Organocatalytic Synthesis of Chiral Spirooxindoles with Quaternary Stereogenic Centers

Abstract

The structure of spirooxindoles is present in a large number of natural compounds, with relevant and different biological activities. The organic synthesis of these compounds has been a synthetic challenge due to the fusion of two or more cycles with one or more contiguous stereogenic centers. In this review, it has been described, the feasibility of organocatalytic asymmetric synthesis for the achievement of chiral spirooxindoles through two‐ or three‐component reaction in the presence of a chiral organocatalyst producing the compounds with high yield, high diastereoselectivity and with high enantiomeric purity. This review covers literature from 2010 to 2019. The most explored reactions for this purpose have been 1,3‐dipolar cycloaddition, Diels‐Alder and nucleophilic heterocyclic carbenes reactions, where their reaction mechanisms showed in this review are an approach of a possible mechanism.

Metal‐Free Reductive Aldol Reactions

“…[24] Several metal-based transformations are known to address this challenge, [25] but only a few methods by organocatalytic means are available. [26] In this direction, Schindler and co-workers in 2018, reported a metal-free reductive aldol strategy that enables the preparation of geometrically defined β,β-disubstituted enolates AA, which were responsible for the creation of a quaternary center, Scheme 14. [27] The method provided efficient and straightforward access to β-hydroxylactones (and lactams) 24 incorporated with an α-quaternary stereocenter in excellent yields and high diastereoselectivities.…”

Stereoselective Domino Reactions in the Synthesis of Spiro Compounds

“…4 For several decades spirooxindoles synthesis has been the object of interest for synthetic chemists; however, its achievement is usually carried out with multiple-step synthesis in low yield and mostly with low stereoselectivity. 5 Although, recently, new spirooxindoles, analogous to natural products, have been efficiently synthesized through domino reactions as we will see throughout this review.…”

Simple amino silyl ether organocatalyst for asymmetric hetero Diels–Alder reaction of isatins with enones

“…Spirooxindole skeleton A is found in many biologically active natural compounds [1][2][3][4][5][6][7] and drugs [8][9][10] such as anti-malarial, [11][12][13] anti-cancer, 14,15 anti-viral, 16 antituberculosis, 17 and anti-proliferative 18 (Scheme 1). Therefore, it is important to establish an effective asymmetric synthetic methodology for the synthesis of chiral spirooxindoles A.…”