Palladium-catalyzed alkynylation of allylic gem-difluorides.

Herein, a palladium-catalyzed regioselective alkynylation, esterification, and amination of allylic gem-difluorides via C-F bond activation/transmetallation/ß-C elimination or nucleophilic attack has been achieved. This innovative protocol showcases an extensive substrate range and operates efficiently under mild reaction conditions, resulting in high product yields and Z-selectivity. Particularly noteworthy is its exceptional tolerance towards a wide array of functional groups. This developed methodology provides effective and convenient routes to access a diverse array of essential fluorinated enynes, esters and amines.

Accessing Benzoazepine Derivatives via Photoinduced Radical Relay Formal [5 + 2] Reaction of Amide/Alkyne Enabled by Palladium Catalysis.

A novel class of alkyne-tethered amides facilitates an unprecedented photoinduced palladium-catalyzed radical relay formal [5 + 2] reaction. This innovative strategy allows for the rapid construction of diverse fused benzoazepine structures, yielding structurally novel and compelling compounds. With a broad substrate scope and excellent functional group tolerance, the methodology synthesizes biologically active compounds. Notably, the resulting tricyclic benzo[b]azepines offer diversification opportunities through simple transformations. DFT calculations elucidate a seven-membered ring closure mechanism involving the alkenyl radical and Pd(I) rebound alongside a concerted metalation-deprotonation (CMD) process.

Palladium-Catalyzed Diversified Synthesis of Monofluorinated Alkenes from Allylic gem-Difluorides through Pd-OH Intermediate.

Significant advancements in synthesis of monofluoroalkenes via palladium-catalyzed reactions involving allylic gem-difluorides and diverse nucleophiles have been achieved. This method allows regioselective arylation, alkylation, allylation, alkenylation, and hydrogenation of allylic gem-difluorides, yielding high Z-selectivity and favorable product yields under mild conditions. Tolerating various functional groups, these transformations utilize a common Pd-OH intermediate. Additionally, employing triple Pd-catalyzed cross-coupling yields diverse trisubstituted alkenes efficiently.

Construction of diverse polycyclic N-heterocycles via cascade allylic amination/Diels-Alder reaction.

An efficient cascade approach for the construction of nitrogen-containing polycyclic compounds from amines tethered with an alkenyl (or alkynyl) group and divinyl carbonates is described. In the presence of Pd(0)-catalyst, an active zwitterionic allylpalladium species is generated and undergoes allylic amination with various amines followed by Diels-Alder reaction to form various polycyclic N-heterocyclic products, including hydrophenanthridines, hydrobenzo[c]azepines (hydro)isoindoles and hydrobenzo[cd]indoles.

Construction of nine-membered N,N,O-heterocycles via Pd-catalyzed [6+3] dipolar cycloaddition.

A new approach for the synthesis of 9-membered N,N,O-heterocycles by Pd-catalyzed [6+3] dipolar cycloaddition of N-iminoisoquinolinium ylides and 2-vinyl oxetanes has been developed. The scope of this cycloaddition was demonstrated with 28 examples. This is another important synthetic strategy for medium-sized rings by employing N-iminoisoquinolinium ylides as ternary synthons.

Catalytic Asymmetric Allylic Substitution/Isomerization with Central Chirality Transposition.

We have developed a catalytic asymmetric allylic substitution/isomerization process with central chirality transposition. This process takes advantage of the ambident reactivity of the 2-indole imine methide generated in situ from racemic tertiary indolylmethanols. The use of a suitable chiral phosphoric acid catalyst and an ortho-directing group allowed regioselective formation a C-C bond at the 3 position but enantiocontrolled construction of a stereogenic center at the 2-benzylic position.

Reductive Opening of Oxetanes Catalyzed by Frustrated Lewis Pairs: Unexpected Aryl Migration via Neighboring Group Participation.

B(C6F5)3 was found to catalyze an unusual double reduction of oxetanes by hydrosilane with aryl migration via neighboring group participation. Control experiments suggested that the phenonium ion serves as the key intermediate. Minor modification of this protocol also led to simple hydrosilylative opening of oxetanes.

Catalytic Enantioselective Synthesis of 2,3-Dihydrobenzo[b]oxepines via Asymmetric Oxetane Opening by Internal Carbon Nucleophiles.

An intramolecular C-C formation process based on catalytic asymmetric oxetane opening by carbon nucleophiles has been developed, which provides rapid access to a range of valuable enantioenriched 2,3-dihydrobenzo[b]oxepines. With the combination of Sc(OTf)3 and a Box ligand, good chemical efficiency and enantioselectivity were achieved under mild conditions. The products are also useful precursors to other valuable structures, such as the bicyclo[3.2.2]nonane derivatives.

Migratory functionalization of unactivated alkyl bromides for construction of all-carbon quaternary centers via transposed tert-C-radicals.

