Synthesis of Glycoborine, Glybomine A and B, the Phytoalexin Carbalexin A and the β‐Adrenoreceptor Antagonists Carazolol and Carvedilol

Abstract

We describe a regioselective synthesis of 4- or 5-substituted carbazoles by oxidative cyclisation of meta-oxygen-substituted N-phenylanilines. Using the regiodirecting effect of a pivaloyloxy group, we prepared 4-hydroxycarbazole, a precursor for the enantiospecific synthesis of the β-adrenoreceptor antagonists (-)-(S)-carazolol (5) and (-)-(S)-carvedilol (6). Regioselective palladium(II)-catalysed cyclisation of different diarylamines led to total synthesis of glycoborine (7) and the first total syntheses of the phytoalexin carbalexin A (8), glybomine A (9) and glybomine B (10). For glybomine B (10), a 5-hydroxycarbazole was converted into the corresponding triflate and utilized for introduction of a prenyl substituent.

Reductive Eliminations from Diarylpalladium(II) Complexes: A Combined Experimental and Computational Investigation

“…. Due to the decreased rigidity, the κ 3 ‐intermediate H can be detected only in some cases and undergoes reductive elimination much more easily than the κ 4 ‐complex A . For both complexes, the eliminations either in the absence or in the presence of one or two molecules of acetic acid have been modeled in analogy to the mechanisms discussed in the previous sections (Figure ).…”

First Total Synthesis of the Cytotoxic Carbazole Alkaloid Excavatine‐A and Regioselective Annulation to Pyrano[2,3‐a]carbazoles and [1,4]Oxazepino[2,3,4‐jk]carbazoles

“…Our group successfully applied all three procedures to the synthesis of various pyranocarbazole alkaloids. [5a], The carbazole framework is most conveniently constructed by the palladium(II)‐catalyzed oxidative cyclization of diarylamines 9 ,, which are readily available by Buchwald–Hartwig amination …”

“…[5a] Compound 11a is prepared from 2‐methyl‐5‐nitrophenol and has been frequently applied to the synthesis of diarylamines. [5a], [11e], [12a], Palladium(0)‐catalyzed coupling of 10 and 11a using SPhos as ligand and cesium carbonate as base provided diarylamine 9a in excellent yield. Microwave heating of a mixture of 9a , pivalic acid, copper(II) acetate, and catalytic amounts of palladium(II) acetate led to 2,8‐dioxygenated carbazole 12a in 82 % yield.…”

Synthesis of Tetranuclear Palladium(II) Complexes and Their Catalytic Activity for Cross‐Coupling Reactions

“…[61] Recently we reported the first total synthesis of carbalexin A( 16)b yp ivaloyloxy-directed, regioselectivep alladium(II)-catalyzed oxidative cyclization of ad iarylamine. [62] Treatmento fc arbalexin A( 16)w ith catalytic amountso f[ CuOH·TMEDA] 2 Cl 2 under air provided biscarbalexine A( 2)i n5 3% yield (Table 2). In agreement with the oxidative coupling of 2-hydroxy-3-methylcarbazole (14), these conditions led to the formation of the triscarbazole 21 as byproduct (29 %y ield).…”

“…[60] In 2009 we described the first total synthesis of carbalexin C (17), [41,63] the precursor for 3,w hich was isolated in 2001 from Glycosmis pentaphylla. [61] We also achieved the first total synthesis of the prenylated analog glybomine B( 18), [62] which had been isolated from Glycosmis arborea. [64] Both 6,6'-dimethoxy substituted 1,1'-bicarbazoles 3 and 6 were synthesized by treatment of 17 and 18 with di-tert-butyl peroxide in chlorobenzene at reflux (Table 2).…”