Bi(OTf)₃‐catalyed One‐pot Synthesis of α‐Halo‐β‐amino Ketones and Acyl Aziridines from 3‐Aryl Propargyl Alcohols

Abstract

A Bi(OTf)3‐catalyed reaction of 3‐aryl propargyl alcohols with sulfonamide and halogen source was firstly investigated, which provided a facile route for the synthesis of a large variety of α‐halo‐β‐amino ketones. The key intermediates, β‐amino ketones, were obtained through tandem Meyer‐Schuster rearrangement reaction of propargyl alcohols and intermolecular Michael addition of α, β‐unsaturated ketones and sulfonamide. Then the in situ generated α‐halo‐β‐amino ketones underwent the base‐promoted intramolecular cyclization to give diverse acyl aziridines in a one‐pot fashion. These transformations are reliable on a large scale. The high yields and convenient experimental operations make it a valuable method for the construction of α‐halo‐β‐amino ketones and acyl aziridine derivatives.

Recent progress in the chemistry of β-aminoketones

“…Zhang et al 146 developed a facile procedure for the synthesis of α-bromo-β-aminoketones 120–122 under catalytic conditions. Consequently, Bi(OTf) 3 -catalyzed reactions of 3-phenyl(aryl)prop-2-yn-1-ol with sulfonamides and N -bromosuccinamide as a source of the halogen yielded the desired series of α-bromo-β-aminoketones 120–122 (Scheme 41).…”

[BCMIM][Cl] ionic liquid catalyzed diastereoselective synthesis of β‐amino ketones via facile, one‐pot, multicomponent Mannich reaction under solvent‐free condition

“…Many pharmacological medications and biologically active intermediates depend on β-amino carbonyl compounds as building blocks [14,15]. Furthermore, β-amino ketones and their derivatives are significant chemicals with significant bioactivities, including anti-inflammatory, antibacterial, antimycobacterial, analgesic, antidiabetic, and anticancer properties [16,17]. Marketed medications containing β-amino ketones are frequently used in clinics, such as Antispasmodic medications Mydocalm (Tolperisone Hydrochloride) and Myonal (Eperisone Hydrochloride) are commonly used to treat spastic paralysis; Ondansetron, a drug used to treat nausea and vomiting brought on by cancer chemotherapy and radiation therapy; Lobeline (Alpha-Lobeline Hydrochloride), a drug used to treat medullary respiratory center stimulating symptoms; Alcaine (Proparacaine) is a prescription medication used for induce anesthesia for eyes examination and procedures; and Proroxan (also known as pyrroxane and pirroksan) is a pharmaceutical drug used as an antihypertensive and in the treatment of Meniere's diseases, motion sickness, and allergic dermatitis [18].…”

Synthesis of primary propargylic alcohols from terminal alkynes using rongalite as the C1 unit

“…The key intermediate 3-(4-(methylthio)phenyl)prop-2-yn-1-ol 3y could be obtained in 77% yield, and could be converted into thiamphenicol through six-step reactions according to literature reports (Scheme 5b). 16…”