Cu-catalyzed regioselective diborylation of 1,3-enynes for the efficient synthesis of 1,4-diborylated allenes

Borylation of 1,3-enynes with bis(boronate)compounds often ends up with the formation of hydroborylated products,leaving the diborylation of 1,3-enynes for the formation of 1,4-diborylated allenes to be challenging.Herein,a copper-catalyzed chemo-,regio-,and stereo-selective diborylation of 1,3-enynes for the efficient construction of 1,4-diborylated allenes under base-free conditions was reported.A wide range of 1,3-enynes bearing various functional groups can participant in the reaction and afforded the corresponding 1,4-diborylated allenes in good to excellent yields,which was enabled by the protocol of Bpin to BF3K conversion.the borylcopper species was supposed to selectively attack the C-C triple bond of the 1,3-enynes.

Enantioselective synthesis of tetrasubstituted allenes via addition/arylation tandem reaction of 2-activated 1,3-enynes

We report the development of a new class of multifunctional chiral guanidine/Pd(0)catalyst system for 1,4-addition/arylation tandem reaction.A variety of tetra-substituted allenes were readily accessible from three-component“one-pot”transformations of acyclic or cyclic 2-activated 1,3-enynes,malonates and halobenzenes under mild reaction conditions.High levels of yield and enantioselectivity were achieved in the construction of stereogenic center and axis using readily available acyclic guanidineamides.The mechanistic studies suggest that the guanidine/Pd(0)collaboration has obvious synergism to both base-dominated conjugate addition,and Pd(0)-dominated Heck-type reaction.

Regiocontrolled Rh(Ⅲ)-catalyzed C-C coupling/C-N cyclization mediated by distinctive 1,2-migratory insertion of gem-difluoromethylene allenes:Reaction development and mechanistic insight

By developing gem-difluoromethylene allenes as viable partners,regiocontrolled Rh(Ⅲ)-catalyzed redoxneutral C-C coupling/C-N cyclization has been realized to build the pyridin-2(1H)-one motifs with the embedment of a Z-configured monofluoroalkene functionality,in which either(hetero)aromatic or vinylic amides were found to be compatible.Integrated experimental and computational mechanistic studies revealed that a tandem regioselective allene 1,2-insertion/β-H elimination/hydrogen transfer/oxidative addition/cyclization/cis-β-F elimination involving an unconventional Rh(Ⅲ)-Rh(I)-Rh(Ⅲ)catalytic cycle accounts for the established transformation.Through further FMO analysis and IGMH maps,a non-covalent weak interaction network between the gem-difluoromethylene part and the OPiv moiety was rationally defined for the unconventional and specific regioselectivity control.

Photoinduced Merging with Copper-or Nickel-Catalyzed 1,4-Cyanoalkylarylation of 1,3-Enynes to Access Multiple Functionalizatized Allenes in Batch and Continuous Flow

A three-component reaction of 1,3-enynes and cyclobutanone oxime esters in the presence of aryl boronic acids or organozinc reagents via the photoredox/copper or photoredox/nickel catalysis has been established.This redox-neutral 1,4-cyanoalkylarylation reaction has demonstrated mild condition,high catalytic reactivity and wide functional group compatibility,allowing access to a variety of functionalized tetra-substituted allene derivatives with high chemo-and regioselectivity.Moreover,using photocatalytic continuous flow technique to promote this process would result in increased yields(70%in flow vs.61%in batch),reduced reaction times(7 min in flow vs.6 h in batch),and easy scale-up(upgrade to gram scale),showcasing its potential as a synthetic platform.

Synthesis of Mono-fluoroallenes through Copper-Catalyzed Defluorinative Silylation of α,α-Difluoroalkylalkynes

A straightforward protocol for the synthesis of mono-fluorinated allenes via catalytic defluorinative silylation of the readily availableα,α-difluoroalkylalkynes with commercially available copper catalyst and phosphine ligand is described.A broad scope ofα,α-difluoroalkylalkynes were well accommodated and a gram-scale synthesis demonstrated the synthetic utility of this methodoglogy.

