Reduction organocatalyst

Scheme 77.3 Example of organocatalyst reduction of enone with the hantzsch ester.

In a recently published report by MacMillan s group [121] on the enantioselective synthesis of pyrroloindoline and furanoindoline natural products such as (-)-flustramine B 2-219 [122], enantiopure amines 2-215 were used as organocatalysts to promote a domino Michael addition/cyclization sequence (Scheme 2.51). As substrates, the substituted tryptamine 2-214 and a, 3-unsaturated aldehydes were used. Reaction of 2-214 and acrolein in the presence of 2-215 probably leads to the intermediate 2-216, which cyclizes to give the pyrroloindole moiety 2-217 with subsequent hydrolysis of the enamine moiety and reconstitution of the imidazolid-inone catalyst. After reduction of the aldehyde functionality in 2-217 with NaBH4 the flustramine precursor 2-218 was isolated in very good 90 % ee and 78 % yield. 

Formamides derived from L-pipecolinic acid act as Lewis base organocatalysts for reduction of A-arylimines with trichlorosilane, giving yields and ees in the high 90s for a wide range of imine substrates.54... 

A new, metal-free protocol involving (heteroaryl)oxazoline catalysts for the enantioselective reduction of aromatic ketones (up to 94% ee) and ketimines (up to 87% ee) with trichlorosilane has been developed. The reaction is characterized by an unusual, long-ranging chiral induction.The enantiodifferentiation is presumed to be aided by aromatic interactions between the catalyst and the substrate.360 Asymmetric reduction of A-arylketimines with trichlorosilane is catalysed by A-methyl-L-amino acid-derived Lewis-basic organocatalysts with high enantioselectivity (up to 92% ee) 61... 

The Shimizu group investigated the potential of another structural type of sulfide organocatalyst, 5- and 6-membered cyclic sulfides [211]. These sulfides were prepared by biocatalytic reduction using baker s yeast. In particular the 5-... 

Serotonin (8) mimics have been used effectively as treatments for a variety of psychiatric illnesses [199-201]. Homotryptamines could be constructed by multistep routes. One-pot synthesis of homotryptamines 277a-k was achieved by the conjugate addition of indoles with acrolein in the presence of the MacMillan organocatalysts (118a, 274) followed by reductive amination (Scheme 60) [201]. 

To date, there have been no examples of asymmetric reductions of ketones by Hantzsch esters and a chiral organocatalyst. 

Although the turnover frequency (TOF) and turnover number (TON) of the various above-described organocatalysts remain modest when compared to metal catalysis, the chiral organocatalysts are of relatively simple structure, and this permits easy tuning of the reaction. Clearly, one can predict many improvements in this area in the future, and undoubtedly new organocatalytic reactions relating to reduction will be introduced, using some of the basic processes described in Section 11.1. 

Fig. 30 Asymmetric aldehyde alkylation using organocatalyst 119 and reductive photoredox catalysis...

Cinchona-Based Organocatalysts for Asymmetric Oxidations and Reductions... 

---