Synthesis of Phosphonic Acids Possessing Isoindolin-1-one Moiety: Unexpected Acid-Catalyzed C-P-Bond Cleavage

Abstract

Phosphonic acids bearing isoindolin-1-one moiety were synthesized by dehydrative aromatization of the corresponding epoxyisoindolyl phosphonates. A mechanism for the unexpected acid catalyzed dephosphorylation was proposed.

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

“…In case of multicomponent reactions, the MW irradiation may also be useful, as the corresponding products can usually be obtained more selectively. Therefore, the development of MW-assisted variations of multicomponent reactions is of Beside the three-component condensation, a few other synthetic routes are also known for the preparation of isoindolin-1-one phosphonates (3), such as the ring opening of tricyclic oxanorbornenes (4) (Scheme 1/B) [19], the ring closure of α-amidophosphonates (5) (Scheme 1/C) [20] or the reaction of trialkyl phosphites with 3-hydroxy-isoindolin-1-ones (6) (Scheme 1/D) [21,22]. In these examples, the target compounds (3) were prepared starting from complex molecules (4-6), which were usually obtained after many reaction steps.…”

“…Beside the three-component condensation, a few other synthetic routes are also known for the preparation of isoindolin-1-one phosphonates ( 3 ), such as the ring opening of tricyclic oxanorbornenes ( 4 ) ( Scheme 1 / B ) [ 19 ], the ring closure of α-amidophosphonates ( 5 ) ( Scheme 1 / C ) [ 20 ] or the reaction of trialkyl phosphites with 3-hydroxy-isoindolin-1-ones ( 6 ) ( Scheme 1 / D ) [ 21 , 22 ]. In these examples, the target compounds ( 3 ) were prepared starting from complex molecules ( 4 – 6 ), which were usually obtained after many reaction steps.…”

Synthesis and Evaluation of 1-Aryl-1-(7-carboxy-isoindolin-1-one-2-yl)methylphosphonic Acid Derivatives as Inhibitors of Protein Tyrosine Phosphatase

“…2 Isoindolin-1-one phosphonic acids 1 (Figure 1), as the first aims of this work, were synthesized by dehydrative aromatization of (2,3,7,7a-tetrahydro-3a,6-epoxyisoindolin-1-one)phosphonates, which have been obtained by tandem acylation/[4+2]-cycloaddition between furfurylaminophosphonates and maleic anhydride. 1 The potential of inhibitors of protein tyrosine phosphatases with two or more anionic groups prompted us to synthesize a series of new derivatives of isoindolin-1-one-2-ylmethylphosphonic acids bearing a benzamide substituent with NO 2 , COOH, or COCOOH groups (compounds 2). Computational docking of (R)-and (S)-enantiomeric forms of the inhibitors into active center of Yersinia PTP, PTPβ, or PTP1B shows that in most cases derivatives 2 are better inhibitors than corresponding stereoisomers of compounds 1.…”

In Vitro Bioactivities of Isoindolin-1-3-Phosophonate Compounds

“…In non-symmetrical preparation of some compounds from isoindolin-1-one they can introduced as building blocks for a Diels-Alder reaction [21][22][23][24][25]. Because of their multi biological properties of isoindoline derivatives, there are many chemical pathways have been reported for the preparation of these heterocycles [26][27][28][29][30][31][32][33][34][35].…”