Metal-Free Cross-Dehydrogenative C–O Coupling of Carbonyl Compounds with N-Hydroxyimides: Unexpected Selective Behavior of Highly Reactive Free Radicals at an Elevated Temperature

Abstract

Cross-dehydrogenative C−O coupling of N-hydroxyimides with ketones, esters, and carboxylic acids was achieved employing the di-tertbutyl peroxide as a source of free radicals and a dehydrogenating agent. The proposed method is experimentally simple and demonstrates the outstanding efficiency for the challenging CH substrates, such as unactivated esters and carboxylic acids. It was shown that N-hydroxyphthalimide drastically affects the oxidative properties of t-BuOOt-Bu by intercepting the t-BuO • radicals with the formation of phthalimide-N-oxyl radicals, a species responsible for both hydrogen atom abstraction from the CH reagent and the selective formation of the C−O coupling product by selective radical cross-recombination. The practical applicability of the developed method was exemplified by the single-stage synthesis of commercial reagent (known as Baran aminating reagent precursor) from isobutyric acid and N-hydroxysuccinimide, whereas in the standard synthetic approach, four stages are necessary.

N‐Alkoxyphtalimides as Versatile Alkoxy Radical Precursors in Modern Organic Synthesis

“…N-alkoxyphthali-mides are easily available and stable reagents, which can be synthesized from NHPI and alkyl halides by nucleophilic substitution, alcohols and NHPI by the Mitsunobu reaction or by modern oxidative CÀ O coupling methods. [5,[26][27][28][29][30][31][32][33][34][35] Their singleelectron reduction leads to phthalimide anion and an alkoxy radical [25] which can be further employed in selective transformations including CÀ H and CÀ C bond cleavage (Scheme 1).…”

Visible-Light-Induced Denitrification Oxygenation Reaction of α-Diazoesters to Construct α-Oxyimido Esters

“…云飞课题组 [9] 报道了一种四丁基碘化铵/叔丁基过氧化 氢(TBHP)体系介导的酯与 N-羟基邻苯二甲酰亚胺分子 间的 C-H/O-H 交叉偶联反应合成 α-氧代酰亚胺酯的 方法(Scheme 1a). 2020 年, Terent'ev 课题组 [10] 采用 3 equiv.二叔丁基过氧化物作为氧化剂, 在 130～150 ℃苯 溶剂中, 用酯或酮与 N-羟基邻苯二甲酰亚胺发生分子 间的交叉脱氢 C-O 偶联反应来构建 α-氧代酰亚胺酯 (Scheme 1b). 2022 年, 胡艾希课题组 [11] 报道了一种电催 化合成 α-氧代酰亚胺酯的方法(Scheme 1c).…”

tert-Butyl Nitrite as a Twofold Hydrogen Abstractor for Dehydrogenative Coupling of Aldehydes with N-Hydroxyimides

“…In the past few years, the redox-active alkyl NHPI esters also demonstrated magnificent applications in decarboxylative cross coupling reactions, affording a series of C–Y (Y = B, C, Si, Se, etc.) bonds (Scheme a). , NHPI esters were generally prepared through the esterification of carboxylic acids with NHPI in the presence of carbodiimides as reagents; however, the formation of the byproduct urea results in purification difficulties. Alternatively, the cross dehydrogenative coupling of aldehydes with N -hydroxysuccinimide (NHSI) or NHPI − could afford N -hydroxyimide esters and therefore has attracted considerable interest.…”

“…In particular, no coupling reaction of 2-oxo-2-phenylacetaldehyde with NHPI has been documented. All of these problems limit the practical applications of transformations mentioned above, and therefore, the NHPI esters were prepared from carboxylic acids with NHPI. , A general synthetically practical method for dehydrogenative coupling of aldehydes and NHPI is still under unexplored, especially for pharmaceutical applications.…”