Remote Stereocontrol of All-Carbon Quaternary Centers via Cobalt-Catalyzed Asymmetric Olefin Isomerization

Asymmetric olefin isomerization has become a powerful tool for positional migration of C=C double bonds to afford valuable chiral olefins.However,the synthesis of optically active all-carbon quaternary stereocenters via this strategy is still rare.Herein,we report a cobaltcatalyzed desymmetric olefin isomerization to access 1-methylcyclohexenes bearingβ-quaternary stereocenters in a chemo-,site-,and stereoselective fashion.Preliminary mechanistic studies have revealed the Co-H insertion/β–Helimination reaction pathway and the origin of remote stereocontrol of all-carbon quaternary centers.The gram-scale synthesis and stereoretentive transformations of spirocyclic products demonstrate the synthetic utility of this reaction.

The xanthate route to all-carbon quaternary centers

This review discusses the numerous routes to all-carbon quaternary centers based on the unique radical chemistry of xanthates. Itsummarizes the various approaches to the synthesis of tertiary xanthates then describes the intra- and intermolecular radicaladditions and combinations thereof that have so far been used to construct quaternary centers.

Construction of remote cyano-substituted quaternary carbon centers via nickel-catalyzed migratory hydrocyanation of unconjugated dienes

The transition-metal-catalyzed migratory functionalization has emerged as a robust protocol for the building of C–C bonds remote from the“initiation”position.However,a similar strategy for the construction of quaternary carbon centers is still underdeveloped and only a limited number of reports exist.Herein,we report a nickel-catalyzed migratory hydrocyanation of unconjugated dienes to construct remote cyano-substituted quaternary carbon centers.This transformation features exceptional regioselectivity,mild reaction conditions,broad substrate scope and high yields.The synthetic utility of this method has been highlighted by a series of product derivatizations,and the potential of this transformation has been extended to synthesize TRPV1 antagonist and the key intermediate in the total synthesis of quebrachamine.Density functional theory(DFT)studies unveiled that the specific catalytic pocket assumed a significant role in the selective formation of cyano-substituted quaternary carbon centers.

Ni-Catalyzed Enantioselective Difunctionalization of Alkynes to Azepine Derivatives Bearing a Quaternary Center and an Unprotected Imine

Comprehensive Summary,The azepine ring is a prominent structural scaffold in biologically significant molecules. In this study, we present a Ni(II)-catalyzed asymmetric difunctionalization of alkynes, involving intermolecular regioselective arylation and intramolecular nitrile addition, enabling the synthesis of enantioenriched azepine derivatives. This reaction simultaneously installs an all-carbon quaternary stereocenter and introduces an unprotected imine functionality, showing great promise for subsequent transformations. The reaction exhibits good tolerance toward various functional groups, resulting in high yields and enantioselectivities. The synthetic utility of this methodology is further demonstrated through gram-scale synthesis and product derivatization. This research offers an efficient approach to the synthesis of seven-membered nitrogen heterocycles.

I_(2)-DMSO-Mediated Multicomponent [2+1+1+1] Annulation Reaction via Ethyl Nitroacetate C-NO_(2), Bond Cleavage as a C1 Synthon: A Route to Multisubstituted β-Pyrrolidinones Derivatives with a Quaternary Center

A[2+1+1+1]cyclization reaction has been developed for the synthesis of multisubstituted 6-pyrrolidinones from commercially available aryl methyl ketones,primary amines,and ethyl nitroacetate.In this I_(2)-DMSO-meditated process,the C-NO_(2) bond of ethyl nitroacetate is cleaved,affording a C1 synthon,and the formation of two C-C and two C-N bonds and a quaternary carbon center are constructed in one pot.This method has good substrate compatibility and permits the late-stage modification of pharmaceutical compounds.

