Jan Klett

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.

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).

Structurally engineered deprotonation/alumination of THF and THTP with retention of their cycloanionic structures

Metalation has served well for over 80 years as a vehicle for transforming inert C[BOND]H bonds in organic compounds to reactive C[BOND]metal bonds.1 Progress in metalation was accelerated greatly by the development of DoM (directed ortho-metalation),2 pioneered by Snieckus, Beak, and others, a special type of lithiation (aromatic C[BOND]H to Cδ−[BOND]Liδ+) reliant on the high polarity of carbon–lithium bonds in organolithium reagents. Many other metals could not engage in metalation due to the lower polarity/lower reactivity of their corresponding carbon–metal bonds. However, this obstacle has now been cleared by the recognition that when part of a mixed-metal system or other multicomponent mixture, these metals (for example, magnesium, zinc, aluminum or manganese) can exhibit greatly enhanced metalating properties often superior in terms of functional-group compatibility or reaction conditions to that of lithium. Interest in these new “low polarity” metalating agents is widespread with coverage in fundamental chemistry journals,3 process chemistry journals,4 interdisciplinary science journals,5 and in news items in scientific media.6 Knochel’s turbo-Grignard reagents (e.g., (iPr)MgCl⋅LiCl) 7 are examples that have been commercialized. A spectacular demonstration of the special reactivity of bimetallic bases came with the α-zincation of tetrahydrofuran (THF) by the sodium dialkyl(amido)zincate [(TMEDA)Na(μ-TMP)(μ-CH2SiMe3)Zn(CH2SiMe3)] (TMEDA=N,N,N′,N′-tetramethylethylenediamine; TMP=2,2,6,6-tetramethylpiperidine) to produce [(TMEDA)Na(μ-TMP)(μ-OC4H7)Zn(CH2SiMe3)].5 Conventional metalation of THF invariably initiates decomposition by ring opening,8 but in this low-polarity zincation the 5-atom ring of the sensitive α-deprotonated THF anion remains intact. However, this reaction is extremely slow (best yield was 52.7 % after 2 weeks) and requires a massive stoichiometric excess of the cyclic ether (i.e., carried out in neat THF solvent). Here we report a vastly superior methodology to the cyclic THF α-anion, mediated by a lithium aluminate base with a higher amido content than the alkyl-rich zincate reagent. An analogous reaction with the sulfur analogue, tetrahydrothiophene (THTP), is also reported.

Alkali‐Metal‐Mediated Manganation(II) of Functionalized Arenes and Applications of ortho‐Manganated Products in Pd‐Catalyzed Cross‐Coupling Reactions with Iodobenzene

Extending the recently introduced concept of “alkali-metal-mediated manganation” to functionalised arenes, the heteroleptic sodium manganate reagent [(tmeda)Na(tmp)(R)Mn(tmp)] (1; TMEDA = N,N,N′,N′-tetra-methylethylenediamine, TMP = 2,2,6,6-tetramethylpiperidide, R = CH2 SiMe3) has been treated with anisole or N,N-diisopropylbenzamide in a 1:1 stoichiometry in hexane. These reactions afforded the crystalline products [(tmeda)Na(tmp)(o-C6H4OMe)Mn(tmp)] (2) and [(tmeda)Na(tmp){o-{C(O)N(iPr)2C6H4}Mn(CH2SiMe3)] (3), respectively, as determined from X-ray crystallographic studies. On the basis of these products, it can be surmised that reagent 1 has acted, at least partially and ultimately, as an alkyl base in the first reaction liberating the silane Me4Si, but as an amido base in the second reaction liberating the amine TMPH. Both of these paramagnetic products 2 and 3 have contacted ion-pair structures, the key features of which are six-atom, five-element (NaNMnCCO) and seven-atom, five-element (NaNMnCCCO) rings, respectively. Manganates 2 and 3 were successfully cross-coupled with iodobenzene under [PdCl2(dppf)] (dppf=1,1′-bis(diphenylphosphino)ferrocene) catalysis to generate unsymmetrical biaryl compounds in yields of 98.0 and 66.2%, respectively. Emphasizing the importance of alkali-metal mediation in these manganation reactions, the bisalkyl Mn reagent on its own fails to metalate the said benzamide, but instead produces the monomeric, donor–acceptor complex [Mn(R)2{(iPr)2NC(Ph)(=O)}2] (5), which has also been crystallographically characterised. During one attempt to repeat the synthesis of 2, the butoxide-contaminated complex [{(tmeda)Na(R)(OBu)(o-C6H4OMe)Mn}2] (6) was obtained. In contrast to 2 and 3, due to reduced steric constraints, this complex adopts a dimeric arrangement in the crystal, the centrepiece of which is a twelve atom (NaOCCMnC)2 ring.

Tuning the Basicity of Synergic Bimetallic Reagents: Switching the Regioselectivity of the Direct Dimetalation of Toluene from 2,5‐ to 3,5‐Positions

Meta-meta metalation: Remarkably, toluene can be directly dimanganated or dimagnesiated at the 3,5-positions using bimetallic bases with active Me3SiCH2 ligands (see scheme, blue). In contrast, n-butyl ligands lead to 2,5-metalation (red). tmp=2,2,6,6-tetramethylpiperidide.

