Transition Metal Mediated Homogeneous Reductive Amination

Transition Metal-Mediated Homogeneous Reductive Amination 

The reaction was not as accommodating as just described and additionally required a cosolvent (10ml of cyclohexane per lOOmmol of MEA) and an acid, which screening identified as methanesulfonic acid (0.2 ml per 100 mmol of MEA). In addition, tetrabutylammonium iodide (20 mg) was required. The combination of these additives enhanced the rate of reaction presumably by aiding solubility in this two phase reaction. 

Although this was an outstanding first example of enantioselective reductive amination that achieved the project s ee target, the final industrial process actually employed the corresponding preformed and isolated imine because ofthe advantage of reducing by one hundredth the catalyst loading compared to the reductive amination process outlined here [8]. 

Importantly, Zhang noted that the reaction did not proceed without the addition of iodine [10]. Furthermore use of Ti(OiPr)4 was not trivial, and replacement by MgSO4, 4 A MS, or TsOH was not helpful. They additionally noted that replacing the chiral /Binaphane ligand with BINAP or BIPHEP resulted in poor ee. The source of nitrogen is important because of the desire to ultimately provide a chiral primary amine screening studies with benzylamine, aniline, o anisidine, m anisidine, p anisidine, and 2,6 dimethylaniline showed p anisidine to be optimal. 

The development ofthese methods for alkanone based substrates would represent 

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Transition Metal-Mediated Homogeneous Reductive Amination... 

Aspects featured in a review of asymmetric reductive aminations have included transition metal-mediated homogeneous-, enantioselective organocatalytic-. 

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