Palladium(Ⅱ)-Catalyzed Markovnikov Hydroalkynylation of Unactivated Terminal Alkenes

Alkynes are versatile synthons in organic synthesis,as well as important structural moieties in bioactive molecules.Recently,transition metal-catalyzed hydroalkynylation of alkenes has been developed with reactive alkenes and alkenes bearing directing groups.However,the regioselective hydroalkynylation of simple alkenes is still challenging.Herein,we have developed a palladium-catalyzed Markovnikov hydroalkynylation of unactivated terminal alkenes,which provides an efficient approach for the synthesis of branched alkynyl compounds under mild conditions.This reaction features excellent functional group tolerance,good reaction yields and excellent regioselectivity.Moreover,the asymmetric hydroalkynylation reaction has also been achieved with moderate enantioselectivity by introducing a sterically bulky chiral Pyox ligand.

Recent Advances and Perspectives in Transition Metal-Catalyzed 1,4-Functionalizations of Unactivated 1,3-Enynes for the Synthesis of Allenes

Classic methods for the synthesis of allenes usually introduce only one functional group into products.In this review,we highlight the recent advances and perspectives in the synthesis of allenes by transition metal-catalyzed 1,4-functionalization of unactivated 1,3-enynes.

Cu/photoredox-catalyzed decarboxylative radical C(sp^(3))–C(sp^(3))cross-coupling reactions

A radical decarboxylative C(sp^(3))–C(sp^(3))cross-coupling of NHPI esters and cyclopropanols was developed by combining photocatalysis and copper catalysis,which presents the efficient access toβ-benzyl ketones in excellent yields.Terpyridin-4′-one used as the ligand is vital for the reaction,which could facilitate the capture of benzylic radicals by alkyl-copper species generated from copper-catalyzed ring-opening of cyclopropanols.The reaction exhibited broad substrate scope and wide functional group compatibility,providing an alternative approach for C(sp^(3))–C(sp^(3))bond formation.

Synergistic asymmetric diarylation of tethered alkenes via C–H functionalization of simple(hetero)arenes

By virtue of the atom-and step-economy, utilization of simple arenes as a supplant of pre-prepared aryl metal species or aryl halides for the synthesis of arylated chiral molecules has attracted great attention from the synthetic community. While transition-metal-catalyzed enantioselective diarylation of tethered alkenes has been employed to prepare important chiral cyclic compounds, the direct use of simple arenes as aryl precursors is still underdeveloped, probably due to the difficulties in the effective control of the reactivity, site-selectivity and/or enantioselectivity. Herein we report an asymmetric Pd/Ag dual metal catalytic system for the non-directed, site-and enantioselective domino Heck/intermolecular C–H functionalization of arenes.Mechanistic studies showed that Pd and Ag act in cooperation in the catalysis and the chiral bisphosphine ligand plays a bifunctional role, i.e., assisting the silver species in the cleavage of the aryl C–H bond, while inducing the enantioselectivity on direct complexation with palladium. This method provides an efficient approach to the corresponding chiral oxindoles with good enantiomeric excesses from a broad scope of arenes, including fluoroarenes, heteroarenes and several complex products derived from medicines or natural products.

Palladium(Ⅱ)-Catalyzed Aminotrifluoromethoxylation of Alkenes:Mechanistic Insight into the Effect of N-Protecting Groups

Summary of main observation and conclusion An eficient palladium-atalyzed regioselective 5 exo aminotrifluoromethoxylation of alkenes has been established herein,which provides practical route towards the synthesis of OCF g-containing prrolidines.tert-Butyloxycarbonyl(Boc)as an amino pro-tecting group plays a signifiant role in both the chemo-and regloselectivities.In addition,preliminary mechanistic studies reveal that the amino protect-ing group of substrates and the counter anion of palladium catalyst play critical roles in reaction efficiency presumably due to an isomerization of alkyl-Pd(Ⅱ)intermediates.Moreover,the asymmetric 5-exo aminrifluoromethoxylation reaction has also been achieved by introducing a serelallyl bulky pyri-dinyl-oxazoline ligand.

Copper-Catalyzed Benzylic C–H Bond Thiocyanation: Enabling Late-Stage Diversifications

The rapid growth of using C–H bond as cross-coupling partners is reshaping the landscape of organic synthesis.C(sp3)–H functionalization via hydrogen atom transfer(HAT)represents the most compelling strategy in this avenue.Here,we demonstrate an efficient method for benzylic C–H bond thiocyanation via copper-catalyzed radical relay.The reaction exhibits broad substrate scope and exquisite benzylic selectivity with C–H substrates as limiting reagents.In addition,the benzyl thiocyanates are readily converted to other pharmaceutically important motifs,including isothiocyanate,thiourea,and others,highlighting the broad utility of this method.

Asymmetric Alkynylation of Tertiary Carbon-Centered Radical via Copper-Catalyzed Radical Relay

Alkynes are frequently found in a high proportion of natural products and bioactive moleculars,as well as a common synthon in organic synthesis,which can be easily transformed to an alkenyl,alkyl,heteroaryl,or carboxylic acid group.The enantioselective construction of alkyne substituted all carbon quaternary stereocenters is rarely reported and still a big challenge.As part of our continuous effort on developing asymmetric radical transformations,we found introducing an amidyl group(CONHAr)adjacent to the tertiary carbon radical could enable the asymmetric radical coupling with alkyne reagents.The amidyl group may stabilize the tertiary carbon radical or coordination with the chiral copper catalyst.Herein,we communicate a copper-catalyzed asymmetric trifluoromethyl-alkynylation ofα-aryl substituted acrylamides,which provides a straightforward and efficient access to chiral quaternary all-carbon centers bearing alkynyl groups in good yields and enantioselectivities.This reaction was also applied for the synthesis of chiral functionalized dipeptide.