Amines, allylic tertiary reduction

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). 

The most conspicuous property of aliphatic amines, apart from their fishy smell, is their high basicity, which usually precludes N-alkylations under acidic reaction conditions (last reaction, Scheme 6.3). Hence, alkylation of amines with tertiary alkyl groups is not usually possible without the use of highly stabilized carbocations which can be formed under basic reaction conditions. Rare exceptions are N-alkyla-tions of amines via radicals (Scheme 4.2), copper-catalyzed propargylations (Scheme 6.3), and the addition of amines to some Michael acceptors and allyl palladium or iridium complexes. Better strategies for the preparation of tert-alkylamines include the addition of Grignard reagents to ketone-derived imines [13] or the reduction of tert-alkyl nitro compounds. 

Benzylic and allylic tertiary amines may be reduced to hydrocarbons using one of two methods. Oxidation to an amine oxide followed by reduction with lithium in liquid ammonia provides one of these... 

The reductive coupling of of dienes containing amine groups in the backbones allows for the production of alkaloid skeletons in relatively few steps [36,46,47]. Epilupinine 80 was formed in 51% yield after oxidation by treatment of the tertiary amine 81 with PhMeSiEh in the presence of catalytic 70 [46]. Notably, none of the trans isomer was observed in the product mixture (Eq. 11). The Cp fuMcTIIF was found to catalyze cyclization of unsubstituted allyl amine 82 to provide 83. This reaction proceeded in shorter time and with increased yield relative to the same reaction with 70 (Eq. 12) [47]. Substitution of either alkene prevented cyclization, possibly due to competitive intramolecular stabilization of the metal by nitrogen preventing coordination of the substituted olefin, and resulted in hydrosilylation of the less substituted olefin. 

Allylic alcohols also may be arylated in / /-methylpyrrolidinone or DMF solution with sodium bicarbonate as the base.81 The use of this base improves the yields of aldehydes obtained compared with tertiary amine bases in the case of aryl bromides with electron-withdrawing substituents, where reduction to an arene is sometimes a problem,... 

Chiral tertiary allylic amines 191 with /ra r-2-phenylsulfonyl-3-phenyloxaziridine 33 also gave rise to amine A -oxides 192, which underwent the [2,3]-Meisenheimer rearrangement to hydroxylamines 193 with a high level of stereoselectivity (Table 14) <1999J(P1)2327>. Reduction of 193 gave the corresponding allylic alcohols 194. 

The features of Red-Al are the following It easily reduces halogenated derivatives even if acetylenic (Section 2.1) tertiary amides lead to aldehydes (Section 3.2.8) and propargylic alcohols and amines are reduced to corresponding allylic alcohols and amines (Section 4.1). Epoxides remain intact unless they carry an alcohol functional group at the a position The reduction is then regioselective (Section 2.3). Aromatic nitriles are reduced, but aliphatic nitriles are not affected (Section 4.3). 

Allylic nitro derivatives such as 5.10 can also suffer similar reductions via ir-allyl complexes [TM3] (Figure 5.7). Tertiary allylic amines such as 5.11 can be transformed into secondary amines via Tr-allylpalladium complexes that are reduced with NaCNBHs [TM3] (Figure 5.7). 

It has been noted that those morphine derivatives in which the nitrogen is allylic (compounds) can be degraded to dihydromethines by reduction of their methiodides with sodium in liquid ammonia (397), and the important observation has been made that a useful alternative to the Hofmann degradation consists in the decomposition of tertiary amine oxides, especially in those cases in which the Hofmann elimination results in loss of the side chain. It will also be noted that double bonds are not isomerized in this process (398) ... 

Direct replacement of an amino group by hydrogen is possible only in certain cases. Such reductive fissions are particularly well known for tertiary amines and quaternary ammonium compounds and occur especially readily with allyl- and benzyl-substituted amines. In the last-mentioned cases the benzyl group is removed as toluene, and this reaction route is used for preparation of secondary from primary aliphatic amines the primary amine is first condensed with benzaldehyde, and the resulting Schiff base is reduced to the alkylbenzylamine this is converted by alkylation into the dialkylbenzyl-amine, from which finally the benzyl group is removed by catalytic hydrogenation 544... 

The. V-alkylation of ephedrine is a convenient method for obtaining tertiary amines which are useful as catalysts, e.g., for enantioselective addition of zinc alkyls to carbonyl compounds (Section D. 1.3.1.4.), and as molybdenum complexes for enantioselective epoxidation of allylic alcohols (Section D.4.5.2.2.). As the lithium salts, they are used as chiral bases, and in the free form for the enantioselective protonation of enolates (Section D.2.I.). As auxiliaries, such tertiary amines were used for electrophilic amination (Section D.7.I.), and carbanionic reactions, e.g., Michael additions (Sections D. 1.5.2.1. and D.1.5.2.4.). For the introduction of simple jV-substituents (CH3, F.t, I-Pr, Pretc.), reductive amination of the corresponding carbonyl compounds with Raney nickel is the method of choice13. For /V-substituents containing further functional groups, e.g., 6 and 7, direct alkylations of ephedrine and pseudoephedrine have both been applied14,15. 

Stille and co-worker developed an attractive route to aza-Claisen precursors. Allylamine reacted with 2-methylpropanal (isobutyraldehyde), for example, to give allylimine 658. When this reacted with 2-methylpropanoyl chloride, N-acyl derivative 659 was produced (94% overall yield from allylamine) and reduction with LiAlH4 give a 98% yield of the tertiary amine, 660. Stille found that conversion of the amine to the ammonium salt by treatment with HCl led to clean conversion to 661 in 82% yield via a [3,3]-sigmatropic rearrangement (an aza-Claisen rearrangement). Reduction of the iminium salt led to an 81% yield of 662 from 661. Stille and co-workers also found that Lewis acids as well as HCl react with the allyl enamine precursor to facilitate the aza-Claisen rearrangement. 2... 

Sucrow provided one of the few examples for the use of an Eschenmoser-Claisen rearrangement involving simple diastereoselection in natural product synthesis (Scheme 7.30) [72, 73]. In a semi-synthesis of sigmastatrienol, the syn isomer 88 was preferentially formed as a consequence of the (Z)-configuration of allylic alcohol 87. Subsequent reduction to the tertiary amine followed by Cope elimination completed the installation of the steroid s side chain [74]. 

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