Regioselective Synthesis of 3-Alkynyl-5-bromo-2-pyrones via Pd-Catalyzed Couplings on 3,5-Dibromo-2-pyrone

Abstract

[reaction: see text] 3,5-Dibromo-2-pyrone underwent facile Pd(0)-catalyzed coupling reactions with various alkynes to give rise to the corresponding 3-alkynyl-5-bromo-2-pyrones with good to excellent chemical yields and regioselectivity.

Regioselective (site-selective) functionalisation of unsaturated halogenated nitrogen, oxygen and sulfur heterocycles by Pd-catalysed cross-couplings and direct arylation processes

“…15 It is presumed, but not proven, that a more reactive organocuprate is formed in the presence of stoichiometric copper(I) iodide, a reasonable assumption in a polar solvent like DMF. More generally, coupling occurs at the 3-position for Sonogashira coupling, 16 Suzuki coupling 17 and amination reactions. 18 The type of bidentate ligand is important for amination, with Xantphos effective for aromatic amines and BINAP for alkyl amines.…”

“…The preferred regioselectivity for the 3-position in 3,5-dibromo-2-pyrone could not be predicted using this method, although the 1 H NMR chemical shifts for Scheme 4 Regioselective couplings of 3,5-dibromo-2-pyrone. [14][15][16][17][18][19] Scheme 5 Regioselective Sonogashira alkynylation of 4,6-dichloro-2-pyrone. 12 It being clear that electronic effects likely dominate the regioselectivity outcome, here a chelating role for the carbonyl moiety of the 2-pyrone could be important, something which could be probed with a 2-pyridone.…”

Chiral Resolution of Racemic 2‐Pyrone Diels‐Alder Cycloadduct by Diastereomeric Salt Formation

“…3,5‐Dibromo‐2‐pyrone 1 is a potent neutral diene that undergoes both normal‐ and inverse‐demand Diels‐Alder cycloaddition reaction with electron poor and rich dienophile, generating bicyclolactone 2 , mostly with high chemical yield and endo/exo selectivity . Moreover, the two bromine atoms can be selectively mono‐functionalized to give 3‐substituted‐5‐bromo‐2‐pyrones 3 or 5‐substituted‐3‐bromo‐2‐pyrones 4 . The aforementioned ambient diene character is retained in these 2‐pyrone derivatives, due to the remaining bromide at C3 or C5 position, allowing the generation of structurally and functionally diverse cycloaddition products (Scheme ) …”

Recent Advances in the Synthesis of 2-Pyrones

“…Additionally, regioselective Sonogashira alkynylations at the C3 position of 3,5-dibromo-2-pyrone ( 143 ) were established with terminal alkynes to afford various synthetically useful 3-alkynyl-5-bromo-2-pyrones ( 170 ) [ 74 ]. Besides above-mentioned coupling reactions, Knochel and co-workers investigated a bromide-copper exchange by the reaction of 3,5-dibromo-2-pyrone ( 143 ) with a sterically hindered cuprate reagent, lithium dineophylcuprate (Me 2 PhCCH 2 ) 2 CuLi, leading to the copper derivative ( 171 ) which can be readily acylated with cyclohexanecarbonyl chloride to provide the ketone ( 172 ) in 76% yield ( Scheme 46 ) [ 75 ].…”