The direct access to 2-amino-5-homoallylfurans has been realized by a palladium-catalyzed tandem cycloisomerization/Heck-type coupling between homoallenyl amides and allyltrialkylsilanes, using a novel DDQ/MnO2 combination as the efficient oxidant. The reaction exclusively affords γ-allylation products in good to excellent yields with broad substrate scope under exceptionally mild reaction conditions. It represents one of the rare examples of the Pd-catalyzed intermolecular Heck-type coupling of allytrialkylsilanes terminated by β-silyl elimination, thus complementing traditional allylation methods because of the excellent γ-selectivity.

A novel copper-catalyzed cascade trifluoromethylation/cyclization of 2-(3-arylpropioloyl)benzaldehydes is described, allowing a direct access to structurally diverse trifluoromethylated naphthoquinones under mild reaction conditions. It represents the first trans-acyltrifluoromethylation of internal alkynes.

Herein we describe a novel, visible light-induced tandem radical addition–cyclization of alkenyl aldehydes with α-bromocarbonyl compounds. A set of cyclic ketones, including indanones, cyclopentenones, 3,4-dihydronaphthalen-1(2H)-ones, and chroman-4-ones, are synthesized at room temperature with high efficiency and good functional group compatibility. It represents the first report on the catalytic 1,2-acylalkylation of unactivated alkenes.

Copper-catalyzed acyltrifluoromethylation of alkenes has been developed for the first time, affording trifluoroethyl indanones and related cyclic ketones in promising yields with excellent diastereoselectivity. The fast incorporation of CF3 and indanone into a single molecule renders it an efficient and valuable tool for the synthesis of biologically active compounds.

A palladium-catalyzed cyclizative sulfonylation of homoallenyl amides using sodium sulfinates as the sulfonylation reagent and PhI(O2CCF3)2 as the oxidant has been realized. The reaction proceeds at room temperature and produces structurally diverse 2-amino-5-sulfonylmethylfurans in good to excellent yields. A Pd(II)/Pd(IV) catalytic cycle has been proposed for the formation of sulfonylated furans. The concurrent formation of a furan moiety and a C(sp3)–sulfur bond in a single operation makes it a very attractive method for organic synthesis.

A palladium-catalyzed cyclizative sulfonylation of homoallenyl amides using sodium sulfinates as the sulfonylation reagent and PhI(O2CCF3)2 as the oxidant has been realized. The reaction proceeds at room temperature and produces structurally diverse 2-amino-5-sulfonylmethylfurans in good to excellent yields. A Pd(II)/Pd(IV) catalytic cycle has been proposed for the formation of sulfonylated furans. The concurrent formation of a furan moiety and a C(sp3)–sulfur bond in a single operation makes it a very attractive method for organic synthesis.

•A copper-catalyzed borylative cyclization of 1,n-enynyl phosphates is described.•Five- to eight-membered cyclic 1,4-dienyl boronates are efficiently assembled.•It represents the first Cu-catalyzed formal intramolecular alkyne allylboration.We report here a room temperature, efficient, and broadly applicable copper-catalyzed borylative cyclization of 1,n-enynyl (n = 6–9) phosphates for the concise synthesis of structurally diverse 5–8 membered cyclic 1,4-dienyl boronates, which represents the first Cu-catalyzed formal intramolecular alkyne allylboration. Subsequent Suzuki-Miyaura coupling provides a facile access to cyclized 1,4-dienes. A mechanism consisting of alkyne borylcupration, intramolecular alkene addition, and β-elimination has been proposed to explain the experimental results.Download high-res image (134KB)Download full-size image

A Cu-catalyzed cascade annulation of enynals with alkenyl or alkynyl α-bromocarbonyls for the synthesis of various cyclohexenone-fused polycyclic compounds is described. Up to six new C–C bonds and four new carbocycles can be established in a single reaction, highlighting the high efficiency and step-economics of this protocol. This reaction offers a novel and straightforward entry to the synthesis of ketones featuring the addition of carbon radicals to aldehydes.

