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

Abstract

Sulfenylated oxindoles: The first asymmetric sulfenylation of N-Boc-protected oxindoles has been developed to provide products containing a tetrasubstituted stereogenic center in high to excellent yields (86-98 %) and, in most cases, excellent enantioselectivities (up to 96 % ee; see scheme).

Enantioselective Synthesis of 5-Alkylated Thiazolidinones via Palladium-Catalyzed Asymmetric Allylic C–H Alkylations of 1,4-Pentadienes with 5H-Thiazol-4-ones

“…They are also versatile intermediates that are widely applicable in asymmetric synthesis . The consequent desire for their preparation has driven the development of abundant asymmetric synthetic approaches to access optically active thiol derivatives . Although these reactions are well suited for the preparation of secondary thiol derivatives, by contrast, few methods are applicable to the enantioselective synthesis of tertiary thiol and thioether derivatives .…”

“…Asymmetric functionalization of easily accessible prochiral organosulfur compounds provides an ideal approach to access chiral, tertiary thiol derivatives. − 5 H -Thiazol-4-ones, first introduced by Palomo in an organocatalytic, asymmetric Michael addition to nitroalkenes, have been recognized as excellent sulfur-containing pronucleophiles to prepare chiral tertiary thiol derivatives. Subsequently, Lu reported a chiral phosphine-catalyzed γ-addition reaction with allenoates .…”

Asymmetric Organocatalytic Electrophilic Heterofunctionalization of Oxindoles

“…In 2012, the Enders group reported the use of squaramide 16 as an effective hydrogen-bonding organocatalyst for the sulfenylationo fN-Boc-protected oxindolesi nh ighp roduct yields with good to excellent enantioselectivities,e specially when 3aryl-substituted oxindoles were employed as substrates (Scheme 16). [47] More recently,ah ighly enantioselective sulfenylation reactiono f3 -benzyl/alkyl-substituted oxindoles with N-(sulfanyl)succinimides was developed by using chiral bicyclic guanidine 17 as ab ifunctionalh ydrogen-bonding-based organocatalyst in highly hydrophobic cyclopentyl methyl ether (CPME, Scheme16). [48] This procedure wasf ound to be applicable to aw ide variety of substituted oxindoles that were never used before,a nd even 3-oxofuranones were sulfenylated with good results.…”

Thiourea-Catalyzed Domino Michael–Mannich [3+2] Cycloadditions: A Strategy for the Asymmetric Synthesis of 3,3′-Pyrrolidinyl-dispirooxindoles

“…During the past several years, our group has investigated the asymmetric synthesis of oxindole derivatives via organocatalysis. 8 As part of our ongoing program we envisioned that the assembly of trifluoromethylated 3,3′-pyrrolidinyl-dispirooxindoles 3 could be achieved through the union of trifluoroethylisatin ketimines 1 9 and 3-olefinic oxindoles 2 10 as substrates via a simple domino Michael-Mannich [3+2] cycloaddition reaction (Scheme 2). Importantly, an asymmetric version of such a domino protocol may be developed by employing enantiopure bifunctional organocatalysts to open a straightforward and stereoselective access to the complex target products 3 bearing a trifluoromethyl group.…”