Joaquín García-Álvarez

A highly efficient copper(I) catalyst for the 1,3-dipolar cycloaddition of azides with terminal and 1-iodoalkynes in water: regioselective synthesis of 1,4-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles

A new water soluble Cu(I) complex that exhibits a versatile and high catalytic activity in the Huisgen cycloadditions of azides and terminal alkynes in aqueous media under mild conditions is the first well-defined Cu(I) catalyst that is active with 1-iodoalkynes in water under aerobic conditions.

Introducing Deep Eutectic Solvents to Polar Organometallic Chemistry: Chemoselective Addition of Organolithium and Grignard Reagents to Ketones in Air

Despite their enormous synthetic relevance, the use of polar organolithium and Grignard reagents is greatly limited by their requirements of low temperatures in order to control their reactivity as well as the need of dry organic solvents and inert atmosphere protocols to avoid their fast decomposition. Breaking new ground on the applications of these commodity organometallics in synthesis under more environmentally friendly conditions, this work introduces deep eutetic solvents (DESs) as a green alternative media to carry out chemoselective additions of ketones in air at room temperature. Comparing their reactivities in DES with those observed in pure water suggest that a kinetic activation of the alkylating reagents is taking place, favoring nucleophilic addition over the competitive hydrolysis, which can be rationalized through formation of halide-rich magnesiate or lithiate species.

Alkali-metal-mediated zincation (AMMZn) meets N-heterocyclic carbene (NHC) chemistry: Zn–H exchange reactions and structural authentication of a dinuclear Au(I) complex with a NHC anion

Merging two evolving areas in synthesis, namely cooperative bimetallics and N-heterocyclic carbenes (NHCs), this study reports the isolation of the first intermediates of alkali-metal-mediated zincation (AMMZn) of a free NHC and a Zn–NHC complex using sodium zincate [(TMEDA)NaZn(TMP)(tBu)2] (1) as a metallating reagent. The structural authentication of (THF)3Na[:C{[N(2,6-iPr2C6H3)]2CHCZn(tBu2)}] (2) and [Na(THF)6]+[tBu2Zn:C{[N(2,6-iPr2C6H3)]2CHCZn(tBu2)}]− (4), resulting from the reactions of 1 with unsaturated free NHC IPr (IPr = 1,3-bis(2,6-di-isopropylphenylimidazole-2-ylidene) and NHC complex ZntBu2IPr (3) respectively demonstrates that in both cases, this mixed-metal approach can easily facilitate the selective C4 zincation of the unsaturated backbone of the NHC ligand. Furthermore, the generation of anionic NHC fragments enables dual coordination through their normal (C2) and abnormal (C4) positions to the bimetallic system, stabilising the kinetic AMMZn intermediates which normally go undetected and provides new mechanistic insights in to how these mixed-metal reagents operate. In stark contrast to this bimetallic approach when NHC-complex 3 is reacted with a more conventional single-metal base such as tBuLi, the deprotonation of the coordinated carbene is inhibited, favouring instead, co-complexation to give NHC-stabilised [IPr·LiZntBu3] (5). Showing the potential of 2 to act as a transfer agent of its anionic NHC unit to transition metal complexes, this intermediate reacts with two molar equivalents of [ClAu(PPh3)] to afford the novel digold species [ClAu:C{[N(2,6-iPr2C6H3)]2CHCAu(PPh3)}] (6) resulting from an unprecedented double transmetallation reaction which involves the simultaneous exchange of both cationic (Na+) and neutral (ZntBu2) entities on the NHC framework.