Construction of 3-Azabicyclo[3.1.0]hexane Backbone by the Reaction of Allenes with Allylamines via Tandem Michael Addition and Copper-Mediated Oxidative Carbanion Cyclization

Main observation and conclusion A facile synthetic method for the construction of 3-azabicyclo[3.1.0]hexane in the presence of copper catalyst system was developed.The reaction proceeds through Michael addition of allylamines with allenes followed by copper-mediated intramolecular oxidative carbanion 5-exo-trig radical cyclization,affording potential biologically active 3-azabicyclo[3.1.O]hexane derivatives in moderate to high yields(42%-85%).

人工真皮覆盖修复指端缺损的疗效

目的探讨人工真皮覆盖修复指端缺损的疗效。方法采用人工真皮覆盖修复25例指端缺损患者(30指)。记录创面愈合情况、瘢痕形成情况、指端感觉功能恢复情况。根据中华医学会手外科学会上肢部分功能评定试用标准评定手功能恢复情况,采用Michigan手概况调查表评定患者对术后手指的主观满意度。结果患者均获得随访,时间3~20个月。创面全部愈合,时间4~6(4.7±0.5)周。术后3个月,温哥华瘢痕量表(VSS)评分0~4(1.2±1.0)分,无明显瘢痕形成;两点辨别觉4~12(7.5±3.5)mm;指端感觉功能恢复情况:S4级10指,S3+级13指,S3级4指,S2级3指。术后3个月,手功能恢复情况:优24指,良4指,差2指;患者对术后手指的主观满意度:非常满意19指,满意9指,一般2指。结论采用人工真皮覆盖修复指端缺损操作简单,临床效果良好,尤其适合基层医院开展。

Palladium-catalyzed regioselective cascade reaction of carbon dioxide,amines and allenes for the synthesis of functionalized carbamates

A palladium-catalyzed regioselective three-component cascade reaction of carbon dioxide,amines and allenes has been developed,providing an expedient and practical method for the construction of a range of functionalized carbamates containing dihydrobenzofuran or indole moiety in moderate to excellent yields.The broad substrate scope,good functional group tolerance and excellent chemo-and regioselectivity are the features of the transformation.

TfOH/Fe（OTf）3 Cocatalyzed Reaction of Arylallenes with Alcohols for Structurally Diverse Indene Derivatives

The indene moiety is an important unit because of its presence in many chemical catalysts, functional materials and biologically relevant molecules. Herein, we report a facile reaction of arylallenes with benzylic or allylic alcohols through TfOH/Fe（OTf）3 cocatalyzed cleavage of sp3 carbon-oxygen. In the presence of 5 mol% TfOH and 5 mol% Fe（OTf）3, a range of arylallenes undergo carbocation initiated cyclization reaction with alkyl alcohols to give structurally diverse polysubstituted indenes in good to excellent yields. H2O is the sole byproduct that makes this transformation highly atom-economic and environmentally benign.

Trace amount of single-atom palladium-catalyzed selective hydrosilylation of allenes

Using fewer catalysts to promote the chemical conversion of more substrates is the dream synthesis pursued by synthetic chemists.Achieving highly selective reactions using trace amounts(<1 ppm)of catalysts is rare and has undoubted practical value.Herein,we designed and synthesized a single-atom Pd-metalated porous organic ligand polymer,denoted as Pd1@POL,and used the polymer to realize the regioselective hydrosilylation of allenes(Pd loading was as low as 0.98 ppm).The synergistic effect of the dispersed catalytic active sites in the catalyst and supports with ligand regulation function can directionally realize the formation of specifically configured hydrosilylation products.The as-fabricated single-atom catalyst(SAC;i.e.,Pd1@POL-5)showed an amazing catalytic efficiency and selectivity for hydrosilylation of allene(turnover number was up to 772,358,which was 200 times higher than previously recorded,and regioselectivity>100:1).The catalyst could be recycled numerous times in a continuous flow system without reductions in activity and selectivity.This work demonstrated the application prospect of the SAC in the synthesis of complex organic compounds and trace amount catalysis,which can lay the foundation for its large-scale and industrialized application in drug synthesis and other fields.

