CN113214069B - 一种手性10-炔丙基蒽酮类化合物及其合成方法 - Google Patents

一种手性10-炔丙基蒽酮类化合物及其合成方法 Download PDF

Info

Publication number
CN113214069B
CN113214069B CN202110381524.XA CN202110381524A CN113214069B CN 113214069 B CN113214069 B CN 113214069B CN 202110381524 A CN202110381524 A CN 202110381524A CN 113214069 B CN113214069 B CN 113214069B
Authority
CN
China
Prior art keywords
propargyl
chiral
alkyl
copper
compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202110381524.XA
Other languages
English (en)
Other versions
CN113214069A (zh
Inventor
徐浩
黄健
李聃冉
郑一诺
向华明
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Central China Normal University
Original Assignee
Central China Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Central China Normal University filed Critical Central China Normal University
Priority to CN202110381524.XA priority Critical patent/CN113214069B/zh
Publication of CN113214069A publication Critical patent/CN113214069A/zh
Application granted granted Critical
Publication of CN113214069B publication Critical patent/CN113214069B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/657—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings
    • C07C49/683—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings having unsaturation outside the aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/22—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/687—Unsaturated compounds containing a keto groups being part of a ring containing halogen
    • C07C49/697—Unsaturated compounds containing a keto groups being part of a ring containing halogen containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
    • C07C49/747—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
    • C07C49/755—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups a keto group being part of a condensed ring system with two or three rings, at least one ring being a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/94—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of polycyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
    • C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/40—Radicals substituted by oxygen atoms
    • C07D307/46—Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/22—Ortho- or ortho- and peri-condensed systems containing three rings containing only six-membered rings
    • C07C2603/24—Anthracenes; Hydrogenated anthracenes

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

本发明涉及有机合成领域，提供了一种手性10‑炔丙基蒽酮类化合物及其不对称合成方法。该手性10‑炔丙基蒽酮类化合物为重要有机合成中间体9(10H)‑蒽酮或临床药物地蒽酚类衍生物，具有重要的有机合成价值和潜在的生物药理活性，对于有机合成方法学或高活性药物的筛选和研发均具有较高的借鉴和参考意义。其合成方法是过渡金属催化的蒽酮类化合物10号位置的不对称炔丙基烷基化反应。该反应在有机溶剂中，仅需以5mol％手性P,N,N‑配体与廉价绿色的金属Cu形成的络合物为催化剂，在温和的反应条件下高产率、高对映选择性的得到10‑炔丙基蒽酮类化合物。此外，本发明的制备方法环境友好性高，适用取代基范围广，操作简便。

Description

一种手性10-炔丙基蒽酮类化合物及其合成方法
技术领域
本发明涉及有机合成技术领域，更具体而言，涉及一种手性10-炔丙基蒽酮类化合物及其合成方法。
背景技术
蒽酮及其衍生物是众多天然产物和药物分子的结构母体，在有机合成和药物化学领域中扮演着至关重要的角色。许多蒽酮衍生物开始被陆续发现具有抗癌、抗菌、消炎、提高免疫力、抑制端粒酶以及抑制细胞增殖等作用，因此新型蒽酮衍生物尤其是新型手性蒽酮类衍生物的合成对于有机合成和药物开发都具有重要的应用价值。