A room-temperature and one-pot synthesis of ε-CF3-substituted amides via the copper-catalyzed trifluoromethylation of alkenes with redox-neutral remote amidation of aldehydes is described. This reaction is featured by an unprecedented 1,5-H atom abstraction from aldehydic C–H bonds by α-CF3-alkyl radicals resulting from the radical trifluoromethylation of alkenes, thus enabling a new possibility of the trifluoromethylation-initiated remote sp2 C–H functionalization.

•A highly diastereoselective and one-step synthesis of 3,4-cyclopenta-1-tetralones is described.•Three new C–C bonds and two new carbocycles can be constructed simultaneously.•This reaction features the use of aldehydes as carbon radical acceptors.A straightforward, efficient, and highly diastereoselective method for the synthesis of 3,4-cyclopenta-1-tetralones has been realized via the copper-catalyzed coupling of 2-vinyl benzaldehydes with 3-alkenyl 2-bromocarbonyls. Subsequent reduction with l-selectride leads to the formation of benzannulated tricyclic alcohols, possessing four continuous stereogenic centers, in high yields with excellent diastereoselectivity.

A novel HOTf-catalyzed oxyarylation of ynol ethers and thioethers has been realized with aryl sulfoxides as the oxyarylating reagents, providing α-arylated esters or thioesters in good to excellent yields. Notably, all atoms of the starting materials were incorporated in the product (100% atom economy) and the reaction proceeded under very mild conditions. It was found that the reaction can be ran under air and that the best yields are obtained under solvent-free conditions.

A Pd-catalyzed divergent cyclization, including cycloisomerization and aerobic oxidative cycloisomerization of homoallenyl amides, is described. Varieties of functionalized 2-amino-5-alkylfurans and 2-amino-5-formylfurans can be selectively synthesized in good to excellent yields. Preliminary mechanistic studies show that peroxide may be a key intermediate for this Pd-catalyzed radical aerobic oxidative cycloisomerization of homoallenyl amides. The mild reaction conditions, high atom economy, and utilization of air as the oxygen source make this protocol very environmentally benign and practical to the synthetic community.

A Selectfluor-mediated fluorohalogenative or difluorinative hydration of ynol ethers is described, giving various α,α-fluorohalo esters including α,α-bromofluoro, α,α-chlorofluoro, α,α-fluoroiodo, and α,α-difluoro derivatives in a highly selective manner under very mild reaction conditions. The resultant products can be applied to the facile synthesis of α-monofluoro-α-amino acids. This reaction represents a new advance in the trifunctionalization of alkynes.

A highly trans-selective Cu-catalyzed carbohalogenation including carbobromination, carboiodination, and carbochlorination of terminal alkynes with activated tertiary alkyl halides has been realized, providing quaternary-carbon-containing alkenyl halides in good yields with excellent regio- and stereoselectivity. Meanwhile, an unprecedented alkyne trans-carboalkynylation process has been achieved via the tandem trans-carbohalogenation/Sonogashira coupling reaction, which furnishes highly functionalized 1,3-enynes in a single chemical transformation.

A Cu-catalyzed, highly regio-, and stereoselective hydroallylation of thioalkynes has been developed with allylboronates as the allylating reagents, providing stereodefined 1,4-dienyl sulfides in good to excellent yields under very mild reaction conditions. The resulting products can been smoothly converted into skipped dienes by a Ni-catalyzed coupling of C–S bonds with Grignard reagents, thus offering a novel efficient method for the regio- and stereoselective synthesis of 1,4-dienes.

A fine-tunable transformation, including Pd-catalyzed acetoxylative, alkoxylative, and hydroxylative cycloisomerization of homoallenyl amides, has been realized with hypervalent iodine organic compounds as the oxidants, giving polysubstituted 2-aminofurans in promising yields at room temperature. The selective formation of three different types of products from the same starting materials makes this reaction particularly attractive and useful for organic synthesis.

