Z‐Selective Synthesis of α‐Sulfanyl Carbonyl Compounds from Internal Alkynes and Thiols via Photoredox Catalysis

Abstract

A synthetically useful Z-selective cascade formal thiyl radical addition, 1,3-double bond isomerization, oxygen trapping reaction, can be promoted by Eosin B under visible light, leading to the construction of 2-aryl-and alkylthio enone derivatives in good yields. An accurate study on the reactivity of different thiols and the screening of the reaction conditions, allowed us to extend this reaction to a large number of substrates, showing a good functional groups tolerance while highlighting the limitations of this procedure. Background experiments and mechanistic studies were also. performed to rationalize this cascade process. The usefulness of this methodology was finally demonstrated via the transformation of a series of α-sulfanyl-enone adducts through selected oxidation reactions, stereoselective synthesis of cyclopropyl ketones, indanones, and pyrazole compounds.

Recent Advances in Visible‐Light‐Driven C−S Bond Formation

“…The regio‐ and stereo‐selective coupling of alkynes 11.1 and thiols 11.2 a – c to obtain (Z)‐α‐sulfanyl enones ( 11.3 a – c ) was achieved in the presence of Eosin B as the photoredox catalysis. (Scheme 11a) [42] . Notably, the nature of thiols can affect both efficiency and selectivity; indeed, thiophenols bearing electron‐withdrawing groups react efficiently under the optimized conditions, whereas with aliphatic thiols and arylthiols bearing electron‐donating substituents an organic base (pyridine) is required.…”

“…It should be noticed, however, that alkynes with longer aliphatic chains (>4 carbon atoms) were not suitable for this method. As hinted above, the coupling of alkynes and thiols was also achieved in the presence of benzyl as the photocatalyst [42] . Ananikov and co‐workers recently optimized a versatile three component thiol‐yne‐ene coupling reaction for the design of highly functionalized homoallylic sulfides 11.7 via Eosin Y photocatalyzed coupling of alkynes 11.4 , thiols 11.5 and vinylsulfides 11.6 (an example in scheme Scheme 11b) [43] …”

“…(Scheme 11a). [42] Notably, the nature of thiols can affect both efficiency and selectivity; indeed, thiophenols bearing electron-withdrawing groups react efficiently under the optimized conditions, whereas with aliphatic thiols and arylthiols bearing electron-donating substituents an organic base (pyridine) is required. It should be noticed, however, that alkynes with longer aliphatic chains (> 4 carbon atoms) were not suitable for this method.…”

“…As hinted above, the coupling of alkynes and thiols was also achieved in the presence of benzyl as the photocatalyst. [42] Ananikov and co-workers recently optimized a versatile three component thiol-yne-ene coupling reaction for the design of highly functionalized homoallylic sulfides 11.7 via Eosin Y photocatalyzed coupling of alkynes 11.4, thiols 11.5 and vinylsulfides 11.6 (an example in scheme Scheme 11b). [43] Thioesters are important molecular scaffolds in drug, natural products and organic transformation due to its biological properties and versatile reactivity.…”

Continuous-Flow Synthesis of Arylthio-Cyclopropyl Carbonyl Compounds

“…Secondly, the acquisition of large quantities of product shows the classic disadvantages linked to batch reactions, such as the control and tuning of optimal reaction conditions for scale-up purposes and the formation of non-negligible amounts of disulfides as unwanted by-products. On the other hand, the continuous-flow synthesis of sulfur-containing adducts from thiols has been successfully performed, highlighting the advantages of these methods [27,28]. Nevertheless, a certain number of continuous-flow cyclopropane derivative synthesis methods have been reported by several authors in the last decade, including light-mediated borocyclopropanation [29] and ethyldiazoacetate addition to styrene [30,31] and the transition-metal-catalyzed synthesis of cyclopropyl phosphonates [32], and esters have been also achieved [33].…”