当前蒽酮参与的不对称催化反应主要是有机小分子催化的Diels-Alder反应和Michael加成反应。过渡金属催化的蒽酮衍生物的不对称催化合成仅有两例报道。因此发展一类过渡金属催化的通过不对称炔丙基取代反应合成蒽酮衍生物具有重要的理论意义和现实意义。传统方法合成10-炔丙基蒽酮类化合物需要将蒽酮与炔丙基卤化物在强碱作用下回流，该方法不仅产率较低，同时会产生蒽醌类化合物副产物，且无法做到手性合成。因此，发展一类高效的方法合成10-炔丙基蒽酮类化合物是亟需解决的问题。
发明内容
本发明提供一种手性10-炔丙基蒽酮类化合物及其合成方法，以解决传统合成方法产率较低、产生蒽醌类化合物副产物以及无法做到手性合成等问题。
为解决上述技术问题，本发明提供了以下技术方案：
本发明一方面提供了一种手性10-炔丙基蒽酮类化合物，所述手性10-炔丙基蒽酮类化合物具有以下两种结构之一：
Figure GDA0003621746060000011
所述式Ⅰ和所述式Ⅱ互为对映异构体，在所述式Ⅰ和所述式Ⅱ中，R1选自C1-C40的烷基、C3-C12的环烷基、带有取代基的C3-C12的环烷基、苯基、取代苯基、苄基、取代苄基、含一个或二个以上杂原子取代的五元或者六元杂环芳香基团或者酯基中的任意一种；R2、R3分别独立地为氢、卤素、羟基、氰基、含有1-20个碳原子的饱和或不饱和烷基、取代或未取代C6-C60芳基、或者含有一个或二个以上杂原子取代或未取代的五元至六十元杂环芳香基团；所述杂原子为氧原子、硫原子、或者氮原子。
优选的，所述C3-C12的环烷基上的取代基、所述苯基上的取代基及所述苄基上的取代基选自C1-C40的烷基、C1-C40的烷氧基、卤素、硝基、酯基、氰基中的至少一种。
优选的，所述手性10-炔丙基蒽酮类化合物具有以下结构之一：
Figure GDA0003621746060000031
Figure GDA0003621746060000041
Figure GDA0003621746060000051
本发明另一方面提供了一种手性10-炔丙基蒽酮类化合物的合成方法，所述合成方法包括：
在碱性添加剂存在下，以手性铜催化剂在第一反应介质中催化炔丙基类化合物与蒽酮类化合物发生不对称炔丙基烷基化反应，得到如上所述的手性10-炔丙基蒽酮类化合物；
其中，控制所述不对称炔丙基烷基化反应的反应温度为-78℃～200℃，所述第一反应介质为质子性溶剂、非质子性溶剂、或者质子性与非质子性混合溶剂；
其中，制备所述手性铜催化剂的方法包括：在惰性气体保护下，将铜盐和手性P,N,N-配体混合于第二反应介质中，在室温下搅拌0.5～2h；
所述手性P,N,N-配体的结构式如式L所示：
Figure GDA0003621746060000061
在所述式L中，R5为C1-C10烷基、C3-C8环烷基、苯基、取代苯基、苄基或者取代苄基中的任意一种；
R4，R6分别独立地为C1-C10烷基、C3-C8环烷基、苯基、取代苯基、萘基、取代萘基、或含一个或多个杂原子取代的五元或六元杂环芳香基团，所述杂原子选自氧、硫、氮原子中的任意一种；
R7为氢、卤素、C1-C10烷基、C3-C8环烷基、苯基、取代苯基、烷氧基、苯氧基、酰基或硝基中的任意一种；
所述R5中取代苯基及取代苄基、所述R4和R6中取代苯基及取代萘基、所述R7中取代苯基上的取代基为C1-C40烷基、C1-C40烷氧基、卤素、硝基、酯基或氰基中的至少一种。
优选的，所述手性P,N,N-配体的结构式具有如下结构式之一：
Figure GDA0003621746060000062
和/或
所述铜盐选自水合醋酸铜、水合硫酸铜、无水醋酸铜、无水硫酸铜、三氟甲磺酸铜、氯化铜、氯化亚铜、碘化亚铜、醋酸亚铜、六水合高氯酸铜、三氟甲磺酸亚铜合苯、六氟磷酸四乙腈铜、四氟硼酸四乙腈铜、或者高氯酸四乙腈铜中的任意一种或者多种的组合；所述反应介质为甲醇、乙醇、二氯甲烷、甲苯、乙腈、二甲苯、氟苯、氯苯、四氢呋喃中的任意一种或者多种的组合。
优选的，所述铜盐和所述手性P,N,N-配体的摩尔比为1:0.1～1:10。
优选的，所述炔丙基类化合物的结构式如式Ⅲ中所示：
Figure GDA0003621746060000071
所述式Ⅲ中，R1为上述所限定的，LG选自F、Cl、Br、I、烷基羧酸酯、烷基碳酸酯、烷基磺酸酯、烷基磷酸酯、苯基、取代苯基碳酸酯、取代苯基羧酸酯、取代苯基磺酸酯或者取代苯基磷酸酯；所述烷基羧酸酯、所述烷基碳酸酯、所述烷基磺酸酯以及所述烷基磷酸酯中的烷基为C1-C40烷基或C3-C12的环烷基；所述取代苯基羧酸酯、所述取代苯基碳酸酯、所述取代苯基磺酸酯以及所述取代苯基磷酸酯中苯基上的取代基为C1-C40烷基、C1-C40的烷氧基、卤素、硝基、酯基或氰基中的至少一种；和/或
所述蒽酮类化合物的结构式如式Ⅳ中所示：
Figure GDA0003621746060000072
所述式Ⅳ中，R2和R3为如上所限定的；和/或
所述碱添加剂选自N,N-二异丙基乙胺、三乙胺、叔丁醇钾、氢氧化钾、氢氧化钠、碳酸钠、碳酸氢钠或者碳酸钾中的至少一种；和/或
所述第一反应介质为包含无水甲醇和无水甲苯的混合溶液，所述混合溶液中，所述无水甲醇和所述无水甲苯的体积比为2:1～5:1。
优选的，所述碱添加剂的摩尔用量为所述炔丙基类化合物的摩尔用量的0.01～10倍；和/或
所述手性铜催化剂的摩尔用量为所述炔丙基类化合物的摩尔用量的0.01～100倍。
优选的，控制所述不对称炔丙基烷基化反应的反应温度为-20℃～0℃。
优选的，所述合成方法还包括：在不对称炔丙基烷基化反应结束后，减压去除反应介质，然后采用硅胶柱层析分离技术进行提纯。
与现有技术相比，本发明提供的手性10-炔丙基蒽酮类化合物为重要有机合成中间体9(10H)-蒽酮或临床药物地蒽酚类衍生物，具有重要的有机合成价值和潜在的生物药理活性，对于有机合成方法学或高活性药物的筛选和研发均具有较高的借鉴和参考意义。本发明提供的手性10-炔丙基蒽酮类化合物合成方法为首次利用手性铜催化剂催化的炔丙基类化合物和蒽酮类化合物的不对称炔丙基取代反应，高对映选择性的合成了10-炔丙基蒽酮类化合物，为10-炔丙基蒽酮类化合物的合成提供了一条环境友好、操作简便、条件温和、价格低廉、对映选择性高的合成路线。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白，下面结合具体实施例对本发明作进一步详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。实施例中未注明具体技术或条件的，按照本领域内的文献所描述的技术或条件或者按照产品说明书进行。所用试剂或仪器未注明生产厂商者，均为商业可得的常规产品。
为实现合成如结构式Ⅰ、Ⅱ所示的手性10-炔丙基蒽酮类化合物，本发明以铜盐和手性P,N,N-配体形成的配合物为催化剂，催化炔丙基类化合物与蒽酮类化合物发生不对称炔丙基烷基化反应，具体合成技术方案如下：
Figure GDA0003621746060000081
其中，将催化反应的反应温度设置在-78℃～200℃范围，优选设置在-40℃～25℃范围，更优选设置为-20℃～0℃，更具体的，优选设置为-20℃或者0℃。反应介质选自质子性溶剂、非质子性溶剂、或者质子性与非质子性混合溶剂；优选为包含无水甲醇与无水甲苯的混合溶液，其中无水甲醇与无水甲苯的体积比为3:1。优选将反应压力设置在0～100个大气压值，更优选设置为常压。控制反应时间大于0.1h，优选反应时间为68-76h，更优选为72h。
