Transition-Metal-Free Synthesis of Aryl Thiocyanates, Aldehydes and Ketones, Azaheterocyclic carboxamides and Styrenyl Ethers

Abstract

Oxidative C-H functionalization to form new C-C, C-N, and C-S bonds has emerged as an elegant and robust synthetic method for accessing useful products, featuring atom economy and straightforwardness. However, many of these methods are based on transition-metal catalysis, which is usually associated with drawbacks such as cost, toxicity and need for non-commercial ligands. As an alternative, transition-metal-free versions have become very important for avoiding more expensive transition metal reagents and to tackle the environmental issues. Potassium persulfate (K2S2O8) has emerged as one of the powerful transition-metal-free reagents in organic synthesis. It is relatively cheap, environmentally friendly powerful oxidant and frequently used for the degradation of environmental and soil carbon pollutants. It has also been widely used as a radical initiator in a number of industrial applications. In this regard, we focused our attention to explore the strength of K2S2O8 for the novel transition-metal-free protocols. We developed an expedient and direct transition-metal-free regioselective thiocyanation of phenols, anilines and heterocycles using NH4SCN and K2S2O8.Transformation is realized via the direct C-H functionalization under transition-metal-free conditions at an ambient temperature in excellent yields. Similarly, we demonstrated a one-pot protocol for the direct and clean transformation of aryl acetic acids to aldehydes and ketones in water using less expensive K2S2O8 as a reagent. The protocol relies on the direct decarboxylation of sp3-hybridized carbon in water without any over oxidation into carboxylic acids with minimal waste. Further, we have developed a transition-metal-free carbamoylation of heterocycles using formamides/NMF/DMF and K2S2O8. The transformation is realized via direct dehydrogenative aminocarbonylation of heterocyclic compounds. The method proved to be practical and a series of primary to tertiary carboxamides were synthesized without any side products. We also developed a novel one-pot transition-metal-free synthesis of Z-selective styrenyl ethers from 2-aryloxy/alkoxy acetophenones via Bamford-Stevens reaction for the first time. The novel methodology described here is practical and scalable. We developed transition-metal free protocols for the direct access of aryl thiocyanates, aldehydes and ketones, pyridylcarboxamides and styrenyl Ethers for the thesis work. All the developed protocols with literature background will be discussed in detail during the pre-synopsis seminar.