Construction of 4‐(Methylthio)isochromenones Skeleton through Regioselective Intramolecular Cyclization of 2‐Alkynylbenzoate Mediated by DMSO/[D₆]DMSO and SOCl₂

Abstract

DMSO/SOCl2 was found to be an effective system for the intramolecular cyclization of 2‐alkynylbenzoates or 2‐alkynylbenzoic acids, which can afford biologically interesting 4‐(methylthio)isochromenones through regioselective electrophilic 6‐endo‐dig cyclization. DMSO plays the roles of both solvent and sulfur source and can also be replaced with its deuterated counterpart [D6]DMSO, enabling the incorporation of the SCD3 moiety into the isochromenone skeleton.

Unexpected Substituent Effects in Spiro-Compound Formation: Steering N-Aryl Propynamides and DMSO toward Site-Specific Sulfination in Quinolin-2-ones or Spiro[4,5]trienones

“…On the basis of our experimental results, previous reports, 10c , 10d , 20 , 23 , 24 and wB97XD/6-311+G(d,p) calculations, 25 we propose substituent-dependent mechanistic pathways for the construction of 3-methylthioquinolin-2-one and 3-methylthiospiro[4.5]trienone skeletons, respectively ( Scheme 3 ). We will discuss these in detail for three different substituents, R = para -H, para -F, and para -OMe, as they represent the various classes of substituents for which different reactivities have been observed.…”

“…With reference to the reactions in our previous work, 20 we initiated our studies by treating N -methyl- N ,3-diphenylpropiolamide 1a (0.5 mmol) with DMSO (1 mL) and SOCl 2 (1.0 mmol) at 25 °C for 12 h. We were pleased to note that the desired 1-methyl-3-(methylthio)-4-phenylquinolin-2(1 H )-one 2a was obtained in 22% yield ( Table 1 , entry 1). When the dosage of SOCl 2 was increased, the yield of 2a improved significantly and the time needed was shortened ( Table 1 , entries 2–3).…”

Synthesis of 3‐Methylthio‐benzo[b]furans/Thiophenes via Intramolecular Cyclization of 2‐Alkynylanisoles/Sulfides Mediated by DMSO/DMSO‐d6 and SOCl2

“…Based on the aforementioned experimental results and previous reports, [ 22 ] we proposed a possible mechanism for the formation of 3‐methylthio‐benzo[ b ]furan 2a (Scheme 2). First, the reaction of DMSO with SOCl 2 gave the reactive CH 3 SCl B in situ, via the key dimethylsulfochlorine cation A , through an interrupted Pummerer process.…”

PhICl2-Mediated Regioselective and Electrophilic Oxythio/Selenocyanation of o-(1-Alkynyl)benzoates: Access to Biologically Active S/SeCN-Containing Isocoumarins

“…Based on these newly gained experimental (control experiments see ESI, Supplementary Scheme S1 , SupplementaryFigure S1, S2 and computational calculation) and computational results as well as previous literature reports ( Kita et al, 1997 ; Woon et al, 2006 ; Ito et al, 2019 ; Xing et al, 2019a ; An et al, 2020 ), a possible mechanistic pathway for the formation of the C4 thiocyanated isocumarins was proposed ( Scheme 4 ). Differing from the previous mechanism ( Kita et al, 1997 ), we tentatively proposed that intermediate A , an ionic form of PhICl 2 , reacted with thiocyanate directly to give the reactive thiocyanogen chloride, which could be supported by the observation of peak of 109.1 ppm in its 13 C NMR analysis ( Tao et al, 2021 ).…”