Hauser base

Hauser bases, also called magnesium amide bases, are magnesium compounds used in organic chemistry as bases for metalation reactions. These compounds were first described by Charles R. Hauser in 1947. Compared with organolithium reagents, the magnesium compounds have more covalent, and therefore less reactive, metal-ligand bonds. Consequently, they display a higher degree of functional group tolerance and a much greater chemoselectivity. Generally, Hauser bases are used at room temperature while reactions with organolithium reagents are performed at low temperatures, commonly at &minus;78 °C.

Structure
Hauser bases with the empirical formula R2NMgX feature halide (X-) bridges in the solid state for bulky amido (R2N) ligands such as 2,2,6,6-tetramethylpiperidine (TMP-) and HMDS-).

Amido-bridged Hauser bases exist when the amido ligand is less bulky, such as Et2N- and Ph3P=N-.

The structures of Hauser bases in solution have been investigated by diffusion-ordered NMR spectroscopy (DOSY). These studies indicate that iPr2NMgCl is subject to the Schlenk equilibrium:


 * iPr2NMgCl (A) (iPr2N)2Mg (B) + MgCl2

This equilibrium is temperature-dependent: heteroleptic (A) are the main species at high temperatures and homoleptic (B) dominate at lower temperatures. Dimeric species with bridging chlorides and amides are also present in the THF solution. At low temperatures, adducts of MgCl2 are present in solution.

Preparation and reactions
The Hauser bases are prepared by treating a secondary amine with a Grignard reagent:
 * R2NH + R′MgX → R2NMgX + R′H X = Cl, Br, I

(:R2NH = diisopropylamine, TMP)

Like many organolithium reagents, Hauser bases are generally used for metalation reagents. iPr2NMgBr selectively magnesiate carboxamides. iPr2NMgX (X = Cl, Br) effect the deprotonation thiophenes. and phenylsulphonyl-substituted indoles.





Turbo-Hauser base
A major disadvantage of Hauser bases is their poor solubility in THF. In consequence, the metalation rates are slow and a large excess of base is required (e.g., 10 equiv.). This circumstance complicates the functionalization of the metaled intermediate with an electrophile. Improved solubility and reactivity can be achieved by adding stoichiometric amounts of LiCl to the Hauser base. These so-called Turbo-Hauser bases like e.g. TMPMgCl·LiCl and iPr2NMgCl·LiCl are commercially available. They show an enhanced kinetic basicity, regioselectivity and functional group tolerance.