Piperidine derivatives diastereoselective synthesis

Chiral and nonracemic A-cyanomethyloxazolidines in diastereoselective synthesis, particularly of pyrrolidine and piperidine derivatives 99CSR383. 

Diastereoselective synthesis, particularly of piperidine derivatives using chiral and nonracemic A-cyanomethyloxazolidines 99CSR383. 

Kunz and coworkers reported the application of an immobilized chiral galacto-sylamine in diastereoselective synthesis of piperidine and amino acid derivates [14]. Preparation of the galactosylamine auxiliary from 1,6-hexandiol and P-D-galactopyranosyl azide (1) required a six-step synthesis protocol. The precursor 2 was loaded onto a polymer bound silane. Reduction of the azide function gave the corresponding immobilized amine 3 (Scheme 12.2). 

Remuson and coworkers reported that highly diastereoselective synthesis of 2,6-cis-disubstituted-4-methylenepiperidines based on a Mannich type intramolecular cyclization of allylsilane [37]. Reaction of p-aminohydroxysilane 116 with carbonyl derivative in the presence of TFA in a mixture of H2O-THF (1 1) led to 4-methylenepiperidine 117. Oxidation with osmium tetraox-ide in the presence of Na3H3lOe in AcOH led to piperidin-4-one followed by the stereoselective reduction with NaBH4 afforded (- -)-241D (13) and its C-4 epimer 118 in a ratio of 83 17 (Scheme 20). 

Asymmetric hydroamination has served as an important strategy for the synthesis of pyrrolidine and piperidine derivatives. Moreover, it has been found to be useful for the synthesis of other five- and six-membered heterocyclic compounds having more than one hetero atom. Asymmetric hydroamination and diastereoselective hydroamination have been found to be extremely useful for the synthesis of natural products and pharmaceutical agents. It is important to note that diastereoselective hydroamination has been... 

Ring-closing reactions promoted by mercuric salts are valuable transformations which find an increasing use in the total synthesis of various natural products.130-140 Several examples of solvomercurations demonstrating the applicability of these transformations to the synthesis of natural product precursors are presented in Table 2. Piperidines (entry a), 141 pyrans (entries b-d), 142-144 and furans (entries e, f)14S>146 have been obtained in good yields and diastereoselectivity. These derivatives serve as starting materials for various natural products and can be demercu-rated under reducing conditions.147... 

Related reactions of acyclic unsaturated amide derivatives S show a reversal of the diastereofa-cial selection according to the geometry of the double bond. This is in contrast to the carbamate series (vide infra)13 which is dependent on the nature of the nucleophile68. The most remarkable feature is the formation of 1,2-syvj-products 6B from the A-isomers. This may be best explained by the steric repulsion between the ester and acyl groups. This complementary and effective diastereoselection provides a stereodivergent synthesis of 2,3-disubstituted piperidines (see also Section D.7.3.1.1.2.2.). 

The only enantioselective synthesis of julandine to date is due to Kibayashi and co-workers (593). Lewis acid-catalyzed condenseition between silyl enol ether 901 and the acyliminium ion formed from the proline-derived lactam 902 was highly diastereoselective (>99% de), giving a 76% yield of the piperidin-2-one 903 (Scheme... 

The use of chiral chloroformates, such as that derived from tranx-2-(a-cumyl)cyclohexanol, allows diastereoselective additions to 4-methoxypyridine. The introduction of a tri-ixo-propylsilyl group at C-3 greatly enhances the diastereoselectivity. The products of these reactions are multifunctional chiral piperidines which have found use in the asymmetric synthesis of natural products. ... 

Rh-catalyzed cyclohydrocarbonylation of functionalized homoallyic amine has been successfully applied to the synthesis of (+)-prosopinine (97) and (-)-deoxyprosophyline (98) (Figure 2-4). Both (+)-prosopine and (-)-deoxyprosophyline have been shown to possess both antibiotic and anesthetic properties. This synthesis uses amino acid derivatives that are subjected to CHC conditions to generate the desired substituted piperidine intermediates. The piperidine intermediates are then further converted to the desired alkaloid by subsequent diastereoselective introduction of the alkyl chains at the C-6 position. 

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