Javier Santamaría

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.

Sequential Five-Component Construction of the Cyclopenta(e)- (1,3)oxazine Skeleton using Stable 2-Azetine Derivatives**

Small-ring heterocycles are of prominent importance because of their potential as bioactive compounds and synthetic building blocks. Whilst the chemistry of three-membered nitrogen heterocycles has been widely reported, studies on their four-membered counterparts have focused primarily on 2-azetidinones and, to a much lesser extent, azetidine rings. The 2-azetine system 1,2-dihydroazete, which has a strained cyclic enamine ring, is particularly elusive. Most 2-azetine compounds undergo spontaneous electrocyclic ring opening to afford their 1-azadiene analogues; as such, there are few examples of stable 2-azetines in the literature and those reported require electron-withdrawing substituents, for example, carbonyl, carboxyl, sulfonyl, or nitro groups, attached to the nitrogen atom. As a consequence, the chemistry of 2azetines remains largely unexplored, and has been predominantly focused on their potential as a precursor to azadienes. Moreover, there are no general synthetic routes to 2azetines. Although, the [2+2] cycloaddition of alkynes and imines appears to be a convenient route to this type of heterocyclic framework, only a few specific examples have been reported; in these cases, electron-rich alkynes, as ynamines, alkynyl selenides, or alkynyl sulphides, are able to form the expected 2-azetine skeleton, which is not isolated but rapidly opens to the azadiene system. The [2+2] cycloaddition of electron-poor alkynes and imines has only previously been suggested as an intermediate in the cyclization reaction between an alkynyl(ethoxy)carbene of tungsten and imine fluorenones to afford pyrroline derivatives. As part of our interest in Fischer-type metal carbenes, we have recently considered more-electrophilic metal carbenes, the so-called non-heteroatom-stabilized carbenes. These compounds are particularly useful in organic synthesis, and our preliminary results have revealed significant differences in the reactivity of both heteroatomand non-heteroatomstabilized systems. Herein, we report the [2+2] cycloaddition reaction of alkynyl-substituted (pentacarbonyl)chromium or -tungsten carbene complexes with imines as a suitable procedure for accessing stable 2-azetine derivatives. Moreover, the conjugation of the resulting azetine unit with the metal carbene allows for a facile synthesis of novel cyclopenta[e][1,3]oxazines involving treatment with alkynes. This threecomponent process (azetine, alkyne, and CO ligand) features cleavage of the azetine C3 C4 bond, rather than the expected N C4 bond, and the formation of three C C bonds and one C O bond (Scheme 1).

The first [4 + 3] annulation of Fischer carbene complexes with azadienes: facile synthesis of azepines

The reaction of 3-iminoprop-1-enylamines 1 with pentacarbonyl(1-methoxyprop-2-enylidene)chromium(0) complexes leads stereoselectively to substituted 5H-6,7-dihydroazepines in high yields; the process takes place at low temperature and is thought to involve a tandem imine cyclopropanation–Cope rearrangement.

A facile and diastereoselective access to substituted cyclopentanones from Fischer alkenyl carbene complexes and 1-amino-1-azadienes

Abstract Fischer alkenyl carbene complexes 1 undergo cyclopentannulation to alkenyl N , N -dimethylhydrazones (1-amino-1-azadienes) 2 to furnish substituted cyclopentenes 3 (45–55%) in a regio and diastereoselective way, along with minor amounts of pyrroles 4 (25–28%). Enantiopure carbene complexes derived from (−)-8-phenylmenthol 7a and (−)-8-(2-naphthyl)menthol 7b afforded, in addition to pyrrole 4a (12–15%), trans , trans -cyclopentenes 8 / 9 (35–43%) and cis , cis -cyclopentenes 10 / 11 (23–25%) with fairly to excellent face selectivity (78% for 7a and 92% for 7b ).

