A New Facile Approach to the Synthesis of 3-Methylthio-Substituted Furans, Pyrroles, Thiophenes, and Related Derivatives

Abstract

2-(methylthio)-1,4-diaryl-2-butene-1,4-dione (3) are prepared from readily available aryl methyl ketones in the presence of copper(II) oxide, iodine, and dimethyl sulfoxide. The success of the cross-coupling reaction of 4-chloroacetophenone with 2-acetylthiophene confirms a proposed self-sorting tandem reaction mechanism. Both Z- and E-isomers of compound 3 are readily converted into the corresponding 3-methylthio 2,5-diaryl furan 7 in good yield through a domino process involving the reduction of the double bond followed by the Paal-Knorr furan synthesis. Meanwhile, 4-bromo-3-methylthio 2,5-diaryl furan 10 is obtained either by the treatment of furan 7 with molecular bromine or by the treatment of diketone 3 with 30% hydrogen bromide in acetic acid solution in one pot. Removal of the methylthio group is accomplished by the treatment of 7 with Raney Ni in ethanol, which affords the diaryl-substituted furan 11 in excellent isolated yield. Selective reduction of the double bond of compound 3 leads to the formation of the saturated 1,4-diketone 13, which is easily converted to the corresponding 3-methylthio-2,5-diaryl-substituted pyrrole 14 and thiophene 15 via the Paal-Knorr cyclization reaction.

Formation of 2‐Acyloxazoles by a Multipathway Coupled Domino Strategy: One‐Pot Metal‐Free Oxidative Cyclization Applicable to Various Substrates

“…On the basis of the aforementioned results and previous reports, [10] a plausible mechanism is proposed as shown in Scheme 3. Initially, the acetophenone, substrate or phenylacetylene is converted into the intermediate phenacyl iodine (1 aa) in the presence of I 2 /IBX or NIS.…”

“…[9] In our previous work, an unstable a-ketoaldehyde intermediate could be obtained from acetophenone, styrene, or phenylacetylene. [10] Furthermore, the a-ketoaldehyde was shown to react with NH 4 OAc to generate 2-acyloxazoles.…”

“…According to the literature, [10] phenacyl iodine (1 aa) can be obtained with acetophenone (1 a), styrene (2 a), or phenylacetylene (3 a) as substrates. Furthermore, it is known that 1 aa can be quantitatively converted into a-ketoaldehyde 1 ab or hydrated hemiacetal 1 ac in DMSO at 100 8C.…”

“…Furthermore, it is known that 1 aa can be quantitatively converted into a-ketoaldehyde 1 ab or hydrated hemiacetal 1 ac in DMSO at 100 8C. [10] Therefore, 1 aa and 1 ac were subjected to the reported reaction conditions and 4 a was obtained in 63 % and 75 % yields, respectively (Scheme 2, Eq. 1 and 2).…”

(Z)-1,4-Bis(2-chlorophenyl)-2-(methylsulfanyl)but-2-ene-1,4-dione

“…The Paal-Knorr selective reduction of double bonds, condensation, and domino reactions of 2-methylthio-1,4-en-diones leads to the formation of biologically and medicinally important heterocyclic compounds such as furan (Yin et al, 2008), pyridazine (Wu et al, 2012), indole-furan (Yang et al, 2011), 1,2-dihydroquinoxaline (Zhang et al, 2013) and beta-enaminones (Vinayaka et al, 2016). The synthesis of these intermediates involves the self-sorting tandem reactions of aryl/heteroaryl methyl ketones, which form a mixture of E/Z products in different ratios.…”