diazo substrates has been reported recently [Eq. (2)].

Reactivity of Stabilized Vinyl Diazo Derivatives toward Unsaturated Hydrocarbons: Regioselective Gold‐Catalyzed Carbon–Carbon Bond Formation

The transition-metal-catalyzed decomposition of simple and unsaturated a-diazo carbonyl derivatives and the subsequent transfer of the carbene unit to saturated and unsaturated substrates is one of the most popular and powerful tools in organic synthesis. In particular, the [2+1] cycloaddition of alkenes and alkynes is recognized as a straightforward and useful approach for the construction of three membered carbocycles. Extensive studies have led to the achievement of high levels of chemo-, diastereo-, and enantioselectivity by employing mostly complexes of copper and rhodium. In spite of the potential of gold catalysis in C C bond formation, the first example of gold-catalyzed carbene transfer from ethyl diazoacetate to unsaturated substrates was reported in 2005 by Nolan, D az-Requejo, P rez et al. After this seminal contribution, few gold-catalyzed transformations involving simple diazo substrates have been reported. On the other hand, the synthetic potential of vinyl diazo derivatives has been well established, particularly in the cycloaddition area, and the reactivity of the carbene carbon versus the vinylogous carbon found to be dependent, at least in part, on the metal catalyst. Continuing with our interest in the development of new transition-metal-catalyzed transformations of stabilized vinyl diazo derivatives, as well as in gold catalysis, we herein report the first studies of the gold-catalyzed reaction of alkenyldiazo compounds and neutral alkenes that results in the room temperature selective C C coupling between the Csp2ACHTUNGTRENNUNG(alkene) and the Cg(alkenyldiazo) atoms. From a synthetic point of view, the alkenyl diazo compound behaves as a ethoxycarbonyl allyl cation in this process, allowing the regioselective preparation of g-substituted, a,b-unsaturated carbonyl compounds (Figure 1). This reactivity pattern contrasts with that observed when other common sources of alkenylgold carbenoids, such as propargylic esters or cyclopropenes, are used (2 + 1 cycloaddition). Preliminary studies on the extension of this new gold-catalyzed carbon– carbon bond-forming process to alkynes and arenes are also reported. For our exploratory studies, we investigated ethyl 2-diazobut-3-enoate (1 a) and 1-hexene (2 a, 4 equiv) as substrates and a series of gold catalysts (5 mol %) in dichloromethane at room temperature. To our delight, we found that the use of IPrAuNTf2 gave (2E)-ethyl deca-2,6-dienoate 3 a in moderate yield (67 %) as a nonseparable 1:1 mixture of 2E,6E/ 2E,6Z diastereoisomers (Scheme 1). This unprecedented

Transmetalation Reactions from Fischer Carbene Complexes to Late Transition Metals: A DFT Study

Transmetalation reactions from chromium(0) Fischer carbene complexes to late-transition-metal complexes (palladium(0), copper(I), and rhodium(I)) have been studied computationally by density functional theory. The computational data were compared with the available experimental data. In this study, the different reaction pathways involving the different metal atoms have been compared with each other in terms of their activation barriers and reaction energies. Although the reaction profiles for the transmetalation reactions to palladium and copper are quite similar, the computed energy values indicate that the process involving palladium as catalyst is more favorable than that involving copper. In contrast to these transformations, which occur via triangular heterobimetallic species, the transmetalation reaction to rhodium leads to a new heterobimetallic species in which a carbonyl ligand is also transferred from the Fischer carbene to the rhodium catalyst. Moreover, the structure and bonding situation of the so far elusive heterobimetallic complexes are briefly discussed.

Zinc-catalyzed cyclopropenation of alkynes via 2-furylcarbenoids.

An unprecedented cyclopropenation reaction of alkynes catalyzed by ZnCl2 is reported. While Simmons-Smith-type carbenoids failed in the [2 + 1]-cycloaddition with alkynes, the use of enynones as the carbene source enables the preparation of substituted 2-furyl cyclopropene derivatives with remarkable scope.

Zinc‐Catalyzed Alkene Cyclopropanation through Zinc Vinyl Carbenoids Generated from Cyclopropenes

The zinc-catalyzed reaction of cyclopropenes with alkenes leading to vinylcyclopropane derivatives is reported. A broad range of alkenes (including highly substituted or functionalized alkenes) is compatible with this protocol. On the basis of trapping experiments and computational studies, this cyclopropanation reaction is proposed to proceed through initial formation of an electrophilic zinc vinyl carbenoid intermediate, which may be involved in a concerted cyclopropanation reaction. The reported protocol represents an unprecedented and simple strategy for the catalytic generation of zinc vinyl carbenoids, which are promising intermediates in organic synthesis.

Copper(I)‐Catalyzed [3+1] Cycloaddition of Alkenyldiazoacetates and Iminoiodinanes: Easy Access to Substituted 2‐Azetines

The copper(I)-catalyzed reaction of alkenyldiazoacetates and iminoiodinanes affords functionalized azetine derivatives. This process is consistent with the formation of an aziridinyldiazoacetate intermediate, which gives rise to the four-membered heterocycles by metal-catalyzed ring expansion. The resulting azetine structure is a direct precursor of azeditine-2-carboxylic acid derivatives (EWG = electron-withdrawing group).

Direct Access to β-Oxodiazo Compounds by Copper(II)-Catalyzed Oxidative Rearrangement of Stabilized Vinyl Diazo Derivatives

The copper(II)-catalyzed reaction of alkenyldiazo compounds with iodosylbenzene leading to β-oxodiazo derivatives is reported. This process occurs via an unprecedented 1,2-shift of the diazoacetate function. A selection of the synthetic applications of a representative member of this new class of functionalized diazo derivatives in the regioselective synthesis of substituted 1,4-dicarbonyl compounds is also reported.