Ag₂O nanoparticle-catalyzed substrate-controlled regioselectivities: direct access to 3-ylidenephthalides and isocoumarins

Abstract

Herein, we disclose the first example of an efficient, silver oxide nanoparticle-catalyzed, direct regioselective synthesis of 3-ylidenephthalides 11-16 and isocoumarins 17-20 via sonogashira type coupling followed by substrate-controlled 5-exo-dig or 6-endo-dig cyclization reaction, respectively. This one pot coupling involves reaction of substituted 2-halobenzoic acid with meta/para-substituted and ortho-substituted terminal alkynes, which proceeded in a regioselective manner resulting in the formation of 3-ylidenephthalides or isocoumarins, respectively, in excellent yields (up to 95%) with complete Z-selectivity. This protocol features relatively broad substrate scope, mild conditions, operational simplicity, and is favourable with aromatic/alicyclic terminal alkynes. The competition experiments and gram-scale synthesis further highlight the importance and versatility of the methodology. The proposed mechanistic pathways illustrate that the regioselectivity is substantially being controlled by the substituent(s) present on the acetylenic phenyl ring.

Synthesis, Bioevaluation, Structure-Activity Relationship and Docking Studies of Natural Product Inspired (Z)-3-benzylideneisobenzofuran-1(3H)-ones as Highly Potent antioxidants and Antiplatelet agents

“…Recently, an efficient synthesis of (Z)-3-benzylideneisobenzofuran-1(3H)-ones in a highly regioselective manner in excellent yields has been reported by our group 31 . Ag 2 ONPs-mediated reaction of several substituted 2-iodobenzoic acids 26a-f (R 1 = H, Br, CH 3 , F, OCH 3 ; X = Br, I) with various p-/m-substituted terminal alkynes 27a-f in the presence of pivalic acid as additive in DMF as solvent at 120 °C for 3 h furnished (Z)-3-benzylideneisobenzofuran-1(3H)-ones 28a-t upto 95% yields via 5-exo-dig cyclization strategy (Fig.…”

“…Then, the functionalized (Z)-3-benzylideneisobenzofuran-1(3H)-ones 28a-t were assessed for their in vitro antioxidant activity using literature procedure (Fig. 3) 31,32 . The results are shown in Table 1.…”

“…In the present study, we report the synthesis a series of functionalized (Z)-3-benzylidineisobenzofuran-1(3H)-ones 28a-t, their antioxidant and AA-induced antiplatelet activities, and structure-activity relationship (SAR) studies. Although compounds 28a-j, 28m-r and 28t have been prepared earlier by other routes; 30 including our route; 31 however, for the first time, substrate-controlled silver oxide nanoparticle (Ag 2 ONPs)-catalyzed synthesis of compound 28a-t have been prepared. Various substituted (Z)-3-benzylidineisobenzofuran-1(3H)-ones 28a-t have shown high order of antioxidant and AA-induced antiplatelet activities using ascorbic acid and aspirin taken as standard reference, respectively.…”

Preparation of 3‐Alkylidenephthalides: Recent Advances

“…Kumar and co‐workers developed in 2018, a practical and regioselective access of phthalides or isocoumarins by a judicious choice of substituents present on the phenyl acetylenic ring (Scheme 23). [28] The reaction was catalyzed by silver oxide nanoparticle (Ag 2 ONPs) in the presence of pivalic acid in DMF at 120 °C by using substituted 2‐halobenzoic acid with o ‐, m ‐, or p ‐substituted terminal alkynes. This one pot reaction involves C−C Sonogashira coupling followed by substrate‐controlled 5‐ exo ‐dig or 6‐ endo ‐dig cyclization reaction.…”

Synthetic Organic Transformations of Transition‐Metal Nanoparticles as Propitious Catalysts: A Review

“…Sandeep Chaudhary and co‐workers reported silver oxide nanoparticle (Ag 2 O NPs) mediated access to 3‐ylidenephthalides and isocoumarins via an efficient Sonogashira like coupling followed by substrate‐controlled 5‐ exo ‐dig or 6‐ endo ‐dig cyclization reactions (Scheme ) . Quite strikingly, 2‐halobenzoic acid reacted with meta/para‐aryl‐substituted terminal alkynes to afford only 3‐ylidenephthalides in excellent yields with ( Z )‐selectivity.…”