Amine oxides, absolute configuration

Fluoroalcohols 1 have been employed in assigning absolute configuration of amines (30), benzothiophene oxides (45), lactones (33,46), oxaziridines (41), and an amine oxide (47). 

When the alcohol is secondary, the possibility for kinetic resolution exists if the titanium tartrate complex is ctqxiUe of catalyzing the enantioselective oxidation of the amine to an amine oxide (or other oxidation product). The use of the standard asymmetric epoxidation complex, i.e. Ti2(tartrate)2, to achieve such an enantioselective oxidation was unsuccessful. However, modification of the complex so that the stoichiometry lies between Ti2(tartrate)i and Ti2(tartrate)i.s leads to very successful kinetic resolutions of p-hydroxyamines. A representative example is shown in equation (13). " The oxidation and kinetic resolution of more than 20 secondary p-hydroxyamines provi s an indication of the scope of the reaction and of some structural limitations to good kinetic resolution. These results also show a consistent correlation of absolute configuration of the resolved hydroxyamine with the configuration of tartrate used in the catalyst. This correlation is as shown in equation (13), where use of (+)-DIPT results in oxidation of the (5)-P-hydroxyamine and leaves unoxidized the (/ )-enantiomer. 

Kobayashi and co-workers obtained better selectivity with a chiral Yb catalyst (Table 12) [40]. When Y-benzylidenebenzylamine A/-oxide was reacted with 3-(2-butenoyl)-l,3-oxazolidin-2-one in the presence of a catalyst prepared from Yb(OTf)3, binaphthol and cw-l,2,6-trimethylpiperidine, the corresponding isoxazoline was obtained in 78% ee (entry 3). Interestingly, the addition of A/-methyl-bis[(7 )-l-(l-naphthyl)ethyl]amine ((/ )-MNEA) instead of c/5-l,2,6-trimethylpiperidine resulted in increased ee (96% ee, entry 6) whereas addition of (5)-MNEA gave the adduct in only 62% ee (entry 7). When, moreover, the reaction was conducted in the absence of 4A MS or in the presence of other additives, inversion of the absolute configurations of the products was observed (Table 13, entries 2 and 3) [41], as had been observed... 

Interestingly, the diastereomeric ratio between 66 and 66 was dependent upon the amine and the solvent, reaching the maximum value (2 1) for diethylphenylamine in diethyl ether. The diastereomeric mixture of 66 and 66 was treated with sulfur giving the phosphinothioates 67. One of the isomers could be obtained in optically pure form by recrystallisation. Its absolute configuration was unequivocally determined by chemical correlation to the known phosphine oxide 69. With this information several nucleophilic... 

Distinct NMR resonances were first observed for the enantiomers of 2,2,2-trifluoro-l-phenylethanol in the presence of (/ )-phenylethylamine. With (/ )-2-naphthylethylamine the magnitude of the non-equivalence was increased. A systematic study of a series of aryl alcohols in the presence of amines showed a consistent correlation between the sense of non-equivalence and the absolute configuration of the alcohol. From the simple solvation models proposed, the reciprocality of the CSA approach is evident, i.e. if chiral A can be used to assay racemic B then chiral B can be used to assay racemic A. With this in mind 1 -(9-anthryl)-2,2,2-trifluoroethanol (15a) was developed as a CSA for chiral amines. It is also effective with alcohols, lactones, a-amino acid esters, a-hydroxy acid esters and sulphoxides and is the most widely used chiral solvating agent. Other more specific solvating agents have been developed. Kagan has developed A -(3,5-dinitrobenzoyl)-l-phenylethylamine,forexample, as a CSA specifically for the assay of chiral sulphoxides prepared from sulphides by a modified Sharpless oxidation (section 6.3.2). 

With a knowledge of the structures of the necines and necic acids and with the location of ester linkages ascertained, it is possible to write structural formulas to represent the pyrrolizidine alkaloids. Configurations (absolute and relative) at asymmetric carbons and double bonds are indicated when the author feels that these have been established with a reasonable degree of certainty. Structures have not been provided where the information is deemed insufficient, so that not all of the alkaloids listed in Table 1 will be given representations. The alkaloids are divided into three main categories monoesters, diesters (two different necic acids), and cyclic diesters. The amine iV -oxides are not given since their structures are obvious from the amines. 

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