Metal‐free Nucleophilic Alkoxylation of in Situ‐Generated Azaoxyallyl Cations: Synthesis of Hindered Dialkyl Ether Derivatives

Abstract

A metal and catalyst-free, environmentally friendly synthesis of hindered dialkyl ether derivatives has been established via the nucleophilic alkoxylation of alcohols and α-halohydroxamates. The reactions of a variety of primary and secondary alcohols with azaoxyallyl cations generated in situ from α-halohydroxamates afforded a wide range of hindered dialkyl ether derivatives in good yields. Moreover, methods for the synthesis of α-alkoxyhydroxamic acids, α-alkoxy amides, and α-hydroxy amides from αalkoxy hydroxamates were established. [a] E. Scheme 1. Representative examples of hindered dialkyl ether synthesis. Scheme 2. Nucleophilic amination and alkoxylation of α-bromohydroxamate.

Aza‐oxyallyl Cations and Their Applications in (3+m) Cycloaddition Reactions

“…and Kim et al. pioneeringly established aza‐oxyallyl cation as alkylating agent [8c–f] . In 2020, Singh and co‐workers synthesized pharmaceutically important congested secondary aryl amines by treating aniline derivatives with aza‐oxyallyl cations (reactive form of functionalized alkylating agent $${\alpha }$$ ‐halo amides) under basic condition in HFIP solvent [8c] .…”

“…Inspired by the above achievements Kim et al., in the same year reported C−O alkylation with aza‐oxyallyl cation. They synthesized wide range of hindered dialkyl ether derivatives 126 through metal and catalyst free, base mediated nucleophilic alkoxylation of primary and secondary alcohols 125 with aza‐oxyallyl cation in aprotic fluorinated solvent CF 3 C 6 H 5 with good yields [8e] . Screening results showed that Cs 2 CO 3 in CF 3 C 6 H 5 was the optimal reaction condition for the said transformation (Scheme 38).…”

“…However, considering the immense synthetic potential shown by this unique intermediate in recent times a dedicated review article in continuation since 2018 would be highly desirable given the significant and diverse advancement in this research field that has been achieved so far for example aza‐oxyallyl cations as a 2‐unit synthon in [2+4]‐cycloaddition reaction, [8a] a novel type of oxindole‐based aza‐oxyallyl cations synthon, [8b] congested and functionalized alkylation of amines (C−N bond) [8c–d] and hydroxyl groups (C−O bond) [8e–f] using aza‐oxyallyl cations as alkylating agents and apart from conventional study a new reactivity of aza‐oxyallyl cations as 1,4‐dipolar in [4+2]‐cycloaddition reaction [8g] . Therefore, a concise and critical review encompassing the latest developments involving aza‐oxyallyl cations as reactive intermediate will certainly provide great impetus for further development of aza‐oxyallyl cation based chemistry.…”