Imine unsymmetrical aminals

Noyori was subsequently able to show that triethylamine salts of formic acid (TEAF) could be used to reduce ketones to alcohols and imines to amines with high enantioselectivities [4]. The byproduct of this reaction is carbon dioxide gas and this prevents the possibility of the reverse reaction. Strangely, aminoalcohol ligands are poor in this reaction, whilst unsymmetrical 1,2-diamines have proven very effective. A particularly effective ligand is mono-N-tosyl-l,2-diphenylethylene-diamine. 

Scheme 1-150. Addition of a Grignard reagent onto an organic cyanide and subsequently of an organolithium onto the resulting A -metallo imine giving an unsymmetrical amine 207.

The stoichiometric hydroamination of unsymmetrically disubstituted alkynes is highly regioselective, generating the azametaUacycle with the larger alkyne substituent a to the metal center [294, 295]. In others words, the enamine or imine formed results from an anti-Markovnikov addition. Unfortunately, this reaction could not be applied to less stericaUy hindered amines. 

Unsymmetric compartmental ligands that allow for the controlled synthesis of unsymmetric Ni2 or heterobimetallic NiM complexes have received particular attention.1876,1892 A wide range of such ligands derived particularly from 2-hydroxy-3-hydroxymethyl-5-methylbenzaldehyde and 2-hydroxy-3-hydroxymethyl-bromo-benzaldehyde has now been prepared and used for Ni com-plexation. These ligands have monopodal iminic pendent arms and either mono- or dipodal aminic pendent arms and the terminal donors of the pendent arms can be provided by pyridine, imidazole, and tertiary amino groups.1893-1897 Complexes are usually prepared by reaction of the requisite Ni11 salts with the preformed ligand. 

Unsymmetrical secondary amines are readily prepared in good yields by the catalytic reduction of Schiff bases at moderate temperatures in high-or low-pressure equipment. Many examples have been cited. The intermediate imines are prepared from primary amines and aldehydes—very seldom from ketones—and may be used without isolation (cf. method 431). For the preparation of aliphatic amines, e.g., ethyl-w-propylamine and n-butylisoamylamine, a prereduced platinum oxide catalyst is preferred with alcohol as the solvent. Schiff bases from the condensation of aromatic aldehydes with either aromatic or aliphatic amines are more readily prepared and are reduced over a nickel catalyst. In this manner, a large number of N-alkylbenzylamines having halo, hydroxyl, or methoxyl groups on the nucleus have been made. Reductions by means of sodium and alcohol and lithium aluminum hydride have also been described,... 

The regiochemistry of deprotonation of imines derived from unsymmetrical ketones is of special significance for the synthetic applications of these anions for carbon-carbon bond formation. This selectivity is sensitive to both the amine moiety and the base used. With imines derived from cyclohexyl- or r-butyl-amine, deprotonation with either Grignard reagents or lithium dialkylamide bases will result in high selectivity (>98 2) for removal of the proton on the less substituted a-carbon as in equations (39) and (40). 3i... 

List and coworkers developed an excellent approach to synthesize p branched amines in optically active forms by combining the enamine and reductive amination processes (Scheme 3.45) [96]. The reductive amination of unsymmetrically a,a disubstituted aldehydes and aniline derivatives proceeded through a tautomerization between imine and enamine forms. Dynamic kinetic resolution occurred under the... 

Since secondary and tertiary amines are obtained by reaction of a primary and secondary amine with the imine intermediate, selected unsymmetric secondary and tertiary amines can be prepared by substituting an added chosen amine for the reacting amines. The product composition of this reductive condensation over an appropriate catalyst depends on the nitrileiamine ratio, and to a lesser extent on solvent. Platinum, Pd, and rhodium-on-carbon, in alcohol or hydrocarbon solvent with about 100% excess of added amine, give good yields of -butyl-n-pentylamine from hydrogenation of valeronitrile in presence of w-butylamine" ... 

Amine-exchange reaction. Unsymmetrical secondary and tertiary amines can be synthesized by dehydrogenation of primary or secondary amines by palladium black (25-200°, 3-20 hr.). The initial step is considered to involve dehydrogenation to an imine followed by addition of the amine and elimination ... 

Using the bifunctional chiral primary amine thiourea catalyst 41 (20 mol%) in CH Clj and in the presence of five equivalents of H O as additive, a highly enanti-oselective direct conjugate addition of a wide range of a,a-unsymmetrically dis-ubstituted aldehydes (only a twofold excess of aldehyde relative to nitroaUcene) to nitroolefins is obtained (see Table 2.1, entry 15, for a representative example) [61], The beneficial role of water is proposed to lie in increasing turnover by eliminating potential catalyst deactivation pathways, and accelerating the final imine hydrolysis. 

Interestingly, as shown in Table 9.4, when unsymmetrical ketones or aldehydes are allowed to react with primary amines (RNH2) the imines that are formed are capable of (E)-(Z) isomerism and both products can co-occur. However, the barrier to isomerization between these geometric isomers can be low enough to make them inseparable at room temperature. 

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