Cu/Pd-catalyzed borocarbonylative trifunctionalization of alkynes and allenes:synthesis ofβ-geminal-diboryl ketones

Functionalized bisboryl compounds have recently emerged as a new class of synthetically useful building blocks in organic synthesis.Herein,we report an efficient strategy to synthesizeβ-geminal-diboryl ketones enabled by a Cu/Pd-catalyzed borocarbonylative trifunctionalization of readily available alkynes and allenes.This reaction promises to be a useful method for the synthesis of functionalizedβ-geminal-diboryl ketones with broad functional group tolerance.Mechanistic studies suggest that the reaction proceeds through borocarbonylation/hydroboration cascade of both alkynes and allenes.

Stereoselective fluoroarylation of 1,1-difluoroallenes enabled by palladium catalysis

A novel protocol for palladium-catalyzed fluoroarylation of 1,1-difluoroallenes was described here.The reaction proceeded smoothly under mild condition and various trifluoromethylated alkenes were obtained in moderate yields with excellent E selectivity.The mechanism involving a vital trifluoromethylated vinyl silver intermediate,which generated through the F-nucleophilic addition to 1,1-difluoroallenes,has been proposed.

Synthesis of α-tertiary allylsilanes by palladium-catalyzed hydrosilylation of 1,1-disubstituted allenes

We herein report an effective hydrosilylation of 1,1-disubstituted allenes with a palladium catalyst modified by a monophosphorus ligand,leading to a series ofα-tertiary allylsilanes in high yields and exceptional regiose-lectivities.The employment of BI-DIME is essential for the high reactivities and selectivities.A chiralα-tertiary allylsilane is formed in excellent ee for the first time by employing a chiral monophosphorus ligand.

Catalytic Enantioselective Simultaneous Control of Axial Chirality and Central Chirality in Allenes

Chiral molecules, which may contain one or more different type（s） of stereocentres, such as central, axial, planar, and helical chiralities, etc., are indispensable in chemistry, pharmaceutical industry, and life science. Despite many advances for the preparation of chiral molecules usually with a single type of chirality have been realized, simultaneous construction of different types of chiralities is still a significant challenge. Here, we wish to report a protocol for preparation of chiral allenes with both central and axial chiralities via a catalytic asymmetric allenylation of different biologically or syn- thetically useful fluorinated or non-fluorinated nucleophiles with readily available racemic allenes by using a single chiral ligand. An echoing between the central chirality and axial chirality for the enantioselectivity was observed. This strategy provides a general and practical approach to functionalized optically active allenes bearing both central and axial chiralities with an excellent enantioselectivity under mild conditions.

Rh/Lewis Acid Catalyzed Regio-, Diastereo- and Enantioselective Addition of 2-Acyl Imidazoles with Allenes

A highly regio-, diastereo- and enantioselective addition of 2-acyl imidazoles or 2-acyl pyridines with allenes promoted by Rh/Lewis acid synergistically catalytic system is described. This atom economic approach leads to the formation of the branched allylic alkylated products including acyclic quaternary all-carbon stereogenic centres in good yields with good to excellent diastereo- and enantioselectivities. Kinetic studies reveal that the rate-determining step in this process is the oxidative addition of Rh（I） with C H bond.

Recent advances of allenes in the first-row transition metals catalyzed C-H activation reactions

Transition-metal-catalyzed C–H activation reaction has proven to be a powerful and efficient tool for the formation of diverse C-C and C–X bond and construction of functional complex molecules.From the viewpoint of sustainable chemistry,the first-row transition metals,such as Mn,Fe,Co,Ni and Cu,have been recognized as cheap,environmentally friendly and reactively effective catalysts for a number of C-H functionalization reactions.However,compared with the commonly used alkenes and alkynes in the first-row transition-metal-catalyzed C–H activations,considerable achievements have just been made by the use of structurally unique and reactively rich allenes as coupling partners in recent years.This review summarizes the recent progress of the first-row transition-metal-catalyzed C–H activations with allenes.

