Cascade Reactions:  A New Synthesis of 2-Benzofuran-2-ylacetamides by Sequential Pd(0)-Catalyzed Deallylation−Pd(II)-Catalyzed Aminocarbonylative Heterocyclization of 1-(2-Allyloxyaryl)-2-yn-1-ols

Abstract

A general and efficient synthesis of 2-benzofuran-2-ylacetamides 5 starting from 1-(2-allyloxyaryl)-2-yn-1-ols 1, amines 4, and CO, in the presence of catalytic amounts of PdI2 in conjunction with PPh3 and KI, has been developed based on the "sequential homobimetallic catalysis" concept, that is, a process in which two different complexes of the same metal, but in two different oxidation states, promote two catalytic cycles in sequence. The first cycle corresponds to a Pd(0)-catalyzed aminodeallylation of 1 with formation of the free phenol 2, which then undergoes Pd(II)-catalyzed aminocarbonylative heterocyclization to give the final product 5.

Synthesis of Heterocycles via Palladium-Catalyzed Carbonylations

“…Instead of esters, amides could also be produced in the presence of amines under the same conditions (Scheme 38a). 122 Applying similar reaction conditions, they also Grigg and co-workers reported palladium-catalyzed multicomponent reactions to interesting benzofurans and related nitrogen heterocycles. 124 Cyclocarboformylation can be achieved regioselectively and provides novel access to aldehydes by applying silane as hydride source.…”

Synthesis of Benzofurans from Ketones and 1,4‐Benzoquinones

“…3‐Unsubstituted 2‐arylbenzofurans are obtained using several methods categorized as follows. (i) In annulations with salicylaldehyde‐based reagents, salicylaldehyde can be indirectly converted into 2‐arylbenzofurans in cooperation with many counter‐reagents, such as aromatic aldehydes,10 protected thiazolium carbinols,11 Wittig reagents,12 and alkynes 13. (ii) In C–C cross‐coupling method based on either Sonogashira or Suzuki reactions,14, 15 enolate arylation with o ‐bromophenol is catalysed by palladium,16 and 2‐(2‐hydroxyphenyl)acetonitrile with potassium aryltrifluoroborates is subjected to one‐step sequential addition/intramolecular annulation 17.…”

A microwave-assisted multicomponent protocol for the synthesis of benzofuran-2-carboxamides

“…Common synthetic approaches to substitued benzofurans include the modification of various arenes, 4,[23][24][25] with carbon-oxygen bond formation [26][27] or through transition-metal catalysts. [28][29][30][31][32][33] One of the most used synthetic strategies, is represented by a three step synthesis starting from amines 6 that are reacted with chloroacetyl chloride to give the chloroacetamide derivatives 7, which are used in the O-alkylation of o-hydroxy aryl ketones to give the intermediates 9 that are finally cyclized to benzofurans 10. (Scheme 1).…”

“…[25][26]29 Such characteristics are not particularly suitable for libraries generation in hit/drug discovery campaigns: the ideal synthetic approach should be fast, versatile, time and step economic and should be suitable, as far as possible, for combinatorial and parallel chemistry applications. 35 As a continuation of our interest in the development of microwave-assisted and multicomponent strategies for the synthesis of biologically active probes, [36][37][38] we wanted to develop a new microwave-assisted procedure for the synthesis of substituted benzofurans in a one-pot fashion, since an efficient multicomponent approach to the synthesis of the benzofurans is still elusive.…”