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

Abstract

An efficient methylthiomethylation of pyrroloisoquinolines and pyrroloquinolines has been reached by the use of ammonium acetate and dimethyl sulfoxide. Methylthiomethylated heterocycles can be obtained in moderate to good yields in most cases, while trace amounts to good yields of methylene-bridged products can be observed. Choice of DMSO activator and its amount have a great influence on the chemoselectivity of this process. It is worth noting that this process can also be scalable. Another feature of this process is that the product can be transformed to sulfone and sulfoxide easily.

Modification of Pyrrolo[2,1‐a]isoquinolines through Iron‐Catalyzed Aminomethylenation with Amines and Dimethyl Sulfoxide

“…Ishikura [11b] and Sawant [11e] have also prepared symmetric and unsymmetric bisheterocycles with heterocycle‐derived thioethers under DMSO‐based reaction systems in their studies respectively. We also found that thioethers can serve as key intermediates for formylation and bromination in our previous studies [13,15] …”

“…The results indicate that thioether 9 may act as a key intermediate in this process. The hypothesis can also be supported by the facts that this kind of thioethers have been easily transformed to other functionalized molecules according to reports from others [2,8,11] and us [13,15] . Previously, further transformations of methylthiomethylenation products prepared in DMSO‐based systems to olefin and aldehyde have been successfully demonstrated by the groups of Huang 8a and Cheng 2a respectively.…”

“…The hypothesis can also be supported by the facts that this kind of thioethers have been easily transformed to other functionalized molecules according to reports from others [2,8,11] and us. [13,15] Previously, further transformations of methylthiomethylenation products prepared in DMSO-based systems to olefin and aldehyde have been successfully demonstrated by the groups of Huang 8a and Cheng 2a respectively. Ishikura [11b] and Sawant [11e] have also prepared symmetric and unsymmetric bisheterocycles with heterocycle-derived thioethers under DMSO-based reaction systems in their studies respectively.…”

“…We also found that thioethers can serve as key intermediates for formylation and bromination in our previous studies. [13,15] It was found that reducing the amount of DABCO to 0.3 equivalent led to a decreased yield of 3 a (10 % NMR yield, Scheme 6, reaction 4). Thioether 9 can be detected in 22 % yield in this case, suggesting that DABCO may have a positive role in this transformation.…”

“…Previously, we have developed several reaction systems for modification of pyrrolo[2,1‐ a ]isoquinolines by the transformation of DMSO with suitable activators [13–15] . Encouraged by recent achievements on developing DMSO‐based reaction systems and also based on our own results, we envisioned more diverse functional groups can be incorporated to heterocycles by transforming DMSO with novel activators.…”