Cycloadditions of 1-iminylphosphirane complexes with allenes

A cascade carbonylative ring expansion and [2+2]/[4+2] cycloaddition of strained 1-iminylphosphirane complexes with aryl allenes were reported.The carbonylative ring expansion of 1-iminylphosphirane complexes provides an azaphosphacyclohexone complex intermediate with a C=P double bond.The following [2+2] or dearomatic [4+2] cycloaddition of this intermediate with allenes is modulated by the aryl substituents on the imino carbon.The regioselective [2+2] cycloaddition with 1,1-diarylallene provides an entry to bicyclo[4.2.0]octan-4-one skeletons featuring a four-membered phosphacyclobutane moiety.While dearomatic [4+2] cycloaddition was preferred with less aromatic naphthalene and yielded octahydrochrysene skeleton containing heteroatoms.

Mechanism of Silver（I）-Catalyzed Enantioselective Synthesis of Axially Chiral Allenes Based on Propargylamines

The silver（1）-catalyzed synthesis picture of axially chiral allenes based on propargylamines has been outlined using density functional theory （DFT） method for the first time. Our calculations find that, the coordination of sil- ver（I） into triple bond of propargylamines at anti-position of nitrogen shows a stronger activation on the triple bond than that at cis-position, which is favorable for the subsequent hydrogen transfer. The NBO charge analysis for the hydrogen transfer affirms the experimental speculation that this step is a hydride transfer process. The energy bar- rier of the anti-periplanar elimination of vinyl-silver is 26.9 kJomol l lower than that of the syn-periplanar elimina- tion, supporting that （--）-allene is the main product of this reaction. In a word, the most possible route for this reac- tion is that the silver（I） coordinates into the triple bond of propargylamines at anti-position of nitrogen, then the formed silver（I） complex undergoes a hydride transfer to give a vinyl-silver, finally the vinyl-silver goes through an anti-periplanar elimination to give （--）-allene. The hydride transfer with the energy barrier of 44.8 kJ.mol-1 is the rate-limiting step in whole catalytic process. This work provides insight into why this reaction has a very high enan- tioselectivity.

指脉氧监测下的Allen试验与经典Allen试验的一致性研究

目的:探讨指脉氧监测下的Allen试验与经典Allen试验结果的一致性。方法:选取2018年3月—2019年10月于我院心脏内科住院的病人5148例,先后采用指脉氧监测下的Allen试验与经典Allen试验对病人双手进行评估。结果:与经典Allen试验相比,双侧指脉氧监测下的Allen试验用时较短(P<0.001),且阴性率更高(右手:0.68%与0.64%,P<0.001;左手:0.51%与0.45%,P<0.001)。两试验的结果存在一致性,左手5148个点中有21个点(0.41%)位于一致性界限范围以外,右手5148个点中有23个点(0.45%)位于一致性界限范围以外。对试验耗时进行受试者工作特征(ROC)曲线分析,二者判读时间节点相似(右手:曲线下面积为0.781,截断点10 s;左手:曲线下面积0.833,截断点9.5 s或10.5 s)。结论:指脉氧监测下的Allen试验与经典Allen试验的判读时间节点及结果均存在一致性,但前者的判读更为直观迅速,可作为一种无创、易得、经济有效的改良方法。

Stereoselective Access to Polypropionates Expedited by the Double Hydroboration of Allenes: Total Synthesis of Antitumor (−)-Pironetin

Polyketides,a large class of secondary metabolites,have been of long-standing interest to the synthetic community due to their intriguing biological activities and structural versatility and complexity.A typical structural unit of various natural products,polypropionate,has prompted enormous efforts in the development of novel synthetic methods and strategies in the past five decades.In this study,a non-aldol-type approach based on double hydroboration of allenes has been developed to provide a powerful method for the stereodivergent construction of various polyol stereotriads and stereotetrads that are amenable for synthesizing polypropionates.The stereochemical control is possibly attributable to the boronate complex that aligned itself as a rigid conformation for the second stereoselective hydroboration reaction by suppressing the barotropic rearrangement of allylborane intermediates.The feasibility of preparing the key polypropionate motif facilitates the efficient synthesis of(-)-pironetin,a potentα-tubulin inhibitor halting the cell cycle at M phase.