Two-Component Assembly of Thiochroman-4-ones and Tetrahydrothiopyran-4-ones Using a Rhodium-Catalyzed Alkyne Hydroacylation/Thio-Conjugate-Addition Sequence

Abstract

β'-Thio-substituted-enones, assembled from the combination of β-tert-butylthio-substituted aldehydes and alkynes, using rhodium catalysis, are shown to smoothly undergo in situ intramolecular S-conjugate addition to deliver a range of S-heterocycles in a one-pot process. Aryl, alkenyl, and alkyl aldehydes can all be employed, to provide thiochroman-4-ones, hexahydro-4H-thiochromen-4-ones, and tetrahydrothiopyran-4-ones, respectively. A variety of in situ oxidations are also performed, allowing access to S,S-dioxide derivatives, as well as unsaturated variants.

New Synthesis of Thioflavanones by the Regioselective Cyclization of 1‐(2‐Benzylthio)phenyl‐3‐phenyl‐2‐propen‐1‐ones with Hydrobromic Acid

“…of lithium diisopropylamide (LDA) afforded thioflavanones through the attack of a sulfur atom to the corresponding chalcone intermediates (Scheme (d)) . The combination of 2‐( tert ‐butylthio)benzaldehyde and arylacetylenes using 5 mol % Rh(nbd) 2 BF 4 /dcpm afforded β'‐( tert ‐butylthio)enone intermediates in situ , which underwent intramolecular S ‐conjugate addition to give thioflavanones after deprotection with an excess of CF 3 COOH (Scheme (e)) . Recently, thioflavanones were also synthesized by the 1,4‐addition of phenylzinc chloride or diarylcuprates to thiochromones in the presence of [Rh(COD)Cl] 2 catalyst or 2 equiv.…”

Development of Conjugate Addition of Lithium Dialkylcuprates to Thiochromones: Synthesis of 2-Alkylthiochroman-4-ones and Additional Synthetic Applications

“…HRMS data for compounds 4Aa , 4Ba – 4Ja , 5 , 7 , and 8 were analyzed by TOF MS. Compounds 4Ab – Ac , 4Ad – Af , and 6 have been fully characterized and reported [ 39 , 43 , 48 , 67 ].…”

“…Synthetic approaches to 2-substituted thiochroman-4-ones utilizing Friedel-Crafts acylation of thiopropanoic acid [ 56 ], hydrogenation of thiochromones [ 57 , 58 , 59 ], and intramolecular thio-Michael addition [ 60 , 61 , 62 , 63 , 64 , 65 , 66 ] have been reported. Recently, a rhodium-catalyzed alkyne hydroacylation/thio conjugate addition sequence in the synthesis of thiochroman-4-ones, including thioflavanones, has also been reported [ 67 ]. In another approach, Wang and coworkers reported an enantioselective Rh-catalyzed conjugate addition to thiochromones [ 68 ].…”

Synthetic Approaches to 2‐Alkylthiochroman‐4‐ones and Thioflavanones

“…These intermediates smoothly underwent in situ intramolecular S ‐conjugate addition with 10 equiv of CF 3 COOH to give the cyclized intermediate ( 69 ), followed by the release of t ‐Bu group to afford 2‐alkyl(aryl)thiochroman‐4‐one derivatives (Scheme 34). 51 …”