Direct C–H Functionalization of Phenanthrolines: Metal- and Light-Free Dicarbamoylations

Abstract

A direct method for C−H dicarbamoylations of phenanthrolines has been developed, which is capable of directly installing primary, secondary as well as tertiary amides. This is a significant improvement on the previous direct method, which was limited to primary amides. The metal-, light-, and catalyst-free Minisci-type reaction is cheap, operationally simple, and scalable. We demonstrate that the step efficiency toward dicarbamoylated phenanthroline targets can now be significantly improved.

Oxamic acids: useful precursors of carbamoyl radicals

“…It is worth noticing that the use of silver salts to decompose persulfate is now unnecessary and has been superseded by the simple heating of the persulfate with DMSO. 24–26 The radicals thus produced add efficiently to a broad range of unsaturated systems, including alkenes, both electron-rich and electron-poor and aromatic heterocycles (Minisci reaction) giving access to diversely functionalized amides. Finally, oxidation of oxamic acids in the presence of alcohols, amines, or thiols gives access to the corresponding urethanes, ureas and thioureas.…”

“…A silver-free version of the above Minisci reaction was recently reported by different laboratories and demonstrated to be efficient for carbamoylation of a variety of heteroarenes, including quinoxalin-2(1 H )-ones, 24 phenanthrolines 25 and 2 H -indazoles (Scheme 3). 26 This procedure relies on the use of (NH 4 ) 2 S 2 O 8 as an oxidant, DMSO/H 2 O as solvents, and a temperature between 40–60 °C to furnish the corresponding amides 3 in moderate to high yield, without the need for a silver salt catalyst or acidification.…”

Direct Hydrodecarboxylation of Aliphatic Carboxylic Acids: Metal- and Light-Free

“…The inspiration for our work was our recent discovery that Minisci-type reactions can proceed under mild conditions without any metal, photocatalyst, or light. 12 The use of DMSO as solvent was thought to allow for the breakdown of S 2 O 8 2– to the active SO 4 – • under mild conditions, without the need for the previously used metal mediation or photolysis. 13 We were also inspired by the original Kochi hydrodecarboxylation [Ag(II), S 2 O 8 2– , and heat], although low yields, poor selectivity, a limited substrate scope, and expensive/unsustainable use of silver have so far limited any widespread utility in synthetic applications.…”

“…The inspiration for our work was our recent discovery that Minisci-type reactions can proceed under mild conditions without any metal, photocatalyst, or light . The use of DMSO as solvent was thought to allow for the breakdown of S 2 O 8 2– to the active SO 4 – • under mild conditions, without the need for the previously used metal mediation or photolysis .…”

Direct Minisci-Type C–H Amidation of Purine Bases

“…Based on previous literature precedent, , the proposed mechanism is presented in Scheme . Deprotonation of 6 by the purine base (e.g., 5 ) forms salt I .…”