Alcohols asymmetric oxidation

Bartoli recently discovered that by switching from azide to p-anisidine as nucleophile, the ARO of racemic trans- 3-substituted styrene oxides could be catalyzed by the (salen)Cr-Cl complex 2 with complete regioselectivity and moderate selectivity factors (Scheme 7.36) [14]. The ability to access anti-P-amino alcohols nicely complements the existing methods for the preparation of syn-aryl isoserines and related compounds [67] by asymmetric oxidation of trans-cinnamate derivatives [68]. 

The complex Pd-(-)-sparteine was also used as catalyst in an important reaction. Two groups have simultaneously and independently reported a closely related aerobic oxidative kinetic resolution of secondary alcohols. The oxidation of secondary alcohols is one of the most common and well-studied reactions in chemistry. Although excellent catalytic enantioselective methods exist for a variety of oxidation processes, such as epoxidation, dihydroxy-lation, and aziridination, there are relatively few catalytic enantioselective examples of alcohol oxidation. The two research teams were interested in the metal-catalyzed aerobic oxidation of alcohols to aldehydes and ketones and became involved in extending the scopes of these oxidations to asymmetric catalysis. 

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

The asymmetric oxidation of organic compounds, especially the epoxidation, dihydroxylation, aminohydroxylation, aziridination, and related reactions have been extensively studied and found widespread applications in the asymmetric synthesis of many important compounds. Like many other asymmetric reactions discussed in other chapters of this book, oxidation systems have been developed and extended steadily over the years in order to attain high stereoselectivity. This chapter on oxidation is organized into several key topics. The first section covers the formation of epoxides from allylic alcohols or their derivatives and the corresponding ring-opening reactions of the thus formed 2,3-epoxy alcohols. The second part deals with dihydroxylation reactions, which can provide diols from olefins. The third section delineates the recently discovered aminohydroxylation of olefins. The fourth topic involves the oxidation of unfunc-tionalized olefins. The chapter ends with a discussion of the oxidation of eno-lates and asymmetric aziridination reactions. 

Catalytic asymmetric hydrosilylation of prochiral olefins has become an interesting area in synthetic organic chemistry since the first successful conversion of alkyl-substituted terminal olefins to optically active secondary alcohols (>94% ee) by palladium-catalyzed asymmetric hydrosilylation in the presence of chiral monodentate phosphine ligand (MOP, 20). The introduced silyl group can be converted to alcohol via oxidative cleavage of the carbon-silicon bond (Scheme 8-8).27... 

A report was concerned with the ability of nitroxyl radicals, such as TEMPO and other related structures, to act as catalysts in the asymmetric oxidation of alcohols. Cyclic voltammetry was used to measure the oxidation potentials of the nitroxyl... 

Reactions where NLE have been discovered include Sharpless asymmetric epoxi-dation of allylic alcohols, enantioselective oxidation of sulfides to sulfoxides, Diels-Alder and hetero-Diels-Alder reactions, carbonyl-ene reactions, addition of MesSiCN or organometallics on aldehydes, conjugated additions of organometal-lics on enones, enantioselective hydrogenations, copolymerization, and the Henry reaction. Because of the diversity of the reactions, it is more convenient to classify the examples according to the types of catalyst involved. 

During the past year, chloroperoxidase (CPO) was found to catalyze the smooth asymmetric epoxidation of functionalized cii-alkenes, such as the unsaturated ester 32. The reaction appears to be limited to 2-alkenes (i.e., methyl group on one side of the alkene), although some branching on the longer alkyl chain is tolerated. Allylic alcohols are oxidized to the corresponding unsaturated aldehydes but without epoxide formation <99TL1641>. 

SCHEME 46. Kinetic resolution of amino alcohols by asymmetric oxidation. 

Allylic alcohols are specific substrates for a particular asymmetric oxidation method. 

The development of simple systems that allow for the asymmetric oxidation of allyl alcohols and simple alkenes to epoxides or 1,2-diols has had a great impact on synthetic methodology because it allows for the introduction of functionality with concurrent formation of one or two stereogenic centers. This functionality can then be used for subsequent reactions that usually fall into the... 

Methodology has been found that allows for the asymmetric oxidation of alkenes and allyl alcohol to the corresponding epoxides or diols. The HKR method is beginning to be used to access chiral epoxides. Although asymmetric oxidations are now being used at scale, they are not used nearly as often as asymmetric reductions. 

Sharpless asymmetric epoxidation of allylic alcohols, asymmetric epoxidation of conjugated ketones, asymmetric sulfoxidations catalyzed, or mediated, by chiral titanium complexes, and allylic oxidations are the main classes of oxidation where asymmetric amplification effects have been discovered. The various references are listed in Table 4 with the maximum amplification index observed. 

R. A. Johnson, K. B. Sharpless, Asymmetric Oxidation Catalytic Asymmetric Epoxidation of Allylic Alcohols, in Catalytic Asymmetric Synthesis (I. Ojima, Ed.), 103, VCH, New York, 1993. 

Chloroperoxidase Enantioselective oxidation of sulfides Enantioselective oxidation of racemic epoxyalcohols Oxidation of benzyl alcohol Epoxidation of styrene Asymmetric oxidations Halogenation reactions [11, 15,77] [15, 48] [14] [78] [79] [80]... 

The use of allylic selenides 166 in oxidation reaction leads to intermediate selenoxides 167, which can undergo [2,3]sigmatropic rearrangements to the corresponding allylic selenenates 168. These componds will lead to allylic alcohols 169 after hydrolysis (Scheme 48). This is also a versatile procedure for the synthesis of optically active allylic alcohols, provided that either an asymmetric oxidation or an optically active selenide is used for the rearrangement. Detailed kinetic and thermodynamic studies of [2,3]sigmatropic rearrangements of allylic selenoxides have also been reported.290-294... 

The large-scale production of esomeprazole is now successfully achieved by asymmetric oxidation of the same sulfide intermediate as is used in the production of omeprazole (Scheme 2.5). Using the titanium-based catalyst originally developed by K. Barry Sharpless for allyl alcohol oxidation [56] and by H.B. Kagan for certain sulfide oxidations [57], a process was developed that could achieve initial enantiomeric excesses of about 94% [53]. During the production process, the optical purity is further enhanced by the preparation of esomeprazole magnesium salt, with subsequent re-crystallization. 

The asymmetric oxidation of indene to the corresponding epoxide (Equation 24) is carried out commercially by Sepracor on a small scale. Chiral indene oxide is an intermediate in the synthesis of crixivan (an HIV protease inhibitor). Reaction is carried out at 5°C with moderately high turnover numbers in the presence of an exotic donor ligand ( P3NO , 3-phenylpropylpyridine N oxide) and sodium hypochlorite as the terminal oxidant. A similar epoxidation of a simple cis olefin (Equation 25) leads to an enantiomerically pure amino-alcohol used in the synthesis of taxol, a potent anticancer drug. 

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