Oxidative couphng, intramolecular

Synthesis of TT-extended porphyrins via intramolecular oxidative couphng 12CC10069. 

The intramolecular C—C coupling occurs by molecular oxygen activation of the methyl group attached to the tertiary nitrogen atom of the benzylisoquinoUne backbone. After optimization of the reaction conditions, " notably the determination of the best co-solvent, toluene, several racemic non-natural substrates were submitted to this oxidative couphng using BBE. Excellent yields and enantiose-lectivities were obtained after this kinetic resolution (Scheme 28.35). 

Corey s retrosynthetic concept (Scheme 9) is based on two key transformations a cationic cyclization and an intramolecular Diels-Alder (IMDA) reaction. Thus, cationic cychzation of diene 50 would give a precursor 49 for epf-pseudo-pteroxazole (48), which could be converted into 49 via nitration and oxazole formation. Compound 50 would be obtained by deamination of compound 51 and subsequent Wittig chain elongation. A stereocontroUed IMDA reaction of quinone imide 52 would dehver the decaline core of 51. IMDA precursor 52 should be accessible by amide couphng of diene acid 54 and aminophenol 53 followed by oxidative generation of the quinone imide 52 [28]. 

The actual synthesis (Scheme 10) commenced with the couphng of diene acid 54 and aminophenol 53 to provide diene amide 55. In situ generation of quinone monoimide 52 under oxidative conditions and subsequent intramolecular Diels-Alder (IMDA) reaction furnished an 8 1 mixture of endo/exo... 

The facile intramolecular oxidative addition of aryl halide which leads to Pd(IV) complex 22 (see Scheme 2.5) provided the basis for the development ofa special type of Pd(II)/Pd(IV) Heck reaction [58,109]. Although 22 fails to react with methylacrylate at room temperature, an insertion reaction leading to the corresponding Heck product takes place in the presence of AgCl04, which removes a iodide ligand generating the required coordination vacancy. Thus, complex 22 (10 mol%), or its Pd(II) precursor 20, catalyzes a Heck-type couphng of 2-iodobenzoic acid with methyl acrylate, driven by iodide precipitation with silver salts (Eq. (2.10)). The reaction is completed within about 3.5 h at room temperature and, in contrast with the... 

Mechanistic investigations showed, that a sequence of tandem intramolecular Buchwald-Hartwig amination and intermolecular Suzuki-Miyaura coupHng is likely to occur as dominant process (for system 103 with simpHfied formulations for oxidative... 

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