PHAL ligand

Olefins of the /ranr-disubstituted type have given diols with excellent enantiomeric purities when dihydroxylated with the (DHQD)2-PHAL/(DHQ-PHAL pair of chiral ligands with osmium tetroxide (see Table 6D.3 [16,26,29,31,35,40,41,46-48]). All the entries but one in Column 9 for diols obtained with these ligands exceed 90% ee (or 90% de). From other entries in Table 6D.3, particularly those of Column 3 for earlier stoichiometric ADs with the DHQD-CLB ligand, good enantioselectivities are anticipated for the dihydroxylation of most trans-disubstituted olefins when the PHAL ligands are used. 

To explain the high enantioselectivity of the AD with the PHAL ligand in such a stepwise process. Sharpless proposed the formation of arrangement 12 with an L-shaped binding pocket that is built up by the phthalazine and one of the methoxyquinolines [26]. 

Conjugated esters are a third class of substrates well suited for the AA. The (3-amino-a-hydroxy esters 68-71, resulting from the AA with PHAL ligands, are components of several small bioactive peptides, like the renin inhibitor KRI1314... 

A few recent studies have described the AA of substrates containing chiral [40, 70, 72, 94, 97, 98] or prochiral [99-102] centers. In the AA of chiral substrates, double diastereoselectivity arose from the interaction of the substrate with the chiral ligand. The AA proceeded with the sense of facial selectivity expected for the DHQD or DHQ ligands. The effect of the chiral center on the facial selectivity has not been investigated. A study of the AA of the chiral alkene 79 with the pseudoenantiomeric forms of the PHAL ligands revealed that the DHQ and the DHQD ligands led to matched (70% de) and mismatched (29% de) reactions, respectively (Scheme 18) [97]. 

C4C1im][PF6] 0s04 NMO Enantioselective dihydroxylation of olefins with H20 and acetone as co-solvents products extracted with tert-butyl methyl ether. Use of a charged chiral PHAL-ligand. [66]... 

The phthalazine (PHAL) (4) [38] and diphenylpyrimidine (PYR) (5) [39] ligands contain two independent alkaloid units, attached to a heterocyclic spacer, while the indolinyl carbamyl (IND) (6) [40] ligand is attached to only one alkaloid. PHAL ligands are recommended for 1,1- and 1,2-trans disubstituted... 

These ligands were superseded with the development of the phthalazine (PHAL) ligands in which two cinchona alkaloid units are connected together.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. 

MPEG with (DHQDV PHAL ligand BuOH/H20 acetone/HjO Sharpless dihydroxylation Precipitation (diethyl ether) [135]... 

PHAL ligands have been observed to perform poorly on substrates possessing pyridine rings vide supra), however both PYR and AQN ligands have been used to effect highly selective AD reaction of l-aryl-l -pyridyl-substituted terminal alkenes such as (5.43). ... 

PEG [Poly(ethylene glycol), molecular weight 400] can be used as an alternative recyclable medium for the AD reaction. Using (DHQD)2 PHAL ligand, OsOa, and NMO in PEG, it was possible to reuse the catalytic system for up to five cycles, producing the desired diols in high yields with excellent enantioselectivities without any loss of catal)dic activity. ... 

Sharpless has noted that the regiochemical outcome with cinnamyl esters is coupled to the ligand system employed [237]. Thus, when AQN ligands (314), were used, benzylic alcohols were preferentially obtained, rather than the benzylic amines observed with PHAL ligands (311). This selectivity trend was utilized by Joullie in the synthesis of the potent microtubule assembly inhibitor ustiloxin D (356, Scheme 9.45) [238]. Under optimized conditions, cinnamyl ester 354 was converted selectively into the desired benzylic alcohol 355 (58% yield). This constitutes one of the structurally more complex substrates to have successfully been employed in catalytic asymmetric aminohydroxylation [238, 239]. 

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