A new version of benzannulation featuring the use of aromatic tert-butyl ynol ethers as the convenient precursors for arylketenes has been developed. Both ynamides and ynol ethers undergo this reaction smoothly, giving 3-amino and 3-alkoxy 1-naphthols in good to excellent yields under the heated reaction conditions. The high efficiency, excellent regioselectivity, good functional group compatibility, and broad substrate scope render this reaction particularly valuable for organic synthesis.

An unprecedented Pd-catalyzed trans-addition of boronic acids to ynamides has been reported, giving α,β-disubstituted enamides in high yields with excellent regio- and stereoselectivity. A possible mechanism involving the palladium carbene intermediate has been proposed to account for the unusual trans-addition.

A mild and efficient preparation of (Z)-β-halo alkenyl sulfides via the K2CO3-promoted hydrothiolation of haloalkynes has been realized, producing (Z)-β-bromo and (Z)-β-chloro vinylic sulfides in high yields with excellent regio- and stereoselectivity. This approach covers a variety of substrates, including both aryl and alkyl haloalkynes. Meaningfully, it allows a facile access to stereodefined (Z)- or (E)-trisubstituted olefins featuring the iterative cross-coupling of carbon–halide and carbon–sulfur bonds of β-halo alkenyl sulfides.

A highly regio- and stereoselective trans-hydrofluorination of N-sulfonyl ynamides has been realized with AgF as the fluorination reagent, affording (Z)-α-fluoroenamides in good to excellent yields. The reaction proceeds under mild reaction conditions and shows good functional group compatibility.

A silver-catalyzed trans addition of carboxylic acids to ynol ethers is described. The reaction has a broad scope with respect to carboxylic acids and ynol ethers, delivering (Z)-α-alkoxy enol esters in good yields with excellent regio- and stereoselectivity. Meaningfully, the Ni-catalyzed selective coupling of alkenyl C–OPiv bonds of (Z)-α-alkoxy enol esters with boronic acids enables a convenient route to the access of (E)-enol ethers. As such, the two-step procedure, consisted of a hydrocarboxylation and a subsequent Suzuki–Miyaura coupling, offers a formal trans hydroarylation of ynol ethers, thus providing a good complementary method to our previous report.

A Pd-catalyzed reductive addition of organohalides, including aryl, alkenyl, and benzyl halides, to ynol ethers has been realized in the presence of 2-propanol, giving α,β- and β,β-disubstituted olefinic ethers in satisfactory yields with excellent regio- and stereoselectivity. It represents the first highly regio- and stereoselective hydroarylation, hydroalkenylation, and hydrobenzylation of ynol ethers.

A Cu-catalyzed divergent hydroboration of thioacetylenes has been achieved, providing (Z)-1-thio- or (Z)-2-thio-1-alkenyl boronates in moderate to high yields with excellent regio- and stereoselectivity, by using pinacolborane or bis(pinacolato)diboron as the hydroborating reagents, respectively. DFT calculations indicate that the sulfur atom plays a key role in determining the regioselectivity through polarizing the C–C triple bonds and participating in the HOMO orbitals. Moreover, the SR group can serve as a good leaving group, resulting in the concise synthesis of six regio- and stereoisomers of trisubstituted alkenes 5 via the iterative cross-coupling of C–B and C–S bonds. Clearly, it will be valuable for assembling stereochemically diverse trisubstituted olefins in organic synthesis.

An efficient Pd-catalyzed addition of boronic acids to silylacetylenes is described, providing β,β-disubstituted (E)- or (Z)-alkenylsilanes in satisfactory yields with excellent regio- and stereoselectivity under mild reaction conditions. It represents the first highly regio- and stereoselective addition of boronic acids to aryl and alkenyl silylacetylenes. Moreover, the sequential Pd-catalyzed boron addition/N-halosuccinimide-mediated halodesilylation reaction results in a stereodivergent approach to β,β-disubstituted alkenyl halides, which can serve as versatile synthetic intermediates for the stereodivergent assembly of (E)- and (Z)-trisubstituted alkenes via transition-metal-catalyzed cross-coupling reactions.

