Recent Advances in Organocatalytic Asymmetric Cycloaddition Reactions Through Ortho‐Quinone Methide Scaffolds

Abstract

This review summarizes the very recent advances in organocatalytic asymmetric cycloaddition reactions involving ortho-quinone methides (o-QMs), a family of versatile species that have proven useful in a broad range of reactions to afford diverse chiral molecules. In the past years, different kinds of organocatalysts have been developed into a privileged class of catalytic systems in asymmetric synthesis.A number of remarkable achievements have been made by many groups around the world. Due to length limitation, this review only summarizes those works published from January 2016 to December 2020. Meanwhile, catalytic systems which combine metal catalysts and organocatalysts will not be discussed in this review.

Enantioselective Synthesis of Spiro Chroman‐Isoindolinones via Formal (4+2) Cycloaddition of In Situ‐Generated ortho‐Quinone Methides with 3‐Methylene Isoindolinones

“…13 C{ 1 H} NMR (75 MHz, CDCl 3 ) δ 169. 6,161.9 (d,J = 245.7 Hz),153.2,146.3,139.0 (d,J = 3.2 Hz),133.1,130.7,130.3,130.2,130.1,129.7,128.5,124.1,122.2,121.9,117.7,115.8 (d,J = 21.4 Hz),88.2,40.3,39.3. 19 .p.…”

“…ortho-Quinone methides (o-QMs) are highly reactive 1-oxabutadienes, which usually act as Michael acceptors and versatile synthetic transient intermediates in catalytic asymmetric conjugate additions and ( 4+ 2) cycloadditions. [6] In addition, ortho-hydroxybenzyl alcohols can convert to o-QM intermediates in the presence of a Brønsted acid and therefore have emerged as active reaction partners to participate in a variety of catalytic asymmetric reactions (Scheme 1). [7] The catalytic asymmetric (4 + 2) cycloaddition of unsaturated carbonyl compounds, for example oxa-Diels-Alder reactions, provides a powerful and direct method to construct valuable and diverse multifunctional oxygen-containing heterocycles with multiple stereogenic centers.…”

Merging dearomatization with redox-neutral C(sp3)–H functionalization via hydride transfer/cyclization: recent advances and perspectives

“…3 Quinone methides (QMs), which can be facilely prepared in situ or beforehand from phenol derivatives, are highly reactive, versatile intermediates in organic synthesis. 24,25 Due to their electron-deficient nature and propensity for aromatization, QMs are theoretically ideal hydride acceptors to initiate hydride transfer. When phenols react with the latent dielectrophilic aldehydes, o-QMs or p-QMs can be generated and initiate the cascade [1,n]-HT/dearomative cyclization to prepare spirocyclohexenones (Scheme 10b).…”

Palladium-catalyzed [4 + 4] cycloadditions for highly diastereo- and enantioselective synthesis of functionalized benzo[b]oxocines

“…8 Among the different building blocks used for asymmetric cycloadditions, ortho -quinone methides ( o -QMs), which feature particularly reactive four-atom intermediates, have been applied in a broad range of cycloadditions for synthesizing cyclic ethers. 9 For example, the asymmetric [4 + n ] ( n = 1, 2, 3) cyclization reactions of o -QMs that provide facile access to five-, six- or seven-membered rings have been well developed. 10 In contrast, o -QMs have scarcely been employed in higher-order cycloaddition to construct chiral eight-membered rings, 11 probably due to the disfavored ring strain and stereochemical control issue during the process.…”