Pd/Cu‐Catalyzed Cross‐Coupling of Densely Substituted Propargylamines with Aromatic Acyl Chlorides Followed by the Treatment with a Base: Access to Dihydro‐3H‐Pyrrol‐3‐Ones

Abstract

Pd/Cu‐catalyzed cross‐coupling of propargylamines with aromatic acyl chlorides (PdCl2, CuI, Ph3P, 40–45 °C) provides α‐aryl(hetaryl)aminoacetylenic ketones in a yield of up to 97%. The latter undergo cyclization to 1,2,5‐triaryl(hetaryl)‐1,2‐dihydro‐3H‐pyrrol‐3‐ones in up to 93% yield after the treatment with KOH or Et2NH (40–55 °C, aqueous ethanol). The one‐pot synthesis of the pyrrol‐3‐ones (in up to 62% yields) by consecutive treatment of the above propargylamines with acyl chlorides (PdCl2/CuI/Ph3P) and a base (KOH) in aqueous ethanol has been also developed.

Dihydropyrrole-3-thiones: one-pot synthesis from propargylamines, acyl chlorides and sodium sulfide

“…It was shown previously 21 that the cross-coupling (stage i ) proceeded almost quantitatively with good tolerance toward the substituents both in propargylamines and acyl chlorides, i.e. being almost independent of the substrate structure.…”

“…Note that in the absence of PdCl 2 , the result was negative: even at a longer reaction time (24 h, other reaction conditions remaining the same), the expected products were not detected and the content of the intermediate aminoacetylenic ketone decreased. 20 These conditions were chosen based on our previous work 21 for stage i and on a short optimization for the closing stage (treatment with Na 2 S). The reaction course was followed by TLC up to the disappearance of the spot belonging to the intermediate aminoacetylenic ketone as well as by IR spectroscopy to observe the CC band (∼2208 cm −1 ) decreasing.…”

“…10% as compared to the one-pot procedure. This is a result of the competitive addition of hydroxide ions (from hydrolysis of Na 2 S) to the triple bond affording dihydropyrrole-3-ones 21 (Scheme 5).…”