Visible‐Light‐Driven Photocatalyst‐ and Additive‐Free Cross‐Coupling of β‐Ketothioamides with α‐Diazo 1,3‐Diketones: Access to Highly Functionalized Thiazolines

Abstract

A photocatalyst‐ and additive‐free, visible‐light‐mediated chemoselective domino protocol was devised to access fully substituted thiazoline derivatives from β‐ketothioamides and α‐diazo 1,3‐diketones at moderate temperature in open air. The reaction proceeds through in situ generation of electrophilic carbenes from α‐diazo 1,3‐diketones by a low‐energy blue LED (448 nm), which undergoes selective coupling with nucleophilic β‐ketothioamides to give thiazolines by successive formation of C−S and C−N bonds in one stretch. Notably, the benign and clean conditions, operational simplicity, sustainability, 100 % carbon economy, high yields, and wide functional‐group tolerance are further attributes of the strategy. A mechanistic rationale for this cascade reaction sequence is well supported by control experiments.

Lightening Diazo Compounds?

“…Photochemically generated carbenes react with β-ketothioamides affording heterocyclic compounds via a cascade of transformations enabling synthesis of substituted thiazolines in very good yields …”

“…103 Photochemically generated carbenes react with β-ketothioamides affording heterocyclic compounds via a cascade of transformations enabling synthesis of substituted thiazolines in very good yields. 104 In their very recent work, Koenigs et al described the formation of carbenes from aryl/aryl diazo compounds and their reactivity with alkynes 65. 5 The reaction is dependent on the type of substituents on the aromatic rings and can lead to cyclopropenation or C−H insertion.…”

Visible light-mediated photolysis of organic molecules: the case study of diazo compounds

“…Intramolecular cyclization by the proximal N atom leads to intermediate 21 , which is followed by the elimination of water to allow the access to the observed thiazolines 18 (Scheme 6b). 23 The authors used an overall low-power light source (blue LEDs, 448 nm, approximate power of 1 W each) in this reaction. It is curious to note that a Wolff rearrangement was not observed in this scenario.…”

“…22 In 2020, Singh and co-workers have reported a blue lightmediated reaction between b-ketothiamides 16 and a-diazo 1,3diketones 17 to afford highly functionalized thiazolines 18 in good yields, 60-90% (Scheme 6a). 23 The reaction mechanism was proposed to start with the blue light-mediated photolysis of the a-diazo 1,3-diketone 17 to produce the corresponding carbene intermediate 19. Then, a nucleophilic attack by the S atom of the b-ketothiamide 16 would take place onto the carbene 19 to afford intermediate 20.…”

Photo-oxidative Ruthenium(II)-Catalyzed Formal [3 + 2] Heterocyclization of Thioamides to Thiadiazoles

“…Our laboratory has a long-standing interest in thermal reactivity/transformation of KTAs to diverse heterocyclic scaffolds . Very recently, we have devised a domino protocol to access thiazoline derivatives employing KTAs . Based on our experience, we became intrigued by studying the photochemical reaction of diazonium salts with KTAs that could be a viable alternative for valuable scaffolds.…”