Oxidative cleavage palladium acetate - oxidants

In 2011, the same group reported unprecedented C3-selective functionalization of pyridine derivatives. The oxidative coupling catalyzed by palladium acetate/l,10-phenanthroline/Ag2CO3 under air afforded the desired olefination product in up to good yields (Scheme 9.7). Moreover, a significant kinetic isotope effect was observed, which is consistent with metal-mediated C-H bond cleavage. 

The relay compound 1025 required for the synthesis of all of these 7-oxygenated carbazole alkaloids was obtained starting from commercially available 4-bromo-toluene (1023) and m-anisidine (840) in two steps and 72% overall yield. Buchwald-Hartwig amination of 4-bromotoluene (1023) with m-anisidine (840) furnished quantitatively the corresponding diarylamine 1024. Oxidative cyclization of 1024 using catalytic amounts of palladium(ll) acetate afforded 3-methyl-7-methoxycarbazole (1025). Oxidation of 1025 with DDQ led to clauszoline-K (98), which, on cleavage of the methyl ether using boron tribromide, afforded 3-formyl-7-hydroxycarbazole (99) (546) (Scheme 5.149). 

The catalytically inactive tris(triphenylphosphane) complex E is formed in an equilibrium reaction from the bis(triphenylphosphane) complex F and a third ligand of triphenylphosphane oxide. Loss an acetate ion from complex E does not occur to give tris(triphenylphos-phane)palladium D. Nor does the analogous acetate cleavage from F occur to give bis(tri-... 

Ozonides are rarely isolated [75, 76, 77, 78, 79], These substances tend to decompose, sometimes violently, on heating and must, therefore, be handled with utmost safety precautions (safety goggles or face shield, protective shield, and work in the hood). In most instances, ozonides are worked up in the same solutions in which they have been prepared. Depending on the desired final products, ozonide cleavage is done by reductive or oxidative methods. Reductions of ozonides to aldehydes are performed by catalytic hydrogenation over palladium on carbon or other supports [80, 81, 82, S3], platinum oxide [84], or Raney nickel [S5] and often by reduction with zinc in acetic acid [72, 81, 86, 87], Other reducing agents are tri-phenylphosphine [SS], trimethyl phosphite [89], dimethyl sulfide (DMS) [90, 91, 92], and sodium iodide [93], Lithium aluminum hydride [94, 95] and sodium borohydride [95, 96] convert ozonides into alcohols. 

The next few steps including the vital palladium-catalysed cyclisation revealed a problem in this synthesis and it is continued in the workbook. An improved synthesis by Trost uses two alkynes in the cyclisation and the problems disappear. This starts from protected mannitol 106 and the oxidative cleavage is followed at once by imine formation 193. Addition of the lithium derivative 194 goes with good selectivity (13 1 in favour of 195). Adjustment of protecting groups and hydrolysis of the acetal leads to the key intermediate37 197. 

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