Rubén Vicente

Recent advances in indole syntheses: New routes for a classic target

Indoles are the most abundant heterocycles in biologically active natural products, pharmaceuticals, agrochemicals, and are relevant substructures in functional materials. As a result, the development of methodologies that enable the synthesis of these compounds is continuously demanded. This review summarizes most recent and relevant approaches towards the preparation of this prevalent structural motif.

Gold-catalyzed synthesis of tetrahydrocarbazole derivatives through an intermolecular cycloaddition of vinyl indoles and N-allenamides.

A gold-catalyzed formal [4+2] cycloaddition of vinyl indoles and N-allenamides leading to tetrahydrocarbazoles is described. Moreover, new multicomponent reactions of vinyl indoles with two allene molecules are reported.

Gold‐Catalyzed Functionalization of Unactivated C(sp3)H Bonds by Hydride Transfer Facilitated by Alkynylspirocyclopropanes

Transition-metal-catalyzed coupling reactions involving unactivated C(sp) H bonds constitute one of the most active research areas in both industry and academia. 2] In particular, the development of methods that enable C C bond formations through the selective cleavage of ubiquitous C(sp) H bonds is highly desirable as it allows for new retrosynthetic disconnections, thus minimizing the number of steps and the generation of waste. A major drawback of this transformation lies in the control of the selectivity. In general, selective functionalizations are achieved by the assistance of directing groups that bring the catalyst closer to the desired C H bond. Alternatively, good control of the selectivity has been reported by the intramolecular thermal or Lewis acid catalyzed 1,5-hydride transfer reaction (HT). In contrast to hydride transfer to electron-poor alkenes, the use of electronically unbiased alkynes as acceptor partners requires the assistance of platinum or gold catalysts. Thus, a variety of goldor platinum-catalyzed cleavages of C(sp) H bonds through intramolecular HT to alkynes have been described recently by the groups of Sames, Gagosz, and others. As a carbocation is initially generated, this strategy has been limited to C(sp) H bonds bearing a stabilizing functionality at the a position (OR, NR2, aryl; Scheme 1a). Considering this limitation, hydride transfer to alkynes from aliphatic, nonbenzylic, positions constitutes a challenging transformation. As part of our research into the synthesis and reactivity of alkynylcyclopropane derivatives, 10] we have recently reported the synthesis of spiro[2,4]heptane derivatives 1 whose particular structure makes them amenable for use in investigations of new metal-catalyzed processes. These compounds have severe geometrical restrictions that place an inactive methylene group close to the alkyne moiety. We hypothesized that this restricted geometry might facilitate the 1,5-hydride transfer to a metal-activated alkyne (Scheme 1b). Herein, we disclose a new gold-catalyzed hydride transfer from an unactivated C(sp) H bond to an alkyne, and the subsequent selective cyclizations. Initially, we studied the reactivity of spirane 1a in the presence of various gold catalysts. We were pleased to find that a high conversion of 1a was achieved when using cationic gold complex [(IPr)Au(NTf2)] in 1,2-dichloroethane (70 8C, 24 h; Scheme 2), thus yielding a mixture of compounds 2–4a (80 % conv., 2a/3a/4a = 2.5:1:1).

Gold‐Catalyzed Rearrangements: Reaction Pathways Using 1‐Alkenyl‐2‐alkynylcyclopropane Substrates

) allowed to design useful trans-formations based on the cleavage of the cyclopropane ring.Inthisscenario,itseemedtousthatthecatalytictransformationsof substrates containing the alkene–cyclopropane–alkyneconnectivity might be a promising approach. Surprisingly,transformations based on the 1-alkenyl-2-alkynylcyclopro-pane framework (1,5-enyne arrangement) are very rare.

Mechanistic Studies on the Rearrangement of 1‐Alkenyl‐2‐alkynylcyclopropanes: From Allylic Gold(I) Cations to Stable Carbocations

An allylic gold(I) cation, proposed as key intermediate in the gold-promoted rearrangement of 1,5-enynes bearing a fixed conformation, has been detected and characterized by NMR spectroscopy. Moreover, its participation in the overall transformation was confirmed. Computational studies indicate that the gold-catalyzed transformation occurs through an uncommon rearrangement. Additionally, this study led us to isolate and characterize a stable homoantiaromatic carbocation.

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.

Zinc‐Catalyzed Functionalization of SiH Bonds with 2‐Furyl Carbenoids through Three‐Component Coupling

A three-component coupling of alk-2-ynals, 1,3-dicarbonyls and silanes is reported. ZnCl2 serves as an inexpensive and low-toxic catalyst for the overall transformation, which involves Knoevenagel condensation, cyclization, and carbene Si-H bond insertion. The process takes place with high atom economy in the absence of organic solvents and shows a broad scope. This reaction is also applicable to the functionalization of oligomeric siloxanes.

Manganese‐Mediated C−H Alkylation of Unbiased Arenes Using Alkylboronic Acids

The alkylation of arenes is an essential synthetic step of interest not only from the academic point of view but also in the bulk chemical industry. Despite its limitations, the Friedel-Crafts reaction is still the method of choice for most of the arene alkylation processes. Thus, the development of new strategies to synthesize alkyl arenes is a highly desirable goal, and herein, we present an alternative method to those conventional reactions. Particularly, a simple protocol for the direct C-H alkylation of unbiased arenes with alkylboronic acids in the presence of Mn(OAc)3 ⋅2H2 O is reported. Primary or secondary unactivated alkylboronic acids served as alkylating agents for the direct functionalization of representative polyaromatic hydrocarbons (PAHs) or benzene. The results are consistent with a free-radical mechanism.

Zinc-catalyzed Meinwald rearrangement of tetrasubstituted 1-alkynyloxiranes to tertiary α-alkynylketones

Easy access to tertiary α-alkynylketones via a Meinwald-type rearrangement of 1-alkynyloxiranes is reported. This transformation is selectively accomplished with an economical zinc catalyst.

Zinc-Catalyzed Synthesis of Conjugated Dienoates through Unusual Cross-Couplings of Zinc Carbenes with Diazo Compounds

Zinc-catalyzed selective cross-coupling of two carbene sources, such as vinyl diazo compounds and enynones, enabled the synthesis of conjugated dienoate derivatives. This reaction involved the unprecedented coupling of a zinc furyl carbene with vinyl diazo compounds through the γ-carbon. Alternatively, dienoates were also prepared by a commutative cross-coupling of zinc vinyl carbenes generated from cyclopropenes and simple diazo compounds.