在该技术方案中，碱添加剂选自任何合适的有机碱或无机碱，控制碱添加剂的摩尔用量为炔丙基类化合物(Ⅲ)的摩尔用量的0.01～10倍，优选为1～3倍，更优选为1倍。控制手性铜催化剂的摩尔用量为炔丙基类化合物(Ⅲ)的摩尔用量的0.01～100倍，优选为1～10倍，更优选为1～5倍。
在该技术方案中，合成手性10-炔丙基蒽酮类化合物前，先制备手性铜催化剂，具体制备方法为：在惰性气体保护下，将铜盐和手性P,N,N-配体混合于第二反应介质如无水甲醇中，在室温下搅拌0.5～2h。其中，手性P,N,N-配体的结构式如式L所示：
Figure GDA0003621746060000091
在所述式L中，R5为C1-C10烷基、C3-C8环烷基、苯基、取代苯基、苄基或者取代苄基中的任意一种；
R4、R6分别独立地为C1-C10烷基、C3-C8环烷基、苯基、取代苯基、萘基、取代萘基、或含一个或多个杂原子取代的五元或六元杂环芳香基团，所述杂原子选自氧、硫、氮原子中的任意一种；
R7为氢、卤素、C1-C10烷基、C3-C8环烷基、苯基、取代苯基、烷氧基、苯氧基、酰基或硝基中的任意一种；
所述R5中取代苯基及取代苄基、所述R4和R6中取代苯基及取代萘基、所述R7中取代苯基上的取代基为C1-C40烷基、C1-C40烷氧基、卤素、硝基、酯基或氰基中的至少一种。
在一些优选实施例中，手性P,N,N-配体具有如下结构式之一：
Figure GDA0003621746060000092
当选用上述结构式的手性P,N,N-配体制成手性铜催化剂时，可以实现在温和的反应条件下、高产率、高对映选择性的得到手性10-炔丙基蒽酮类化合物。
本发明提供的技术方案具有以下优点：
1.反应活性高、对映选择性好，反应条件温和。
2.起始原料廉价易得，避免使用空气敏感或不稳定的反应物。
3.手性配体合成简便，催化剂廉价易得，用量少。
4.比较传统的方法，该方法可以方便地合成各种手性10-炔丙基蒽酮类化合物。
实施例1：
Figure GDA0003621746060000101
在氮气保护下，在25mL干燥的Schlenk管中加入Cu(OAc)2(0.01mmol,3.7mg)，手性P,N,N-配体L1(0.012mmol,5.7mg)，抽换N2三次，加入1mL无水甲醇作溶剂，室温下搅拌1小时，制得手性铜催化剂。
在氮气保护下，继续向Schlenk管中加入9(10H)-蒽酮Ⅳ-1(0.2mmol)，再加入0.5mL无水甲苯(用于溶解9(10H)-蒽酮Ⅳ-1)，后加入苯基炔丙醇乙酸酯Ⅲ-1(0.5mmol)和0.5mL无水甲醇，在-20℃下，向Schlenk管中加入DIPEA(N,N-二异丙基乙胺、0.5mmol,87μL)，并于-20℃下反应。用TLC板监测反应结束后，将溶液转移至尖底瓶中，减压除去溶剂，硅胶柱层析分离可得到目标产物Ⅰ-1(洗脱剂:石油醚:乙酸乙酯＝150:1-80:1)，产率：80％。
制备得到的Ⅰ-1的核磁共振(1H NMR和13C NMR)、高分辨质谱检测、高效液相色谱数据为：白色固体；80％yield(即产率)；1H NMR(400MHz,CDCl3)δ8.14(dd,J＝7.4,1.6Hz,2H),7.72(d,J＝7.6Hz,1H),7.62(t,J＝8.2Hz,1H),7.50–7.36(m,3H),7.23(d,J＝23.4Hz,2H),7.13(t,J＝7.6Hz,2H),6.82(dd,J＝7.4,1.5Hz,1H),6.72(d,J＝7.6Hz,2H),4.62(d,J＝3.9Hz,1H),4.30–4.25(m,1H),2.29(d,J＝2.5Hz,1H)；13C NMR(100MHz,CDCl3)δ184.66,141.50,141.50,140.32,136.29,134.06,133.79,132.30,131.73,128.90,128.85,128.62,128.04,127.74,126.86,126.77,82.06,76.02,50.22,49.09；HRMS:calcd.for[M+H]+C23H16O＝309.1274,found:309.1272；
Figure GDA0003621746060000102
HPLC conditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝254nm,majorenantiomer:tR＝11.3min,minor enantiomer:tR＝34.1min；92％ee。
实施例2：
0℃下反应生成产物Ⅰ-1；
将实施例1中的反应温度-20℃改为0℃，其余同实施例1，得到化合物Ⅰ-1。产率：82％，ee值90％。
实施例3：
-40℃下反应生成产物Ⅰ-1；
将实施例1中的反应温度-20℃改为-40℃，其余同实施例1，得到化合物Ⅰ-1。产率：79％，ee值89％。
实施例4：
常温下，10mol％催化剂催化生成反应生成产物Ⅰ-1；
将实施例1中的反应温度-20℃改为常温，催化剂用量5mol％改为10mol％，其余同实施例1，得到化合物Ⅰ-1。产率：88％，ee值87％。
实施例5：
常温下，10mol％催化剂在甲醇中催化生成反应生成产物Ⅰ-1；
将实施例1中的反应温度-20℃改为常温，催化剂用量5mol％改为10mol％，溶剂改为甲醇，其余同实施例1，得到化合物Ⅰ-1。产率：87％，ee值86％。
实施例6：
常温下，10mol％催化剂(Cu(CH3CN)4BF4/L1)在甲醇中催化生成反应生成产物Ⅰ-1；
将实施例1中-20℃改为常温，催化剂用量5mol％改为10mol％，Cu(ClO4)2·6H2O改为Cu(CH3CN)4BF4，溶剂改为甲醇，其余同实施例1，得到化合物Ⅰ-1。产率：80％，ee值77％。
实施例7-17的具体实施方式，参考实施例1，除改变相应的炔丙醇酯底物外，其余均同实施例1。制备得到的化合物的核磁共振(1H NMR和13C NMR)、高分辨质谱检测、高效液相色谱数据为：
实施例7：
(R)-10-(1-(o-tolyl)prop-2-yn-1-yl)anthracen-9(10H)-one
Ⅰ-2(结构式详见下文):88％yield；white solid；1H NMR(400MHz,CDCl3)δ8.21(d,J＝7.8Hz,2H),7.61–7.54(m,2H),7.50–7.41(m,2H),7.28(t,J＝7.4Hz,1H),7.20–7.14(m,2H),6.98(t,J＝7.4Hz,1H),6.70(d,J＝7.8Hz,1H),6.53(d,J＝7.8Hz,1H),4.47–4.42(m,2H),2.28(s,3H),2.16(d,J＝2.4Hz,1H)；13C NMR(100MHz,CDCl3)δ185.16,142.52,139.54,135.42,135.35,134.22,134.07,132.52,131.12,130.51,130.25,129.96,127.93,127.81,127.79,127.76,127.06,126.87,125.72,82.10,76.09,48.48,45.83,19.27；HRMS:calcd.for[M+Na]+C24H18O＝345.1250,found:345.1248；
