Bromination of phenyl ether and other aromatics with bromoisobutyrate and dimethyl sulfoxide

Modification of Pyrrolo[2,1-a]isoquinolines and Pyrrolo[1,2-a]quinolines with Ammonium Acetate and Dimethyl Sulfoxide via Methylthiomethylation

“…In some cases, trace amount of formylation products (<5% NMR yield) can be detected suggesting further transformation of compound 2a to formylated pyrroloisoquinoline is not preferred under the current conditions unlike our previous study . While in the work from the Cheng group, formylation products were obtained as the major products when treating indoles under the same reaction conditions.…”

“…The results suggest that the formation of compound 2a′ in this system is reversible and can be transformed to compound 2a , while compound 2a is inactive and cannot be transformed anymore under the current system. Although methylthiomethylated heterocycles can be used for the preparation of methylene-bridged indoles by Ishikura et al and for further formylation of pyrroloisoquinolines in our previous study, the current conditions are not suitable for their conversion. We also determined the ratio of 2a and 2a′ by crude 1 H NMR at the time points of 1 h ( 2a / 2a′ = 1.1:1), 2 h ( 2a / 2a′ = 2.1:1), 3 h ( 2a / 2a′ = 2.5:1), and 4 h ( 2a / 2a′ = 4.6:1) as shown in eq 6.…”

“…Known compound; white solid, 56.3 mg, 67% yield; purified by a silica gel flash chromatography (hexane/EtOAc = 3/1); 1 H NMR (400 MHz, CDCl 3 ) δ 7.43–7.27 (m, 5H), 6.66 (s, 1H), 6.33 (s, 1H), 4.23 (s, 2H), 4.10 (t, J = 6.5 Hz, 2H), 3.84 (s, 3H), 3.56 (s, 3H), 3.25 (s, 3H), 3.02 (t, J = 6.5 Hz, 2H), 2.12 (s, 3H).…”

“…We have also developed a formylation and bromination of pyrroloisoquinolines by the use of bromoisobutyrate and dimethyl sulfoxide as carbonyl source as well as brominating reagent (eq 5). , Interestingly, it was found that methylthiomethylation products could be isolated when pyrroloisoquinolines were treated with DMSO and ammonium acetate during our previous study. We believe that the combination of DMSO and NH 4 OAc would be a useful way for direct methylthiomethylation of pyrroloisoquinolines and pyrroloquinolines, thus providing various structurally diversified molecules possessing privileged frameworks .…”

Bromination of Pyrrolo[2,1-a]isoquinolines with Acetyl Bromide and Dimethyl Sulfoxide

“…In this case, methylene-bridged pyrroloisoquinoline 8 has been observed in 79% yield together with the formylation product in 21% NMR yield. The generation of aldehyde 10 can be regarded as another important evidence for the in situ generation of thioether 7 , as thioether 7 has also been proven to be a key intermediate for the DMSO-based formylation reaction …”