A Pd-catalyzed, highly regio- and stereoselective addition of boronic acids to ynamides has been realized. This protocol generates (Z)-α,β-disubstituted enamides in high yields with excellent regio- and stereoselectivity under the mild reaction conditions, thereby providing a good complementary method for the diverse synthesis of multifunctional enamides. A wide collection of functional groups are found to be tolerated. It represents a straightforward and useful means to assemble stereodefined enamides from readily available starting materials.

A Pd-catalyzed addition of boronic acids to ynol ethers has been realized, delivering trisubstituted vinyl ethers in good yields with perfect control of the regio- and stereoselectivity. The reaction proceeds under mild conditions and exhibits excellent functional group compatibility. Moreover, the resultant products can be converted into pentasubstituted benzenes via the tandem Diels–Alder/aromatization reaction.

An operationally simple and practical protocol for the synthesis of (E)-α-halo vinyl sulfides has been achieved via a highly regio- and stereoselective hydrohalogenation of alkynyl thioethers using lithium halides in HOAc or propionic acid at room temperature. It permits the formation of (E)-α-chloro and (E)-α-bromo vinyl sulfides in satisfactory yields with good to excellent stereoselectivities. Moreover, this work results in a new method for the assembly of stereodefined (E)- or (Z)-trisubstituted alkenes featuring the first coupling of the C–X bond of (E)-α-halo vinyl sulfides followed by a subsequent Ni-catalyzed coupling of the C–S bond with Grignard reagents.

A novel copper-catalyzed, base-free direct thiolation of xanthines and related heterocycles is described, featuring the use of inexpensive Cu(OAc)2·H2O as the catalyst, O2 as a clean and cheap oxidant, and easy-to-handle disulfides as the thiolation reagents. It works well for both aryl and alkyl disulfides. Moreover, the resultant products can be converted into 8-(hetero)aryl- or alkenyl-substituted xanthines in good yields via the Liebeskind–Srogl coupling reaction.

A highly regio- and stereoselective synthesis of stereodefined β,β-disubstituted alkenyl ethers featuring the sequential hydroboration/Suzuki–Miyaura coupling of ynol ethers has been described. A number of functional groups, including OMe, Ac, CO2Et, CN, halides, and alkyl, (hetero)aryl, and alkenyl groups, are well-tolerated under the reaction conditions. Furthermore, it allows a facile entry to the labile diarylacetaldehydes by TFA-mediated hydrolysis of β,β-disubstituted vinyl ethers.

Described herein is a novel method for the synthesis of 3,4,5-trisubstituted 2-oxazolones featuring the first Pd-catalyzed dehydrogenative alkenylation of 2-oxazolones, which is realized by employing 10 mol % of Pd(OAc)2 as the catalyst and the use of readily available Cu(OAc)2 as the oxidant. A wide range of functional groups, such as F, Cl, Br, OMe, ester, ketone, amide, alkyl, and aryl substituents, are found to be compatible under the reaction conditions. The utilization of the C–H functionalization strategy provides a straightforward, convenient, and highly atom-economical approach for the construction of 3,4,5-trisubstituted 2-oxazolones. It is worth noting that the 4-alkenyl 2-oxazolones can be smoothly converted into naphtho[1,2-d]oxazol-2-ones via a photochemical transformation.

An unprecedented Pd-catalyzed hydrohalogenation of alkynyl halides for the regio- and stereoselective synthesis of (Z)-1,2-dihaloalkenes has been realized using [(allyl)PdCl]2 as the catalyst and cis,cis-1,5-cyclooctadiene as the ligand. The advantages of this protocol are well illustrated by the assembly of trisubstituted (Z)-enynes and multifunctional benzenes via iterative cross-coupling reactions or tandem Diels–Alder–aromatization reactions, respectively.

