Reduction enamines

Indole synthesis.3 A general indole synthesis involves reaction of an o-nitrotoluene derivative with dimethylformamide dimethyl acetal in refluxing DMF with removal of the methanol to form a nitro N,N-dimethyl enamine. Reduction of the nitro group is accompanied by spontaneous cyclization to an indole. Catalytic hydrogenation is generally preferred for this step. 

Prochiral imines to chiral amines Chiral enamine reductions Ir/Perfluoroalkyl modified-phosphinodihydrooxazoles/B(ArF)4 (it,R)-Et-DuPHOS-Rh+X X = B(f)4 or CF3S03]... 

Table 1. Experimental design and yield in the enamine reduction...

Triprotection of the 12-16-membered tetraazacycles was also achieved through organometallic approaches. Chromium(O) or molybdenum(O) tricarbonyl triamino complexes (e.g., 163-165) <1995JOM215> are substituted with acylhalogenides or aldehydes and N-monosubstituted products are obtained after oxidative deprotection in strong acid and acylamide/enamine reduction to amines <1995TL79>. 

When the reaction was peformed without an acid catalyst four products were formed, the tricyclic diamine 1 (23%), exo-5-morpholinobicyclico[2.2.1]heptan-2-one (1%), 2-mor-pholinobicyclo[2.2.1]hepta-2,5-diene (2%) and an enamine reduction product, enJo-2-mor-pholinobicyclo[2.2.1]hept-5-ene (3%). It has been shown that the yield of the tricyclic diamine increased as the reaction was extended. 

Fig. 16.2 Solvents in tbe study on enamine reduction. Selected test items Formamide...

Fig. 2.14 Rh-catalyzed enamine reductions in the absence of an N-acyl group (a) enamine ester substrate, (b) enamine amide substrate.

As with reductive aminations and imine reductions that employ sodium cyanoborohydride, a significant number of enamine reductions now are reported to afford products stereoselectively. Two representative examples include a reduction and subsequent transformation of a bicyclic enamine (eq 47) and the reduction of a highly functionalized enamine (eq 48) In both instances the... 

Hussaini SR, Moloney MG. 2,5-Disubstituted pyrrolidines versatile regioselective and diastereoselective synthesis by enamine reduction and subsequent alkylation. Org. Biomol. Chem. 2003 1(11) 1838-1841. 

Scheme 14.20 Imine/enamine reduction en route to HIV integrase inhibitor 56. ...

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