Regiodivergent Hydrosilylation of Polar Enynes to Synthesize Site-Specific Silyl-Substituted Dienes.

Herein, we present catalyst-regulated switchable site-selective hydrosilylation of enynes, which are suitable for a wide range of alkyl and aryl substituted polar enynes and exhibit excellent functional group compatibility. Under the optimized conditions, silyl groups can be precisely installed at various positions of 1,3-dienes. While α- and γ-silylation products were obtained under platinum-catalytic systems, ß-silylation products were delivered with [Cp*RuCl]4 as catalyst. This process lead to the formation of 1,3-dienoates with diverse substitutions, which would pose challenges with other methodologies.

Cu-Catalyzed Regioselective Silylation of Chloro-Substituted Allenyl-Bdan.

A copper-catalyzed efficient regioselective silylation reaction of chloro-substituted allenyl-Bdan was developed. Under mild reaction conditions, allenyl and propargyl silane compounds can be selectively obtained in moderate to high yields by adjusting the bases and solvents used in the reactions. This study offers direct and efficient methods for synthesizing multifunctionalized allenyl and propargyl silane compounds from the same initial material of chloro-substituted allenyl-Bdan.

Synthesis and Transformation of Bis(silyl)-Substituted Conjugated Vinylallene Compounds.

We develop a copper-catalyzed disilylation of polysubstituted pent-1-en-4-yn-3-yl acetate derivatives, which in one pot furnishes the bis(silyl)-substituted vinylallenes in moderate yields under mild reaction conditions. The reaction shows broad substrate scope and single stereoselectivity. Besides, we develop a method to decrease the electrocyclization temperature of vinylallenes for the synthesis of methylenecyclobutenes by installing bis(silyl) substituents. And the effect of a silyl substituent on electrocyclization of vinylallenes was studied via DFT computation. The synthetic method features broad substrate scope and excellent stereoselectivity.

Regio- and enantioselective CuH-catalyzed 1,2- and 1,4-hydrosilylation of 1,3-enynes.

We report a copper-catalyzed ligand-controlled selective 1,2- and 1,4-hydrosilylation of 1,3-enynes, which furnishes enantiomerically enriched propargyl- and 1,2-allenylsilane products in high yields with excellent enantioselectivities (up to 99% ee). This reaction proceeds under mild conditions, shows broad substrate scope for both 1,3-enynes and trihydrosilanes, and displays excellent regioselectivities. Mechanistic studies based on deuterium-labeling reactions and density functional theory (DFT) calculations suggest that allenylcopper is the dominant reactive intermediate under both 1,2- and 1,4-hydrosilylation conditions, and it undergoes metathesis with silanes via selective four-membered or six-membered transition state, depending on the nature of the ligand. The weak interactions between the ligands and the reacting partners are found to be the key controlling factor for the observed regioselectivity switch. The origin of high enantiocontrol in the 1,4-hydrosilylation is also revealed by high level DLPNO-CCSD(T) calculations.

Copper-Catalyzed Enantioselective Desymmetric Protosilylation of Prochiral Diynes: Access to Optically Functionalized Tertiary Alcohols.

In this protocol, a copper-catalyzed desymmetric protosilylation of prochiral diynes was developed. The corresponding products were obtained in moderate to high yields and enantiomeric ratios. This approach provides a simple method for synthesizing functionalized chiral tertiary alcohols in the presence of a chiral pyridine-bisimidazoline (Pybim) ligand.

Copper-Catalyzed Regio- and Stereoselective Three-Component Coupling of Allenyl Ethers with gem-Dichlorocyclobutenones and B2pin2.

The three-component coupling method for regio- and stereoselective difunctionalization of allenes with allenyl ethers, bis(pinacolato)diboron, and gem-dichlorocyclobutenones as electrophiles was reported, yielding a variety of highly functionalized cyclobutenone products tethering with an alkenylborate fragment. The polysubstituted cyclobutenone products also underwent diverse transformations.

Copper-Catalyzed Borylation and Silylation of Dichlorocyclobutenones.