Figure GDA0003621746060000121
HPLC conditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝234nm,major enantiomer:tR＝8.5min,minorenantiomer:tR＝9.9min；85％ee。
实施例8：
(R)-10-(1-(m-tolyl)prop-2-yn-1-yl)anthracen-9(10H)-one
Ⅰ-3(结构式详见下文):90％yield；white solid；1H NMR(400MHz,CDCl3)δ8.15(d,J＝7.6Hz,2H),7.70(d,J＝7.6Hz,1H),7.61(t,J＝7.6Hz,1H),7.49–7.36(m,3H),7.02–6.99(m,2H),6.79(d,J＝7.4Hz,1H),6.54–6.52(m,1H),6.48(s,1H),4.58(d,J＝3.8Hz,1H),4.23(t,J＝3.2Hz,1H),2.27(d,J＝2.6Hz,1H),2.18(s,3H)；13C NMR(100MHz,CDCl3)δ184.65,141.66,140.36,137.66,136.20,134.10,133.82,132.29,131.60,129.67,128.96,128.60,128.36,127.92,127.70,126.80,126.69,125.90,82.12,75.97,50.29,49.08,21.38；HRMS:calcd.for[M+H]+C24H18O＝323.1430,found:323.1427；
Figure GDA0003621746060000122
HPLC conditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝254nm,major enantiomer:tR＝8.9min,minorenantiomer:tR＝27.6min；93％ee。
实施例9：
(R)-10-(1-(p-tolyl)prop-2-yn-1-yl)anthracen-9(10H)-one
Ⅰ-4(结构式详见下文):85％yield；white solid；1H NMR(400MHz,CDCl3)δ8.15(d,J＝7.4Hz,,2H),7.70(d,J＝7.6Hz,1H),7.60(td,J＝7.6,1.6Hz,1H),7.48–7.34(m,3H),6.94(d,J＝7.8Hz,2H),6.79(d,J＝7.4Hz,1H),6.62(d,J＝7.8Hz,2H),4.56(d,J＝3.8Hz,1H),4.24(t,J＝3.2Hz,1H),2.29(s,3H),2.25(d,J＝2.4Hz,1H)；13C NMR(100MHz,CDCl3)δ184.75,141.76,140.36,137.37,134.02,133.75,133.41,132.30,131.64,128.95,128.74,128.58,127.66,126.88,126.76,82.17,75.93,50.26,48.82,21.24；HRMS:calcd.for[M+Na]+C24H18O＝345.1250,found:345.1260；
Figure GDA0003621746060000131
HPLCconditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝214nm,major enantiomer:tR＝10.3min,minor enantiomer:tR＝31.8min；91％ee。
实施例10：
(R)-10-(1-(4-fluorophenyl)prop-2-yn-1-yl)anthracen-9(10H)-one
Ⅰ-5(结构式详见下文):83％yield；white solid；1H NMR(400MHz,CDCl3)δ8.16–8.13(m,2H),7.72(d,J＝7.6Hz,1H),7.62(td,J＝7.6,1.6Hz,1H),7.50–7.41(m,3H),6.91–6.88(m,1H),6.82–6.78(m,2H),6.66–6.58(m,2H),4.59(d,J＝3.8Hz,1H),4.26–4.24(m,1H),2.32(d,J＝2.4Hz,1H)；13C NMR(100MHz,CDCl3)δ184.46,163.51,161.06,141.07,140.29,133.98,133.71,132.30,131.90,130.48,130.40,128.74,128.65,127.84,126.90,126.86,114.99,114.77,82.13,76.07,50.06,48.26；HRMS:calcd.for[M+Na]+C23H15FO＝349.0999,found:349.1005；
Figure GDA0003621746060000132
HPLC conditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝254nm,majorenantiomer:tR＝13.8min,minor enantiomer:tR＝25.3min；91％ee。
实施例11：
(R)-10-(1-(4-chlorophenyl)prop-2-yn-1-yl)anthracen-9(10H)-one
Ⅰ-6(结构式详见下文):85％yield；white solid；1H NMR(400MHz,CDCl3)δ8.16(d,J＝7.6Hz,2H),7.70(d,J＝7.6Hz,1H),7.61(td,J＝7.6,1.4Hz,1H),7.50–7.39(m,3H),7.11–7.09(m,2H),6.85(d,J＝6.6Hz,1H),6.65(d,J＝8.2Hz,2H),4.58(d,J＝4.0Hz,1H),4.24(t,J＝3.1Hz,1H),2.30(d,J＝2.4Hz,1H)；13C NMR(100MHz,CDCl3)δ184.52,141.17,140.02,134.98,133.99,133.70,133.65,132.39,131.86,130.18,128.79,128.57,128.20,127.90,127.01,126.96,81.66,76.37,50.02,48.52；HRMS:calcd.for[M+H]+C23H15ClO＝343.0884,found:343.0880；
Figure GDA0003621746060000141
Figure GDA0003621746060000142
HPLCconditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝224nm,major enantiomer:tR＝14.9min,minor enantiomer:tR＝27.4min；92％ee.
