Palladium‐Catalyzed Cascade Cyclization/Alkynylation Reactions

Abstract

Palladium‐catalyzed cascade cyclization reactions have witnessed significant improvements in recent years. Among them, palladium‐catalyzed cascade cyclization/alkynylation are especially attractive, which can assemble structurally diverse monocyclic, bicyclic, fused polycyclic, and spirocyclic skeletons with excellent chemoselectivities. In this Minireview, palladium‐catalyzed cascade cyclization/alkynylation have been summarized and discussed in detail with focus on oxypalladation and aminopalladation‐initiated cascade cyclization, intramolecular Heck‐type cascade cyclization, carbocyclizations, cascade cyclizations, and other types of cascade cyclization reactions. Some significant and representative synthetic methodologies and their synthetic applications and reaction mechanisms have also been described.

Recent developments in palladium-catalyzed C–S bond formation

“…The authors proposed that this approach may involve a Pd(II)/Pd(IV) catalytic cycle process. As shown in Scheme 8, cyclopalladation of 2-phenylpyridine (19) affords the vinyl palladacycle complex Int-10. Afterwards, oxidative addition of palladacycle complex Int-10 with N-( phenylthio)benzamide (19) gives Pd(IV) intermediate Int-11.…”

“…18 Recently, we have summarized palladium-catalyzed cascade cyclization/ alkynylation reactions for the assembly of structurally diverse alkyne derivatives with excellent chemoselectivities. 19 Additionally, we also made some important achievements in transition metal-catalyzed coupling reactions for the synthesis of a wide range of organosulfur frameworks. 20 In this minireview, we highlight the significant and representative achievements in palladium-catalyzed sulfenylation and sulfonylation from 2010 to the beginning of 2020, including our recent contributions.…”

Recent advances in metal catalyzed or mediated cyclization/functionalization of alkynes to construct isoxazoles

“…15 Recently, in 2019, we also elucidated the palladium-catalyzed cascade cyclization/ alkynylation reactions for the synthesis of structurally diverse monocyclic, bicyclic, fused polycyclic, and spirocyclic skeletons with excellent chemoselectivities. 16 In this review, we will present a comprehensive summary of the most recent advancements (from 2010 until the beginning of 2020) in this rapidly developing area of synthesis of more elaborated isoxazole derivatives by metal catalyzed or metal mediated crosscoupling from alkynes, including our recent contributions. It is worth noting that this review will cover some synthetic methodologies which have been recently reviewed elsewhere and these will not be discussed in detail.…”

“…Based on the above-mentioned formation of 4-alkynylation and 4-alkenylation isoxazole derivatives, this cascade cyclization/functionalization strategy was extended to the synthesis of functionalized 4-alkynylisoxazoles. Satisfyingly, a highly regioselective palladium-catalyzed three-component cascade cyclization/alkynylation of alkynone O-methyloximes (14), propargyl p-toluenesulfonate (15), and secondary amines (16) was efficiently developed in ionic liquids (Scheme 7). 25 A whole variety of conventional solvents such as DMSO, DMF, toluene, and DCE were observed; however, all of them were found to be less effective.…”

“…Initially, trans-oxypalladation of alkynone O-methyloximes (14) produces the vinyl palladium species Int-8. In the meantime, the alkynylamine intermediate Int-9 was generated in situ from propargyl p-toluenesulfonate (15) and secondary amines (16). Subsequently, alkyne intermediate Int-9 coordinates with the vinyl palladium species Int-8 and forms palladium intermediate Int-10.…”