Amines, cyclic amine oxides, synthesis

Iron complexes can also catalyze allylic amination [31,32]. Enders et al. have demonstrated the nucleophilic addition of various acyclic and cyclic amines to the optically active l-methoxycarbonyl-3-methyl-(T)3-allyl)-tetracarbonyliron cation 49 formed in high yield from reaction of 48 with iron carbonyls. Oxidative removal of the tetracarbonyliron group by reaction with CAN gives 50 with high optical purity and retention of the stereochemistry (Eq. (12)) [31]. The reaction proceeds well for the different amines, and has been used for the synthesis of a compound showing cytotoxic activity against diverse cell lines [31b]. 

The utility of reductive amination with NaBHsCN in synthesis is contained in reviews and successful applications have been compiled through 1978. Table 7 provides a variety of examples taken from more recent accounts and chosen to illustrate the versatility and compatibility of the process with diverse structural types and chemoselectivity demands. Thus, esters (entries 2-4, 8-12), amides (entries 3, 6-9, 12), nitro groups (entry 13), alkenes (entry 2), cyclopropyl groups (entry 2), organometallics (entry 5), amine oxides (entry 14) and various heterocyclic rings (entries 1, 3, 5-10) all survive intact. Entry 6 illustrates that deuterium can be conveniently inserted via the readily available NaBDjCN, and entry 15 demonstrates that double reductive amination with diones can be utilized to afford cyclic amines. 

An important group of alkene-forming reactions, some of which are useful in synthesis, are pyrolytic eliminations. Included in this group are the pyrolyses of carboxylic esters and xanthates, of amine oxides, sulfoxides and selenoxides. These reactions take place in a concerted manner, by way of a cyclic transition state and therefore proceed with syn stereochemistry, such that the hydrogen atom and the leaving group depart from the same side of the incipient double bond (in contrast to the eliminations discussed in Section 2.1) (2.14). 

Thioethers. A mixture of diphenyl sulfoxide and HMPA treated with SmL in THF under N2 at 20 for 1 min, diluted with hexane, and filtered through Florisil - diphenyl sulfide. Y 94%. The method can also be used for the rapid deoxygenation of sulfones (which may be viewed as protected thioethers). E Diphenyl sulfone under the same conditions - diphenyl sulfide. Y 93%. Esters remained intact and, in some cases, sulfoxides were selectively reduced in the presence of ketones. F.e. inch formation of cyclic tert. amines from N-oxides, tert. phosphines from phosphine oxides, and distannanes from distannoxanes, s. Y. Handa et al., J. Chem. Soc. Chem. Commun. 1989, 298-9 review of synthesis and use of polysulfoxides s. V.A. Nikonov, G.V. Leplyanin, Sulfur Reports 9, 1-23 (1989). 

For the most part, the routes developed for the synthesis of members of the makaluvamine family have mimicked the proposed biosynthesis route shown in Scheme 9.1. Specifically, pathways have been devised that involve construction of the pyrroloiminoquinOTie skeleton through initial formation of the quinone moiety followed by either imine formation, oxidation of the cyclic amine, or direct iminoquinone formation of substrates possessing an azide side chain. 

The oxidation of amines by mercuric acetate is an old reaction (54) which up until recent years was employed primarily to modify alkaloid structures (55). A systemic study of the oxidizing action of mercuric acetate by Leonard and co-workers led to the development of a general method for the synthesis of enamines from cyclic tertiary amines. An observation made after a large number of compounds were oxidized, but which is worth noting at the onset, is that a tertiary hydrogen alpha to the nitrogen atom is removed preferentially to a secondary a-hydrogen. 

The most general method for synthesis of cyclic enamines is the oxidation of tertiary amines with mercuric acetate, which has been investigated primarily by Leonard 111-116) and applied in numerous examples of structural investigation and in syntheses of alkaloids 102,117-121). The requirement of a tram-coplanar arrangement of an a proton and mercury complexed on nitrogen, in the optimum transition state, confers valuable selectivity to the reaction. It may thus be used as a kinetic probe for stereochemistry as well as for the formation of specific enamine isomers. 

The formation of an enamine from an a,a-disubstituted cyclopentanone and its reaction with methyl acrylate was used in a synthesis of clovene (JOS). In a synthetic route to aspidospermine, a cyclic enamine reacted with methyl acrylate to form an imonium salt, which regenerated a new cyclic enamine and allowed a subsequent internal enamine acylation reaction (309,310). The required cyclic enamine could not be obtained in this instance by base isomerization of the allylic amine precursor, but was obtained by mercuric acetate oxidation of its reduction product. Condensation of a dihydronaphthalene carboxylic ester with an enamine has also been reported (311). 

The direct conversion of alcohols and amines into carbamate esters by oxidative carbonylation is also an attractive process from an industrial point of view, since carbamates are useful intermediates for the production of polyurethanes. Many efforts have, therefore, been devoted to the development of efficient catalysts able to operate under relatively mild conditions. The reaction, when applied to amino alcohols, allows a convenient synthesis of cyclic urethanes. Several transition metal complexes, based on Pd [218— 239], Cu [240-242], Au [243,244], Os [245], Rh [237,238,246,247], Co [248], Mn [249], Ru [224,250-252], Pt [238] are able to promote the process. The formation of ureas, oxamates, or oxamides as byproducts can in some cases lower the selectivity towards carbamates. 

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