实施例12：
(R)-10-(1-(4-bromophenyl)prop-2-yn-1-yl)anthracen-9(10H)-one
Ⅰ-7(结构式详见下文):79％yield；white solid；1H NMR(400MHz,CDCl3)δ8.17(d,J＝7.6Hz,2H),7.70(d,J＝7.6Hz,1H),7.62(t,J＝7.4Hz,1H),7.51–7.39(m,3H),7.28(s,2H),6.83(d,J＝7.4Hz,1H),6.61(d,J＝8.0Hz,2H),4.58(d,J＝4.0Hz,1H),4.23(t,J＝3.2Hz,1H),2.30(d,J＝2.5Hz,1H)；13C NMR(100MHz,CDCl3)δ184.53,141.22,139.96,135.60,134.01,133.72,132.42,131.86,131.19,130.54,128.82,128.55,127.93,127.06,127.00,121.81,81.54,76.44,50.02,48.65；HRMS:calcd.for[M+K]+C23H15BrOK＝424.9938,found:424.9936；
Figure GDA0003621746060000143
Figure GDA0003621746060000144
HPLC conditions:CHIRALPAK IAcolumn,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝224nm,major enantiomer:tR＝15.7min,minor enantiomer:tR＝30.3min；83％ee。
实施例13：
(R)-methyl-4-(1-(10-oxo-9,10-dihydroanthracen-9-yl)prop-2-yn-1-yl)benzoate
Ⅰ-8(结构式详见下文):90％yield；yellow solid；1H NMR(400MHz,CDCl3)δ8.15(d,J＝7.6Hz,2H),7.81(d,J＝8.4Hz,2H),7.71(d,J＝7.6Hz,1H),7.61(t,J＝8.2Hz,1H),7.50–7.35(m,3H),6.82(d,J＝8.0Hz,1H),6.77(d,J＝7.6Hz,1H),4.61(d,J＝4.0Hz,1H),4.35–4.26(m,1H),3.89(s,3H),2.32(d,J＝2.5Hz,1H)；13C NMR(100MHz,CDCl3)δ184.46,166.81,141.69,141.15,139.83,133.94,133.66,132.44,131.84,129.48,129.32,128.90,128.73,128.53,127.93,127.03,126.97,81.31,76.63,52.23,49.97,49.07；HRMS:calcd.for[M+H]+C25H18O3＝367.1329,found:367.1327；
Figure GDA0003621746060000151
HPLC conditions:CHIRALPAK AD-H column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝234nm,minor enantiomer:tR＝27.9min,major enantiomer:tR＝32.2min；93％ee。
实施例14：
(R)-10-(1-(4-methoxyphenyl)prop-2-yn-1-yl)anthracen-9(10H)-one
Ⅰ-9(结构式详见下文):80％yield；yellow solid；1H NMR(400MHz,CDCl3)δ8.07(d,J＝7.6Hz,2H),7.60(d,J＝7.6Hz,1H),7.51(t,J＝7.6Hz,1H),7.39–7.27(m,3H),6.72(d,J＝7.4Hz,1H),6.55(q,J＝8.6Hz,4H),4.46(d,J＝3.8Hz,1H),4.13(t,J＝3.0Hz,1H),3.66(s,3H),2.18(d,J＝2.4Hz,1H)；13C NMR(100MHz,CDCl3)δ184.68,159.12,141.65,140.41,134.01,133.73,132.29,131.67,129.92,128.94,128.59,128.41,127.67,126.87,126.77,113.40,82.32,75.89,55.36,50.35,48.40；HRMS:calcd.for[M+H]+C24H18O2＝339.1380,found:339.1373；
Figure GDA0003621746060000152
Figure GDA0003621746060000153
HPLC conditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝224nm,majorenantiomer:tR＝16.1min,minor enantiomer:tR＝33.8min；89％ee。
实施例15：
(R)-10-(1-(3,4-dichlorophenyl)prop-2-yn-1-yl)anthracen-9(10H)-one
Ⅰ-10(结构式详见下文):94％yield；white solid；1H NMR(400MHz,CDCl3)δ8.18(dd,J＝9.3,2.8Hz,2H),7.69(d,J＝7.6Hz,1H),7.63(t,J＝7.4Hz,1H),7.53–7.41(m,3H),7.20(d,J＝8.2Hz,1H),6.89–6.84(m,1H),6.77(d,J＝2.1Hz,1H),6.54(dd,J＝8.2,2.1Hz,1H),4.57(d,J＝3.8Hz,1H),4.20(t,J＝3.2Hz,1H),2.33(d,J＝2.4Hz,1H)；13C NMR(100MHz,CDCl3)δ184.35,140.79,139.68,136.71,133.97,133.66,132.49,132.14,131.97,131.85,130.80,129.88,128.71,128.53,128.11,128.06,127.07,81.03,76.81,49.86,48.27；HRMS:calcd.for[M+H]+C23H14Cl2O＝399.0314,found:399.0306；
Figure GDA0003621746060000161
HPLC conditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝214nm,major enantiomer:tR＝15.1min,minorenantiomer:tR＝25.8min；88％ee.
实施例16：
(R)-10-(1-(thiophen-2-yl)prop-2-yn-1-yl)anthracen-9(10H)-one
Ⅰ-11(结构式详见下文):82％yield；yellow solid；1H NMR(400MHz,CDCl3)δ8.19–8.16(m,2H),7.70(d,J＝7.8Hz,1H),7.60(td,J＝7.6,1.4Hz,1H),7.49–7.39(m,3H),7.12(dd,J＝5.0,1.4Hz,1H),6.96–6.93(m,1H),6.78(dd,J＝5.0,3.6Hz,1H),6.33(d,J＝3.6Hz,1H),4.62(d,J＝3.6Hz,1H),4.49(t,J＝3.2Hz,1H),2.29(d,J＝2.6Hz,1H)；13C NMR(100MHz,CDCl3)δ184.60,140.95,140.14,139.39,134.00,133.62,132.41,132.00,128.58,128.45,127.87,127.17,126.92,126.77,126.63,125.31,81.55,77.48,77.16,76.84,75.57,50.51,44.21；HRMS:calcd.for[M+H]+C21H14O4S＝315.0838,found:315.0835；
Figure GDA0003621746060000162
Figure GDA0003621746060000163
HPLC conditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝254nm,major enantiomer:tR＝12.7min,minorenantiomer:tR＝18.4min；91％ee。
实施例17：
(R)-10-(1-(furan-2-yl)prop-2-yn-1-yl)anthracen-9(10H)-one
Ⅰ-12(结构式详见下文):84％yield；yellow oil；1H NMR(400MHz,CDCl3)δ8.18–8.13(m,2H),7.71(dt,J＝8.0,1.2Hz,1H),7.47(t,J＝7.8Hz,1H),7.42–7.37(m,2H),7.33–7.16(m,4H),7.05(d,J＝7.4Hz,2H),5.49(d,J＝3.6Hz,1H),4.46(t,J＝3.0Hz,1H),2.18(dd,J＝2.6,1.0Hz,1H)；13C NMR(100MHz,CDCl3)δ185.05,150.88,142.19,141.90,139.52,133.95,133.71,132.80,131.72,128.58,128.14,127.84,127.77,127.18,126.89,110.86,109.62,78.40,75.82,47.22,43.42；HRMS:calcd.for[M+H]+C21H14O2Na＝321.0886,found:321.0903；
Figure GDA0003621746060000171
Figure GDA0003621746060000172
HPLC conditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝214nm,major enantiomer:tR＝10.7min,minor enantiomer:tR＝17.8min；82％ee。
实施例18-22的具体实施方式，参考实施例1，除改变相应的炔丙醇酯底物中的离去基团(将离去基团由乙酸酯基改为五氟苯甲酸酯基)外，其余均同实施例1。制备得到的化合物的核磁共振(1H NMR和13C NMR)、高分辨质谱检测、高效液相色谱数据为：
实施例18：
(R)-10-(5-phenylpent-1-yn-3-yl)anthracen-9(10H)-one
Ⅰ-13(结构式详见下文):87％yield；white solid；1H NMR(400MHz,CDCl3)δ8.26(t,J＝8.8Hz,2H),7.60–7.43(m,5H),7.35(d,J＝7.4Hz,1H),7.23–7.13(m,3H),7.01(d,J＝7.2Hz,2H),4.33(d,J＝3.4Hz,1H),2.88–2.83(m,1H),2.79–2.72(m,1H),2.58–2.50(m,1H),2.13(d,J＝2.0Hz,1H),1.73–1.65(m,1H),1.51–1.41(m,1H)；13C NMR(100MHz,CDCl3)δ184.66,141.50,140.32,136.29,134.06,133.79,132.30,131.73,128.90,128.85,128.62,128.04,127.74,126.86,126.77,82.06,76.02,50.22,49.09；HRMS:calcd.for[M+H]+C25H20O＝337.1587,found:337.1581；
Figure GDA0003621746060000173
HPLC conditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝234nm,minorenantiomer:tR＝9.4min,major enantiomer:tR＝10.0min；90％ee。
实施例19：
(R)-10-(1-(benzyloxy)but-3-yn-2-yl)anthracen-9(10H)-one
Ⅰ-14(结构式详见下文):84％yield；white solid；1H NMR(400MHz,CDCl3)δ8.27–8.23(m,2H),(dd,J＝10.1,6.3Hz,2H),7.56(t,J＝7.4Hz,1H),7.48–7.41(m,8H),7.39–7.33(m,2H),4.66(d,J＝4.0Hz,1H),4.63–4.58(m,2H),3.53–3.49(m,1H),3.40(t,J＝10.0Hz,1H),3.26–3.21(m,1H),1.86(d,J＝2.4Hz,1H)；13C NMR(100MHz,CDCl3)δ185.46,143.56,139.79,137.69,134.38,133.86,132.78,131.85,129.08,128.72,128.24,128.18,127.89,127.67,127.47,127.20,127.05,79.52,75.66,73.32,69.48,43.34,42.31；HRMS:calcd.for[M+H]+C25H20O2＝353.1536,found:353.1533；
Figure GDA0003621746060000181
HPLC conditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝234nm,major enantiomer:tR＝10.5min,minorenantiomer:tR＝11.2min；93％ee.
