Asymmetric amino-hydroxylation

Amino-Hydroxylation. A related reaction to asymmetric dihydroxylation is the asymmetric amino-hydroxylation of olefins, forming v/c-ami noalcohols. The vic-hydroxyamino group is found in many biologically important molecules, such as the (3-amino acid 3.10 (the side-chain of taxol). In the mid-1970s, Sharpless76 reported that the trihydrate of N-chloro-p-toluenesulfonamide sodium salt (chloramine-T) reacts with olefins in the presence of a catalytic amount of osmium tetroxide to produce vicinal hydroxyl p-toluenesulfonamides (Eq. 3.16). Aminohydroxylation was also promoted by palladium.77... 

The enantioselective ring opening of epoxides with salen-Cr complexes yields intermediates for the manufacture of ( )-9-[2-(phosphonomethoxy)propyl]ade-nine [67] (a prophylactic against SIV infection). Os-catalyzed asymmetric amino-hydroxylation (ligand modified by cinchona alkaloids) leads to a-hydroxy-j6-phenylalanine, a derivative for the C13 chain of taxol [68]. 

Hydroxyacetone 96 is a reagent in an even more remarkable reaction the asymmetric direct three-component Mannich reaction. It is combined with an aromatic amine 98 and the inevitable isobutyraldehyde 89 with proline catalysis to give a very high yield of a compound 99 that might have been made by an asymmetric amino-hydroxylation. The proline enamine of hydroxyacetone, must react with the imine salt formed from the amine and isobutyraldehyde. This is a formidable organisation in the asymmetric step. 

Secondary amines can be formed from the same starting materials 136 by tandem Grignard addition andborohydride reduction.43 The reduction shows goodFelkin-Anh selectivity (chapter 21) and the silyl group can be cleaved from the products 140, as they are safe from racemisation, to give a range of amino alcohols 141. Compounds like these can also be made by asymmetric amino-hydroxylation (chapter 25). 

The asymmetric amino-hydroxylation reaction provides a very short synthesis of the side chain of the anticancer agent Taxol . The substrate isopropyl cinnamate was converted to the chiral 1,2-hydroxy amide 98 as essentially a single enantiomer after recrystallization (5.96). Hydrolysis then gave the required amine, as its hydrochloride salt. 

Formation of the chiral 1,2-amido-alcohol 12 can be achieved in a single transformation by using the asymmetric amino-hydroxylation reaction (see Section 5.3.3). For the regioisomer 12, the linker anthraquinone (AQN) rather than the normal phthalazine (PHAL) is required. For the enantiomer 12, the cinchona alkaloid dihydroquinidine (DHQD) is required. Hence, the reagents and conditions effective for the formation of 12 are ... 

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