Sequential one-pot approach for the synthesis of functionalized phthalans via Heck-reduction–cyclization (HRC) reactions

Abstract

An efficient and practical method is described for the direct synthesis of 1,3-dihydroisobenzofurans, an important structural motif present in biologically active natural or synthetic compounds.

[Pd]‐Catalyzed Intermolecular Coupling and Acid Mediated Intramolecular Cyclodehydration: One‐Pot Synthesis of Indenes

“…The moderate yield of indene 4gc could be due to formation of undesired allylic alcohol along with usual ketone 3gb through simple Mizoroki–Heck coupling of sterically constrained allylic alcohol 2b . [18c] As seen above (cf. Table ), in addition to electronically neutral simple phenyl allylic alcohols, the process was smooth with electron deactivating groups (F, Cl and Br) and with electron rich OMe functional group on the aromatic ring of allylic alcohol 2 (Table , 4gi , 4gj and 4gk ).…”

“…To begin with, we wanted to optimize the Heck reaction in 1,2‐dichloroethane (DCE). In our laboratory, we have extensively used Heck coupling between iodoarenes and allylic alcohols. Iodoarene 1a and allylic alcohol 2a were chosen as the model substrates for Heck coupling in DCE, and the results are shown in Table .…”

“…In turn, these secondary alcohols can be easily accessed by reducing in situ formed ketone 3 by Heck coupling. [18b]…”

One-pot Jeffery-Heck and Reduction Sequence: Synthesis of Alcohols and Applied to the Synthesis of Flavan Natural Products

“…In this regard, we identified either CH 3 CN or DMF as suitable solvents, because they are compatible for both [Pd]‐catalysis and reduction steps (Table ). Therefore, initially the reaction was performed in the presence of 5 mol % of Pd(OAc) 2 catalyst, base NaHCO 3 (3 equiv), benzyltriethylammonium chloride as additive (1 equiv) in CH 3 CN (2 mL) at 50 o C for 24 h followed by reduction with NaBH 4 . Notably, as expected, furnished the alcohol 4 a , albeit in moderate yield (Table , entry 1).…”

“…[13] In continuation of our interests in exploring the [Pd]-catalysis towards versatile synthetic protocols and one-pot methods, [14] very recently, we have developed an efficient protocol for concise synthesis of functionalised iso-benzofurans via a sequential up-to Heck coupling and reduction (one-pot for two reactions), and then the crude work-up reaction mixture was subjected to acid mediated cyclization (second pot step). [15] Herein we report a sequential domino one-pot Jeffery-Heck coupling (for 3-aryl carbonyl compounds) followed by reduction for the synthesis of 1,3diphenylpropan-1-ols from readily available iodo arenes and allylic alcohols, potential synthetic precursors of flavans. We have also found that these 3-aryl carbonyl compounds also have been accessed via hydroarylation of Michael acceptors.…”