Structural Basis for Regioisomerization in the Alkali-Metal-Mediated Zincation (AMMZn) of Trifluoromethyl Benzene by Isolation of Kinetic and Thermodynamic Intermediates

Performed with a desire to advance knowledge of the structures and mechanisms governing alkali-metal-mediated zincation, this study monitors the reaction between the TMP-dialkylzincate reagent [(TMEDA)Na(TMP)(tBu)Zn(tBu)] 1 and trifluoromethyl benzene C6H5CF32. A complicated mixture of products is observed at room temperature. X-ray crystallography has identified two of these products as ortho- and meta-regioisomers of heterotrianionic [(TMEDA)Na(TMP)(C6H4-CF3)Zn(tBu)], 3-ortho and 3-meta, respectively. Multinuclear NMR data of the bulk crystalline product confirm the presence of these two regioisomers as well as a third isomer, 3-para, in a respective ratio of 20:11:1, and an additional product 4, which also exhibits ortho-zincation of the aryl substrate. Repeating the reaction at 0 °C gave exclusively 4, which was crystallographically characterized as [{(TMEDA)2Na}+{Zn(C6H4-CF3)(tBu)2}−]. Mimicking the original room-temperature reaction, this kinetic product was subsequently reacted with TMP(H) to afford a complicated mixture of products, including significantly the three regioisomers of 3. Surprisingly, 4 adopts a solvent-separated ion pair arrangement in contrast to the contacted ion variants of 3-ortho and 3-meta. Aided by DFT calculations on model systems, discussion focuses on the different basicities, amido or alkyl, and steps, exhibited in these reactions, and how the structures and bonding within these isolated key metallic intermediates (prior to any electrophilic interception step), specifically the interactions involving the alkali metal, influence the regioselectivity of the Zn−H exchange process.

Deep eutectic solvents: biorenewable reaction media for Au(I)-catalysed cycloisomerisations and one-pot tandem cycloisomerisation/Diels–Alder reactions

Cycloisomerisation reactions of (Z)-enynols into furans can be conveniently performed, for the first time, in the eutectic mixture 1ChCl/2Gly as a solvent and under standard bench conditions (at room temperature and under air) by using the new bis(iminophosphorane)–Au(I) complex [Au2Cl2(μ2-S,S-CH2{P(NP(S)(OPh)2)Ph2}2)] as a catalyst. Furthermore, a one-pot tandem reaction involving the fast cycloisomerisation of (Z)-enynols followed by an intermolecular atom economical process, i.e. the Diels–Alder reaction with activated alkynes or alkenes, is reported. This tandem cycloisomerisation/Diels–Alder reaction proceeds also in the eutectic mixture 1ChCl/2Gly, in the absence of co-catalysts and under aerobic conditions, giving rise to the corresponding 7-oxanorbornadienes and 7-oxanorbornenes under the principles of the so-called Green Chemistry.

Lewis base stabilized lithium TMP-aluminates: an unexpected fragmentation and capture reaction involving cyclic ether 1,4-dioxane

Three Lewis base variations of the synthetically useful aluminate [L x Li(TMP)((i)Bu)Al((i)Bu)2], where L is TMPH, Et3N or PhC(=O)N(i)Pr2, are reported, together with the reaction of the benzamide complex with 1,4-dioxane, which surprisingly leads to fragmentation of the cyclic ether and capture of its alkoxy vinyl ether residue within a novel dilithium dialuminium hexaalkyl aggregate.

Neutral and cationic (η6-arene)-ruthenium(II) complexes containing the iminophosphorane-phosphine ligand Ph2PCH2P(=N-p-C5F4N)Ph2: influence of the arene ring in catalytic transfer hydrogenation of cyclohexanone

