Paracyclophane‐based Silver Phosphates as Catalysts for Enantioselective Cycloisomerization/Addition Reactions: Synthesis of Bicyclic Furans

Abstract

This manuscript discloses the first use of chiral phosphates based on C2-symmetric paracyclophane scaffolds as chiral counterions in transition metal catalysis, showing that they may compare favorably with other known chiral phosphates, such as the TRIP phosphate. The targeted catalytic reaction is a silver(I) promoted domino heterocyclization of 2-(1-alkynyl)-2-alken-1-one derivatives, in the presence of C-, or Nnucleophiles, which provides an efficient access to substituted bicyclic furans. Results show that high levels of enantioselectivity can be attained with either paracyclophane-based phosphates or TRIP phosphates, when the nucleophilic reactants display N-H functions in appropriate positions, near to the nucleophilic center. Therefore, the involvement of H-bonding between the NH function and the phosphate in the enantiodetermining step is postulated.N-(4-((2-Phenyl-4,5,6,7-tetrahydrobenzofuran-4-yl)amino)phenyl)acetamide (4g)Following the general procedure with AgPF 6 , the crude residue was purified by flash chromatography (eluent: nheptane 100% to n-heptane/EtOAc 50:50) to afford compound 4 g in 28% yield (9.7 mg). 1 H NMR (500.2 MHz, CDCl 3 ), d (ppm) = 7.60 (d, J = 7.6 Hz, 2H), 7.34 (t, J = 7.6 Hz, 2H), 7.28 (d, J = 7.6 Hz, 2H), 7.21 (t, J = 7.6 Hz, 1H), 7.05-

Silver(I)-Mediated Cascade Reaction of 2-(1-Alkynyl)-2-alken-1-ones with 2-Naphthols

“…As the chiral silver salts have been widely employed in asymmetric catalysis, , we then attempted to develop an asymmetric version of the current reaction. After several silver salts and chiral phosphoric acids (please see Supporting Information for details) were screened, the combination of AgTFA with CPA1 gave the most encouraging outcome by furnishing 4a in 72% yield and 71:29 er (Scheme ).…”

The Use of Domino Reactions for the Synthesis of Chiral Rings

“…A synthesis of chiral bicyclic furans 72 was disclosed in 2018 by Marinetti and Betzer through a silver-catalyzed domino reaction of 2-(1-alkynyl)-2-cyclohexenone 69 with 5-substituted indoles 70 (Scheme 19). 26 The process was catalyzed by preformed chiral silver phosphate 71 and evolved through successive cycloisomerization and addi-…”

Recent Advances of Biphenylene: Synthesis, Reactions and Uses

“…Recently, Marinetti, Betzer and co‐workers developed biphenylene‐based silver phosphates 101 and used them in consecutive cycloisomerization and enantioselective addition (Scheme ) . The silver catalysts activated internal alkyne 103 to promote cyclization, and the bicyclic furan intermediate was prepared in situ.…”