Part I: Diastereoselective Reactions Involving β‐Mono‐ and β,β′‐Disubstituted Alkylidene Oxindoles: Pondering Alkene Geometry

Abstract

Diastereoselective reactions supported by metals and nonmetals offer a multifaceted path for the synthesis of robust intermediates of value to academia and industry. The reactions that involve mono‐ and disubstituted electron‐rich and electron‐deficient olefins offer facile construction of stereogenic carbon centers. Recent advances in the development of methods and an understanding of the chemistry of oxindoles has led to approaches that provide high levels of facial control, regiocontrol and diastereoselectivity. Part I of this focus review is devoted to the chemistry of β‐monosubstituted alkylidene oxindoles. Herein, we discuss reports made over the last decade of diastereoselective reactions that involve oxindole‐containing trisubstituted alkenes, which lead to the generation of stereogenic centers and the formation carbocyclic and heterocyclic skeletons.

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

“…There is extensive application of 3-phenacylideneoxindoles generating diverse reaction strategies following the regioselective and diastereoselective synthesis of carbocyclic and heterocyclic frameworks [ 31 – 32 ]. During our preliminary investigations as shown in Table 1 , we commenced our study by reacting two equivalents of ( E )-3-(2-(4-chlorophenyl)-2-oxoethylidene)indolin-2-one ( 1a ) under reflux conditions with one equivalent of tosylhydrazine ( 2 ) as hydrogen source in ethanolic solution in the presence of K 2 CO 3 as base.…”

Spiro‐2‐oxindoles via 1,3‐dipolar cycloadditions. A decade update

“…The synthetic methodologies developed for the construction of 3‐methylene‐ and 3‐(monosubstituted)‐ alkylidene 2‐oxindoles, [25] as well as their usefulness in organic synthesis, [26,27] have been reviewed recently. Such trisubstituted alkenes constitute the ideal starting reagents for the construction of three‐ to seven‐membered 3‐spiro(carbo)‐ or 3‐spiro(hetero)‐cyclic indoles [15] .…”

Advances in the Synthesis of Benzo‐Fused Spiro Nitrogen Heterocycles: New Approaches and Modification of Old Strategies

“…Some approaches to the synthesis of spirocyclic heterocycles through the [m + n] cycloaddition reactions have recently been reflected in a review article on the use of this unique dipolarophile in the synthesis of various 2-indolone derivatives. [175,176] The simplest member of the benzo-fused nitrogen heterocycles family, [177] encumbered by an exocyclic double bond, is 3-methylene oxindole. The compound has relatively low stability in concentrated solutions and previously, more than 30 years ago, was isolated as a yellow solid with a purity of ca.…”

“…An unpleasant moment when using 3‐alkylidene indol‐2‐one derivatives as starting substrates for building a spirocyclic fragment on their backbone in some cases is a complication of the composition of the reaction mixture due to the formation of diastereomeric pairs. Some approaches to the synthesis of spirocyclic heterocycles through the [ m + n ] cycloaddition reactions have recently been reflected in a review article on the use of this unique dipolarophile in the synthesis of various 2‐indolone derivatives [175,176] . The simplest member of the benzo‐fused nitrogen heterocycles family, [177] encumbered by an exocyclic double bond, is 3‐methylene oxindole.…”