Reduction of enamines

Enamines are reduced to amines in good yields with Et3SiH/TFA.529 533 This reagent combination causes a variety of indoles to undergo stereoselective cis 

The enamide double bond is reduced in preference over that of the enone moiety in each of the two examples shown below (Eqs. 324 and 325).536,537 Other enamides are reduced under similar conditions.235,537,538 

103 is possibly produced by a 1,2-addition of the N-acyl imine generated from the enamide 101 via tautomerization,4H-l,3-oxazine 102is formed froma 1,4-conjugate addition followed by cyclization via an ehmination of HOSiCl3 [63]. 

Reduction of C=N Bonds Catalyzed by Recoverable Lewis Base Catalysts 

Entry Lewis base catalyst (loading, mol%) Reaction conditions R R Yield (%) (% ee) References 

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The chemical reduction of enamines by hydride again depends upon the prior generation of an imonium salt (111,225). Thus an equivalent of acid, such as perchloric acid, must be added to the enamine in reductions with lithium aluminum hydride. Studies of the steric course (537) of lithium aluminum hydride reductions of imonium salts indicate less stereoselectivity in comparison with the analogous carbonyl compounds, where an equatorial alcohol usually predominates in the reduction products of six-membered ring ketones. 

Olefins are also the products of hydroboratlon of enamines, followed by treatment of the organoborane products with hot acid (543,544). The reduction of enamines with sodium borohydride and acetic acid (545) and the selective reduction of dienamines with sodium borohydride to give homo-allylic tertiary amines (138-140,225,546,547), has been applied to the synthesis of conessine (548) and other aminosteroid analogs (545,549-552). Further examples of the reduction of imonium salts by sodium borohydride can be found in the reduction of Bischler-Napieralski products, and other cyclic imonium salts (102). 

Greater stereoselectivity for the formation of equatorial amines has been found in the reduction of enamines with formic acid or formamides (553-559). The selective formation of 3-a-amino-5- -steroids by this method and of 3- 3-amino-5- 3-steroids by catalytic reduction (5<50) of the corresponding enamines is of interest. 

An unexpected reduction of enamines by secondary amines such as pyrrolidine, piperidine, and particularly hexamethyleneimine was discovered in the formation of the norbomanone enamines and extended to hexamethyleneiminocyclopentene (561,562). 

Supplemental References for Table 22. Organosilane Reduction of Enamines... 

Coordination of the aluminum atom of the reducing complex was proposed to take place both to the oxygen atom of the hydroxy group and to the nitrogen atom of the amino group. The asymmetric reduction of enamine perchlorates and ketimines with menthol and bomeol chiral auxiliary reagents (50,51) presumably involves coordination of aluminum to the nitrogen atom of the substrate. 

For a review of the reduction of enamines and indoles with NaBH, and a carboxylic acid, see Gribble Nutaitis Org. Prep. Proced. Int. 1985, 17, 317-384. Enamines can also be reduced by formic acid sec Nilsson Carlson Acta Chem. Scand. Sect. B 1985, 39, 187. 

The Wallach-Leuckart reductive alkylation of ammonia, and primary and secondary amines, by means of aldehydes and ketones, and the methylation of secondary amines according to Clarke and Eschweiler,3160 all possess a reduction step which is very similar to that observed in the reduction of enamines.317... 

There are already a few reviews1,2 and a comprehensive book3 surveying the chemistry of enamines. This contribution aims at offering a view on the oxidation and reduction of enamines, covering the widest possible literature on these subjects. We apologize for any unintentional omissions. 

The reduction of enamine unit occurs much more rapidly than that of the carbonyl group. Therefore, this reagent can be used to perform reductive amination of aldehydes and ketones, by simply reacting the carbonyl compound with a fourfold excess of the amine. In a similar manner, reductive methylation of amines could be accomplished by addition of formaldehyde to the amine119. 

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