ABSTRACT
Regioselective phosphonation of pyridines is an interesting transformation in synthesis and medicinal chemistry. We report herein a metal-free approach enabling access to various 4-phosphonated pyridines. The method consists of simply activating the pyridine ring with a Lewis acid (BF3·OEt2) to facilitate the nucleophilic addition of a phosphine oxide anion. The formed sigma complex is subsequently oxidized with an organic oxidant (chloranil) to yield the desired adducts in good to excellent yields. We furthermore showed that access to C2-phosphoinated pyridines can be achieved in certain cases with strong Lewis basic phosphorus nucleophiles or with strong Lewis acidic pyridines. Both experimental and computational mechanistic investigations were undertaken and allowed us to understand the factors controlling the reactivity and selectivity of this reaction.
ABSTRACT
The synthesis of sulfilimines and sulfoximines with N-mesyloxycarbamates in presence of catalytic iron(II) chloride hydrate is described. The use of 1-butylimidazole as a base proved instrumental in enabling a homogeneous reaction mixture compatible with continuous flow processes. The amination is applicable to a wide range of substrates, and affords the desired product in good to excellent yields within 1 to 60â minutes.
ABSTRACT
The chemoselective amination of alkyl bromides and chlorides with aqueous ammonia and hydroxylamine was achieved in continuous flow to produce primary ammonium salts and hydroxylamines in high yields. An in-line workup was designed to isolate the corresponding primary amine, which was also telescoped in further reactions, such as acylation and Paal-Knorr pyrrole synthesis. Monosubstituted epoxides are also compatible with the reaction conditions.
