Oxidation-reduction reactions Stereoselectivity

H. Alper, Pure Appl. Chem., 1988, 60, 35-38. Metal Catalyzed Carbonylation and Oxidation-Reduction Reactions. W. Oppolzer, Pure Appl. Chem., 1988, 60, 39-48. Metal-Directed Stereoselective Eunctionalizations of Alkenes in Organic Synthesis. 

It is important to select stoichiometric co-reductants or co-oxidants for the reversible cycle of a catalyst. A metallic co-reductant is ultimately converted to the corresponding metal salt in a higher oxidation state, which may work as a Lewis acid. Taking these interactions into account, the requisite catalytic system can be attained through multi-component interactions. Stereoselectivity should also be controlled, from synthetic points of view. The stereoselective and/or stereospecific transformations depend on the intermediary structure. The potential interaction and structural control permit efficient and selective methods in synthetic radical reactions. This chapter describes the construction of the catalytic system for one-electron reduction reactions represented by the pinacol coupling reaction. 

The multi-component systems developed quite recently have allowed the efficient metal-catalyzed stereoselective reactions with synthetic potential [75-77]. Multi-components including a catalyst, a co-reductant, and additives cooperate with each other to construct the catalytic systems for efficient reduction. It is essential that the active catalyst is effectively regenerated by redox interaction with the co-reductant. The selection of the co-reductant is important. The oxidized form of the co-reductant should not interfere with, but assist the reduction reaction or at least, be tolerant under the conditions. Additives, which are considered to contribute to the redox cycle directly, possibly facilitate the electron transfer and liberate the catalyst from the reaction adduct. Co-reductants like Al, Zn, and Mg are used in the catalytic reactions, but from the viewpoint of green chemistry, an electron source should be environmentally harmonious, such as H2. 

Enzyme and Nonenzyme Catalysts By nature, enzymes themselves are chiral and they catalyze a variety of chemical reactions with stereoselectivity. These reactions include oxidation, reduction, and hydration. Examples of enzymes are oxidases, dehydrogenases, lipases, and proteases. Metoprolol, an adrenoceptor-blocking drug, is produced using an enzyme-catalyzed method. 

Reaction of several dialdose derivatives, for example 197, with furan or 2-methylfuran gave, in the presence of chloroacetic acid, condensation products with high stereoselectivity. The (S) configuration was assigned to the major diastereoisomer 198.401 The thiazole adduct (199) obtained from aldehyde 197 and 2-trimethylsilylthiazole can be converted to the 6-epimer (200) by an oxidation-reduction sequence (Scheme 20).402... 

Typically reported topics are solvolytic reactions, oxidations, reductions, and C-C coupling reactions. The saponification of activated esters in aqueous micelles is a typical model for an enzyme mimetic reaction. The influence of the micellar medium on the reaction rate has been investigated, as well as the alteration of the stereoselectivity. Models of metalloenzymes were developed with the ligands 1-3 [8]. 

Therefore, despite lower stereoselectivity (3 1) in the epoxidation step the benzyl ether 118 (Scheme 20) was converted into 123 and then converted into tetrahydrofu-ran 124. After Swem oxidation a mixture of the aldehydes is generated the isomer with the correct stereochemistry at C-2 cyclizes to the hemiacetal 125 whereas the second C-2 epimer did not cyclize and was thus easily removed by chromatography. By Wittig reaction 125 was transformed into 126 which was smoothly debenzylated under Hanesssian s conditions (15) to give alcohol 127. Inversion of configuration at C-2 was achieved by an oxidation reduction sequence with complete stereocontrol. 

The allylic alcohol was subjected to an Eschenmoser-Claisen rearrangement with dimethylacetamide dimethylacetal to introduce the C14 substituent in a stereoselective manner. Reduction of the amide to the corresponding aldehyde with phenyl silane in the presence of Ti(0/Pr)4 was followed by an acid-promoted closure of the C-ring of codeine. In order to prevent N-oxidation, the amine was converted to the corresponding tosylamide, via debenzylation and treatment with tosyl chloride, before the allylic alcohol was introduced by the reaction of the alkene with selenium dioxide (65). The stereochemistry of the C6 hydroxy functionality was corrected by applying the well-known oxidation/reduction protocol [46, 60] before the benzylic double bond was reductively removed under Birch conditions. Codeine (2) was obtained in 17 steps with an overall yield of approximately 0.6%. 

The catalytic mechanism of the asymmetric reduction of alkenes catalyzed by ene-reductases has been studied in great detail [977] and it has been shown that a hydride (derived from a reduced flavin cofactor) is stereoselectively transferred onto Cp, while a Tyr-residue adds a proton (which is ultimately derived from the solvent) onto Cot from the opposite side (Scheme 2.134). As a consequence of the stereochemistry of this mechanism, the overall addition of [H2] proceeds in a trans-fashion with absolute stereospecificity [978]. This reaction is generally denoted as the oxidative half reaction . The catalytic cycle is completed by the so-called reductive half reaction via reduction of the oxidized flavin cofactor at the expense of NAD(P)H, which is ultimately derived from an external H-source via another... 

The synthesis of optically pure L-phenylglycine via the deracemization of mandelic acid was reported via three steps (racemization, enantioselective oxidation and stereoselective reductive amination). Racemization by mandelate racemase combined with simultaneous oxidation and reduction reactions with cofactor recycling gave the amino acid in 97% ee and 94% yield (Scheme 4.43) [96]. 

Oxidative Heck reactions via Pd(II) C—H functionalization of terminal alkenes with pinacol boranes have been described for the preparation of styrenes and derivatives through electrophilic Pd(II) catalysis (Scheme 3.20). ° Treatment of a functionalized allylic precursor with the Pd(II) catalysts listed facilitated an allylic C—H activation. Subsequent transmetallation of the aryl boronic acid and reductive elimination afforded the desired olefin with excellent stereoselectivity. The scope of the transformation allows for a variety of activating and deactivating substituents on the aryl boronic acid as well as numerous functional groups on the starting alkene. A tandem allylic C—H oxidation/vinylic arylation protocol has also been reported. " ... 

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