Pre-inverse-crowns: synthetic, structural and reactivity studies of alkali metal magnesiates primed for inverse crown formation

Two new alkali metal monoalkyl-bisamido magnesiates, the potassium compound [KMg(TMP)2nBu] and its sodium congener [NaMg(TMP)2nBu] have been synthesised in crystalline form (TMP = 2,2,6,6-tetramethylpiperidide). Devoid of solvating ligands and possessing excellent solubility in hydrocarbon solvents, these compounds open up a new gateway for the synthesis of inverse crowns. X-ray crystallography established that [KMg(TMP)2nBu] exists in three polymorphic forms, namely a helical polymer with an infinite KNMgN chain, a hexamer with a 24-atom (KNMgN)6 ring having endo-disposed alkyl substituents, and a tetramer with a 16-atom (KNMgN)4 ring also having endo-disposed alkyl substituents. Proving their validity as pre-inverse-crowns, both magnesiates react with benzene and toluene to generate known inverse crowns in syntheses much improved from the original, supporting the idea that the metallations take place via a template effect. [KMg(TMP)2nBu] reacts with naphthalene to generate the new inverse crown [KMg(TMP)2(2–C10H7)]6, the molecular structure of which shows a 24-atom (KNMgN)6 host ring with six naphthalene guest anions regioselectively magnesiated at the 2-position. An alternative unprecedented 1,4-dimagnesiation of naphthalene was accomplished via [NaMg(TMP)2nBu] and its NaTMP co-complex “[NaMg(TMP)2nBu]·NaTMP”, manifested in [{Na4Mg2(TMP)4(2,2,6-trimethyl-1,2,3,4-tetrahydropyridide)2}(1,4-C10H6)]. Adding to its novelty, this 12-atom (NaNNaNMgN)2 inverse crown structure contains two demethylated TMP ligands as well as four intact ones. Reactivity studies show that the naphthalen-ide and -di-ide inverse crowns can be regioselectively iodinated to 2-iodo and 1,4-diiodonaphthalene respectively.

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.

Ligand exchange between arylcopper compounds and bis(hypersilyl)tin or bis(hypersilyl)lead: Synthesis and characterization of hypersilylcopper and a stannanediyl complex with a Cu-Sn bond

Bis(hypersilyl)tin (1) and bis(hypersilyl)lead (2) [hypersilyl= Hyp = tris(trimethylsilyl)silyl] undergo ligand exchange reactions with other carbene homologues to yield heteroleptic distannenes or diplumbenes. Here we report the extension of this reaction principle to coordinatively unsaturated arylcopper(I) compounds. The primary reaction products are probably adducts with the carbene homologues as Lewis base and the arylcopper compounds as Lewis acids. This is followed by rearrangement to the adducts HypCu-E-(Hyp)Ar* (E = Sn (6) and Pb (7); Ar* = C(6)H(3)Mes(2)-2,6,) of hypersilylcopper (9) and the heteroleptic stannanediyl or plumbanediyl. The complex may be the final product or may dissociate into its component parts, free hypersilylcopper (9) and the appropriate heteroleptic carbene homologue. The colorless hypersilylcopper forms a trimer (9), in the solid state with short Cu Cu contacts (238.4-241.5 pm). All observed Cu-Si bonds are relatively long. However, shorter distances (234.9-237.4pm) alternate with longer ones (249.2 pm), such that quasi-monomeric hypersilylcopper units can be identified. The dark green complex 6 exhibits a shorter Cu-Si bond (227.3 pm), The Sn-Cu bond length was determined to be 249.9 pm. The turquoise plumbanediyl Pb(Hyp)Ar* (8) is the first strictly monomeric mixed aryl silyl derivative, even in the solid state. The steric repulsions are obviously less than in the parent homoleptic compounds because the Pb-C bond in 8 is shorter (229.0 pm) and the C-Pb-Si angle (109.2 degrees) is markedly smaller.

Structural and magnetic insights into the trinuclear ferrocenophane and unexpected hydrido inverse crown products of alkali-metal-mediated manganation(II) of ferrocene.

With the aim of introducing the diisopropylamide [NiPr(2)](-) ligand to alkali-metal-mediated manganation (AMMMn) chemistry, the temperature-dependent reactions of a 1:1:3 mixture of butylsodium, bis(trimethylsilylmethyl)manganese(II), and diisopropylamine with ferrocene in hexane/toluene have been investigated. Performed at reflux temperature, the reaction affords the surprising, ferrocene-free, hydrido product [Na(2)Mn(2) (mu-H)(2){N(iPr)(2)}(4)]2 toluene (1), the first Mn hydrido inverse crown complex. Repeating the reaction rationally, excluding ferrocene, produces 1 in an isolated crystalline yield of 62 %. At lower temperatures, the same bimetallic amide mixture leads to the manganation of ferrocene to generate the first trimanganese, trinuclear ferrocenophane, [{Fe(C(5)H(4))(2)}(3){Mn(3)Na(2)(NiPr(2))(2) (HNiPr(2))(2)}] (2) in an isolated crystalline yield of 81 %. Both 1 and 2 have been characterised by X-ray crystallographic studies. The magnetic properties of paramagnetic 1 and 2 have also been examined by variable-temperature magnetisation measurements on powdered samples. For 1, the room-temperature value for chiT is 3.45 cm(3) K mol(-1), and on lowering the temperature a strong antiferromagnetic coupling between the two Mn ions is observed. For 2, the room-temperature value for chiT is 4.06 cm(3) K mol(-1), which is significantly lower than the expected value for three isolated paramagnetic Mn(II) ions.