''Turbo''-Hauser bases are amido magnesium halides that contain stoichiometric amounts of LiCl. These mixed Mg/Li

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...

s of the type R₂NMgCl⋅LiCl are used in organic chemistry as non-nucleophilic bases for metalation reactions of

aromatic In chemistry, aromaticity is a chemical property of cyclic (ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to sat ...

and

heteroaromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...

substrates. Compared to their LiCl free ancestors ''Turbo''-Hauser bases show an enhanced kinetic

basicity In chemistry, there are three definitions in common use of the word base, known as Arrhenius bases, Brønsted bases, and Lewis bases. All definitions agree that bases are substances that react with acids, as originally proposed by G.-F. ...

, excellent regioselectivity, high functional group tolerance and a better solubility.

Preparation

Typically ''Turbo''-Hauser bases are prepared by treating an

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...

with a Grignard reagent and

lithium chloride Lithium chloride is a chemical compound with the formula Li Cl. The salt is a typical ionic compound (with certain covalent characteristics), although the small size of the Li+ ion gives rise to properties not seen for other alkali metal chlori ...

. In some cases they are prepared by treating a

lithium amide Lithium amide or lithium azanide is an inorganic compound with the chemical formula . It is a white solid with a tetragonal crystal structure. Lithium amide can be made by treating lithium metal with liquid ammonia: : Other lithium amides The c ...

with MgCl₂: : : Common ''Turbo''-Hauser bases: R'2NH = ''i''Pr₂NMgCl·LiCl (''i''Pr-''Turbo''-Hauser base), TMPMgCl·LiCl, TMP (''Turbo''-Hauser base or ''Knochel''-Hauser Base)

Structure

In solution, ''Turbo''-Hauser bases participate in temperature- and concentration-dependent equilibria. Diffusion-Ordered Spectroscopy (DOSY) show that at room temperature and high concentrations (0.6 M) dimeric 'i''Pr₂NMgCl·LiClsub>2 remains intact solution.

Solid State Structure

The ''i''Pr-''Turbo''-Hauser base crystallizes as a dimeric amido bridged

contact ion pair In chemistry, the intimate ion pair concept, introduced by Saul Winstein, describes the interactions between a cation, anion and surrounding solvent molecules. In ordinary aqueous solutions of inorganic salts, an ion is completely solvated and sh ...

(CIP). Due to the high steric demand of the

TMP TMP can refer to any of the following: Chemistry * 2,2,6,6-Tetramethylpiperidine, an organic chemistry reagent * Thymidine monophosphate, a nucleotide * Trimethoprim, an antibiotic * Trimethyl phosphate, a solvent * Trimethylolpropane, a precurso ...

ligand the dimerization process is sterically hindered. This is why the TMP-''Turbo''-Hauser base crystallizes as a monomeric CIP. In both structures LiCl coordinates to the magnesium amides. The solid state structure of TMPMgCl·LiCl is retained almost completely in THF solution independently of temperature and concentration. Due to the high steric demand of the TMP ligand, the THF ligand dissociates from the magnesium cation. This dissociation gives a magnesium amido complex with enhanced reactivity for deprotonation of C-H bonds. :

Reactions

''Turbo''-Hauser bases are used as

metalation Metalation (Alt. spelling: Metallation) is a chemical reaction that forms a bond to a metal. This reaction usually refers to the replacement of a halogen atom in an organic molecule with a metal atom, resulting in an organometallic compound. In th ...

deprotonation Deprotonation (or dehydronation) is the removal (transfer) of a proton (or hydron, or hydrogen cation), (H+) from a Brønsted–Lowry acid in an acid–base reaction.Henry Jakubowski, Biochemistry Online Chapter 2A3, https://employees.csbsju. ...

reagents. In this way, they resemble some

organolithium reagent In organometallic chemistry, organolithium reagents are chemical compounds that contain carbon–lithium (C–Li) bonds. These reagents are important in organic synthesis, and are frequently used to transfer the organic group or the lithium atom ...

s. The lithiated compounds, however, are only stable at low temperatures (e.g. -78 °C) and suffer competing addition reactions (like e.g. Chichibabin reactions). In contrast, the magnesium compounds are less reactive. The magnesium amide complex is stabilized by LiCl. ''Turbo''-Hauser bases display a high functional group tolerance and greater chemoselectivity at high and low temperatures. The resulting reagent is then quenched with an electrophile. ''i''Pr₂NMgCl·LiCl and TMPMgCl·LiCl react differently. The TMP-''Turbo''-Hauser base easily metalates ethyl-3-chlorobenzoate in the C2 position, while the same reaction carried out with the ''i''Pr-''Turbo''-Hauser base resulted in no metalation at all. Instead, an addition-elimination reaction occurs. Example Turbo Hauser Rktn 3

Another difference is illustrated by the differing rates of deprotonation of isoquinoline in THF solution. Whereas TMPMgCl·LiCl required only 2h and 1.1 equivalents, ''i''Pr₂NMgCl·LiCl needed 12h and 2 equivalents for comparable metalation. Example Turbo Hauser Rktn 4

The differing reactivity of the TMP vs iPr-based reagents is related to the fact that the TMP is always a terminal ligand whereas iPr₂N is sometimes bridging (μ-). Generally, in

organolithium In organometallic chemistry, organolithium reagents are chemical compounds that contain carbon–lithium (C–Li) bonds. These reagents are important in organic synthesis, and are frequently used to transfer the organic group or the lithium atom ...

chemistry monomeric species display the most active kinetic species. This could explain why reactions of the monomeric TMP-''Turbo''-Hauser base are much faster than that of dimeric ''i''Pr-''Turbo''-Hauser base. The regioselective ortho deprotonation reactions of TMPMgCl·LiCl could stem from a sufficient complex-induced proximity effect (CIPE) between the bimetallic aggregate and the functionalized (hetero)aromatic substrate.

Related reagents

* Turbo-Grignard reagents used for halide/Mg exchange reactions. "Turbo-Grignards", as they are often called, are aggregates with the formula -PrMgCl·LiClsub>2 *Organozinc-LiCl complexes

References

{{Reflist Magnesium compounds *