Reductions, organocatalytic

In 2007, AntiUa and coworkers disclosed the first asymmetric organocatalytic reduction of acyclic a-imino esters (Scheme 23) [39], Chiral VAPOL phosphate (5)-16 (5 mol%) served as a catalyst for the transfer hydrogenation of the latter (62) employing commercially available dihydropyridine 44a to give both aromatic and aliphatic a-amino esters 63 in very high yields (85-98%) and enantioselectivities (94-99% ee). 

An enantioselective organocatalytic reductive amination has been achieved using Hantzsch ester for hydrogen transfer and compound (21) as catalyst. This mild and operationally simple fragment coupling has been accomplished with a wide range of ketones in combination with aryl and heterocyclic amines.359... 

An alternative method for the organocatalytic reduction of imines employs Bronsted acids as catalysts and Hantzsch dihydropyridine as a reducing reagent. This topic is described in Chapter 11 (on Bronsted acids) [86]. 

Asymmetric Organocatalytic Reduction of Olefins 395 Table 11.1 Organocatalytic reduction of conjugated aldehydes by Hantzsch ester 4 [14]. 

We have developed a straightforward strategy for the synthesis of an important class of lepidopteran sex pheromones starting from simple dialdehydes. The combination of a Wittig reaction and an organocatalytic reduction represents a useful sequence for the nontrivial two-carbon homologation of aldehydes. 

Development of the First Highly Enantioselective Organocatalytic Reduction of Ketimines... 

Based on the above activation mechanism we wondered whether it would be possible to develop a biomimetic, organocatalytic reductive amination or transfer hydrogenation of ketimines. We reasoned that the activation of the imine by catalytic protonation through the Brpnsted acid should enable the hydrogen transfer from a suitable NADH mimic to yield the corresponding amine (Fig. 2). Hence, initial experiments focused on the examination of various Brpnsted acids in combination with different hydride sources (Rueping et al. 2005a). 

Figure 7.3 Organocatalytic reductive amination product examples.

Scheme 10.42 Mechanistic proposal for organocatalytic reduction of pyridines.

Asymmetric organocatalytic reductions mediated by dihydropyridines 070BC3407. 

Scheme 1.40 Asymmetric organocatalytic reductive Michael cycUzation...

Scheme 8.24 Organocatalytic reductive aldol reaction by Sugiura and Nakajima [41a].

Soon afterward, MacMillan s group properly explored this organocatalytic reductive amination, observing that the ortho-triphenylsilyl phosphoric acid 17n in the presence of 5-A MS facilitates the desired coupling of acetophenone and 4-OMe-aniline in high conversion and with excellent levels of enantiocontrol at 40 C (87% yield, 94% ee) [55]. Authors report also the reduction of the pyruvic acid-derived cyclic imino ester with excellent enantioselectivity. However, implementation of the corresponding ethyl-substituted imine resulted in a dramatic decrease in... 

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