Trimethylchlorosilane and Silicon Tetrachloride in Two Novel Methodologies for the Efficient and Mild Aldol Addition of β‐Keto Esters and Malonates to Aldehydes

Abstract

Efficient and mild aldol additions of bketo esters and malonates to aldehydes are described using two novel protocols in the presence of silicon tetrachloride and trimethylchlorosilane, respectively. Scope and limitations of the methods have been discussed. Moreover the stability of the obtained products, trimethylsilyl protection of the hydroxy group, as well as the role of both silicon tetrachloride and trimethylchlorosilane in attaining the final products have been analyzed.

On the Necessity of One‐Pot Tautomer Trapping in Asymmetric Michael Reactions of Arylideneisoxazol‐5‐ones

“…In the course of our recent research work on the development of new synthetic methodologies, we succeeded in the entrapping of unstable intermediates with the aid of protecting groups in one‐pot multicomponent reactions . Intramolecular entrapping in the presence of additional functional groups installed on the substrate also revealed as a useful strategy for the obtaining of isoindoline based heterocyclic compounds via organocatalytic cascade reactions .…”

Enantiomerically Pure Bithiophene Diphosphine Oxides as Catalysts for Direct Double Aldol Reactions

“…The use of tetrachlorosilane in combination with catalytic amount of chiral Lewis bases to promote stereoselective reactions nowadays is a well-established methodology. [1][2][3] Seminal works by Denmark and colleagues [4][5][6] with chiral phosphoroamides have shown the versatility of the catalytic system that opened avenues to several different synthetic applications. 7 Soon after, Nakajima and colleagues [8][9][10][11][12][13][14] and we [15][16][17] demonstrated that phosphine oxides could also coordinate SiCl 4 and generate hypervalent cationic silicon species in situ as chiral Lewis acids able to promote stereoselective direct aldol reactions.…”

Synthesis and Reactivity of the 3‐Substituted Isoindolinone Framework to Assemble Highly Functionalized Related Structures

“…Isoindolinones are interesting heterocyclic compounds due to their presence in many naturally occurring substances ( Figure 1) [1a,1b] and because of their extensive use in therapeutic activities [1][2][3][4] such as antihypertensive, [1c] antipsychotic [1d-1f] anesthetic, [1g,1h] anxiolytic, [1i] antiviral, [1j-1l] and antileukemic [1m] agents. In particular, some examples of biologically active compounds of general formula I that possess anxiolytic, sedative, hypnotic, and muscle relaxant activity, are described in Figure 2. [1n] Therefore, much attention has been devoted to the development of new methods for the synthesis of 3-substituted isoindolinones, which constitute valuable scaffolds in many synthetic routes.…”

“…[2,3] However, in spite of the considerable interest in the field, construction of this heterocyclic core often requires the use of metal catalysts and/or inflexible multistep syntheses. [1][2][3] In this context, as part of our ongoing research on the challenging aldol additions of active methylene compounds, [4] we have recently reported a series of simple methodologies for the synthesis of 3-substituted isoindolinones. [5][6][7] All these methods are based on the aldol reaction of several classes of readily enolizable 1,3-dicarbonyl compounds with 2-cyanobenzaldehyde in the presence of triethylamine, [5] or by conveniently exploiting electroinitiated [6] or organocatalyzed procedures.…”

“…In these studies we have demonstrated that the intramolecular trapping of the aldol adduct a is the key requisite that drives these difficult reactions to completion due to the unstable nature of the Scheme 1. aldol intermediates a. [4,5] All the tandem processes are promoted by weak bases, which both generate the nucleophilic species and deprotonate the intermediate b.…”