MoOPH Stereoselectivity

Asymmetric hydroxylation of chiral imides The (Z)-spdium enolates of the chiral imides 2 and 3 undergo asymmetric hydroxylation on reaction with 2-(phen-ylsulfonyl)-3-phenyloxaziridine (1). The products [(R)-4 and (S)-6] are solvo-lyzed to (R)- and (S)-a-hydroxy esters. This hydroxylation can also be effected with MoOPh, which is much less reactive than 1 but slightly more stereoselective. In general 1 is preferred to MoOPh because of the higher yields. 

This reagent is particularly useful for stereoselective hydroxylation. Thus the lactone 2 is oxidized by 1 to a single produet (3), whereas oxidation with MoOPH results in a mixture of 3 and the cpimer 4. 

The technique has been applied to the total synthesis of ( )-oxylubimin (134) through hydroxylation of dienol ether (135).The stereoselectivity is good, particularly when compared to the equivalent select -vities obtained using MCPB A, MoOPH or manganese triacetate. 

Taking stereoselectivity a stage further, MoOPH has been successfully employed in the enantioselec-tive oxidation of esters bearing an enolate face discriminating chiral auxiliary.Thus exposure of the... 

A comparative study contrasting this oxidation with that of MoOPH indicated a markedly improved yield and stereoselectivity (Scheme 20). Although undoubtedly a valid example, the distinction is unlikely to be so universally clear cut and both of these valuable reagents will be useful in synthetic application. 

Stereoselective trans a-hydroxylation of (5)-dihydro-5-(t-butyldiphenylsiloxymethyl)-2(3/f)-furanone can be realized in good yield by enolization and reaction with the Oxodiperox-ymolybdenum(pyridine)(hexamethylphosphoric triamide) complex (MoOPH) (eq 10). Appropriate manipulation of the resulting trans-hydroxylactone provides 1,3-polyols typified by (18), as well as tetrahydropyran (19) which is a key intermediate in mevinic acid syntheses. ... 

In a typical reaction, the lithium enolate of the carbonyl compound 247 is prepared in the usual way and reacted with yellow MoOPH to give the hydroxylated product 248 and blue molybdenum compounds so that the reaction is self-indicating. The best feature of the method is that it uses lithium enolates since the regioselective preparation of these intermediates is much easier to control than that of other metal enolates. Hence 2-phenylcyclohexanone 249 gives a single regioisomer of the hydroxyketone 250 from kinetic enolisation with good stereoselectivity. 

The message is that you should not treat a-hydroxy carbonyl compounds with base if they can enolise on the hydroxyl side. Because MoOPH is not an epoxidising agent, there is good chemo-selectivity if the molecule also contains alkenes. This steroid example 256 shows that good yields and high stereoselectivity can be obtained. 

There is stereoselectivity here, as in the last example, and both are determined by the substrate, that is the molecule being hydroxylated. The reagent MoOPH is large and it attacks the less hindered side of the substrate under kinetic control. Some control can be achieved in the interesting hydroxylation of aspartic acid enolates.41 The lithium enolate of the dimethyl ester of N-protected aspartic acid 259 gives high svn selectivity in hydroxylation next to only one of the two ester groups 260. 

R) or (3S)-3-Hydroxyaspartutes. These amino acids can be prepared in high diastereoselectivity by hydroxylation of the enolate of N-(9-phenylfluorenyl)aspartates. Thus this derivative 1 of L-aspartic acid on treatment with a base followed by reaction with MoOPH provides the 3-hydroxy derivative, syn- and anti-2. The stereoselectivity of this hydroxylation is highly dependent on the base and the solvent. The highest sy/i-selectivity is obtained with LHMDS, LiN[Si(CH3)3]2, as base in THF-DMPU or THF-HMPA. The highest a/iri-selectivity is obtained by treatment first with BuLi and then with LHMDS in THF. 

---