Despite remarkable recent advances in transition-metal-catalyzed C(sp3)-C cross-coupling reactions, there remain challenging bond formations. One class of such reactions include the formation of tertiary-C(sp3)-C bonds, presumably due to unfavorable steric interactions and competing isomerizations of tertiary alkyl metal intermediates. Reported herein is a Ni-catalyzed migratory 3,3-difluoroallylation of unactivated alkyl bromides at remote tertiary centers. This approach enables the facile construction of otherwise difficult to prepare all-carbon quaternary centers. Key to the success of this transformation is an unusual remote functionalization via chain walking to the most sterically hindered tertiary C(sp3) center of the substrate. Preliminary mechanistic and radical trapping studies with primary alkyl bromides suggest a unique mode of tertiary C-radical generation through chain-walking followed by Ni-C bond homolysis. This strategy is complementary to the existing coupling protocols with tert-alkyl organometallic or -alkyl halide reagents, and it enables the expedient formation of quaternary centers from easily available starting materials.

Selective single C-F bond arylation of trifluoromethylalkene derivatives.

A strategically novel single C-F bond functionalization of CF3-derived molecules, which shows a prominent advantage for the expedient construction of difluoromethylene-bridged organic scaffolds, is disclosed. The reported protocol consists of SN2' amination, N-alkylation and palladium-catalyzed allylic substitution reactions, which enables straightforward arylation and alkenylation of vinyltrifluoromethane derivatives. Furthermore, this strategy is characterized by its broad substrate scope with respect to both CF3-alkene and arylboronic acid derivatives.

Intermolecular Carboamination of Unactivated Alkenes.

Herein, we report the first example of group transfer radical addition of O-vinylhydroxylamine derivatives onto unactivated alkenes. By utilizing O-vinylhydroxylamine derivatives as both the N- and C-donors, this reaction enables intermolecular carboamination of unactivated alkenes in an atom economical fashion. As the process is initiated through N-radical addition followed by C-transfer, linear carboamination products are afforded. This differs from canonical radical carbofunctionalization of olefins, which typically favors branched product owing to initiation by C-radical addition.

Highly regio- and stereoselective trans-iodofluorination of ynamides enabling the synthesis of (E)-α-fluoro-ß-iodoenamides.

A highly regio- and stereoselective trans-iodofluorination reaction of ynamides with NIS and Et3N·3HF has been achieved, affording (E)-α-fluoro-ß-iodoenamides in moderate to good yields. The reaction proceeds under mild reaction conditions and exhibits good functional group compatibility.

Pd/Cu-Catalyzed tandem head-to-tail dimerization/cycloisomerization of terminal ynamides for the synthesis of 5-vinyloxazolones.

An attractive and novel methodology involving Pd/Cu-catalyzed tandem head-to-tail dimerization/cycloisomerization of terminal ynamides for the synthesis of 3,5-disubstituted oxazolones was developed. Under Pd(PPh3)2Cl2/CuI cooperative catalyzed reaction conditions, it provided efficient access to 5-vinyloxazolones with exceptional functional group tolerance and good chemoselectivity. The control experiments demonstrated that Pd(PPh3)2Cl2 serves a key role in the dimerization of terminal ynamides and shows low catalytic activity in the intramolecular cyclization. Moreover, the hetero-Diels-Alder reaction of product 5-vinyloxazolones was also described, which provided polycyclic oxazolones in good yield.

Formation of α-chalcogenyl acrylamides through unprecedented chalcogen-mediated metal-free oxyfunctionalization of ynamides with DMSO as an oxidant.

A novel chalcogen-mediated oxyfunctionalization mode of ynamides for the synthesis of α-chalcogenyl acrylamides has been developed. Independent of metal catalysts, external oxidants and additives, this mild process afforded a range of structurally diverse α-chalcogenyl acrylamides, including α-selanyl acrylamides and α-tellanyl acrylamides. Interestingly, diverse ynamides tolerated in this approach gave different stereoselectivities.

Regioselective iodoamination of terminal ynamides for the synthesis of α-amino-ß,ß-diiodo-enamides.

A mild and efficient methodology involving the I2/TBHP-mediated intermolecular iodoamination of ynamides with amines for the synthesis of α-amino-ß,ß-diiodo-enamides was developed. This reaction provides the first intermolecular iodoamination of terminal alkynes to diiodo-enamines and can be easily applied to a wide range of substrates.

VEGF promotes cardiac stem cells differentiation into vascular endothelial cells via the PI3K/Akt signaling pathway.

Recent research suggested that cardiac stem cells (CSCs) may have the clinical application for cardiac repair. However, their characteristics and the regulatory mechanisms of their growth and differentiation have not been fully investigated. Vascular endothelial growth factor (VEGF, VEGF-A) is a major regulator of physiological and pathological angiogenesis. But the homing role of VEGF for CSCs is unclear. In this report, CSCs were isolated, purified, and expanded in vitro from rat heart. VEGF, SU5416 (VEGF receptor blocker), and Wortmannin (PI3K/Akt signaling pathway inhibitor) were used for differentiation into vascular endothelial cells (VECs). Real-time qPCR was selected to confirm the role of PI3K/Akt signaling pathway in VECs differentiation from rat CSCs. The result of real-time qPCR demonstrated that PI3K/Akt signaling pathway plays an important role in rat CSCs differentiated into VECs. So, our research provides a theoretical basis and experimental evidence for therapeutic application of rat CSCs to treat cardiac repair.