Chiral Calcium VAPOL Phosphate Mediated Asymmetric Chlorination and Michael Reactions of 3-Substituted Oxindoles

Abstract

We disclose a novel high yielding and highly enantioselective chiral calcium VAPOL phosphate-catalyzed chlorination of 3-substituted oxindoles with N-chlorosuccinimide (NCS). The reaction conditions are also shown to be effective for the catalytic enantioselective Michael addition of 3-aryloxindoles to methyl vinyl ketone.

Organocatalytic, Asymmetric Synthesis of 3‐Sulfenylated N‐Boc‐Protected Oxindoles

“…Oxindoles with a heteroatom at the C‐3 position have received considerable attention owing to their potential applications in medicinal chemistry 1g–m. Recently, various methods for the asymmetric synthesis of 3‐fluorooxindoles,4 3‐chlorooxindoles,5 3‐aminooxindoles,6 and 3‐hydroxyoxindoles7 have been reported. Many oxindoles with a thio group at the carbon stereocenter have been found to have anticancer, antifungal, or antitubercular activities 1k–m.…”

“…In contrast, 3-aryloxindoles 1 e-h were found to be more reactive precursors for the sulfenylation reaction. The corresponding reactions were completed within a shorter time (6 h) giving the products 3 e-h in excellent yields (91-98 %) and high enantioselectivities (85-87 % ee; Table 2, entries [5][6][7][8].…”

Catalytic Enantioselective α‐Chlorination of Carbonyl Compounds

“…A plied chiral calcium VAPOL phospate 11 as a catalyst for chlorination with NCS. [21] The reaction afforded the desired products with excellent enantioselectivity (Scheme 15). A dramatic drop in enantioselectivity occurred when 3-methyloxindole was used as the substrate in both catalyst systems (7 % ee with 10/nickel(II) and 62 % ee with 11).…”

Chiral Ca-, Sr-, and Ba-Catalyzed Asymmetric Direct-Type Aldol, Michael, Mannich, and Related Reactions

“…Several electron-donating and withdrawing aromatic enamides were tested, and the enantioselectivites of the desired 2-hydrazinoketones and 1,2-diamines were high. Antilla et al reported chiral calcium VAPOL phosphate-mediated asymmetric 1,4-addition reactions of 3-substituted oxindoles (Table 13) [59]; for reviews of asymmetric reactions of oxindole, see [60][61][62][63]. It was showed that VAPOL phosphate could be applied, and the desired products were obtained in excellent yields with high enantioselectivities.…”