Palladium-Catalyzed Cascade Difluoroalkylation and Phosphinoylation of 2-Vinyloxy Arylalkynes: Selective Synthesis of Difluoroalkyl-Containing Tetrasubstituted Alkenylphosphine Oxides

Abstract

A Pd-catalyzed difluoroalkylation/cyclization/phosphinoylation of 2-vinyloxy arylalkynes with ethyl difluoroiodoacetate and diarylphosphine oxides has been successfully developed. This reaction allows the formation of C sp3 −CF 2 , C sp3 −C sp2 , and C sp2 −P(O) bonds in one step, providing a straightforward route to difluoroalkyl-containing tetrasubstituted alkenylphosphine oxides with complete stereoselectivities under mild conditions.

Lewis/Brønsted acid-mediated cyclization/amidation of 1,6-enynes with nitriles: access to 3-enamide substituted dihydrobenzofurans

“…Based on the above experimental results and previous works, 5,6,11–14 a possible mechanism is proposed for this cyclization reaction (Scheme 4). Firstly, BF 3 ·Et 2 O coordinates with the oxygen of 1,6-enyne 1a to afford intermediate A .…”

“…Classical synthetic methods include intramolecular Friedel–Crafts reaction and Wittig reaction, 3 as well as transition metal-catalyzed C–C and C–O formation reactions. 4 In recent years, the cyclization of phenol-linked 1,6-enynes has been regarded as a powerful transformation that allows for the construction of benzofuran derivatives, 5,6 which can construct a 2,3-dihydrobenzofuran skeleton bearing a functional exocyclic C–C double bond in one-step, among which oxygen, 6 a carbon, 6 b hydrogen, 6 c sulfur 6 d and phosphorus 6 e functional groups have been developed. Most of them require pre-functionalized radical precursors, which would react with enyne under transition-metal catalysis to generate an alkenyl radical intermediate, followed by atom transfer or oxidative addition to give a metal intermediate.…”

Difunctionalization of Dienes, Enynes and Related Compounds via Sequential Radical Addition and Cyclization Reactions

“…Gao, Ying and their coworkers reported a Pd-induced radical reaction for the synthesis of difluoroalkyl- and alkenylphosphinyl-functionalized heterocycles in 2021. The reaction of 2-vinyloxy arylalkynes, ICF 2 CO 2 Et and diphenylphosphine oxides in DCE under the catalysis of PdCl 2 (PPh 3 ) 2 and Xantphos gave product 59 in good yields and stereoselectivity ( Scheme 59 ) [ 71 ]. A reaction mechanism suggests that the CF 2 CO 2 Et radical derived from ICF 2 CO 2 Et under the catalysis of Pd II adds to the C=C double bond of 2-vinyloxy arylalkynes followed by 5- exo cyclization and iodine atom transfer from PdI, through the oxidative addition of Pd 0 to vinyl iodide, formation of diphenylphosphine oxide complex, reductive elimination of Pd catalyst to give product 59a .…”

Highly Stereoselective Synthesis of 2,2‐Disubstituted Vinylphosphonates via Aryl to Vinyl 1,4‐Palladium Migration

“…[ 2 ] Moreover, they also served as versatile synthetic intermediates for the preparation of ligands [ 3 ] and more complicated molecules. [ 4 ] Consequently, the efficient construction of these structures has received considerable research interest, and many successful methods have been described, mainly including the addition of P(O)H compounds to alkynes, [ 5 ] cross‐coupling of P(O)H and prefunctionalized alkenes, [ 6 ] phosphonylation of alkenes via radical ways, [ 7 ] Knoevenagel condensation of carbonyl compounds and methylphosphonate derivatives, [ 8 ] and so on [ 9 ] .…”