We report copper-catalyzed borylation and silylation of dichlorocyclobutenones, which furnish the boron-substituted and silicon-substituted polyfunctionalized cyclobutenones in high yields. The reactions proceed under mild reaction conditions, show broad substrate scope, and display high chemoselectivity. In addition, a series of transformations of the corresponding products has been realized.

Copper-Catalyzed Enantioselective Hydrosilylation of Allenes to Access Axially Chiral (Cyclohexylidene)ethyl Silanes.

A novel strategy of copper-catalyzed regio- and enantioselective hydrosilylation of 4-substituted vinylidenecyclohexanes with silanes was developed. In this protocol, various allenes and silanes were used to afford the corresponding (cyclohexylidene)ethyl silanes in moderate to high yields with good enantioselectivities.

Copper-Catalyzed Markovnikov Selective 3,4-Hydrosilylation of 2-Substituted 1,3-Dienes.

A copper-catalyzed regioselective Markovnikov 3,4-hydrosilylation of 2-substituted 1,3-dienes has been accomplished. A wide range of 2-substituted 1,3-dienes and trihydrosilanes are compatible under the optimal conditions. The bisphosphine ligand with a rigid backbone provides the Markovnikov 3,4-hydrosilylation product in better yield and selectivity. Besides, the synthetic utilities of the allylsilanes also were demonstrated by their flexible derivatizations.

Copper-Catalyzed Enantioselective 1,4-Protosilylation of Alkynyl-substituted Enones to Synthesize the Highly Diastereomeric Chiral Homoallenylsilanes.

A copper-catalyzed 1,4-protosilylation of α-alkynyl-enones to form the functionalized chiral homoallenylsilanes was developed. In the presence of a chiral monopyridine oxazoline ligand, a variety of trisubstituted allene derivatives bearing a contiguous stereogenic center and axis were prepared in good yields with excellent enantioselectivities and diastereoselectivities.

Synthesis of Allenyl-Bdan via Cu(I)-Catalyzed Borylation of Propargyl gem-Dichlorides.

A copper-catalyzed borylation of propargyl dichlorides was developed under mild reaction conditions. The corresponding chloro-substituted allenyl-Bdan products were obtained in good yields. The utilities of allenyl-Bdan products were examined by their diverse derivatizations.

Copper-Catalyzed Regiodivergent and Enantioselective Hydrosilylation of Allenes.

A copper-catalyzed regiodivergent hydrosilylation of a wide range of simple allenes is reported. Linear and branched allylsilanes were formed by judicious choice of solvents. Furthermore, branched allylsilanes were obtained with high enantioselectivity (up to 97% enantiomeric excess) with the aid of a C2-symmetric bisphosphine ligand in the unprecedented asymmetric allene hydrosilylation.

Chelation-Controlled Stereospecific Cross-Coupling Reaction between Alkenes for Atroposelective Synthesis of Axially Chiral Conjugated Dienes.

In this protocol, an efficient palladium-catalyzed asymmetric synthesis of axially chiral conjugated dienes via alkenyl C-H olefination is reported. The corresponding atropisomeric styrenes containing a conjugated diene scaffold were obtained in good yields with good enantioselectivities. This synthetic strategy features an easy operation, mild reaction conditions, a wide functionality tolerance, and high efficiency.

Dienylation of N-benzoylhydrazones with CF3-substituted homoallenylboronates in water.

A convenient method for the dienylation of N-benzoylhydrazones in water has been developed. This protocol expanded the synthetic application of functionalized homoallenylboronates to provide the useful 2-aminomethyl-1,3-diene derivatives with high efficiency (up to 99% yield) and stereoselectivity without using any catalyst, additive or inert atmosphere. Furthermore, the transformation of a 2-aminomethyl-1,3-diene derivative to synthesize a functionalized pyrrolidine derivative was also explored.

Synthesis of Structurally Diverse Allylsilanes via Copper-Catalyzed Regiodivergent Hydrosilylation of 1,3-Dienes.

