Aminohydroxylation using chloramine

Two procedures have been developed for the aminohydroxylation of a, 3-unsat-urated amides Procedure A for products that are insoluble in the reaction mixture and Procedure B for soluble products (Scheme 12.17) [48]. These differ only in that the former requires a 10-25% excess of chloramine-T and t-BuOH as the cosolvent, while the latter uses only one equivalent of the chloramine salt and MeCN as the cosolvent. The excess of chloramine-T in Procedure A allows better turnover near the end of the reaction, and the trace amount of p-toluenesulfonamide byproduct can be removed by recrystallization. However, elimination of the necessity to remove p-toluenesulfonamide far outweighed the inconvenience of slightly longer reaction times needed in procedure B without the use of excess chloramine salt. 

Subsequently, stoichiometric asymmetric aminohydroxylation was reported.78 Recently, it was found by Sharpless79 that through the combination of chloramine-T/Os04 catalyst with phthalazine ligands used in the asymmetric dihydroxylation reaction, catalytic asymmetric aminohydroxylation of olefins was realized in aqueous acetonitrile or tert-butanol (Scheme 3.3). The use of aqueous rerr-butanol is advantageous when the reaction product is not soluble. In this case, essentially pure products can be isolated by a simple filtration and the toluenesulfonamide byproduct remains in the mother liquor. A variety of olefins can be aminohydroxylated in this way (Table 3.1). The reaction is not only performed in aqueous medium but it is also not sensitive to oxygen. Electron-deficient olefins such as fumarate reacted similarly with high ee values. 

Sharpless and co-workers first reported the aminohydroxyIation of alkenes in 1975 and have subsequently extended the reaction into an efficient one-step catalytic asymmetric aminohydroxylation. This reaction uses an osmium catalyst [K20s02(OH)4], chloramine salt (such as chloramine T see Chapter 7, section 7.6) as the oxidant and cinchona alkaloid 1.71 or 1.72 as the chiral ligand. For example, asymmetric aminohydroxylation of styrene (1.73) could produce two regioisomeric amino alcohols 1.74 and 1.75. Using Sharpless asymmetric aminohydroxylation, (IR)-N-ethoxycarbonyl-l-phenyl-2-hydroxyethylamine (1.74) was obtained by O Brien et al as the major product and with high enantiomeric excess than its regioisomeric counterpart (R)-N-ethoxycarbonyl-2-phenyl-2-hydroxyethylamine (1.75). The corresponding free amino alcohols were obtained by deprotection of ethyl carbamate (urethane) derivatives. 

According to the original protocol [3] alkenes can be converted to racemic iV-tosyl protected 9-amino alcohols in the presence of catalytic amounts of osmium tetroxide using N-chloramine-T as the nitrenoid source and water as the hydroxyl source. However, unlike the AD-process, the aminohydroxylation of unsymmetrical alkenes can lead to two regio-isomeric products which was a drawback in... 

Since excellent results were obtained in the asymmetric aminohydroxylation in homogeneous phase by Sharpless [169], heterogeneous systems appeared to be of great interest. Nandanan has reported the first heterogeneous osmium tetroxide-catalyzed asymmetric aminohydroxylation of various olefins using polymer-supported bisdehydroquinine ligand 273 (Scheme 111) [170]. When chloramine T was used as nitogen source, yields and ee were moderate with all olefins. 

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