When asymmetric aminocatalysis meets the vinylogy principle

Abstract

Over the past decade, asymmetric aminocatalysis has become a reliable synthetic platform for generating stereogenic centres at the α and β positions of unmodified carbonyl compounds with very high fidelity. More recently, chemists have become interested in using aminocatalysis for targeting stereocentres even more remote from the catalyst's point of action. The key to success is the ability of the amine catalyst to propagate the electronic effects inherent to aminocatalytic reactivity modes (i.e. the HOMO-raising and the LUMO-lowering activating effects) through the conjugated π-system of poly-unsaturated carbonyls while transmitting the stereochemical information at distant positions. This feature article outlines how the combination of aminocatalysis with the principle of vinylogy has brought about the development of dienamine, trienamine, and vinylogous iminium ion activations, novel strategies for the asymmetric functionalisation of carbonyl compounds at their γ-, ε-, and δ-positions, respectively.

Regioselective inverse Diels-Alder reaction of unsymmetrical tetrazines with aldehydes and ketones

“…The regioselectivity of the products formed was consistent with what one would expect according to the zwitterionic models of alignment of dienophiles with unsymmetrical dienes during the Diels-Alder reaction. 22 In this case, the transition state of the intermediate favors placement of the secondary amine and the phenyl substituent of the tetrazine on the same side (Scheme 2).…”

Organocatalytic Asymmetric 1,6‐Addition/1,4‐Addition Sequence to 2,4‐Dienals for the Synthesis of Chiral Chromans

“…[1] Given the intriguing properties of chiral chroman derivatives,w ed ecided to investigate the feasibility of an ovel organocatalytic asymmetric cascade reaction between hydroxyarenes and 2,4-dienals through vinylogous iminiumion activation, [2] thus giving rise to the chroman core structure.H owever,s everal challenging issues have to be addressed for such an approach. Theregioselectivity has to be taken into account as both electrophile and nucleophile have multiple reaction sites (Scheme 1).…”

Highly Stereoselective Synthesis of Natural‐Product‐Like Hybrids by an Organocatalytic/Multicomponent Reaction Sequence

“…[1] Scaffold decoration entails the utilization of both combinatorial and rationally designed approaches to functionalize biologically validated molecular targets.S caffold generation, in contrast, focuses on the application of methodologies capable of generating structures which cover al arger part of the chemical and biological space. [14] Hence,c ombination of aminocatalysis with the available repertoire of MCRs provides endless possibilities for scaffold generation. Relevant strategies for exploring the broader chemical space by targeting dissimilar chemotypes,e ither previously validated by nature or derived from chemists synthetic expertise,include biology-, [3] function-, [4] and diversity-oriented [5] syntheses.…”

“…[10] Looking at the repertoire of MCRs,o ne realizes the ubiquity of the carbonyl component, that is,k etones or aldehydes,inthese reactions.Only recently,early efforts have been directed towards the implementation of an aminocatalytic asymmetric functionalization of such carbonyl functionalities followed by as ubsequent MCR. [14] Hence,c ombination of aminocatalysis with the available repertoire of MCRs provides endless possibilities for scaffold generation. [14] Hence,c ombination of aminocatalysis with the available repertoire of MCRs provides endless possibilities for scaffold generation.…”

“…[11,13] Aminocatalysis has been applied with great success in the a-, b-, gand even e-asymmetric functionalization of carbonyls. [14] Hence,c ombination of aminocatalysis with the available repertoire of MCRs provides endless possibilities for scaffold generation. In an endeavor to demonstrate the potential of this concept, we focused on the development of astereocontrolled organocatalytic/multicomponent sequence leading to compounds with skeletal complexity resembling natural products.…”