Reductive alkylation affected carbons

Reductive amination of benzaldehyde with (R)-81 provided the corresponding benzyl amine, which was reductively alkylated with formaldehyde to give 82 (Scheme H) " Compound 82 was debenzylated by hydrogenation in the presence of Pearlman s catalyst to afford frovatriptan ((/J)-6). Alternatively, monomethylation of amine (/ )-81 was affected by treatment with carbon disulfide and dicyclohexylcarbodiimide in pyridine to provide isothiocyanate 83, which was reduced with sodium borohydride to give (l )-6. 

Secondary amines can be prepared from the primary amine and carbonyl compounds by way of the reduction of the derived Schiff bases, with or without the isolation of these intermediates. This procedure represents one aspect of the general method of reductive alkylation discussed in Section 5.16.3, p. 776. With aromatic primary amines and aromatic aldehydes the Schiff bases are usually readily isolable in the crystalline state and can then be subsequently subjected to a suitable reduction procedure, often by hydrogenation over a Raney nickel catalyst at moderate temperatures and pressures. A convenient procedure, which is illustrated in Expt 6.58, uses sodium borohydride in methanol, a reagent which owing to its selective reducing properties (Section 5.4.1, p. 519) does not affect other reducible functional groups (particularly the nitro group) which may be present in the Schiff base contrast the use of sodium borohydride in the presence of palladium-on-carbon, p. 894. 

In the reductive alkylation of ammonia with cyclohexanone, Skita and Keil found that, although cyclohexylamine was obtained in 50% yield over a nickel catalyst, over colloidal platinum dicyclohexylamine was produced as the predominant product even in the presence of an excess molar equivalent of ammonia. Steele and Rylander compared the selectivity to primary amine, secondary amine, and alcohol in the reductive alkylation of ammonia with 2- and 4-methylcyclohexanones over 5% Pd-, 5% Rh-, and 5% Ru-on-carbon as catalysts.18 As seen from the results shown in Table 6.2, the formation of secondary amine is greatly depressed by the methyl group at the 2 position. Thus over Pd-C the secondary amine was formed predominantly with cyclohexanone and 4-methylcyclohexanone while the primary amine was produced in 96% selectivity with 2-methylcyclohexanone. Over Ru-C the alcohol was formed quantitatively with 4-methylcyclohexanone without the formation of any amines, whereas with 2-methylcyclohexanone the alcohol was formed only to an extent of 57%, accompanied by the formation of 4 and 39% of the secondary and primary amines, respectively. These results indicate that secondary amine formation is affected by the steric hindrance of the methyl group to a much greater extents than is the formation of the primary amine or the alcohol. The results with Ru-C and Rh-C also indicate... 

A virus in both sialidase inhibition and plaque-reduction assays. Alkyl ethers up to twelve carbon atoms in length exhibited similar inhibitory activity to Zanamivir against influenza A virus sialidase, however, showed a pronounced improvement in plaque-reduction assay compared to the parent triol 1. Alkylation of the C-7 hydroxyl with two-carbon substituents bearing terminal hydroxyl, amino, azido, and acetamido groups yielded inhibitors 61-64 and did not significantly affect the binding and had similar potency to that of ethyl or propyl ethers 65 or 66 (Fig. 9). 

Functional Group Transformations Functional group transformations help us in the conversion of a functional group to an aldehyde or a ketone without affecting the carbon skeleton of the molecule. Aldehydes can be synthesised by the oxidation of primary alcohols, or by the reduction of esters, acid chlorides, or nitriles. Since nitriles can be obtained from alkyl halides, this a way of adding an aldehyde unit (CHO) to an alkyl halide ... 

In conclusion to this section, we should emphasize that since ethers are less reactive with lithium than the alkyl carbonates or the esters (reviewed in previous sections), salt and contaminant reduction may be highly important in affecting the surface chemistry developed on lithium in ethers (compared with alkyl carbonate and esters). 

Our examples will first center on the complexes Ir(CO)(R)(R0L2X (R and R = H, alkyl, or aUcoxy L = PPhs or P(/ -tolyl)3 X = halide or H), which reductively eliminate a number of different products. The reactions are summarized in Table 11. The reactions described in Table 11 show that reductive elimination from Ir results in formation of different types of bonds. These reductive elimination reactions occur under very similar conditions, indicating that the nature of R and R does not significantly affect the rate. However, the coupling of two sp carbon centers does not occur. Theoretical studies have suggested that the directionality of the sp hybrid inhibits bond formation. ... 

A currently employed method for dehalogenation of alkyl halides is to use a Li- or Na-alcohol reagent system. This method is effective not only for simple alkyl halides but also for the reduction of a halogen atom attached to a bridgehead. Carbon-carbon unsaturated bonds are not affected under the conditions, as shown in Scheme 5. ... 

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