Expeditious synthesis of (±)-diethyl 2-alkyl- and 2-aryl-(3-oxoisoindolin-1-yl)phosphonates catalysed by OSU-6

Abstract

A one-step strategy to prepare (AE)-diethyl 2-alkyl-and 2-aryl-(3-oxoisoindolin-1-yl)phosphonates is reported via a modified Kabachnik-Fields condensation of 2-carboxybenzaldehyde with an amine and triethyl phosphite using OSU-6, an MCM-41 type mesoporous hexagonal silica, as the catalyst. The reaction proceeds to form the target compounds in high yields with minimal purification requirements. The method is successful for benzylic, aromatic and aliphatic amines. An additional advantage of the current method is that the catalyst can be recycled up to four times with useful activity. Fig. 1 Biologically active isoindolinones.

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

“…Recently, an efficient method was developed for the synthesis of ethyl (2-alkyl- and 2-aryl-3-oxoisoindolin-1-yl)phosphonates 71 from 2-formylbenzoic acid ( 55 ), triethyl phosphite and amines 70 using OSU-6, a novel MCM-41-type hexagonal mesoporous silica, as a catalyst ( Scheme 17 ) [ 44 ]. The important advantages of this methodology is that the (3-oxoisoindolin-1-yl)phosphonates 71 are obtained in high yields from benzylic, aliphatic and aromatic amines possessing both, electron-donating and electron-withdrawing groups, in shorter reaction times with minimum purification requirements.…”

Efficient conversion of acids and esters to amides and transamidation of primary amides using OSU-6

“…Our recent endeavors have demonstrated the potency of OSU-6 as a catalyst for the formation of 3-oxoisoindoline-1carbonitriles and carboxamides 33 as well as 2-alkyl-and 2-aryl-(3-oxoisoindolin-1-yl)phosphonates. 34 OSU-6 is an MCM-41 type, hexagonal, mesoporous silica developed by Al Othman and Apblett. 35 It has acidic properties (due to aging with 2 M HCl during its preparation) and robust characteristics similar to SBA-15 but is more readily available.…”

Study on the Microwave-Assisted Batch and Continuous Flow Synthesis of N-Alkyl-Isoindolin-1-One-3-Phosphonates by a Special Kabachnik–Fields Condensation

“…Isoindolin-1-ones (1) and their derivatives, such as 3-acyl-and 3-alkylidene-isoindolin-1-ones, may be considered as an important compound family among N-heterocycles [1][2][3][4] (Figure 1). This moiety can be found in a number of biologically active natural compounds and synthetic derivatives as well [5][6][7]. As a special subgroup, isoindolin-1-ones bearing a carboxylic ester or carboxylic amide function (2) may show anticancer- [5], antiarrhythmic- [8] or sodium channel modulator activities [9].…”

“…Only a few examples have been reported on the synthesis of isoindolin-1-one phosphonates by the three-component condensation of 2-formylbenzoic acid, amines and dialkyl phosphites (Scheme 1/A) [7,[12][13][14][15][16][17]. This process is somewhat analogous to the 'regular' Kabachnik-Fields reaction [18]; however, the carboxyl group of the 2-formylbenzoic acid allows a special ring closure step, as the speciality of this transformation.…”