A mild and operationally simple approach to highly functionalized oxazolones has been developed, which involves an intramolecular oxypalladation of N-alkynyl tert-butyloxycarbamates, followed by either protonolysis of the alkenyl C–Pd bond to afford 3,5-disubstituted oxazolones or allylation with allyl halides in the presence of Ag2CO3 to generate 3,4,5-trisubstituted oxazolones, respectively.

A novel palladium-catalyzed approach for the assembly of 3,4,5-trisubstituted oxazolones has been achieved by the coupling of N-alkynyl tert-butyloxycarbamates with aryl halides and related electrophiles, which involves an oxidative addition followed by oxypalladation/reductive elimination. The reaction provides a convenient access to diversely substituted oxazolones in satisfactory yields and shows good functional group compatibility.

Described herein is a Pd-catalyzed haloallylation of aromatic ynol ethers and allyl chlorides, allowing facile access to (1E)-α-chloroenol ethers in a highly regio- and stereoselective manner. The synthetic utility of this method is demonstrated well by the synthesis of the stereodefined multisubstituted enol ethers and α-allylated carbonyl compounds.

A highly efficient and selective synthesis of (1E)- or (1Z)-1,2-dihalo-1,4-dienes viaPd-catalyzed coupling of haloalkynes and allylic halides is described. The (1E)-1,2-dihalo-1,4-dienes were generated in good yields with excellent stereoselectivities (1E/1Z up to >98/2), while (1Z)-1,2-dihalo-1,4-dienes were produced in excellent yields and stereoselectivities (1Z/1E up to >98/2) by simply adding stoichiometric lithium halides.

An atom-economic approach to the regio- and stereoselective assembly of highly substituted enamides is described via the Pd-catalyzed chloroallylation of ynamides at room temperature, which offers a simple and practical alternative to the stereodefined multisubstituted enamides.

A Pd-catalyzed coupling of haloalkynes with allyl acetate has been reported, providing a convenient method for the stereoselective synthesis of (Z)-β-haloenol acetates in good yields. The synthetic utility of this method is demonstrated by the formation of functionalized enol acetates via the Suzuki–Miyaura or Sonogashira coupling of the resulting (Z)-β-haloenol acetate products.

A highly regio- and stereoselective method for the synthesis of cis-1,2-dihaloalkenes through Pd-catalyzed coupling of haloalkynes and α,β-unsaturated carbonyls has been reported. Excellent stereoselectivities (Z/E up to >98:2) were observed in most cases. This method was subsequently applied to synthesize the functionalized conjugated enyne via the mono-Sonogashira coupling reaction of cis-1-chloro-2-iodoalkene.

A palladium-catalyzed protocol for effective synthesis of 1,3-oxazolidines has been reported. This method is featured by the high diastereoselectivity (dr up to >98/2) and using the readily available 2-butene-1,4-diol derivatives and imines as substrates.A highly diastereoselective palladium-catalyzed synthesis of 1,3-oxazolidines using the readily available 2-butene-1,4-diol derivatives and imines as substrates has been reported.

An unprecedented Pd-catalyzed hydrohalogenation of alkynyl halides for the regio- and stereoselective synthesis of (Z)-1,2-dihaloalkenes has been realized using [(allyl)PdCl]2 as the catalyst and cis,cis-1,5-cyclooctadiene as the ligand. The advantages of this protocol are well illustrated by the assembly of trisubstituted (Z)-enynes and multifunctional benzenes via iterative cross-coupling reactions or tandem Diels–Alder–aromatization reactions, respectively.

A mild and efficient preparation of (Z)-β-halo alkenyl sulfides via the K2CO3-promoted hydrothiolation of haloalkynes has been realized, producing (Z)-β-bromo and (Z)-β-chloro vinylic sulfides in high yields with excellent regio- and stereoselectivity. This approach covers a variety of substrates, including both aryl and alkyl haloalkynes. Meaningfully, it allows a facile access to stereodefined (Z)- or (E)-trisubstituted olefins featuring the iterative cross-coupling of carbon–halide and carbon–sulfur bonds of β-halo alkenyl sulfides.

