Efficient synthesis of conjugated alkynyl cycloalkenones: Pd(PPh₃)₄–AgOAc‐ catalyzed direct coupling of 1‐alkynes with 3‐oxocycloalkenyl triflates

Abstract

Palladium -silver acetate-catalyzed cross coupling of vinyl triflates and 1-alkynes was investigated. This strategy offered a very straightforward and efficient method for access to conjugated alkynyl cycloalkenones from the conjugated vinyl triflates and 1-alkynes. Moreover, the triflates derived from 1,3-cycloalkadione needed no further purification and could be reacted immediately with 1-alkynes to provide the conjugated alkynyl cycloalkenones in excellent overall yields.

Asymmetric Total Syntheses of (+)-5-epi-Schisansphenin B and the Proposed Structure of (+)-15-Hydroxyacora-4(14),8-diene

“…17 Preparation of Enone-Aldehyde 5. The synthesis started from triflate 6, 18 which was obtained from commercially available 1,3-cyclopentadione (10) in a quantitative yield using triflic anhydride and 2,6-lutidine as a base. The spiro precursor, enone-aldehyde 5, was prepared from 6 and 7 via the palladium-catalyzed redox-relay Heck alkenylation.…”

“…Filtration through a pad of Celite and concentration in vacuo gave a residue, which was purified by silica gel column chromatography (EtOAc/ hexanes = 1:4) to give 7 (2.61 g, 71%) as a yellowish oil: IR (neat) ν 3354, 2958, 1739, 1467, 1367, 1048, 972 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 5.60−5.45 (m, 1H), 5.40−5.25 (m, 1H), 3.61 (t, J = 6.3 Hz, 2H), 2.35−2.15 (m, 3H), 0.97 (d, J = 6.8 Hz, 6H); 13 3-Oxocyclopent-1-en-1-yl Trifluoromethanesulfonate (6). 18 To a stirred solution of 1,3-cyclopentadione (10) (505 mg, 5.15 mmol) in CH 2 Cl 2 (51 mL) at −30 °C was added 2,6-lutidine (1.5 mL, 12.88 mmol) and triflic anhydride (1.0 mL, 6.18 mmol). The reaction mixture was stirred at −30 °C for 3 h and then quenched with 1 M HCl.…”

“…The resulting solution was stirred for 10 min, and then added a solution of crude product in THF (10 mL) and tributyltin hydride (0.43 mL, 1.61 mmol). The mixture was heated to 50 °C for 5 h. After cooling to room temperature, solvent was evaporated in vacuo to a residue, which was purified by gradient silica gel chromatography (EtOAc/hexanes = 0:1 to 1:7) to give 17 (198 mg, 70%, 2 steps) as a yellowish oil: [α] D 26 = +25.4 (c 1.00, CDCl 3 ); IR (neat) ν 2960, 2929, 1732, 1712, 1252, 1086, 1047, 710 cm −1 ; 1 H NMR (500 MHz, CDCl 3 ) δ 7.01 (dd, J = 5.0, 3.0 Hz, 1H), 4.16 (q, J = 7.0 Hz, 2H), 2.47−2.35 (m, 4H), 2.20−2.10 (m, 2H), 2.08−2.00 (m, 1H), 1.95−1.93 (m, 1H), 1.86−1.80 (m, 1H), 1.75− 1.67 (m, 2H), 1.58−1.51 (m, 1H), 1.27 (t, J = 7.0 Hz, 3H), 0.92 (d, J = 6.5 Hz, 3H), 0.67 (d, J = 6.5 Hz, 3H); 13 (18). To a stirred suspension of methyltriphenylphosphonium bromide (330 mg, 0.92 mmol) and dry molecular sieve 4 Å (30 mg) in THF (1.7 mL) was added a solution of t-BuOK (1 M in THF, 0.80 mL, 0.80 mmol) at room temperature and stirred for 10 min.…”

Palladium-Catalyzed Decarboxylative Coupling of Alkynyl Carboxylic Acids and Alkenyl Tosylates for the Synthesis of Enynones

“…One of the most efficient methods is the Sonogashira coupling of alkenyl halides and terminal alkynes . Alkenyl triflates were also employed as coupling partners in the synthesis of 3-(1-alkynyl)-2-cyclohexen-1-ones . Fu and co-workers reported a palladium-catalyzed coupling reaction with 3-oxocyclohex-1-enyl tosylates and terminal acetylenes .…”

Synthesis of β-Substituted Cyclic Enones via Phosphonium Salt-Activated, Palladium-Catalyzed Cross-Coupling of Cyclic 1,3-Diones

“…Those intermediates could subsequently undergo Pd- or Ni-catalyzed cross-coupling or utilize the addition–elimination protocol to furnish β-substituted cyclic enones (Scheme ). In our drug discovery programs, we are particularly interested in the β-substituted cyclic enones as useful synthons for developing novel compounds exhibiting significant biological activity. We envisioned the enolizable cyclic 1,3-diones is suited for generating activated intermediates, such as A , in situ with phosphonium salts.…”