Aldimine coupling

Reductive coupling of imines.2 Aromatic ketimines are reduced to the corresponding secondary amines by Sml2, but aromatic aldimines couple to 1,2-diamines (equation II). 

Reductive coupling of aldimines obtained from aromatic aldehydes and aromatic amines to generate vicinal diamines mediated by indium was carried out in aqueous ethanol (Eq. 11.59)." Small indium rods were used in this study. No side-product was observed due to unimolecular reduction. The presence of NH4CI was found to accelerate the reaction. The reaction fails completely in CH3CN, DMF, or wet DMF. The use of nonaromatic substrates also resulted in the failure of the reaction. 

More recently, Tamaru and co-workers reported nickel-catalyzed reductive coupling of dienes with in situ-generated aldimines from aldehydes and amines (Equation (88)).446,446a The reaction exhibits high regio- and diastereoselectivity. 

For use of conjugated enones as nucleophilic partners in catalytic intermolecular reductive couplings to aldimines, see ... 

Various phenyl-substituted ketimines and aldimines react with metallocenes 1 and 2, in a manner that depends on the substituents present [41]. In all cases, elimination of the al-kyne is observed. Complex 2b reacts with PhN=CMePh to give the r 2-complex 64, which is stabilized by an additional pyridine ligand [41a], In the reactions of 1 or 2a with the ketimine HN=CPh2, hydrogen transfer generates complexes 65. Two molecules of the aldimine PhN=CHPh are coupled by 2a to give the cyclic diamido complex 66 [41b]. 

The [Ir(cod)2]BARF complex also showed high catalytic activity in the hydrogena-tive coupling of alkyne with aldimines to lead to reductive couphng products, aUyl amines [69]. 

Leaving precise mechanistic arguments aside, it should be stressed that an a,/9-unsatu-rated carbonyl compound can behave as a latent nucleophile with the assistance of a hydrosilane and a low-valence rhodium complex. With this simplification, isocyanates 18 and aldimines 20 were used as electrophiles for a similar protocol. Both were successfully incorporated with the aid of [Rh(COD)(P(OPh)3)2]OTf to afford 19 and 21, respectively (Scheme 6.5) in a reaction that was similar to the aldol-type coupling [11]. 

Later in 2007, Gong utilized If and saturated derivative 2 in a direct Mannich reaction between in situ generated N-aryl imines and cyclic ketones as well aromatic ketones (Scheme 5.3) [10], It was found that electron poor anilines as coupling partners gave the highest enantioselectivities. The authors postulate that acid promoted enolization of the ketone forms the reactive enol which adds to the protonated aldimine. 

Reductive coupling of aromatic aldimines leading to vicinal diamines proceeds with SmU, and is strongly accelerated by addition of a catalytic amount of or a stoichiometric amount of Yb(OTf)3. In the former... 

Coupling of aldimines.1 The Ti(II) reagent obtained from TiCl4 and Mg effects reductive coupling of aryl aldimines to 1,2-diarylethylenediamines as a 1 1 mixture of meso- and /-isomers. 

Synthesis of homoallylic amines has been reported by a three-component coupling of aldimines, diiodomethane, and alkenylzirconocenes, in the presence of dimethylzinc (Scheme 28).296,296a The formation of homoallylic products is rationalized by the mechanism shown in Scheme 29. The //////-relationship of the final product is explained by a cyclic chair-like transition state. This type of homologation was used to form f, -dicyclop ropy I ruethylamines by a double C,C-cr-bond insertion into bicyclobutanes (Scheme 30).297 During the course of this cascade process, 10 C,C-bonds are formed, and the final product is isolated in one step with a high diastereoselectivity. 

In the presence of metallic zinc and a catalytic amount of BiCl3, the reductive coupling between a-diketones and aldehydes takes place to yield a,/3-dihydroxyketones with moderate //-selectivity (Equation (48)).83 The reaction proceeds even in aqueous media. Phenylglyoxal and methylglyoxal can be converted to the corresponding coupling products. The reductive coupling of aldimines to vicinal diamines can also be accomplished by the action of Bi-KOH in methanol at room temperature.84... 

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