Robert E. Mulvey

Synthetic and structural developments in hetero-s-block-metal chemistry: new ring-laddering, ring-stacking and other architectures

Hetero-alkali metal organic compounds are of interest because they can exhibit superior reactivity to conventional organolithium reagents. Structurally well-defined mixed lithium–sodium and mixed lithium–sodium–potassium compositions, based on a variety of organic ligands, are surveyed here. A complicated assortment of architectures with lithium-rich, sodium-rich, or equimolar metal stoichiometries is revealed. These structures are analysed with respect to the ‘ring-laddering’ and ‘ring-stacking’ concepts used previously in the rationalisation of organolithium structures. Important homometallic structures, which have appeared since these concepts were reviewed, are also included. Finally, an intriguing new class of mixed lithium–magnesium amide, based around an oxo or peroxo core, is described.

Synergic sedation of sensitive anions: alkali-mediated zincation of cyclic ethers and ethene.

Zinc-Based Bases Conventional methods of stripping a proton from a hydrocarbon yield an alkali metal-coordinated carbanion as the preliminary product. In certain cases, however, this preliminary product falls apart before it can be used for further constructive synthetic purposes. Kennedy et al. (p. 706; see the Perspective by Marek) show that in such cases, zinc ions can act as potent stabilizers. Specifically, a bimetallic base incorporating both sodium and zinc ions was used to deprotonate the common cyclic ethers tetrahydrofuran and tetrahydropyran. Zinc coordination to the carbanion inhibited an otherwise rapid ring-opening decomposition pathway. Similarly, a zinc-potassium combination facilitated deprotonation of ethylene to a stabilized product. Tandem coordination by zinc and an alkali metal increases the reactivity of carbon-hydrogen bonds of organic molecules. Deprotonation of alkyl and vinyl carbon-hydrogen bonds for synthetic purposes is often hindered not merely by the need for an exceptionally strong base, but by the inherent instability of the resultant anion. Metalation of cyclic ethers adjacent to oxygen, for example, has invariably initiated a ring-opening decomposition pathway. Here, we show that the use of a bimetallic base can overcome such instability through a cooperative combination of zinc-carbon and sodium-oxygen bonding. Both tetrahydrofuran and tetrahydropyran reacted cleanly over days at room temperature to yield α-zinc–substituted products that were sufficiently stable to be isolated and crystallographically characterized. A related zincation-anion trapping strategy, with sodium replaced by potassium, induced clean deprotonation of ethene to yield a stable product. Preliminary electrophilic quenching experiments with the α-zinc–substituted cyclic ethers and benzoyl chloride gave satisfactory yields of the tetrahydrofuran-derived ketone but only trace amounts of the tetrahydropyran-derived ketone.

Directed ortho-meta′- and meta-meta′-dimetalations: A template base approach to deprotonation

The regioselectivity of deprotonation reactions between arene substrates and basic metalating agents is usually governed by the electronic and/or coordinative characteristics of a directing group attached to the benzene ring. Generally, the reaction takes place in the ortho position, adjacent to the substituent. Here, we introduce a protocol by which the metalating agent, a disodium-monomagnesium alkyl-amide, forms a template that extends regioselectivity to more distant arene sites. Depending on the nature of the directing group, ortho-meta′ or meta-meta′ dimetalation is observed, in the latter case breaking the dogma of ortho metalation. This concept is elaborated through the characterization of both organometallic intermediates and electrophilically quenched products. A network of sodium and magnesium ions helps direct double deprotonation of aryl rings. Bring your own template for deprotonation When manufacturing pharmaceuticals and agrochemicals, chemists need to add substituents to specific carbon sites in hexagonal benzene rings. If theres already a substituent on the ring, it can often direct a base to deprotonate the site next to it. But what if you want the base to attack the site two carbons away? Martínez-Martínez et al. devised a method to do this by taking advantage of the sodium and magnesium counterions associated with their base. These ions form a template that orients the base to attack the more distant site. Science, this issue p. 834

Cleave and capture chemistry illustrated through bimetallic-induced fragmentation of tetrahydrofuran

The cleavage of ethers is commonly encountered in organometallic chemistry, although rarely studied in the context of new, emerging bimetallic reagents. Recently, it was reported that a bimetallic sodium-zinc base can deprotonate cyclic tetrahydrofuran under mild conditions without opening its heterocyclic (OC(4)) ring. In marked contrast to this synergic sedation, herein we show that switching to the more reactive sodium-magnesium or sodium-manganese bases promotes cleavage of at least six bonds in tetrahydrofuran, but uniquely the ring fragments are captured in separate crystalline complexes. Oxide fragments occupy guest positions in bimetallic, inverse crown ethers and C(4) fragments ultimately appear in bimetallated butadiene molecules. These results demonstrate the special synergic reactivity that can be executed by bimetallic reagents, which include the ability to capture and control, and thereby study, reactive fragments from sensitive substrates.

