Mannich bases, reduction

The p-substituted amino ketones can be reduced readily to the more stable P-dialkylamino alcohols, many of which are useful local anaesthetics. Thus the local anaesthetic Tutocaine is made from the Mannich base derived from formaldehyde, methyl ethyl ketone and dimethylamine, followed by reduction and conversion into the p-aminobenzoate ... 

Asymmetric cyclization to apyrrolizuline. Treatment of the secondary amine 2 with methanolic HC1 followed by reduction of the Mannich base 3 gives the alkaloid (+ )-trachelanlhamidine (4) in about 40% yield. Use of the chiral salt 1 results in asymmetric cyclization to give (+ )-4 in 33% enantiomeric excess. Unfortunately the chemical yield is low. 

Based on our previously developed organocatalytic Mannich methodology (Enders et al. 2005b) we planned a synthetic strategy towards (+)-polyoxamic acid (49) starting from a suitable Mannich base, which would utilize a diastereoselective reduction of the ketone functionality to the corresponding secondary alcohol and an oxidation step to con-... 

Reducing agents have two main effects on Mannich bases, namely, hydrogenolysis of a bonds and reduction of unsaturated functional groups. 

Borohydride reduction of compounds 284 (Fig, 110) makes it possible to obtain N-methyl arylamines, but is limited to NH Mannich bases, as the N-mcthyl derivatives undergo only carbonyl reduction. 

Homocyclic ketones 290 (X = CH2) and 291 predominantly undergo a type B attack, although the reduction with sodium borohydride increases the amount of the minor A isomer. Attack from the A side prevails slightly only in the 6-phenyl-substitutcd Mannich base 290 (X = CH,. R = Ph). ... 

The heterocyclic Mannich bases of oxa- and thia-cyclohexanone (290, X = O, S) obey the general rule of predominant B attack in hydride reductions. The synthesis of A diastereomer requires the use of aluminum isopropoxide (Meerwein-Pondoif), which always favors the opposite direction of attack with respect to metal hydride. 

A further, equally relevant contribution of Mannich bases to oiganic chemistry is their use as intermediates in the synthesis of other compounds, as indicated in Fig. 80. This shows the variety of reactions that Mannich bases may provide, such as the formation of unsaturated derivatives, amino group replacement, cyclization, etc. Other reactions (reduction and oxidation, acylation, etc.), involving substrate or amine moiety, are also reported in the literature. The polymerization reaction, not included in the figure, is treated in Chapter 111., , ... 

When the unsaturated moiety is prochiral, the reaction stereoselectivity may deeply affect the nature of the product. In the reduction of carbonyl Mannich bases containing a chiral center, the formation of a diasteieomeiic mixture of aminoalcohols (Fig. 113) is to be expected. The relative amounts of isomers arc determined by steric hindrance of the asymmetric center as well as by the nature of the reducing agent. On varying the reaction conditions, it is often possible to affect the diastercomeric ratio of the aminoalcohols produced, so as to obtain the predominance of either isomer. This can be particularly relevant in the synthesis of pharmacologically active substances. 

The reduction of acetylenic Mannich bases exhibits several interesting stereochemical features. The triple bond can be partially hydrogenated with di-isobutyl aluminum hydride, thus giving E-allylamines 293. This reagent provides very good stereoselectivity, the mechanism of which has been investigated. - ... 

This reaction was discovered during preparation of the Mannich base from the ethynyl A-nor steroid 1. Allene 3 is obtained from this reaction as a side product in 31% yield. Allene 3 is also available from 2 by quaternization and L1A1H4 reduction. ... 

Reduction of —CH2N(CH3)i to —CH3 The quaternary ammonium salts of Mannich bases are reduced to the corresponding methyl compounds by NaBHaCN in HMPT. 

The Mannich base is polarographically active, the carbonyl group being reduced to the corresponding alcohol (Zuman and Horak, 1962). During the elimination reaction this reduction wave decreases (Fig. 9) and the change of its height can be used for evaluation of the kinetics. But... 

The synthesis of sparteine, following the hypothesis of Schopf, can be accomplished from acetone, formaldehyde, and piperidine (57). The resulting Mannich base is dehydrogenated with mercuric acetate and the resultant intermediate spontaneously cyclizes to 8-ketosparteine (LIT), from which Wolff-Kishner reduction generates d -sparteine (II). 

The reduction of ammonium salts, formed by reacting Mc2S04 with benzylic Mannich bases 2,54, by NaCNBH3 in HMPA at 70°C, leads to methylated aromatic... 

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