Reduction, Oxidation, and Control of Stereochemistry

Organometallic compounds tend to be reducing in character and so tend to be applied in reduction. High-valent coordination compounds tend to be used in oxidation. Even in oxidation the intermediacy of species with M—C bonds has been proposed, which makes it difficult to maintain the somewhat artificial distinction between organometallic and coordination compounds in this area. 

Directed and Asymmetric Oxidation The traditional method of asymmetric synthesis involves modifying the substrate with a resolved chiral auxiliary and finding a reagent that introduces an asymmetric center in a defined way relative to the auxiliary. The auxiliary is then removed, ideally leaving a single enantiomer of the product. This method requires a mole of auxiliary per mole of product formed. A more sophisticated approach is to mimic Nature s own solution the use of an enantiomerically pure catalyst. In this case the handedness of the product is decided by the handedness of the catalyst, and only a small amount of resolved catalyst produces a large amount of asymmetric product. 

OSO4 is the best reagent for the cis-dihydroxylation of alkenes. Sharpless has proposed that an organometallic species is an intermediate, as shown in Eq. 14.44. Of great practical importance, use of a chiral amine as L with an 

Normally, the most electron-rich, and therefore the most highly alkyl-substituted, alkene reacts first, but the vanadium catalyst shows strong di- 

Jacobsen has found a system using 14.6 that catalyzes asymmetric epoxi-dation of alkenes with ArlO as oxidant and does not require that the substrate contain a hydroxy group. For example, Z—PhCH=CHMe is converted to the epoxide with an 84% e.e. 

FIGURE 14.2 Nozaki-Hiyama-Kishi reaction in which a Cr(Ill) alkyl intermediate adds to a carbonyl compound. 

The Sharpless epoxidation provides good examples of both directed and asymmetric catalytic reactions. It has long been known that alkenes can be epoxidized with peracids, which deliver an electrophilic oxygen atom, as shown 

Normally, the most basic, and therefore the most highly alkyl-substituled alkene reacts first, but the vanadium catalyst shows strong directing effects that allow the catalyst to overcome the usual selectivity order if an allylic or homoallylic -OH group is present (e.g., Eq. 14.47). In cyclic compounds the stereochemistry of the final epoxide is determined by the directing effect of the -OH group to which the catalyst binds (Eq. 14.48). Peracids tend to give the other isomer of the product, by a simple steric effect. 

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The unique feature of the Horner-Wittig reaction is that the addition intermediate can be isolated and purified, which provides a means for control of the reaction s stereochemistry. It is possible to separate the two diastereomeric adducts in order to prepare the pure alkenes. The elimination process is syn, so the stereochemistry of the alkene that is formed depends on the stereochemistry of the adduct. Usually the anti adduct is the major product, so it is the Z-alkene that is favored. The syn adduct is most easily obtained by reduction of (3-ketophosphine oxides.269... 

Further variations on the epoxyketone intermediate theme have been reported. In the first (Scheme 9A) [78], limonene oxide was prepared by Sharpless asymmetric epoxidation of commercial (S)-(-)- perillyl alcohol 65 followed by conversion of the alcohol 66 to the crystalline mesylate, recrystallization to remove stereoisomeric impurities, and reduction with LiAlH4 to give (-)-limonene oxide 59. This was converted to the key epoxyketone 60 by phase transfer catalyzed permanganate oxidation. Control of the trisubstituted alkene stereochemistry was achieved by reaction of the ketone with the anion from (4-methyl-3-pentenyl)diphenylphosphine oxide, yielding the isolable erythro adduct 67, and the trisubstituted E-alkene 52a from spontaneous elimination by the threo adduct. Treatment of the erythro adduct with NaH in DMF resulted... 

The titanium trichloride-diethylaluminum chloride catalyst converted butadiene to the cis-, trans,-trans-cyclododecatriene. Professor Wilke and co-workers found that the particular structure is influenced by coordination during cyclization between the transition metal and the growing diene molecules. Analysis of the influence of the ionicity of the catalyst shows effects on the oxidation and reduction of the alkyls and on the steric control in the polymerization. The lower valence of titanium is oxidized by one butadiene molecule to produce only a cis-butadienyl-titanium. Then the cationic chain propagation adds two trans-butadienyl units until the stereochemistry of the cis, trans, trans structure facilitates coupling on the dialkyl of the titanium and regeneration of the reduced state of titanium (Equation 14). 

Other workers have concentrated on the introduction of functionality into ring C of tabersonine (78). Danieli et al. (252) introduced the 17-hydroxy group by oxidation of tabersonine by means of phenylseleninic anhydride. Presumably, the Va,17-didehydrotabersonine initially produced suffers nucleophilic attack by water during workup, the stereochemistry of attack being controlled by the adjacent ethyl group. Oxidation of the product, 377, at C-16 by means of peracid also proceeds preferentially at the /3-face to give the V-oxide 378 of the desired diol. Reductive methylation and acetylation then complete the partial synthesis of vindorosine (43) (Scheme 24) (252). 

Atom-transfer addition of primary and secondary bromide oxazolidinones to alkenes in the presence of Lewis acids has been investigated and the effects of solvent, temperature, and catalyst were determined. The best Lewis acids were found to be Sc(OTf)3 and Yb(OTf)3 and control was possible using chiral auxiliary oxazolidinones. Tertiary bromides did not react (Scheme 37). Stereochemistry of reduction of the cw-mesityl-alkene (53) with BusSnH proceeds to give the ( )-alkene (54) as the major product ( Z = 9 1). Theoretical calculations at the BLYP/6-31G level were undertaken to rationalize the stereochemistry. Asymmetric hydroxylation of the benzylic position of a range of substrates can be achieved by using a chiral dioxomthenium(VI) porphyrin (55). The oxidation proceeds via a rate-limiting H-abstraction to produce a benzylic radical intermediate. ... 

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