Phthalazine ligands

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. 

These ligands were superseded with the development of the phthalazine (PHAL) ligands in which two cinchona alkaloid units are connected together. The two most widely used ligands are the phthalazine ligands (DHQD)2-PHAL 93 and (DHQ)2-PHAL and these are used in the two commercially available asymmetric dihydroxylation mixes - AD-mix-a and AD-mix-p. 

More recently discovered ligands21 include the diphenylpyrazinopyridazine (DPP) 98 and anthraquinone (AQN) 99 ligands as well as the diphenyl analogue of the phthalazine ligands (DP-PHAL) 97. 

Figure 8.5. Ligands for the Sharpless AD process, (a) The phthalazine ligand (PHAL class), recommended for most substitution types [74,75]. (b) The diphenylpyrimidine ligand (PYR class), used for mono- and tetrasubstituted olefins...

Use of these phthalazine ligands and addition of a sulfonamide results in cnantio-selcctivitics of 95-99.5% in the case of nonterminal alkcncs. In general, reactions with ligand 1 are somewhat more cnantioselectivc than those with ligand 2. 

However, the use of these dihydroquinidine and dihydroquinine phthalazine ligands does not improve the enantiosclcctivity of c/.v-disubstituted alkencs.2 The problem in this case can be solved by use of carbamate ligands such as (9-0-indolinylcarbamoyl)dihydroquinidine, DHQO-IND (I). 

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