An unprecedented Pd-catalyzed trans-addition of boronic acids to ynamides has been reported, giving α,β-disubstituted enamides in high yields with excellent regio- and stereoselectivity. A possible mechanism involving the palladium carbene intermediate has been proposed to account for the unusual trans-addition.

A highly efficient and selective synthesis of (1E)- or (1Z)-1,2-dihalo-1,4-dienes viaPd-catalyzed coupling of haloalkynes and allylic halides is described. The (1E)-1,2-dihalo-1,4-dienes were generated in good yields with excellent stereoselectivities (1E/1Z up to >98/2), while (1Z)-1,2-dihalo-1,4-dienes were produced in excellent yields and stereoselectivities (1Z/1E up to >98/2) by simply adding stoichiometric lithium halides.

Described herein is a Pd-catalyzed haloallylation of aromatic ynol ethers and allyl chlorides, allowing facile access to (1E)-α-chloroenol ethers in a highly regio- and stereoselective manner. The synthetic utility of this method is demonstrated well by the synthesis of the stereodefined multisubstituted enol ethers and α-allylated carbonyl compounds.

A Pd-catalyzed addition of boronic acids to ynol ethers has been realized, delivering trisubstituted vinyl ethers in good yields with perfect control of the regio- and stereoselectivity. The reaction proceeds under mild conditions and exhibits excellent functional group compatibility. Moreover, the resultant products can be converted into pentasubstituted benzenes via the tandem Diels–Alder/aromatization reaction.

Copper-catalyzed cascade annulation of γ,δ-unsaturated α-bromocarbonyls with biaryl or (Z)-arylvinylacetylenes is presented, giving an expeditious access to dibenzocycloheptanes and related compounds in moderate to high yields. It provides a novel method for the one-pot synthesis of cycloheptane and cycloheptene-fused polycyclic scaffolds featuring a rare 7-endo-trig radical cyclization.

Copper-catalyzed acyltrifluoromethylation of alkenes has been developed for the first time, affording trifluoroethyl indanones and related cyclic ketones in promising yields with excellent diastereoselectivity. The fast incorporation of CF3 and indanone into a single molecule renders it an efficient and valuable tool for the synthesis of biologically active compounds.

A Cu-catalyzed cascade annulation of enynals with alkenyl or alkynyl α-bromocarbonyls for the synthesis of various cyclohexenone-fused polycyclic compounds is described. Up to six new C–C bonds and four new carbocycles can be established in a single reaction, highlighting the high efficiency and step-economics of this protocol. This reaction offers a novel and straightforward entry to the synthesis of ketones featuring the addition of carbon radicals to aldehydes.

A Selectfluor-mediated fluorohalogenative or difluorinative hydration of ynol ethers is described, giving various α,α-fluorohalo esters including α,α-bromofluoro, α,α-chlorofluoro, α,α-fluoroiodo, and α,α-difluoro derivatives in a highly selective manner under very mild reaction conditions. The resultant products can be applied to the facile synthesis of α-monofluoro-α-amino acids. This reaction represents a new advance in the trifunctionalization of alkynes.

An operationally simple and practical protocol for the synthesis of (E)-α-halo vinyl sulfides has been achieved via a highly regio- and stereoselective hydrohalogenation of alkynyl thioethers using lithium halides in HOAc or propionic acid at room temperature. It permits the formation of (E)-α-chloro and (E)-α-bromo vinyl sulfides in satisfactory yields with good to excellent stereoselectivities. Moreover, this work results in a new method for the assembly of stereodefined (E)- or (Z)-trisubstituted alkenes featuring the first coupling of the C–X bond of (E)-α-halo vinyl sulfides followed by a subsequent Ni-catalyzed coupling of the C–S bond with Grignard reagents.