Unprecedented copper-catalyzed regiodivergent hydrosilylation reactions of substituted 1,3-dienes with hydrosilanes have been developed. The 1,2- and 1,4-hydrosilylations of 1-(hetero)aryl-substituted 1,3-dienes were highly selectively controlled via variation of the catalytic systems. Meanwhile, the 1,4-hydrosilylation reaction of 2-aryl-substituted 1,3-dienes with diphenylsilane was also successfully realized for the first time. These methods provide convenient and efficient approaches for the synthesis of structurally diverse allylsilanes.

Copper-Catalyzed Chemoselective Silylative Cyclization of 2,2'-Diethynylbiaryl Derivatives.

In this protocol, copper-catalyzed diverse silylative carbocyclization reactions of 2,2'-diethynylbiaryl derivatives with silaboronate were reported. Three new and novel types of domino reactions for the copper-catalyzed transformation of silaboronate were discovered. The corresponding cyclobuta[l]phenanthrene, bis((silyl)methyl)phenanthrene, and silyl-substituted exocyclic diene products were chemoselectively formed with high efficiency.

Synthesis of Enynic and Allenic Orthoesters via Defluoromethoxylation of 2-Trifluoromethyl-1,3-enynes.

In this protocol, the chemoselective defluoromethoxylation reactions of 2-trifluoromethyl-1,3-enynes were developed. The enynic and allenic orthoesters were selectively produced in good to excellent yields via multiple substitution processes under mild reaction conditions, respectively. The enynic orthoester products were proved capable of acting as efficient "platform molecules" to access various functionalized allenyl compounds.

miR-140 inhibits osteogenic differentiation of human periodontal ligament fibroblasts through ras homolog gene family, member A -transcriptional co-activator with PDZ-binding motif pathway.

Osteogenesis induced by mechanical stretch is the main factor affecting the orthodontic treatment. Due to the masticatory force transmitted by tooth, human periodontal ligament fibroblasts (hPDLFs) could enhance osteogenic differentiation, and remolding of periodontal. Therefore, in-depth study of hPDLFs osteogenic differentiation and its regulatory mechanism is helpful in the understanding of periodontal remolding promoted by orthodontic force. In the present study, 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide showed that miR-140 inhibited the viability of hPDLFs cells. Moreover, we provided evidence that miR-140 inhibited alkaline phosphatase (ALP) activity, Alizarin Red S (ARS) activity and the mRNA expression of osteogenesis associated genes, including ALP, runt-related transcription factor 2, collagen 1, and osteocalcin. Besides, double-luciferase reporter result demonstrated that Ras homolog gene family, member A (RhoA) was a downstream target gene of miR-140, and by inhibiting RhoA-transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway, miR-140 suppressed the osteogenesis differentiation of hPDLFs. Furthermore, overexpression of RhoA or TAZ promoted ALP activity, ARS activity and osteogenesis associated genes expression, which was inhibited by miR-140 mimics. Our findings not only provided a possible mechanism of hPDLFs osteogenic differentiation but also proposed the clinical application of miR-140 inhibitor to target RhoA-TAZ for orthodontic treatment.

Copper-Catalyzed Anti-Markovnikov Hydrosilylation of Terminal Alkynes.

A copper-catalyzed anti-Markovnikov hydrosilylation of alkynes with PhSiH3 was reported. This reaction represents a notable and efficient example on copper-catalyzed hydrosilylatioin of alkynes, which shows excellent recognition between the terminal and internal triple bonds. Various (hetero)aromatic and aliphatic substituted terminal alkynes underwent this reaction to afford the (E)-vinylsilanes in high yields and with excellent regioselectivity.

Catalytic Asymmetric Conjugate Protosilylation and Protoborylation of 2-Trifluoromethyl Enynes for Synthesis of Functionalized Allenes.

The Cu-catalyzed 1,4-protosilylation and protoborylation of trifluoromethyl-substituted conjugated enynes were developed to access functionalized homoallenylsilanes and homoallenylboronates. This protocol also provides a general method to synthesize optically active homoallenylsilanes and homoallenylboronates in moderate to excellent yields with high enantiomeric excess by using new designed chiral bisoxazoline ligands. Simultaneously, the transformations of homoallenylsilanes and homoallenylboronates were also explored to synthesize useful building blocks.