Direct Synthesis of Indoles from Azoarenes and Ketones with Bis(neopentylglycolato)diboron Using 4,4′-Bipyridyl as an Organocatalyst

Abstract

Multifunctionalized indole derivatives were prepared by reducing azoarenes in the presence of ketones and bis(neopentylglycolato)diboron (B 2 nep 2 ) with a catalytic amount of 4,4′-bipyridyl under neutral reaction conditions, where 4,4′bipyridyl acted as an organocatalyst to activate the B−B bond of B 2 nep 2 and form N,N′-diboryl-1,2-diarylhydrazines as key intermediates. Further reaction of N,N′-diboryl-1,2-diarylhydrazines with ketones afforded N-vinyl-1,2-diarylhydrazines, which rearranged to the corresponding indoles via the Fischer indole mechanism. This organocatalytic system was applied to diverse alkyl cyclic ketones, dialkyl, and alkyl/aryl ketones, including heteroatoms. Methyl alkyl ketones gave the corresponding 2-methyl-3substituted indoles in a regioselective manner. This protocol allowed us to expand the preparation of indoles having high compatibility with not only electron-donating and electron-withdrawing groups but also N-and O-protecting functional groups.

Cobalt-catalysed CH-alkylation of indoles with alcohols by borrowing hydrogen methodology

“…Based on the importance of indoles and their derived compounds, the synthesis and functionalization of these heterocyclic compounds continues to be important for academic research and the pharmaceutical industry. 7–14…”

Advances in organocatalyzed synthesis of organic compounds

“…This was quenched by HOBnep, which produced enamine F and O(Bnep) 2 , followed by indole derivative 1 by aniline elimination, analogous to Fischer indole synthesis. 39…”

“…The atom of nitrogen of compound C reacts nucleophilically with the carbonyl of cyclohexanone, for producing intermediate D and eliminating HOBnep to produce species E. This was quenched by HOBnep, which produced enamine F and O(Bnep) 2 , followed by indole derivative 1 by aniline elimination, analogous to Fischer indole synthesis. 39 …”

“…The tube was rinsed with ethyl acetate, and the solvent that was used is evaporated to obtain compound 1 with 95% yield. 39 The same technique was followed with azoxybenzene as a precursor and 3.3 equivalents of B 2 nep 2 , giving compound 2 in 92% yield. For the synthesis of compound 4, 4,4 0 -bipyridyl interacts with B 2 nep 2 in CH 3 CN for 16 h at room temperature, yielding intermediate compound 3.…”

Bis(neopentylglycolato)diboron (B2nep2) as a bidentate ligand and a reducing agent for early transition metal chlorides giving MCl4(B2nep2) complexes

“…4 In fact, treatment of commercially available B 2 pin 2 and B 2 nep 2 with inorganic and organic anions produces anionic sp 2 –sp 3 diboron adducts as the key intermediates with strong reducing ability. 5…”