Cu(II)-catalyzed reaction of α-keto thioesters with trimethylsilyl azide (TMSN) proceeds with the transformation of the thioester group into urea through C-C and C-S bond cleavages, constituting a practical and straightforward synthesis of N-acylureas. When diphenyl phosphoryl azide (DPPA) is used instead as the azide source in an aqueous environment, primary amides are formed via substitution of the thioester group. The reactions are proposed to proceed through Curtius rearrangement of the initially formed α-keto acyl azide to generate an acyl isocyanate intermediate, which reacts further with an additional amount of azide or water and rearranges to afford the corresponding products. To demonstrate the potentiality of the method, one-step syntheses of pivaloylurea and isovaleroylurea, displaying anticonvulsant activities, have been carried out.
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.
Substituted oxabicyclo derivatives bearing two quaternary carbon centers and five contiguous stereocenters have been synthesized from C3‐thioester/‐ester substituted dienones, a simple and linear pluripotent molecular platform. The conversion proceeds from neat reactants, possibly via a thermally‐driven pericyclic cascade manifold involving sequential (E)‐s‐trans to (E)‐s‐cis isomerization, oxa‐6π‐electrocyclization, and intermolecular, regioselective [4π+2π] cycloaddition. The proposed mechanism has been substantiated by intermediate trapping experiments and DFT studies. Such dienones have also been exploited to effect stereoselective cross Diels‐Alder cycloadditions with olefins and sequential Diels‐Alder/retro‐Diels‐Alder reactions with activated alkynes. The reaction is greatly influenced by the substituent effect exerted by the C3‐thioester/‐ester group.
α‐Ketothioesters undergo triphenylphosphine (PPh3)‐catalyzed cyclization with acetylenedicarboxylate esters smoothly, in contrast to α‐ketooxoesters which require more drastic conditions with the limited substrate scope. The reaction works well with a wide range of α‐ketothioesters, delivering highly functionalized α,β‐unsaturated γ‐butyrolactones in moderate to excellent yields. The higher reactivity of the thioester derivatives is seemingly due to a favourable intramolecular non‐bonding electrostatic 1,4‐interaction involving C−S σ* orbital on the sulphur atom and the lone pair of electrons in the electron‐donating oxygen atom. This is apparent from the X‐ray crystallographically determined internuclear distance between the sulphur and ketone (C=O) oxygen atoms (2.71–2.85 Å), which is significantly less than the sum of their van der Waals radii (3.25–3.30 Å). The substitution on the S atom is oriented diametrically away from the ketone O atom to maximize the interaction between them. The trend is also seen in the 1,4‐S⋅⋅⋅O contact between the S and furan O atoms (2.70 Å) in the γ‐butyrolactone products.
We report a direct synthesis of 2-thioxooxazolidin-4-ones and oxazolidine-2,4-diones from a-keto thioesters with sodium thiocyanate or potassium cyanate, respectively. The reactions proceed through nucleophilic substitution of a thioester with thiocyanate/cyanate anion, thiolate anion addition to carbonyl carbon, and subsequent intramolecular CÀO heterocyclization.
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