实施例20：
(R)-10-(5-(methylthio)pent-1-yn-3-yl)anthracen-9(10H)-one
I-15(结构式详见下文):90％yield；yellow oil；1H NMR(400MHz,CDCl3)δ8.28–8.25(m,2H),7.71(d,J＝7.8Hz,1H),7.58(t,J＝7.6Hz,2H),7.47(t,J＝8.0Hz,3H),4.41(d,J＝3.2Hz,1H),3.21–3.16(m,1H),2.60–2.54(m,1H),2.47–2.40(m,1H),2.12(d,J＝2.4Hz,1H),1.86(s,3H),1.60–1.52(m,1H),1.41–1.32(m,1H)；13C NMR(100MHz,CDCl3)δ185.12,142.12,141.34,133.83,133.28,132.59,132.42,128.70,128.57,127.78,127.68,127.18,127.09,83.33,74.73,46.53,41.22,31.85,30.12,15.14；HRMS:calcd.for[M+H]+C20H18OS＝307.1151,found:307.1148；
Figure GDA0003621746060000182
HPLCconditions:CHIRALPAK IBN column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝214nm,minor enantiomer:tR＝12.3min,major enantiomer:tR＝12.9min；87％ee.
实施例21：
(R)-tert-butyl-4-(2-(10-oxo-9,10-dihydroanthracen-9-yl)but-3-yn-1-yl)piperidine-1-carboxylate
I-16(结构式详见下文):90％yield；white solid；1H NMR(400MHz,CDCl3)δ8.28–8.25(m,2H),7.69(d,J＝7.6Hz,1H),7.59(t,J＝7.6Hz,2H),7.50–7.43(m,3H),4.37(s,1H),3.99(s,2H),3.00(d,J＝10.7Hz,1H),2.59(s,2H),2.12(s,1H),1.58(d,J＝13.2Hz,1H),1.46(s,1H),1.42(s,9H),1.11–0.99(m,3H),0.85–0.75(m,1H)；13C NMR(100MHz,CDCl3)13C NMR(101MHz,CDCl3)δ185.22,154.83,142.21,141.41,133.91,133.41,132.55,132.37,128.61,128.51,127.78,127.67,127.19,127.09,83.82,79.36,74.52,46.97,39.91,37.61,33.70,32.86,30.91,28.54；HRMS:calcd.for[M+H]+C28H31NO3＝430.2377,found:430.2375；
Figure GDA0003621746060000191
Figure GDA0003621746060000192
HPLC conditions:CHIRALPAK IAcolumn,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝214nm,minor enantiomer:tR＝16.0min,major enantiomer:tR＝19.3min；84％ee。
实施例22：
(R)-10-(7-chlorohept-1-yn-3-yl)anthracen-9(10H)-one
I-17(结构式详见下文):94％yield；white solid；1H NMR(400MHz,CDCl3)δ8.26(t,J＝7.0Hz,2H),7.67(d,J＝7.8Hz,1H),7.58(t,J＝7.6Hz,2H),7.50–7.44(m,3H),4.39(d,J＝3.2Hz,1H),3.41(t,J＝6.4Hz,2H),2.91–2.85(m,1H),2.11(d,J＝2.4Hz,1H),1.71–1.54(m,3H),1.45–1.30(m,2H),1.16–1.06(m,1H)；13C NMR(100MHz,CDCl3)δ185.25,142.29,141.45,133.94,133.43,132.56,132.34,128.68,128.51,127.77,127.66,127.20,127.08,83.78,74.57,46.91,44.82,42.88,32.19,30.54,25.14；HRMS:calcd.for[M+H]+C21H19ClO＝323.1197,found:323.1192；
Figure GDA0003621746060000193
HPLCconditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝254nm,major enantiomer:tR＝12.9min,minor enantiomer:tR＝15.4min；89％ee。
实施例23-28的具体实施方式，参考实施例1，除改变相应的炔丙醇酯底物和蒽酮类底物外，其余均同实施例1。制备得到的化合物的核磁共振(1H NMR和13C NMR)、高分辨质谱检测、高效液相色谱数据为：
实施例23：
(R)-1,8-dihydroxy-10-(1-phenylprop-2-yn-1-yl)anthracen-9(10H)-one
I-18(结构式详见下文):82％yield；yellow solid；1H NMR(400MHz,CDCl3)δ11.87(d,J＝8.2Hz,2H),7.51(d,J＝8.0Hz,1H),7.30(t,J＝8.0Hz,1H),7.23–7.19(m,1H),7.15–7.11(m,3H),6.93–6.87(m,2H),6.67(d,J＝7.4Hz,2H),6.31(d,J＝7.4Hz,1H),4.50(d,J＝3.8Hz,1H),4.15(t,J＝3.2Hz,1H),2.35(d,J＝2.4Hz,1H)；13C NMR(100MHz,CDCl3)δ193.43,162.12,162.05,142.76,142.04,135.79,135.74,135.37,128.87,127.93,127.88,119.76,119.68,117.11,116.91,116.75,82.18,75.87,50.71,50.13；HRMS:calcd.for[M+H]+C23H16O3＝341.1172,found:341.1186；
Figure GDA0003621746060000201
HPLCconditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝234nm,minor enantiomer:tR＝9.4min,major enantiomer:tR＝20.4min；90％ee。
实施例24：