Construction of highly congested quaternary carbon centers by NHC catalysis through dearomatization

A NHC-catalyzed hypervalent iodine reagents and transition-metal free redox-neutral dearomatization of phenols is reported.This protocol provides an efficient access for highly congested quaternatry carbon centers construction.It also features operationally simplicity,mild reaction conditions and good functional group tolerance.Moreover,the reported procedure can be easily emplified to 1 g scale.Mechanism study reveals the dearomative transformation possibly undergoes a single electron transfer process with NHC radical cation as a reactive intermediate.

Asymmetric construction of all-carbon quaternary stereocenters in the total synthesis of natural products

Structure units containing all-carbon quaternary stereogenic center are found in many bioactive natural products. However, enantioselective construction of this type of structure units has been a formidable challenge for synthetic community due to the steric hindrance enforced by all-carbon quatemary stereocenters. In this review, we present the achievements made by Chinese scientists in the area of asymmetric synthesis of all-carbon quaternary stereocenters in natural products during the past two years.

Highly enantioselective construction of CF_(3) -bearing all-carbon quaternary stereocenters: Chiral spiro-fused bisoxazoline ligands with 1,1'-binaphthyl sidearm for asymmetric Michael-type Friedel-Crafts reaction

A novel class of chiral spiro-fused bisoxazoline ligands possessing a deep chiral pocket was prepared.The developed ligands have been employed in the nickel-catalyzed highly enantioselective Michael-type Friedel-Crafts reaction, affording the products bearing a trifluoromethylated all-carbon quaternary stereocenter with moderate to excellent yields(up to 99%) and good to excellent enantioselectivies(up to> 99.9% ee). Moreover, a proposed model of chiral pocket revealed that the attack of indole from the Re-face of β-CF_(3)-β-disubstituted nitroalkene was favorable.

Copper-catalyzed tandem radical amination/1,2-carbon migration of allylic alcohols: Direct access to α-quaternary-β-amino ketones

A novel nitrogen‐centered radical‐induced1,2‐carbon migration reaction of allylic alcohols has been developed.This method provides easy access to a variety ofα‐quaternary‐β‐amino ketones under mild reaction conditions.The reaction has a wide substrate scope and operational simplicity.Mechanistic studies suggest that1,2‐carbon migration is induced by regioselective nitrogen‐centered radical addition to the alkene unit.?2018,Dalian Institute of Chemical Physics,Chinese Academy of Sciences.Published by Elsevier B.V.All rights reserved.

Nickel-Catalyzed Enantioselective C(sp^(3))–H Arylation of Ketones with Aryl Ethers via Selective C_(Ar)–O Cleavage to Construct All-Carbon Quaternary Stereocenters

We designed thenickel-catalyzed enantioselective C(sp^(3))–H arylation of ketones with phenol-derived aryl pyrimidyl ethers via selective cleavage of the C(aryl)–O bond to construct all-carbon quaternary stereocenters.This method exhibits good functional group compatibility and broad substrate scope.Drug molecule donepezil can directly transform into corresponding highly optically pure derivatives with this developedmethodology.Mechanistic studies reveal that C(aryl)–O cleavage of aryl pyrimidyl ether probably proceeded by means of an anionic organo-Ni(0)intermediate.

Pentanidium-Catalyzed Direct Assembly of Vicinal All-Carbon Quaternary Stereocenters through C(sp^(3))–C(sp^(3))Bond Formation

The stereoselective construction of vicinal all-carbon quaternary stereocenters has long been a formidable synthetic challenge.Direct asymmetric coupling of a tertiary carbon nucleophile with a tertiary carbon electrophile is themost straightforward approach,but it is sterically and energetically disfavored.Herein,we describe a catalytic asymmetric substitution,where racemic tertiary bromides coupled directly with racemic secondary or tertiary carbanion.