Gold(I)-Catalyzed Addition of Silylacetylenes to Acylsilanes: Synthesis of Indanones by CH Functionalization through a Gold(I) Carbenoid

A gold(I)-catalyzed synthesis of indanones from trimethylsilylacetylenes and acylsilanes is presented. The reaction is initiated through a synergistic acylsilane activation-gold acetylide formation and involves consecutive alkyne σ-gold(I) addition, π-activation, and 1,2-migration of a silyl group. Studies performed on the reaction mechanism allowed to establish the nature of the silyl migrating group and invoke the participation of a gold(I) carbenoid intermediate. The reaction is completed by a gold(I) C-H functionalization step.

Intermolecular and Regioselective Access to Polysubstituted Benzo- and Dihydrobenzo[c]azepine Derivatives: Modulating the Reactivity of Group 6 Non-Heteroatom-Stabilized Alkynyl Carbene Complexes

We highlight the versatility of non-heteroatom-stabilized tungsten-carbene complexes 3 synthesized in situ, which have been used in a modular approach to access 2-benzazepinium isolable intermediates 5. By employing very mild conditions, benzazepinium derivatives 5 have been obtained in high yield from simple compounds, such as acetylides 2, Fischer-type alkoxycarbenes 1, and phenylimines 4. The process, involving a formal [4+3] heterocycloaddition, occurs in a totally regioselective manner, which differs from the approach previously observed in similar procedures for other carbene analogues. This work, which involves three components, reveals a control of the reactivity of non-heteroatom-stabilized carbene complexes 3 ([4+3] vs. [2+2]-heterocycloaddition reactions) depending on the acetylide substitution pattern. The influence of the substitution pattern in the behavior of the complexes has been computationally analyzed and rationalized. Finally, elaboration of the 2-benzazepinium intermediates allows access to 3H-benzo[c]azepines 6 and 3H-1,2-dihydrobenzo[c]azepines 7-9 with high control of the substitution of the nine positions of the heterocycle.

Beyond Fischer and Schrock carbenes: non-heteroatom-stabilized group 6 metal carbene complexes – a general overview

Non-heteroatom-stabilized group 6 metal carbene complexes are a particular type of Fischer carbene complex that lacks stabilizing heteroatoms. The aim of this review is to provide a comprehensive overview of the usefulness of these organometallic reagents in organic synthesis. Thus, the diverse methodologies that have been developed for their synthesis are initially disclosed, followed by their reactivities. In this regard, the decisive role of these complexes in early studies of alkene metathesis and cyclopropanation and enyne metathesis is highlighted, as well as their participation in insertion reactions. However, the major part of the review highlights recent achievements in both stoichiometric and catalytic processes, which have led to the synthesis of structurally diverse carbo- and heterocycles, acyclic compounds, and even metal carbene complexes of other groups by transmetallation reactions.

Understanding the Mechanism of the Divergent Reactivity of Non-Heteroatom-Stabilized Chromium Carbene Complexes with Furfural Imines: Formation of Benzofurans and Azetines

The mechanisms of the reaction between non-heteroatom-stabilized alkynyl chromium carbene complexes prepared in situ and furfural imines to yield benzofurans and/or azetines have been explored by means of density functional theory method calculations. The reaction proceeds through a complex cascade of steps triggered by a nucleophilic addition of the imine nitrogen atom. The formation of two benzofuran regioisomers has been explained in terms of competitive nucleophilic attacks to different positions of the carbene complex. Each of these regioisomers can be obtained as the major product depending on the starting materials. The overall sequence could be controlled to yield benzofurans or azetines by adjusting the substituents present in the initial carbene complex. This mechanistic information allowed for the preparation of new benzofurans and azetinylcarbenes in good yields.

Unexpected [4 + 2] Cycloaddition through Chromium Non-Heteroatom-Stabilized Alkynyl Carbene Complexes: Regioselective Access to Substituted 6-Azaindoles

A formal [4 + 2] heterocycloaddition of non-heteroatom-stabilized alkynyl carbene complexes and iminopyrroles is described. The reaction implies a totally regioselective synthesis of 6-azaindole derivatives through the formation of the pyridine ring. The mechanism of the reaction has been explored by means of density functional theory calculations, which showed a preference for the [4 + 2] cycloaddition instead of the [2 + 2] or [3 + 3] cycloadditions observed with other imines. The structure of the products also shows an unusual connectivity pattern from carbene complexes.