Asymmetric Formal (3 + 2) Cyclocondensation of Coumarin-3-Formylpyrazoles as 3-Carbon Partners with 3-Hydroxyoxindoles via Esterification/Michael Addition Sequence

Abstract

The first enantioselective formal (3 + 2) cyclocondensation involving α,β-unsaturated pyrazoleamides as 3-carbon partners was accomplished in a stepwise fashion. The stepwise esterification/Michael addition sequence is promoted by Zn(OTf) 2 and quinine-squaramide derivative, respectively. The protocol enables access to spiro-fused pentacyclic spirooxindoles from coumarin-3-formylpyrazoles and 3-hydroxyoxindoles in good to satisfactory overall yields (up to 91%) with excellent dr (all cases >20:1 dr) and high ee values (up to 99%). Mechanistic investigations contributed to shedding light on the enantioselective event of the process.

Recent advances in organocatalytic cascade reactions for enantioselective synthesis of chiral spirolactone skeletons

“…Similar to α, β-unsaturated acyl phosphonates, the α, β-unsaturated N-acylated succinimides 77 can also serve as biselectrophilic species in the spirolactonization reaction of 3-hydroxyoxindoles 69. In 2017, Ming et al [103] .…”

Chiral cyclopropenimine-catalyzed enantioselective Michael additions between benzophenone-imine of glycine esters and α,β-unsaturated pyrazolamides

“…Among various synthetic methods to chiral pyroglutamic acids and their derivatives, the asymmetric conjugated addition between glycinates and α,β-unsaturated esters followed by lactamization is a highly straightforward strategy. 3 In the past few decades, the development of asymmetric 1,4-conjugate additions of glycine imine esters to various α,β-unsaturated carbonyl compounds has gained considerable attention, and various catalysts including alkaline-earth-metals, 4 transition metals, 5 phase transfer catalysts, 6 and Brønsted base catalysts 7 were used to produce chiral pyroglutamic acids and their corresponding derivatives both in high yields and selectivities. Soloshonok 8 and co-workers have developed a type of Ni( ii ) complex of glycine Schiff bases for the asymmetric synthesis of β-substituted pyroglutamic acids via Michael additions of chiral oxazolidinone derived Michael acceptors.…”

Trimethylindolenines as C–N synthons for the assembly of spiro[oxindole-thioxoimidazolidine-indoline] hybrids in formal [3+2] cycloadditions

“…Considerable efforts have been devoted to the development of various methods for the construction of tricyclic and tetracyclic spirooxindoles. 6 However, reports about the preparation of pentacyclic or hexacyclic spirooxindoles are limited, 7 probably due to their molecular complexity (Scheme 1a). Thus, the development of an efficient methodology for the enhancement of the structural diversity of these polycyclic spirooxindole molecules remains highly desirable but challenging.…”