Brønsted acid-catalyzed 1,6-hydrophosphination of propargylic para-quinone methides and aza-para-quinone methides for the rapid construction of phosphorus-substituted quaternary carbon centers

An intriguing Brønsted acid-catalyzed 1,6-hydrophosphination of in situ generated propargylic para-quinone methides(p-QMs)and aza-para-quinone methides(aza-p-QMs)with H-phosphorus oxides via dehydration/1,6-addition under ultrasonic irradiation is described.This methodology provides a rapid and green approach for the construction of diarylmethyl phosphorus oxides bearing phosphorus-substituted quaternary carbon centers in high yields(up to 98%yield)within merely 5min.This environmentally benign protocol represents a unique example of 1,6-conjugate additions of propargylic p-QMs and aza-p-QMs for site-selective C-P bond formation in an operationally simple and atom-economical manner.The use of readily available Brønsted acid catalyst,operationally simplicity,high yields,and high atom economy make this protocol very facile,practical,easily scaled-up and environmentally friendly.

Construction of quaternary carbon centers by KOtBu-catalyzed α-homoallylic alkylation of lactams with 1,3-dienes

We report a KOtBu-catalyzed α-homoallylic alkylation of lactams with 1,3-dienes. With this transitionmetal-free and atom-economical protocol, a variety of α-homoallylic alkylated lactams bearingα-quaternary carbon centers were formed in a 2,1-addition manner with excellent regioselectivity. Acation–π interaction between the in situ-generated potassium enolate and the diene is proposed to play akey role in accelerating this transformation.

第四纪沉积物ESR年代学研究进展

在缺少第四纪火山活动的区域,沉积物成为第四纪地质构造和地貌、环境演化等方面研究的主要年代学测量对象。对于老于200ka的沉积物,电子自旋共振(ESR)是潜在的测量方法之一。ESR信号中心会在光晒退或热事件的作用下衰减或"回零"。对于第四纪沉积物而言,在最后一次埋藏事件发生之前,只存在阳光晒退作用,因此了解各ESR信号中心的光晒退特征是准确测量其年代的关键问题。文中简单介绍了ESR测年方法的理论基础,以及剂量率(D)和等效剂量(ED)的测量方法,总结了各ESR信号中心的光晒退特征,回顾了它们在地质年代学中的应用。对各信号中心的光晒退特征和应用的对比表明,石英Ti心ESR信号比较适合第四纪沉积物年代学测量,是第四纪沉积物年代学研究的又一有效手段。

塔里木盆地腹地第四纪沉积物粒度特征及其沉积环境

利用MS-2000型激光粒度仪及相关软件,对位于塔里木盆地腹地的塔中KT2号钻孔进行粒度测试与分析,绘制频率曲线图、概率累计曲线图等,结合其他测试数据、资料,进行沉积环境分析。结果表明塔里木盆地在早更新世以河湖相沉积为主,其晚期出现了风成相沉积;中更新世早期以洼地湖泊相沉积为主,但风成相沉积作用明显加强,至中更新世晚期,发展成为以风成相为主,经晚更新世到全新世,沙漠大规模形成,并逐步发展。气候总体由温暖湿润变为寒冷干旱。

泥河湾盆地东坡遗址ESR年代学初步研究

中国泥河湾盆地以发育我国北方晚新生代湖相地层和数目众多的古人类文化遗址而闻名于世，是研究中国北方第四纪地质与环境、新旧石器和早期人类演化的一个关键地区。东坡遗址是泥河湾遗址之一，形成时代一直没有确定。根据古地磁和区域地质等分析，初步认为东坡遗址形成时代不早于距今780ka。本文利用石英Ti心ESR法对泥河湾东谷坨剖面B／M界限样品进行了测量，年龄为750±88ka，这表明利用该方法对泥河湾层水相沉积物进行测年是可行的。我们利用同样方法和参数对东坡遗址进行ESR年代学研究，结果表明东坡遗址文化层的形成时代为距今304±12ka到333±23ka，平均年龄为321±15ka。

