Copper-Catalyzed Oxidative Alkylation (Methylation) of Phosphonamides and Phosphinamides Using Dicumyl Peroxide

Abstract

An effective and practical CuI-catalyzed methodology toward N-alkyl or N-methyl phosphonamides and phosphinamides was herein demonstrated. The transformation took place readily under the oxidative conditions, and plenty of N-alkylated (methylated) amides (30 examples) were successfully furnished in high efficiency (up to 92% yields). Dicumyl peroxide was considered to act either as the oxidant for the alkylation reaction or as methyl donator for the methylation protocol.

Copper‐Catalyzed Oxidative C(sp3)−H/N−H Cross‐Coupling of Hydrocarbons with P(O)−NH Compounds: the Accelerating Effect Induced by Carboxylic Acid Coproduct

“…In the deuterium‐labelling experiments of 1 a , the reaction using [D 8 ]‐toluene was slower than that using toluene. Meanwhile, a demethylation reaction of DTBP was found to take place in [D 8 ]‐toluene (not detected in toluene) ,,. In the 1 H NMR spectrum of products, when the reaction of 1 a was performed in a 1:1 mixture of toluene and [D 8 ]‐toluene, 1.80 H was observed in the benzylic position, evidencing the H‐atom abstraction (HAA) of toluene is more favorable than demethylation of DTBP and the C−D scission of [D 8 ]‐toluene (Scheme a, k H /k D values up to 9.0).…”

Recent Advances in Methylation: A Guide for Selecting Methylation Reagents

“…It can be used as a guide for chemists wanting to apply the best methylation conditions in their work. Despite the fact that only methylation chemistry is covered in this review, certain methods also work well for accessing other alkyl groups, such as cyclic (cyclopropyl, ‐pentyl, and ‐hexyl) alkyl groups, benzylation, etc …”

“…The application of DCP in Scheme 15 includes:1 )2-methylation of pyridines 137 achieved through the reduction of 2-methylatedp yridine oxides 136; [85] 2) in the absence of metal cat-alysts, methylated pyrimidinones and pyridinones 138 were synthesized; [86] 3) in the presence of catalytic Pd(OAc) 2 ,m ethylation is ortho selectively (139,140), presumably owing to chelation-directed CÀHa ctivation; [87] 4) am onoN -methylation of phosphonamides and phosphinamides 141 was furnishedb y using CuI as the catalysta nd 1,10-phenanthroline (Phen) as the ligand in as ealed tube; [88] 5) as imilarc helation-directed CÀH activation was proposed for the formation of the ortho-methylated amides 142. [89] Chemistry towards 143 in Scheme 16 represents au seful complementt ot he traditional a-methylation of 1,3-dicarbonyl compounds, in which toxic methyl iodide is often used.…”

Copper‐Catalyzed (Di)Arylmethylation of Phosphorylamides Under Oxidative Conditions

“…Phosphonamides and phosphinamides, which are generally called phosphorylamides, have drawn widespread research interests for the exceptional structures and broad applications in the communities of clinical explorations and material science Furthermore, chiral P(O)–N‐cored motifs have been prepared for asymmetric syntheses, and novel methodologies have been developed from the flexible molecules toward some biologically active heterocycles in the presence of different transition metallic catalysts . Despite that rapid growth in the field has been wittnessed, the topic remained underexploited because of the fragilities of the P–N bonds and unusually stable N–H bonds to other amides, meaning the direct N ‐functionalization of the amides with the reservation of the P–N bonds remained a great challenge up to date. On the other hand, new transformations are still severely desired for the improvement of the diversity of phosporylamides.…”

“…Amines, amides, sulfonamides, and sulfoximines can be readily benzylated by straightforward procedures. Encouraged by the successful establishment of methylation/alkylations and arylation of phosphorylamides, we wish to describe our novel studies on benzylation of the same substrates by (di)arylmethanes, and the oxidative transformation enjoyed the superiorities including the high generality and P–N bond reservation under the oxidative conditions [Scheme , Equation (2)].…”