Abstract Ruthenium(II) dimers [{Ru(η 6 -arene)(μ-Cl)Cl} 2 ] ( 1a – f ) readily react with the iminophosphorane–phosphine ligand Ph 2 PCH 2 P(N- p -C 5 F 4 N)Ph 2 ( 2 ), in dichloromethane at room temperature, to afford the neutral derivatives [Ru(η 6 -arene)Cl 2 { k 1 - P -Ph 2 PCH 2 P(N- p -C 5 F 4 N)Ph 2 }] (arene=C 6 H 6 ( 3a ), 1- i Pr-4-C 6 H 4 Me ( 3b ), 1,3,5-C 6 H 3 Me 3 ( 3c ), 1,2,3,4-C 6 H 2 Me 4 ( 3d ), 1,2,4,5-C 6 H 2 Me 4 ( 3e ), C 6 Me 6 ( 3f )). Treatment of 3a – f with AgSbF 6 in dichloromethane yields the cationic species [Ru(η 6 -arene)Cl{ k 2 - P , N -Ph 2 PCH 2 P(N- p -C 5 F 4 N)Ph 2 }][SbF 6 ] ( 4a – f ). The catalytic activity of complexes 3 and 4 in transfer hydrogenation of cyclohexanone by propan-2-ol has been studied. Among them, the cationic derivative [Ru(η 6 -C 6 Me 6 )Cl{ k 2 - P , N -Ph 2 PCH 2 P(N- p -C 5 F 4 N)Ph 2 }][SbF 6 ] ( 4f ) shows the highest activity. Electrochemical data for 3 and 4 are also reported.

Exploiting Deep Eutectic Solvents and Organolithium Reagent Partnerships: Chemoselective Ultrafast Addition to Imines and Quinolines Under Aerobic Ambient Temperature Conditions

Shattering the long-held dogma that organolithium chemistry needs to be performed under inert atmospheres in toxic organic solvents, chemoselective addition of organolithium reagents to non-activated imines and quinolines has been accomplished in green, biorenewable deep eutectic solvents (DESs) at room temperature and in the presence of air, establishing a novel and sustainable access to amines. Improving on existing methods, this approach proceeds in the absence of additives; occurs without competitive enolization, reduction or coupling processes; and reactions were completed in seconds. Comparing RLi reactivities in DESs with those observed in pure glycerol or THF suggests a kinetic anionic activation of the alkylating reagents occurs, favoring nucleophilic addition over competitive hydrolysis.

New reactivity and structural insights of alkali-metal-mediated alumination in directed ortho-alumination of a tertiary aromatic amide.

The first reported sodium alkyl(TMP)aluminate reagent to be synthesised and crystallographically characterised, [TMEDA.Na(mu-TMP)(mu-(I)Bu)Al((I)Bu)2], reacts as an amido base towards phenylacetylene to form crystalline [(TMEDA)2.Na(mu-CCPh)(mu-(I)Bu)Al((I)Bu)2]; whereas the congeneric TMEDA-stabilised lithium (TMP)aluminate exhibits dual alkyl/amido basicity in its reaction with N,N-diisopropylbenzamide to form a novel heterobimetallic-heterotrianionic crystalline complex [{PhC(=O)N(iPr)2}.Li{2-[1-C(=O)N(iPr)2]C6H4}{Me2NCH2CH2N(Me)CH2}Al(iBu)2], which, in addition to having an ortho-deprotonated benzamide ligand, also contains a methyl-deprotonated TMEDA ligand and a neutral benzamide molecule ligated to lithium.

Pd(II)-catalyzed cycloisomerisation of γ-alkynoic acids and one-pot tandem cycloisomerisation/CuAAC reactions in water

Cycloisomerisation reactions of γ-alkynoic acids into cyclic enol-lactones can be conveniently performed in pure water as a solvent and under aerobic conditions by using a novel iminophosphorane–Pd(II) complex trans-[PdCl2{μ2-N,S-(PTA)NP(S)(OEt)2}]2 as a catalyst. It is important to note that the catalytic system could be recycled up to 10 consecutive runs. In addition and for the first time, a one-pot tandem orthogonal reaction involving the fast cycloisomerisation of γ-alkynoic acids, followed by an intermolecular atom economical process, i.e. the 1,3-dipolar cycloaddition of azides with terminal alkynes (CuAAC), is reported. This new tandem cycloisomerisation/click reaction proceeds also in water, at room temperature and under aerobic conditions, giving rise to unprecedented bicyclic triazol-enol-lactones under the principles of the so called “Green Chemistry”.