Sequential C–H Functionalization Reactions for the Enantioselective Synthesis of Highly Functionalized 2,3-Dihydrobenzofurans

Abstract

The enantioselective synthesis of 2,3-dihydrobenzofurans was achieved by using two sequential C-H functionalization reactions, a rhodium-catalyzed enantioselective intermolecular C-H insertion followed by a palladium-catalyzed C-H activation/C-O cyclization. Further diversification of the 2,3-dihydrobenzofuran structures was possible by a subsequent palladium-catalyzed intermolecular Heck-type sp(2) C-H functionalization.

igand-Accelerated ortho-C-H Olefination of Phenylacetic Acids

“…The synthetic utility of this C–H olefination reaction has recently been demonstrated in the total synthesis of (+)-lithospermic acid 19d and related analogs. 20 …”

Pd‐Catalyzed Synthesis of Oxygen‐Containing Heterocycles

“…Both the tertiary and secondary alcohols are suitable to this methodology, albeit lower yield for secondary alcohol presumably owing to the potential oxidation. Later, Yu and Davies further elaborated this fascinating reaction in the enantioselective synthesis of highly functionalized 2,3-dihydrobenzofurans (Scheme 3.31) [60]. Through a rhodium-catalyzed enantioselective intermolecular C-H insertion and following palladium-catalyzed C-H activation/C-O cyclization sequence, a variety of 2,3-dihydrobenzofurans were synthesized with a high regio-, diastereo-, and enantioselectivity.…”

Catalytic asymmetric synthesis of (−)-E-δ-viniferin via an intramolecular C–H insertion of diaryldiazomethane using Rh2(S-TFPTTL)4

“…[9][10][11][12][13][14][15][16][17][18] In this context, we have provided a protocol for the asymmetric synthesis of 2-aryl-3-methoxycarbonyl-2,3-dihydrobenzofurans 5 via intramolecular C-H insertion of phenyldiazoacetates 4 catalyzed by dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate], Rh 2 (S-PTTL) 4 (2a), in which high enantioselectivity (up to 94% ee) and perfect cis diastereoselectivity are achieved (Scheme 1). 9,10,13,14 Using this catalytic method, we recently achieved the asymmetric synthesis of dihydrobenzofuran neolignans, (À)-epi-conocarpan, (+)-conocarpan, 10a and (À)-trans-blechnic acid.…”