ESR测年技术在第四纪冰川年代学中的研究综述

近些年，宇宙成因核素暴露年代、光释光和放射性碳埋藏年代等方法在第四纪冰碛物的年代测定中已经取得显著进展．但对于第四纪冰川沉积物10万年甚至百万年以上的冰碛物样品的埋藏年代和暴露年代，由于方法自身问题或沉积物后期地质地貌过程的改造，使上述方法存在定年方面的挑战．而电子自旋共振（ESR）广泛的测年范围，使其在第四纪样品的测年中发挥着不可替代的作用．目前，石英ESR信号的衰退特征已有许多研究进展，但是对于冰碛物中的ESR信号的研究还很少．ESR测年方法由于缺乏测年机理的研究，西方学者和国内一些测年学者对这种方法的定年存有疑虑．因此，我们在典型冰川区开展对冰碛物中石英砂ESR信号变化的机理研究，得到人工研磨可以使ESR信号强度下降到原来值的53％～69％，但并不能使ESR信号完全归零．如果在以后的研究中能够找出这些残留信号值大小，并予以扣除，将会大大提高ESR冰碛物测年精度．在今后的研究中应探求其测年机理，提高测试样品的石英纯度，增强ESR测年信号的精度，使这种方法成为冰碛物交叉测年中独立可信的测年方法之一，为第四纪冰川研究中的老冰碛物的定年提供准确的年代依据．

含季碳中心环状氨基原甲酸酯类化合物的非对映选择性合成

目的通过简单快速的方法,在温和反应条件下,高非对映选择性地制备合成了一类含季碳中心且具有环状骨架的氨基原甲酸酯类化合物。方法以2-氨基-3-氰基取代吡喃类化合物为原料,通过醋酸碘苯促进的氧化重排反应,合成出一系列具有并环结构的α-氨基原甲酸酯类化合物。经过条件筛选,确定了最佳反应条件为:在室温下以乙醇作为反应溶剂,醋酸碘苯(1.1倍)作为氧化剂,反应浓度为0.1mol/L。在该反应条件下,通过简单的过滤和洗涤就能够分离得到相关目标产物。结果在确定的最优条件下,合成了一系列具有不同电子效应、位阻效应的结构类似物,分离收率最高可达92%,非对映选择性最高可达>95:5d.r.,所有目标产物均通过核磁共振和高分辨质谱等分析方法确定结构。最后,本文提出了该化学转化可能的反应机理。结论具有环状骨架的原甲酸酯是一类富有多种潜在生理活性的有机小分子化合物,对于这类物质的合成方法研究已经成为药物化学及有机合成的热点方向之一。通过本研究找到了一种温和、实用的方法对这类化合物进行快速制备合成,该合成策略为开发具有创新化学骨架的药物,特别是抗生素类药物提供了新的思路。

α-取代内酯的立体选择硝基乙烯化反应研究

研究了α-取代内酯的立体选择硝基乙烯化反应.从金属离子对反应时间、温度及产率的影响实验中发现，Zn2+增加了反应活性．用1HNMR光谱确定了产物双键的立体构型，并初步探讨了反应历程．

三种消毒剂对体检中心物体表面消毒效果与使用成本的比较研究

目的对3种消毒剂在体检中心物体表面消毒的消毒效果及使用成本进行比较,为体检中心优选合适的物体表面消毒方式提供依据。方法分别使用I型复合双链季铵盐卫生湿巾、500mg/L含氯消毒剂、75%乙醇擦拭消毒健康体检中心采血台、彩超机和乳腺红外线诊断仪的表面,在消毒前、消毒后即刻、消毒后30min及1h分别对各区域进行棉拭子涂抹采样及培养。结果受检物体表面细菌菌落数采血台为(78.4±6.2)cfu/cm2,彩超机为(36.2±2.1)cfu/cm2,乳腺红外线诊断仪为(45.9±3.0)cfu/cm2。3种消毒剂消毒后各时间点采样菌落数与消毒前比较,差异有统计学意义(均P<0.01)。I型复合双链季铵盐卫生湿巾消毒效果在消毒后即刻、消毒后30min及1h优于500mg/L含氯消毒剂、75%乙醇(P<0.05,P<0.01);每次消毒成本I型复合双链季铵盐卫生湿巾最低。结论 3种消毒剂对各监测表面均有良好的消毒效果,但I型复合双链季铵盐卫生湿巾的消毒持续效果优于其他两种,且使用成本低,使用方便、侵蚀性小,适用于体检中心物表消毒。