Pd-Catalyzed Site-Selective Mono-allylic Substitution and Bis-arylation by Directed Allylic C–H Activation: Synthesis of anti-γ-(Aryl,Styryl)-β-hydroxy Acids and Highly Substituted Tetrahydrofurans

Abstract

An efficient palladium-catalyzed site-selective arylation of γ-vinyl-γ-lactone by aryl boronic acid has been developed. γ-Vinyl-γ-lactone 1a has been contemplated as allyl electrophile donor for allylic arylation via π-allyl palladium intermediate using 1.5 equiv of aryl boronic acid 2. Using 3.0 equiv of the latter resulted in mono-arylation by allylic substitution and subsequent site-selective second arylation by directed allylic C-H activation giving stereoselectively anti-γ-(aryl,styryl)-β-hydroxy acids. Presence of O was crucial for the second arylation via Pd(II) catalysis. Thus, a good synergy of dual catalysis by Pd(0) and Pd(II) was observed. This methodology has been elaborated to synthesize highly substituted tetrahydrofurans including aryl-Hagen's gland lactone analogues via intramolecular iodoetherification.

The Potential of β‐Hydroxy‐γ‐vinyl‐γ‐lactone in the Synthesis of Natural Products and Beyond

“…6:1 ratio, the products were isolated as methyl esters) in good yields (Scheme 21). [50] In the ortho-methyl compound 87o, the (Z)-isomer was formed predominantly. We explored the iodocyclization on the crude acid intermediates 88 formed to give the -hydroxy-γ-styryl lactones 89a-f obtained by iodocyclizationiodoelimination sequence.…”

“…This isomerization goes through the formation of π‐allylpalladium and hence a suitable nucleophile would add to the terminal position to give linear products. Reaction of lactone 1 with Pd(OAc) 2 (5 mol‐%) in presence of TMEDA (10 mol‐%) and 1.5 equivalent of arylboronic acids provided the linear allylic arylated products 87a‐o as E/Z mixtures (in 3:1 to 6:1 ratio, the products were isolated as methyl esters) in good yields (Scheme ) . In the ortho‐methyl compound 87o , the ( Z )‐isomer was formed predominantly.…”

“…When the arylboronic acid was used in 3.0 equivalents along with Pd(OAc) 2 (10 mol‐%) and TMEDA (20 mol‐%), a remarkable allylic C–H activation based double arylation occurred in presence of O 2 to furnish γ‐aryl‐γ‐styryl‐β‐hydroxy compounds 91a‐m in good yields with exclusive ( E )‐double bond (Scheme ) . No traces of 1,1‐bis‐aryl‐compounds were detected.…”

Enantioselective syntheses and sensory properties of 2‐Alken‐4‐olides

“…24,25,36 The ee values of these intermediates were not determined due to no suitable chiral column available in our lab for their resolution. 24,25,36 The ee values of these intermediates were not determined due to no suitable chiral column available in our lab for their resolution.…”

“…The residue was diluted with water and adjusted pH to 8 by The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate, 5/1) to afford (3R,4R)-or (3S,4S)-4a-f as a light yellow oil in 84-88% yield, the spectral data of which were in accord with those in literature. 24,25,36 The ee values of these intermediates were not determined due to no suitable chiral column available in our lab for their resolution.…”