(R)-1,8-dichloro-10-(1-phenylprop-2-yn-1-yl)anthracen-9(10H)-one
I-19(结构式详见下文):86％yield；white solid；1H NMR(400MHz,CDCl3)δ7.41(t,J＝6.8Hz,2H),7.33(t,J＝7.8Hz,1H),7.27–7.19(m,5H),6.87(d,J＝7.4Hz,2H),6.76(d,J＝7.6Hz,1H),4.36(d,J＝5.2Hz,1H),4.08–4.06(m,1H),2.34(d,J＝2.4Hz,1H)；13CNMR(100MHz,CDCl3)δ182.52,142.10,141.00,136.48,133.00,132.89,132.77,132.64,131.66,131.16,130.94,130.89,128.82,128.44,128.10,127.61,127.11,81.56,76.84,51.78,48.92；HRMS:calcd.for[M+H]+C23H14Cl2O＝377.0494,found:377.0502；
Figure GDA0003621746060000202
HPLC conditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝224nm,major enantiomer:tR＝15.4min,minorenantiomer:tR＝43.2min；86％ee。
实施例25：
(R)-4,5-dichloro-10-(1-phenylprop-2-yn-1-yl)anthracen-9(10H)-one
I-20(结构式详见下文):86％yield；yellow solid；1H NMR(400MHz,CDCl3)δ8.18–8.13(m,2H),7.71(d,J＝8.0Hz,1H),7.49–7.37(m,3H),7.31–7.21(m,4H),7.05(d,J＝7.4Hz,2H),5.49(d,J＝3.6Hz,1H),4.46(t,J＝3.0Hz,1H),2.18(d,J＝1.6Hz,1H)；13C NMR(100MHz,CDCl3)δ184.13,139.64,137.08,136.69,136.37,135.66,135.15,133.75,132.96,129.02,128.77,128.65,128.45,127.95,125.98,125.69,81.19,78.12,46.17,43.74；HRMS:calcd.for[M+K]+C23H14Cl2O＝415.0053,found:415.0048；
Figure GDA0003621746060000211
HPLC conditions:CHIRALPAK IG column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝254nm,major enantiomer:tR＝9.8min,minorenantiomer:tR＝11.9min；80％ee。
实施例26：
(R)-1,8-dihydroxy-10-(5-phenylpent-1-yn-3-yl)anthracen-9(10H)-one
I-21(结构式详见下文):92％yield；yellow solid；1H NMR(400MHz,CDCl3)δ12.07(d,J＝13.4Hz,2H),7.43(dt,J＝15.2,8.0Hz,2H),7.24(t,J＝7.2Hz,2H),7.19–7.15(m,1H),7.05(d,J＝7.0Hz,1H),6.99(d,J＝7.5Hz,1H),6.94–6.90(m,2H),6.79(d,J＝7.4Hz,1H),4.24(d,J＝3.4Hz,1H),2.81–2.72(m,2H),2.59–2.52(m,1H),2.18(d,J＝2.4Hz,1H),1.74–1.66(m,1H),1.56–1.46(m,1H)；13C NMR(100MHz,CDCl3)δ194.06,162.40,162.33,144.23,142.72,140.98,136.12,135.62,128.56,128.50,126.21,119.75,119.19,117.07,116.80,116.61,83.49,75.09,47.44,43.44,33.74,33.32；HRMS:calcd.for[M+H]+C25H20O3＝369.1485,found:369.1483；
Figure GDA0003621746060000212
HPLC conditions:CHIRALPAK IA column,hexane/iPrOH＝95/5,flow rate＝1mL min-1,λ＝234nm,minorenantiomer:tR＝7.2min,major enantiomer:tR＝8.2min；90％ee。
实施例27：
(R)-1,8-dihydroxy-10-(1-(4-methoxyphenyl)prop-2-yn-1-yl)anthracen-9(10H)-one
I-22(结构式详见下文):85％yield；yellow solid；1H NMR(400MHz,CDCl3)δ11.90(d,J＝8.4Hz,2H),7.50(t,J＝8.0Hz,1H),7.32(t,J＝8.0Hz,1H),7.14(d,J＝7.6Hz,1H),6.93–6.87(m,2H),6.66(d,J＝8.4Hz,2H),6.56(d,J＝8.4Hz,2H),6.35(d,J＝7.4Hz,1H),4.47(d,J＝3.6Hz,1H),4.11(t,J＝3.0Hz,1H),3.76(s,3H),2.34(d,J＝2.4Hz,1H)；13C NMR(100MHz,CDCl3)δ194.06,162.40,162.33,144.23,142.72,140.98,136.12,135.62,128.56,128.50,126.21,119.75,119.19,117.07,116.80,116.61,83.49,75.09,47.44,43.44,33.74,33.32；HRMS:calcd.for[M+H]+C24H18O4＝371.1278,found:371.1281；
Figure GDA0003621746060000221
HPLC conditions:CHIRALPAK IG column,hexane/iPrOH＝80/20,flow rate＝1mL min-1,λ＝224nm,major enantiomer:tR＝12.9min,minorenantiomer:tR＝15.8min；79％ee。
实施例28：
(R)-methyl-4-(1-(4,5-dihydroxy-10-oxo-9,10-dihydroanthracen-9-yl)prop-2-yn-1-yl)benzoate