Unmasking Representative Structures of TMP-Active Hauser and Turbo-Hauser Bases†

The molecular engines that drive enhanced magnesiations are unveiled through structural elucidation of a 2,2,6,6-tetramethylpiperidide (TMP) Hauser base and its turbo model (see structure; Mg green, Li violet, C purple, O red, N blue, Cl yellow).

Closer Insight into the Reactivity of TMP−Dialkyl Zincates in Directed ortho-Zincation of Anisole: Experimental Evidence of Amido Basicity and Structural Elucidation of Key Reaction Intermediates

The new dialkyl(aryl) lithium zincates [(THF)2Li(C6H4−OMe)MeZnMe] (4), [(TMEDA)Li(C6H4−OMe)MeZnMe] (6), [(THF)3Li(C6H4−OMe)tBuZntBu] (7), and [(PMDETA)Li(C6H4−OMe)tBuZntBu] (8) have been prepared by co-complexation reactions of lithiated anisole with the relevant dialkylzinc compound and the relevant Lewis base. These new heterobimetallic compounds have been characterized in solution using 1H, 13C{H}, and 7Li NMR spectroscopy, and the molecular structures of 6 and 8 have been elucidated by X-ray crystallography. In 6 the distinct metals are connected through the anisole ligand which binds in an ambidentate fashion (through carbon−zinc and oxygen−lithium contacts) and also through one of the methyl groups, to close a [LiOCCZnC] six-membered ring; whereas 8 displays an open structure where anisole connects the two metals (in the same mode as in 6) but with the tert-butyl groups exclusively bonded terminally to zinc. Reactivity studies of zincates 4 and 7 with the amine TMP(H) supply experimental evidence that these heterobimetallic compounds are intermediates in the two-step deprotonation reaction of anisole by TMP−dialkyl zincates and show the relevance of the alkyl groups in the efficiency of TMP−dialkyl zincate bases. In addition, important solvent effects have also been evaluated. When hexane is added to THF solutions of compounds 4 or 7, the homoleptic tetraorganozincate [(THF)2Li2Zn(C6H4−OMe)4] (5) is obtained as the result of a disproportionation process. This lithium-rich zincate has also been spectroscopically and crystallographically characterized.

An alternative picture of alkali-metal-mediated metallation: cleave and capture chemistry

This perspective article takes an alternative look at alkali-metal-mediated chemistry (exchange of a relatively inert C-H bond for a more reactive C-metal bond by a multicomponent reagent usually containing an alkali metal and a less electropositive metal such as magnesium or zinc). It pictures that the cleavage of selected C-H bonds can be accompanied by the capturing of the generated anion by the multi (Lewis acid)-(Lewis base) character of the residue of the bimetallic base. In this way small atoms or molecules (hydrides, oxygen-based anions) as well as sensitive organic anions (of substituted aromatic compounds, ethers or alkenes) can be captured. Cleave and capture reactions which occur in special positions on the organic substrate are also included.

Mixed‐Metal Sodium–Magnesium Macrocyclic Amide Chemistry: A Template Reaction for the Site Selective Dideprotonation of Arene Molecules

A remarkable pair of macrocyclic amides has been synthesized and crystallographically characterized; these consist of a twelve-membered (N6Na4Mg2)2+ cationic ring host with [C6H3(CH3)]2- or (C6H4)2- dianionic guests (see picture) derived from toluene and benzene, respectively.

Split personality of lithium chloride: recent salt effects in organometallic recipes.

Jekyll and Hyde: Pinches of LiCl can catalyze orthometalations of halogen-substituted arenes and addition reactions of unsaturated esters, mediated by lithium diisopropylamide. Larger salt portions can transform weak organometallic bases (e.g., Grignard reagents, zincates) into “turbo” reagents of high reactivity and functional group tolerance. But the presence of LiCl, especially as an overlooked metathesis by-product can be detrimental to other catalytic reactions.

Remarkable reaction of hetero-S-block-metal amides with molecular oxygen: Cationic (NMNMg)(2) ring products (M = Li or Na) with anionic oxo or peroxo cores

Deliberate treatment of solutions of amines with molecular oxygen has given rise to magnesium-substituted derivatives of classical alkali metal amide ring structures (NMNMg)2 (M=Li or Na), but with oxo or peroxo cores. The picture shows the structure of the sodium compound [{(Me3 Si)2 N}4 Na2 Mg2 (O2 )x (O)y ].