Ferrocene-based bifunctional organocatalyst for highly enantioselective intramolecular Rauhut–Currier reaction

Asymmetric Intramolecular Rauhut–Currier Reaction and Its Desymmetric Version via Double Thiol/Phase-Transfer Catalysis

“… a Unless noted otherwise, reactions were performed with bis­(enones) 1 (0.1 mmol, X = CH 2 , R 1 = R 2 ), PTC C5 (20 mol %), thiol T2 (40 mol %), and K 2 CO 3 (60 mol %) in toluene (1 mL) at room temperature. b Yield of the isolated product. c Determined by HPLC analysis on a chiral stationary phase. d Data in parentheses were obtained on a 1.0 mmol scale. e The absolute configuration of product 2a was determined by comparing rotation data with literature reports . The other products were assigned by analogy. f With C4 (20 mol %). …”

“…Based on the above considerations, initially, we investigated the asymmetric intramolecular RC reaction of simple bis­(enones) 1a to establish the suitability of the double activation catalytic system . It was pleasing that the combination of 2-mercaptobenzoic acid T1 and chiral PTC C1 derived from cinchonine could smoothly promote the conversion of substrate 1a at 50 °C, and the expected RC product 2a was isolated in a moderate yield albeit with low enantioselectivity (Table , entry 1).…”

“…As summarized in Table , bis­(enones) 1 with different aryl and heteroaryl groups underwent the RC reaction smoothly to give the corresponding six-membered RC products 2a–i in good to excellent results (Table , entries 1–9), even on a larger scale (entry 1, data in parentheses), whereas C4 was employed instead of C5 in some cases for better enantiocontrol. In addition, an unsymmetric bis­(enones) bearing both an electron-withdrawing group and an electron-donating group afforded the corresponding 2j as a single product with excellent regio- and stereocontrol, which is superior to that under phosphine catalysis (entry 10) . Moreover, an aromatic/aliphatic hybrid bis­(enones) also proceeded smoothly to give product 2k , exclusively, albeit with lower enantioselectivity (entry 11).…”

“…It also has important application in the synthesis of many natural products . The catalytic asymmetric RC reaction of linear bis­(enones) substrates has been investigated extensively, mainly relying on the catalysis of chiral Lewis basic phosphines (Scheme a) . Besides, stoichiometric chiral N-protected cysteine was applied with excellent enantiocontrol, and excess strong bases were required for good conversions (Scheme b) .…”

“…Very recently, our group uncovered a double activation system by combining 2-mercaptobenzoic acid and suitable chiral Brønsted bases, which efficiently catalyzed the asymmetric intermolecular cross-RC reaction of 2-cyclopentenone and activated alkenes . Considering the high efficiency of this novel catalytic system, we envisioned that it would be applicable to the asymmetric intramolecular RC reaction of linear bis­(enones) precursors. , Moreover, as outlined in Scheme d, the reversible sulfur-addition of thiol catalysts to prochiral bis­(enones) would lead to the different early desymmetric generation of the key ion pair intermediates IV in a potentially stereoenriched manner under chiral phase-transfer catalysis (PTC), thus the following cyclization would deliver the expected cyclic products diastereoselectively, finally furnishing a previously unreported desymmetric intramolecular RC reaction process for linear bis­(enones).…”