Organocatalytic asymmetric synthesis of highly functionalized spiro-thiazolone–cyclopropane-oxindoles bearing two vicinal spiro quaternary centers

Abstract

Spiro-thiazolone–cyclopropane-oxindoles with three contiguous stereocenters, including two vicinal quaternary centers, were obtained via an organocatalytic asymmetric Michael/alkylation cascade reaction.

Syntheses and Applications of Spirocyclopropyl Oxindoles: A Decade Review

“…[ 49 ] In another case, addition of 10 with alkenyl‐thiazolones 99 in the presence of Takemoto's bifunctional aminothiourea catalyst XIII , afforded highly functionalized spiro‐thiazolone cyclopropane‐oxindoles 100 (Scheme 31). [ 50 ] The reaction proceeds via Michael‐alkylation [2+1] cascade where both the substrates are activated simultaneously by the thiourea catalyst XIII via multiple H‐bond interactions as depicted in 101 .…”

Organocatalytic Synthesis of Chiral Spirooxindoles with Quaternary Stereogenic Centers

“…Two important biologically active heterocyclic fragments thiazol‐4‐one and spirocyclopropanooxindole were linked via an organocatalytic asymmetric Michael/ alkylation cascade reactions to produce spiro‐thiazolone‐cyclopropane‐oxindole 137 . Reactions were carried out with 3‐chlorooxindole 134 and 5‐alkenyl thiazolone 135 in the presence of K 2 HPO 4 and toluene, as additive and solvent at the same time, to furnish the spirocyclopropaneoxindole 137 in 76 % yield and with poor diastereoselectivity (dr 1.5: 1) due to the absence of the chiral catalyst 136 .…”

“…On the one hand, the amino group of 136 acts as a base by abstracting the proton atom at C‐3 of 134 , and thiourea moiety activates 135 via hydrogen bonds, where both substrates were carried out an asymmetric Michael addition to form II . Subsequent alkylation reaction leads to the formation of cyclopropane ring via removal of the chlorine atom to produce the spiro‐thiazolone‐cyclopropane‐oxindole 137 with three contiguous stereogenic centers two of which are quaternary stereocenters, as depicted in Scheme …”

Recent Advances in Catalytic Asymmetric Reactions of Thiazolones, Rhodanines and Their Derivatives

“…Wang (Scheme 38). [46] With Takemoto's chiral bifunctional aminothiourea catalyst C45, they obtained a variety of spiro-thiazolone-cyclopropane-oxindoles 132 in 60-86% yields with 73-93% ee and 3.8:1-9.4:1 dr. Notably, the cyclopropane skeleton with contiguous stereocenters including two vicinal quaternary centers was constructed in one-step with high asymmetric induction.…”