Amparo Luna

Grubbs’ Ruthenium-Carbenes Beyond the Metathesis Reaction: Less Conventional Non-Metathetic Utility

ed via -hydride elimination, collapsing into the 1,3diene derivative 419. Alternatively, the formation of this product might be interpreted as a result of the direct thermal ene-type reaction of allenenes 418. To understand the latter process, compound 418b was refluxed in CH2Cl2 without the catalyst Ru-2 for a prolonged time, but no reaction took place. In addition, when heated at higher temperature (refluxing in toluene or xylene), the thermal [2 + 2]-cycloaddition between the terminal olefin and the distal double bond of the allenyl moiety furnished the corresponding cyclobutane derivative. When trienyne 421 was subjected to ring-closing metathesis reaction conditions using the second-generation Grubbs’ catalyst Ru-2, an unusual nonmetathetic activity was observed, with the cycloisomerization product being obtained as the major product. The main fraction of the reaction of trienyne 421 was found to be a mixture of the metathesis product 422 and the cycloisomerization adduct 423 (1:2 ratio) in 45% combined yield. Besides 422 and 423, a minor product 424 was isolated (11%) along with starting material 421 (6.5%). When the Hoveyda-Grubbs’ catalyst Ru-3 was used, further cycloisomerization occurred and all that was isolated was a mixture of 422 and 423 in a 1:4 ratio (45% yield) and 421 (6.5%) (Scheme 132).109 This result suggested that the alkyne was more reactive toward the ruthenium-carbene complex than the terminal alkene for trienyne 421. Therefore, initial coordination preferentially occurred at the alkyne to give the metallacyclopentene 425 (path a). Scheme 138. Vinylcyclopropane Epimerization Catalyzed by Carbene Ru-1 Scheme 139. Tandem RCM-Dehydration Catalyzed by Ru-1a 3854 Chemical Reviews, 2009, Vol. 109, No. 8 Alcaide et al.

Controlled rearrangement of lactam-tethered allenols with brominating reagents: a combined experimental and theoretical study on α- versus β-keto lactam formation.

N-Bromosuccinimide (NBS) smoothly promotes the ring expansion of lactam-tethered allenols to efficiently afford cyclic α- or β-ketoamides with good yields and high chemo-, regio-, and diastereoselectivity, through controlled C-C bond cleavage of the β- or γ-lactam nucleus. Interestingly, in contrast to the rearrangement reactions of 2-azetidinone-tethered allenols, which lead to the corresponding tetramic acid derivatives (β-keto lactam adducts) as the sole products, the reactions of 2-indolinone-tethered allenols under similar conditions give quinoline-2,3-diones (α-keto lactam adducts) as the exclusive or major products. To rationalize the experimental observations, theoretical studies have been performed.

Ring enlargement versus selenoetherification on the reaction of allenyl oxindoles with selenenylating reagents.

Lactam-tethered allenols, readily prepared from α-oxolactams, were used as starting materials for divergent reactivity with selenenylating reagents. Either oxycyclization (spirocyclic selenolactams) or ring expansion (selenoquinolones) can be achieved through the choice of both reagents and substrates. The biological activity of some of the synthesized heterocycles has additionally been evaluated in four human cancer cell lines.

Metal-catalyzed rearrangements of 3-allenyl 3-hydroxyindolin-2-ones in the presence of halogenated reagents

The reactions of 3-allenyl 3-hydroxyoxindoles with a variety of halogenated reagents in the presence of catalytic amounts of precious metal salts were explored. Both, rearrangement and oxycyclization reactions to give 4-(1-halovinyl)-quinolinediones or spirocyclic halooxindoles, respectively, are competitive pathways. The kind of functionalization is substrate and reaction conditions dependent.

Direct FeX3-based stereocontrolled access to (Z)-3-alkenyl-oxindoles from allenols.

Iron trihalides (FeCl(3) and FeBr(3)) smoothly promote the halogenation/rearrangement of 2-indolinone-tethered allenols to efficiently afford 3-halodienyl-oxindoles with good yield and total selectivity. Also, 2-halo-1,3-dienes are synthetically interesting building blocks for the preparation of functionalized 3-alkenyl-oxindoles through a Suzuki-Miyaura reaction.

Gallium-Catalyzed Domino Arylation/Oxycyclization of Allenes with Phenols

The synthesis of dihydrobenzofuran-appended oxindoles has been accomplished taking advantage of an unprecedented reaction between allenols and phenols under metal catalysis.

An Alternative to Precious Metals: Hg(ClO4)2·3H2O as a Cheap and Water-Tolerant Catalyst for the Cycloisomerization of Allenols

Hg(ClO4)2·3H2O, a cheap, water-tolerant, and stable salt, catalyzes the cycloisomerization reaction or α-allenols to 2,5-dihydrofurans in an efficient and selective manner. The reaction is general and can be applied to differently functionalized substrates, including alkyl-substituted, aryl-substituted, enantiopure, and tertiary allenols. In addition, density functional theory (DFT) calculations were performed to obtain insight into various aspects of the controlled reactivity of α-allenols under mercury catalysis. They suggest a dual activation of the allenol by the Hg complex that drives the reaction to the chemoselective formation of 2,5-dihydrofurans.

Novel achievements with an old metal: copper-promoted synthesis of four-membered azacycles

The synthesis of four-membered azacycles is of importance because of the chemical and biological relevance of these compounds. Recent progress in copper-catalyzed reactions has been applicable to a variety of research fields, such as heterocyclic synthesis. The aim of the current review is to summarize the synthesis of strained four-membered ring taking advantage of copper catalyzed and mediated processes.

De Novo Synthesis of α-Hydroxy Ketones via Gallic Acid-Promoted Aerobic Coupling of Terminal Alkynes with Diazonium Salts

An unprecedented metal-free direct preparation of unprotected α-hydroxy ketones from terminal alkynes under mild conditions with diazonium salts as the arene source and without the requirement of irradiation is described. The process is general and fully compatible with a wide variety of substitution in both reactants. Experimental and computational evidence strongly suggest the involvement of radical species in the transformation.

Gold-Catalyzed Divergent Ring-Closing Modes of Indole-Tethered Amino Allenynes

Indole-tethered amino allenynes were chemodivergently cyclized for the controlled preparation of fused polycyclic indoles using gold catalysis. Double cyclization of terminal allenynes afforded hexacyclic 15 H-indolo[1,2,3-de]quinolino[3,2,1-ij]quinoxalines, in which allenynes bearing a substituted alkyne at the terminal end generated 12,13-dihydro-7 H-indolo[3,2-c]acridines, which are 5-membered cyclized adducts. Density functional theory calculations were performed to shed light on this difference in reactivity.