Lewis Acid-Promoted Typical Friedel–Crafts Reactions Using DMSO as a Carbon Source

Abstract

This study reports a mild and efficient synthetic protocol for the synthesis of symmetrical and unsymmetrical diarylmethanes (DAMs). Using DMSO as the C1 source and TMSOTf as the Lewis acid promoter, a series of functionalized symmetrical and unsymmetrical DAMs were synthesized in high yields. Gratifyingly, DMSO plays a dual role as a solvent and a C1 source and can also be replaced with its deuterated counterpart, DMSO-d 6, enabling the incorporation of the -CD2 moiety into the diarylmethane skeleton. The developed approach has been applied to a wide range of substrates having various functional groups, and this protocol has also been extended to the synthesis of an anti-breast cancer agent and an anticoagulant agent using common feedstock compounds. In addition, the postulated mechanism has been explicitly demonstrated via control experiments.

Cooperative Friedel–Crafts Alkylation of Electron‐Deficient Arenes via Catalyst Activation with Hexafluoroisopropanol**

“…Disappointingly, under various reaction conditions previously optimized for the FC reaction of aromatic aldehydes [13][14][15][16] there was no diarylated product (5) formation at room temperature (entry 4).…”

“…Recently, our group has published several protocols for typical FC reactions by using activated nucleophiles [13–16] . Thus, we were curious to develop a general protocol for FC reaction which can be used with deactivated arene nucleophiles under ambient reaction condition.…”

“…[7] Recently, our group has published several protocols for typical FC reactions by using activated nucleophiles. [13][14][15][16] Thus, we were curious to develop a general protocol for FC reaction which can be used with deactivated arene nucleophiles under ambient reaction condition. Towards such aim, we became interested in developing a FC alkylation of electron-deficient arene nucleophiles with aldehydes and ketones.…”

TMSOTf‐Promoted Synthesis of Quinazolin‐4(3H)‐one Utilizing DMSO as a Carbon Source

“…The generated intermediate 4 c will proceed with the reaction by intramolecular cyclization (4 d) and then oxidation under the available condition to form the final desired product 3 [21] . It is important to note that the triflate (TfO − ) will be regenerated to TfOH (Trifilic acid) to enable the DMSO to generate the intermediate x1 and then x4 to complete the catalytic cycle [2d] …”

NH4OAc/DMSO-Promoted Benzylation of Pyrrolo[2,1-a]isoquinolines

“…A series of moieties can be tethered to the target (hetero)­arene with a methylene group, such as a same or different (hetero)­arene, thioether, and amino moieties (Scheme ). Several DMSO-based approaches for the synthesis of symmetric bisheteroarenes have been well established in the past decades. Recently, DMSO-based constructions of unsymmetric bis-heteroarenes have also been achieved by three groups.…”