Soft–Hard Acid–Base‐Controlled C−H Trifluoroethoxylation and Trideuteriomethoxylation of Anilides

Abstract

Phenyliodinetrifluoroacetate (PIFA)-mediated dehydrogenative CÀHe therification of anilides is reported for the synthesis of -OCH 2 CF 3 and -OCD 3 incorporated aryl ethers. Nucleophilicity of the added nucleophiles and soft-hard acid-base (SHAB) principle were rationalized to understandt hose reactions. Anilides and PIFAl ed to the electrophiles either softer nitrenium ions or harder carbenium ions. The harder nucleophile alcohols exclusively reacted with the carbenium ions to produce aryl ethers.

Fluorination and Fluoroalkylation Reactions Mediated by Hypervalent Iodine Reagents

“…[39] The product formation seemed to be the result of two discrete Csp 3 À F bond construction (Scheme 18). The in situ generation of aryliodonium difluoride from p-iodotoluene, selectfluor, and amine • HF and its reaction with olefin (93) yields a transient cation (95), which facilitates an activationdisplacement sequence to afford vicinal difluoride (94) and regenerate p-iodotoluene, maintaining the catalytic cycle. Preliminary efforts on the development of an enantioselective variant were also made in this work, but poor e.r.…”

“…[93] Furthermore, PhI(OCOCF 3 ) 2 -mediated alkoxylation of anilides (320) with CF 3 CH 2 OH yielded aryl-OCH 2 CF 3 (321) at room temperature under transitionmetal-and additive-free conditions, which supplied a useful synthetic tool that may have important applications in both academia and pharmaceutical industry (Scheme 63). [94] Nucleophilicity and soft-hard acidbase principle were employed to understand the reaction pathways. [94] As described in Scheme 63, nucleophilic attack of N-center of anilide (320 a) to iodine of PhI(OCOCF 3 ) 2 generates 322 with the elimination of trifluoroacetic acid, which further decomposes to electrophile as either softer nitrenium ion (324) or harder carbenium ion (323).…”

“…[94] Nucleophilicity and soft-hard acidbase principle were employed to understand the reaction pathways. [94] As described in Scheme 63, nucleophilic attack of N-center of anilide (320 a) to iodine of PhI(OCOCF 3 ) 2 generates 322 with the elimination of trifluoroacetic acid, which further decomposes to electrophile as either softer nitrenium ion (324) or harder carbenium ion (323). The Narylation could be explained via 324 with the byproduct (iodobenzene), while the C-alkoxylation was rationalized via 323 in the presence of CF 3 CH 2 OH.…”

Nitrenium Ions from Amine‐Iodine(III) Combinations

“…Trifluoroethoxy (−OCH 2 CF 3 ) and trideuteriomethoxy (−OCD 3 ) containing aromatic compounds are significant due to their several physiochemical properties. Recently, Mal and co‐workers have reported a PIFA‐mediated soft‐hard‐acid‐base (HSAB) controlled para ‐selective C−H functionalization of anilides for the incorporation of −OCH 2 CF 3 and −OCD 3 groups (Figure g) . Here CF 3 CH 2 OH or CD 3 OD was used as solvent which acted as the nucleophile to react with a carbenium ion (Figure h).…”

An Intramolecular C(sp2)–H Amidation Using N‐Iodosuccinimide

“…Small‐molecule systems chemistry is an increasingly popular approach to understanding the complexity of chemical reactions and working towards implementing them in a simplified manner. Cooperative multiple weak interactions like hydrophobic effects, halogen bonding, charge‐transfer interactions, cation–π interactions, anion–π interactions, hard–soft acid–base (HSAB) control, etc. are being explored in chemical reaction systems .…”