Regioselective oxidative coupling

Palladium(II) effects orthometalation of acetanilides to form the corresponding palladacycles [185]. De Vries, van Leeuwen, and coworkers exploited this reactivity to achieve regioselective oxidative coupling of acetaniUdes and n-butyl acrylate that proceeds efficiently with BQ as the stoichiometric oxidant (Eq. 46) [ 186], The use of TsOH as an additive and acetic acid as a cosolvent significantly improves the results. Inferior results are observed with hydrogen peroxide or copper(II) acetate as the stoichiometric oxidant, but efforts to use molecular oxygen were not described. 

Hull KL, Lanni EL, Sanford MS (2006) Highly regioselective oxidative coupling reactions synthetic and mechanistic investigations. J Am Chem Soc 128 14047-14049... 

The next step involves an intramolecular ortho-para phenolic coupling of R-reticuline to form the crucial C12-C13 bond of morphine, a process initially proposed on theoretical grounds by Barton and Cohen.27 Some eight years later, experimental proof was obtained for this regioselective oxidative coupling from in vivo studies.216 Further... 

Figure 4. Regioselective Oxidative Coupling The final step for the completion of the pentacyclic ring system of the morphine alkaloids involves the closure of the C4-C5 ether bridge. Synthetic salutaridine has been transformed in vivo to thebaine, codeine, and morphine in Papaver sominiferum. Reduction of the dienone was proposed,30 and indeed, hydride reduction of salutaridine produces a mixture of two epimeric alcohols. However, upon feeding 7-3H labelled salutaridinol epimers to Papaver somniferum, only the S-isomer was converted into thebaine an indication that the reaction is enzyme mediated.31 >32 This finding contradicted earlier work by Barton in which the configuration of the alcohol was assigned as R (See description of Barton s synthesis, ref. 50).

Regioselective oxidative coupling of 4-hydroxystilbenes has been investigated [38]. 

Alternatively, 3-vinylthiophenes 13 can be prepared through regioselective oxidative coupling of thiophene-2-carboxylic acid derivatives 11 with different alkenes 12 in the presence of a rhodium catalyst ([Cp RhCl2]2) and copper (II) acetate monohydrate as oxidant (Scheme 7) [32]. Thereby, the carboxylic group facilitates ort/io-olefination and is subsequently removed by decarboxylation in a one-pot sequence. Additionally, benzo[Z>]thiophenes can equally be coupled effectively with butyl acrylate giving rise to the vinylated product in a yield of 70%. 

The regioselectivity and syn stereochemistry of hydroboration-oxidation coupled with a knowledge of the chemical properties of alkenes and boranes contribute to our under standing of the reaction mechanism... 

Nitrosofurazans provide a regioselective access to unsymmetrical azoxyfurazans. Thus, oxidative coupling of 3-nitroso-4-methylfurazan with amines... 

As a mechanistic hypothesis, the authors assumed a reduction of the Fe(+2) by magnesium and subsequent coordination of the substrates, followed by oxidative coupling to form alkyl allyl complex 112a. A ti—c rearrangement, followed by a syn p-hydride elimination and reductive elimination, yields the linear product 114 with the 1,2-disubstituted ( )-double bond (Scheme 29). This hypothesis has been supported by deuterium labeling experiments, whereas the influence of the ligand on the regioselectivity still remains unclear. 

Since enol silyl ethers are readily accessible by a number of methods in a regioselective manner and since the trialkylsilyl moiety as a potential cationic leaving group facilitates the termination of a cyclization sequence, unsaturated 1-trialkylsilyloxy-1-alkenes represent very promising substrates for radical-cation cyclization reactions. Several methods have been reported on the synthesis of 1,4-diketones by intermolecular oxidative coupling of enol silyl ethers with Cu(II) [76, 77], Ce(IV) [78], Pb(IV) [79], Ag(I) [80] V(V) [81] or iodosoben-zene/BFa-etherate [82] as oxidants without further oxidation of the products. 

Benzodioxanes (6, 516). The earlier synthesis of benzodioxanes by oxidative coupling of catechol derivatives with methoxypropenylphenols has been extended to the first synthesis of the complex benzodioxane silybin (3) shown in equation (I).2 The starting materials are (2R,3R)-dihydroqucrcctin (I) and coniferyl alcohol (2). In this case, the reaction is not regioselective, 3 and the isomeric 4 being obtained in nearly equal amounts. 

In the next step (R)-reticuline is first transformed to the dienone salutaridine by regioselective para-ortho oxidative coupling, catalyzed by a stereo- and regioselective... 

One remarkable process is the photochemical synthesis of 3,4-dihydro-2H-l,3-oxazin-4-ones from a-sulfonyloxy-(3-keto amides (obtained by coupling of P-keto-carboxylic acids with amines, followed by treatment with an iodanyl mesylate). This allows the regioselective oxidation of less-activated C—H bonds and a C—O bond formation which is unusual for a Norrish-Yang reaction [69]. The formation of a 1,6-0—C biradical has been postulated as an intermediate (Scheme 9.42). 

Compared to allocolchicine, jerusalemine bears an extra C-10 hydroxyl group which raises regioselectivity issues. These were solved using a formal phenolic oxidative coupling of the two benzenoid moieties in phenol 65. The coupling was accomplished using the Umezawa... 

More involved studies of the oxidation of plant phenols [27], as well as the introduction of thallium and hypervalent iodine complexes and the use of electrochemical methods, have emphasized the importance of another intermediate involved in oxidative coupling reactions, namely the phenoxonium ion 8 [28-30]. Due to its ionic nature, reaction through an oxo-nium ion can improve the regioselectivity of bond formation and lead to fewer unwanted products (for example, no coupling via the oxygen atom). The coupling reaction can then be viewed as an electrophilic aromatic substitution between 17 and a nucleophilic aromatic unit 15 (Scheme 5). 

In a recent paper, the same authors showed that iron(III) chloride can mediate the oxidative coupling of substituted aryl ethers with an observed regioselectivity that depends on the substitution pattern [66] meta-substituted phenol ethers 77 led to polymers (Scheme 18a) whereas para-substituted phenol ether 79 gave predominantly biphenyl structures (Scheme 18b). ortho-Substituted phenol ether 81 provided a dimer with the Ar-Ar bond at a position para to one of the methoxy substituents (Scheme 18c). 

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