Oxidative Cascade Reactions

SCHEME 3.14 Previous examples of oxidative iminium and acyliminium ion formation. 

RADICAL CATION FRAGMENTATION REACTIONS IN ORGANIC SYNTHESIS 

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Aromatization can also be accomplished by oxidative cascade reactions-a strategy often utilized by natural product biosynthesis [33]. For example, the phenoxazinone chromophore of actinomycin was proposed to be generated by a six-electron oxidation of aminophenols catalyzed by a copper-containing oxidase (Scheme 7.8) [34]. 

As an oxidative cascade reaction with Mn(OAc)3, treatment of tetra-olefinic (3-keto ester (308) with Mn(OAc)3 in acetic acid generates a steroidal skeleton (309) via quartet 6-endo-trig ring closure, in one-pot reaction (eq. 3.129). 

Silyl allenes such as 48 and enol acetates such as 50 were particularly effective substrates for these reactions. The oxidative cascade reaction of trisubstituted alkene substrate 52 demonstrated a powerful application of ETIC chemistry to form bicycle 53 through consecutive carbon-carbon and carbon-oxygen bond construction. Highly diastereoselective reactions were observed when the nucleophile was... 

M. Uyanik, D. Nakashima, K. Ishihara, Baeyer-ViUiger oxidation and oxidative Cascade reactions with aqueous hydrogen peroxide catalyzed by lipophilic Li[B(C5p5)4] and Ca[B(C5p5)4]2, Angew. Chem. Int. Ed. 51 (2012) 9093-9096. 

Fig. 13.6 A m ulti-enzyme one-pot example cascade conversion of glycerol into a heptose sugar through consecutive phosphorylation, oxidation, aldol reaction and dephosphorylation [11],...

Abstract The use of Co building block in presence of water or an alcohol to functionalise alkenes by hydroxycarbonylation or alkoxycarbonylation reactions is reviewed in this chapter. The hydroxyl groups can be present in the substrate itself so cascade reactions can occur. Palladium precursors are largely involved in these reactions and this analysis of the literature focuses on the mechanisms involving Pd(0), Pd(H)(X)L2, PdX2 and an oxidant like CuCl systems. Introduction of chiral L or L2 ligands or even the presence of chiral carbon atoms in the substrate lead to asymmetric carbonylation reactions. 

Fig. 3 Concept of nanoengineering of oxide catalytic surface in terms of nanoreactor array, some of the possibilities offered by this concept (in particular in terms of realizing multifunctional catalysts for cascade reactions in nanoconfined liquids) and a SEM image of an array of Xi02 nanotubes produced by anodic oxidation of Ti foils. Source Centi et alN...

Oxidatively generated oxocarbenium ions have been used for intramolecular epoxide activation. Cascade reactions to form oligotetrahydrofuran products that demonstrated a strong preference for the exo-cyclization pathway were achieved in good yields when disubstituted epoxides were used as substrates. High stereoselectivity was observed in these reactions, with complementary diastereomers being formed from diastereomeric (g) epoxides.257... 

Chromans possessing a fused isoxazolidine moiety 505 can be accessed via a palladium-catalyzed allene insertion-intramolecular 1,3-dipolar cycloaddition cascade reaction between ( )-fV-(2-hydroxybenzylidene)methanamine oxide, allene, and aryl iodides. This process creates two rings, two stereocentres and a quaternary carbon centre in one-pot (Equation 210) <2002CC1754>. 

The synthetic utility of this cascade reaction was underscored by the facile transformation of crotyl tiglate into 1,3-diol 137 (Scheme 7.39).82 Silver-catalyzed silylene transfer to crotyl tiglate produced silalactone 136 nearly quantitatively as a 97 3 mixture of diastereomers. Diol 137 was generated from silalactone after reduction of the lactone moiety with lithium aluminum hydride followed by oxidation of the C-Si bond 65>66 81... 

Both cationic and anionic precursors were used to generate the 02SOH radical (44) which is the presumed intermediate of OH radical attack on S02 to form S03 in the last step of the sulfur oxidation cascade [198]. The hydrogen sulfite cation was produced by dissociative ionization of methanesulfonic acid and used to generate radical 44, albeit in a low yield [209]. A improved preparation and NR mass spectrometric characterization of 44 relied on an anion precursor, 02SOH , which was made by termolecular associative reaction of S02 with OH-[210]. Neutralization with Xe of 02SOH- produced stable radical 44 that gave rise to a dominant survivor cation in the -NR+ mass spectrum [211]. 

Some mechanistic aspects of the above cascade reaction deserve comment. Thus, after the intermolecular addition of the nucleophilic acyl radical to the alkene, the electrophilic radical adduct A, instead of undergoing reduction, reacts intramolecularly at the indole 3-position (formally a 5-endo cyclization) to give a new stabilized captodative radical B, which is oxidized to the fully aromatic system. (For a discussion of this oxidative step, see Section 1.5.)... 

Triethylamine is converted into thienopentathiepin 39 and heptathiocane 40 by the unprecedented cascade reaction with S2CI2 in the presence of DABCO. Oxidation of an A -ethyl group of EtsN by a complex of S2CI2 with l,4-diazabicyclo[2.2.2]octane (DABCO) (X-S-S-Cl) affords an enamine, which reacts with X-S-S-Cl to give a thioamide followed by elimination of X-SH. The condensation of this thioamide with the enamine followed by cyclization and oxidation affords the thiophene 39 (Scheme 9) <20030L1939>. 

However, oxidations based on addition of O-centered radicals to unsaturated compounds appear to be a highly desirable synthetic goal, especially when the new C—O bond could be formed under the mild conditions that are typical for radical reactions. If this radical addition would involve C = C triple bonds, the resulting reactive vinyl radical would be highly suitable for the promotion of intramolecular cascade reactions. 

Harano and co-workers found that the cascade reaction of pyridine iV-oxides with allenes, after 1 1 cycloaddition and 1,5-sigmatropic rearrangement, added ketene in what they determined was a stepwise [2+2] cycloaddition <03CPB1068>. In some cases the addition of the ketene is stereoselective. 

Two groups have reported the synthesis of the pentaketide epoxyquinols which differ in the approach to the epoxide 5, oxidation and subsequent electrocyclisation of which generates a 2//-pyran. Various dimerisation modes in which the pyran acts as either diene or dienophile then yield the epoxyquinols <05JOC79, 05TL547>. The reaction of this epoxide and a related cyclohexenone with reactive dienophiles circumvented the dimerisation and the cascade reaction produced the endo DA products <05JOC79>. 

Other cascade sequences have also been observed to occur from the thermolysis of isoxazolines, thereby increasing the utility of the nitrile oxide cycloaddition reaction. For example, in the context of synthesizing testosterone derivatives, Guarna and coworkers reported that the reaction of a nitrile oxide derived from oxime 89 with 76 gave isoxazoline 90 (Scheme 15) (91TL6395). Hydrolysis of the ketal moiety provided cycloadduct 91, which was heated at reflux in DMF to furnish 92 in 30% yield. 

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