Transition‐Metal‐Free Reduction of α‐Keto Thioesters with Hydrosilanes at Room Temperature: Divergent Synthesis through Reagent‐Controlled Chemoselectivities

Abstract

The combination of hydrosilanes with a Brønsted or Lewis acid as a promoter can be used for the reagent-controlled chemoselective reduction at room temperature of conjugated C=C bond, enone moiety, or the carbonyl of (β,γ-unsaturated) α-keto thioesters, providing facile access to β,γ-saturated α-keto thioesters, αhydroxy thioesters, or silyl ethers. The reaction pathway and the chemoselectivity can be fine-tuned through the judicious choice of the hydrosilane or the reaction conditions. The reactions tolerate a wide range of functional groups including labile thioesters and the products are generally obtained in moderate to excellent yields. Unsymmetrical thioethers can also be synthesized using PMHS and catalytic B(C 6 F 5 ) 3 via reductive deoxygenation of both the carbonyl groups. The applicability has been highlighted by the amine-mediated and coupling reagent-free syntheses of saturated α-keto amides from β,γ-unsaturated α-hydroxy thioesters and β,γsaturated α-keto thioesters.

C3‐Thioester/‐Ester Substituted Linear Dienones: A Pluripotent Molecular Platform for Diversification via Cascade Pericyclic Reactions

“…The requisite dienones 1 were readily prepared in pure form from the corresponding α‐keto thioesters or esters following our previous reports. When 1 a was kept at ambient temperature (30 °C), 3 a was formed within a few days in 45% yield along with 50% of the recovered starting materials (Table , entry 1); the yellow crystalline solid slowly turned to a light green gummy liquid with the progress of the reaction.…”

Recent Advances in the Synthesis and Applications of α‐Ketothioesters

“…Unsymmetrical thioethers 100 a – c could thus be synthesized using 2.0 equivalent polymethylhydrosiloxane (PMHS)/1 mol% B(C 6 F 5 ) 3 via reductive deoxygenation of both the carbonyl groups (Scheme 55). The reactions tolerated a wide range of functional groups and the products were generally obtained in moderate to excellent yields [82] . The difference in outcome in Scheme 54 (with hydrosilanes containing one Si−H) and Scheme 55 (with PMHS containing multiple Si−H bonds) may be explained on the basis of the “dual Si−H effect” of PMHS, in which two proximate Si−H groups cooperatively accelerate the reductive deoxygenation of the α‐ketothioesters to unsymmetrical thioethers 100 (Scheme 55).…”

“…Das et al. found that it is possible to use inexpensive and commercially available hydrosilanes as reducing agents for the chemoselective reduction of the keto group of α‐ketothioesters 4 at room temperature [82] . It should be noted that hydrosilanes are mild, practical, and selective reducing agents and their reactivity can be fine‐tuned by changing the substituents on the silicon atom [83] .…”

“…The authors further highlighted the applicability of the developed procedures by primary and secondary amine‐mediated synthesis of β,γ‐saturated α‐ketoamides 104 a – d from β,γ‐unsaturated α‐hydroxythioesters 102 in moderate to excellent yields (Scheme 57). [82] The reaction was proposed to proceed through the amine‐catalyzed isomerization of allylic alcohols via intermediates I , II , and III , which undergoes subsequent amidation with primary and secondary amines to yield 104 (Scheme 58).…”

“… [36,79] . In the next section, chemoselective reduction of various functionalities such as the keto group, thioester moiety, C=C bond, or the enone moiety of α‐keto thioesters or its β,γ‐unsaturated analogues in the presence of other reducible functional groups will be reported (Section 3.5) [80–84] …”