Hydroxylations, enantioselective

Scheme 12.8. Enantioselective Hydroxylation Using Chiral Diamines...

Enantioselective hydroxylation of the double bond in C=N nitrones with diphenylsilane, using RU2CI4-I(S)-(—)-p-tolbinap 2(NEh) [p-tolbinap = 2, 2 -bis(di-p-tolylphosphino)-1,1 -binaphthyl] as a catalyst at 0°C, gives the corresponding optically active /V,N -disubstituted hydroxylamines (482). 

The tra x-[Ru (0)2(por)] complexes are active stoichiometric oxidants of alkenes and alkylaro-matics under ambient conditions. Unlike cationic macrocyclic dioxoruthenium I) complexes that give substantial C=C bond cleavage products, the oxidation of alkenes by [Ru (0)2(por)] affords epoxides in good yields.Stereoretentive epoxidation of trans- and cw-stilbenes by [Ru (0)2(L)1 (L = TPP and sterically bulky porphyrins) has been observed, whereas the reaction between [Ru (0)2(OEP)] and cix-stilbene gives a mixture of cis- and trani-stilbene oxides. Adamantane and methylcyclohexane are hydroxylated at the tertiary C—H positions. Using [Ru (0)2(i)4-por)], enantioselective epoxidation of alkenes can be achieved with ee up to 77%. In the oxidation of aromatic hydrocarbons such as ethylbenzenes, 2-ethylnaphthalene, indane, and tetrahydronaphthalene by [Ru (0)2(Z>4-por )], enantioselective hydroxylation of benzylic C—H bonds occurs resulting in enantioenriched alcohols with ee up to 76%. ... 

Scheme 12.7 gives some examples of enantioselective hydroxylations using these reagents. 

Enantioselective hydroxylation of 2-benzyl (3-ketoesters was catalysed by [RuCl(OEt3)(PNNP)]/aq. H O /CH Cy thus ethyl 2-benzyl-3-oxo-butanoate gave ethyl 2-hydroxy-2-benzyl-yoxo-butanoate. Better results were obtained with cumyl hydroperoxide as co-oxidant [14]. The reagent Ru(CO)(TPP) or Ru(CO) (TMP)/(Cl3pyNO)/aq. HBr/C Hy40°C oxidised 5 3-steroids to the corresponding Sp-hydroxy derivatives with retention of configuration [15]. 

Iron-containing cytochrome P-450 constitutes the most famous example of a selective C-H bond oxidizer. Although the exact nature of the mechanism remains controversial, the reaction most likely proceeds through radical intermediates [2]. The hydroxylation of activated C-H bonds has also been carried out in the presence of synthetic porphyrin complexes. In these biomimetic processes, ruthenium plays a relatively minor role when compared with iron. Zhang et al. [50], however, recently reported the enantioselective hydroxylation of benzylic C-H bonds using ruthenium complexes supported by a D4-sym-metric porphyrin bearing a crafted chiral cavity. Thus, complex 23 reacts in a stoichiometric manner with ethylbenzene to give phenethyl alcohol with a... 

C.R., Kasrayan, A., BSckvall, J.-E. and Arnold, F.H. (2006) Enantioselective hydroxylation of 2-arylacetic acid derivatives and buspirone catalyzed by engineered cytochrome P450 BM-3. Journal of the American Chemical Society, 128, 5058-6059. 

Zeolite-encapsulated perfluorinated ruthenium phthalocyanines catalyze the oxidation of cyclohexane with t-BuOOH [146]. A dioxoruthenium complex with a D4-chiral porphyrin ligand has been used for the enantioselective hydroxylation of ethylbenzene to give a-phenylethyl alcohol with 72% e.e. [147]. 

Double bonds in the side chains of aromatic compounds undergo hy-droxylation in the same way as those in simple alkenes [784]. With some compounds, such as stilbene, enantioselective hydroxylation can be accomplished with chiral compounds, which, by complexing osmium tetrox-ide, form enantiomeric products in high enantiomeric excesses (equation 83) [951, 1033]. 

Enantioselective hydroxylation of double bonds also occurs in biochemical oxidation by Pseudomonas putida [1073]. 

Table 18 Enantioselective hydroxylation of prochiral cyclic ketone enolates. ... 

R) -( + )-2-Acetyl-5,8-dimethoxy-l,2,3,4-tetrahydro-2-naphthol (173) is a key intermediate in the asymmetric synthesis of anthracycline antitumor agents demethoxyadriamycin (174 X = Y = OH) and 4-demethoxydaunomycin (174 X = Y = H) <94JOCli84>. The crucial step in a highly efficient asymmetric synthesis of (173) involves the enantioselective hydroxylation (>95% ee) of the potassium enolate of (171) with (—)-[(8,8-dimethoxycamphoryl)sulfonyl]-oxaziridine (158) to afford (172). Conversion to (173) was accomplished in three steps in 50% overall yield from (171) without racemization (Scheme 32). 

Hilker et al. [59] studied the Novozym 435-catalyzed copolymerization of racemic a,a -dimethyl-l,4-benzenedimethanol with secondary hydroxyl groups with dimethyl adipate. Due to CALB enantioselectivity, hydroxyl groups at (R) stereocenters preferably reacted to form ester bonds with liberation of methanol. The reactivity ratio was estimated as (R)/(S) = 1 x 106. In situ racemization of monomer stereocenters from (S) to (R) by ruthenium catalysis allowed the polymerization to proceed and reach high functional group conversations. Readers should also refer to Chapter 11 for more information on chiral discriminations by lipases. 

Several examples exist in the literature in which cyclic ketone enolates are enantioselectively hydroxylated by chiral, nonracemic Davis oxaziridine reagents. In contrast to their acyclic counterpart, the enolate geometry is fixed in cyclic systems. During the preparation of enantiomerically pure (-)-blebbistatin, the enolate of the quinolone 61 was reacted with the Davis reagent 5 to afford the optically enriched 62 with 82% yield and 86% ee.54 The related reagent 6 was used in the synthesis of (-t-)-o-trimethylbrazilin, which was... 

The utility of Davis chiral oxaziridine reagents has been more recently applied to the synthesis of optically active a-hydroxy phosphonates. Two groups have been largely responsible for developments in this area. Principally, Wiemer and co-workers have demonstrated the highly enantioselective hydroxylation of a series of benzyl phosphonates. As shown below for 69, hydroxylation makes use of oxaziridine 6, proceeding in moderate... 

Camphor-derived, V- s u 1 fo n y 1 ox azi ri d in es 51-58 are chiral oxidants which are able to oxidize a variety of substrates enantioselectively. They have been used for the epoxidation of alkenes (Section D.4.5.2.I.), the preparation of chiral sulfoxides and selenoxides (Section D.4.11.2.1.), and enantioselective hydroxylation of enolates (Section D.4.I.). 

Scheme 24 Enantioselective hydroxylation of oxindoles with molecular oxygen...

Tybring, G. Bottiger, Y. Widen, J. Bertilsson, L. Enantioselective hydroxylation of omeprazole catalyzed by CYP2C19 in Swedish white subjects. Clin. Pharmacol. Ther. 1997, 62, 129-137. 

Recently, an efficient and enantioselective hydroxylation reaction of C—H bonds using an environmentally benign and easily accessible oxidant (H2O2) catalyzed by a water-soluble chiral manganese porphyrin complex C30 was developed by Simonneaux and co-workers. The corresponding secondary alcohols 161 were delivered as the major products, albeit only moderate enantiomeric excess was obtained (Scheme 1.63). Notably, imidazole was found to play an important role in this catalytic system, working as an axial ligand to the Mn center. 

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