I-23(结构式详见下文):89％yield；yellow solid；1H NMR(400MHz,CDCl3)δ11.91(d,J＝9.2Hz,2H),7.84(d,J＝8.0Hz,2H),7.53(t,J＝8.0Hz,1H),7.30(d,J＝8.0Hz,1H),7.15(d,J＝7.4Hz,1H),6.96–6.90(m,2H),6.83(d,J＝8.0Hz,2H),6.25(d,J＝7.4Hz,1H),4.54(d,J＝3.8Hz,1H),4.23(t,J＝3.2Hz,1H),3.92(s,3H),2.39(t,J＝2.4Hz,1H)；13C NMR(100MHz,CDCl3)δ193.45,166.83,162.26,162.22,142.52,141.41,141.31,135.96,135.48,129.67,129.29,128.94,119.75,119.59,117.07,117.04,116.80,81.38,76.60,52.32,50.56,50.11；HRMS:calcd.for[M+K]+C25H18O5＝437.0786,found:437.0776；
Figure GDA0003621746060000222
HPLC conditions:CHIRALPAK IG column,hexane/iPrOH＝90/10,flow rate＝1mL min-1,λ＝224nm,major enantiomer:tR＝29.4min,minorenantiomer:tR＝33.8min；91％ee。
Figure GDA0003621746060000231
Figure GDA0003621746060000241
实施例29：
Figure GDA0003621746060000242
与实施例1不同的是，手性P,N,N-配体由L1改成L2，制备得到产物Ⅱ-1。产率：81％，ee值94％。
实施例30：
0℃下反应生成产物Ⅱ-1；
将实施例29中的反应温度-20℃改为0℃，其余同实施例29，得到化合物Ⅱ-1。产率：84％，ee值89％。
实施例31：
-40℃下反应生成产物Ⅱ-1；
将实施例29中的反应温度-20℃改为-40℃，其余同实施例29，得到化合物Ⅱ-1。
产率：80％，ee值90％。
实施例32：
常温下，10mol％催化剂催化生成反应生成产物Ⅱ-1；
将实施例29中的反应温度-20℃改为常温，催化剂用量5mol％改为10mol％，其余同实施例29，得到化合物Ⅱ-1。产率：86％，ee值81％。
实施例33：
常温下，10mol％催化剂在甲醇中催化生成反应生成产物Ⅱ-1；
将实施例29中的反应温度-20℃改为常温，催化剂用量5mol％改为10mol％，溶剂改为甲醇，其余同实施例29，得到化合物Ⅱ-1。产率：86％，ee值85％。
实施例34：
常温下，10mol％催化剂(Cu(CH3CN)4BF4/L3)在甲醇中催化生成反应生成产物Ⅱ-1；
将实施例29中-20℃改为常温，催化剂用量5mol％改为10mol％，Cu(ClO4)2·6H2O改为Cu(CH3CN)4BF4，溶剂改为甲醇，其余同实施例29，得到化合物Ⅱ-1。产率：81％，ee值79％。
实施例35：
具体实施方式参考实施例29，除改变相应的炔丙醇酯底物外，其余均同实施例29，制备得到的化合物Ⅱ-2(结构式详见下文)，产率：86％；ee值86％。
(S)-10-(1-(o-tolyl)prop-2-yn-1-yl)anthracen-9(10H)-one
实施例36：
具体实施方式参考实施例29，除改变相应的炔丙醇酯底物外，其余均同实施例29，制备得到的化合物Ⅱ-3(结构式详见下文)，产率：91％；ee值：93％。
(S)-10-(1-(m-tolyl)prop-2-yn-1-yl)anthracen-9(10H)-one
实施例37：
具体实施方式参考实施例29，除改变相应的炔丙醇酯底物外，其余均同实施例29，制备得到的化合物Ⅱ-4(结构式详见下文)，产率：86％；ee值：90％。
(S)-10-(1-(p-tolyl)prop-2-yn-1-yl)anthracen-9(10H)-one
实施例38：
具体实施方式参考实施例29，除改变相应的炔丙醇酯底物外，其余均同实施例29，制备得到的化合物Ⅱ-5(结构式详见下文)，产率：85％；ee值：90％。
(S)-10-(1-(4-fluorophenyl)prop-2-yn-1-yl)anthracen-9(10H)-one
实施例39：
具体实施方式参考实施例29，除改变相应的炔丙醇酯底物外，其余均同实施例29，制备得到的化合物Ⅱ-6(结构式详见下文)，产率：84％；ee值：90％。
(S)-10-(1-(4-chlorophenyl)prop-2-yn-1-yl)anthracen-9(10H)-one
实施例40：
具体实施方式参考实施例29，除改变相应的炔丙醇酯底物外，其余均同实施例29，制备得到的化合物Ⅱ-7(结构式详见下文)，产率：80％；ee值：85％。
(S)-10-(1-(4-bromophenyl)prop-2-yn-1-yl)anthracen-9(10H)-one
实施例41：
具体实施方式参考实施例29，除改变相应的炔丙醇酯底物外，其余均同实施例29，制备得到的化合物Ⅱ-8(结构式详见下文)，产率：91％；ee值：92％。
(S)-methyl-4-(1-(10-oxo-9,10-dihydroanthracen-9-yl)prop-2-yn-1-yl)benzoate
实施例42：
具体实施方式参考实施例29，除改变相应的炔丙醇酯底物外，其余均同实施例29，制备得到的化合物Ⅱ-9(结构式详见下文)，产率：83％；ee值：88％。
(S)-10-(1-(4-methoxyphenyl)prop-2-yn-1-yl)anthracen-9(10H)-one
实施例43：
具体实施方式参考实施例29，除改变相应的炔丙醇酯底物外，其余均同实施例29，制备得到的化合物Ⅱ-10(结构式详见下文)，产率：93％；ee值：90％。
(S)-10-(1-(3,4-dichlorophenyl)prop-2-yn-1-yl)anthracen-9(10H)-one
实施例44：
具体实施方式参考实施例29，除改变相应的炔丙醇酯底物外，其余均同实施例29，制备得到的化合物Ⅱ-11(结构式详见下文)，产率：85％；ee值：90％。
(S)-10-(1-(thiophen-2-yl)prop-2-yn-1-yl)anthracen-9(10H)-one
实施例45：
具体实施方式参考实施例29，除改变相应的炔丙醇酯底物外，其余均同实施例29，制备得到的化合物Ⅱ-12(结构式详见下文)，产率：85％；ee值：85％。
(S)-10-(1-(furan-2-yl)prop-2-yn-1-yl)anthracen-9(10H)-one
实施例46：
具体实施方式，参考实施例29，除改变相应的炔丙醇酯底物中的离去基团(将离去基团由乙酸酯基改为五氟苯甲酸酯基)外，其余均同实施例29，制备得到的化合物Ⅱ-13(结构式详见下文)，产率：86％；ee值：91％。
(S)-10-(5-phenylpent-1-yn-3-yl)anthracen-9(10H)-one
实施例47：
具体实施方式，参考实施例29，除改变相应的炔丙醇酯底物中的离去基团(将离去基团由乙酸酯基改为五氟苯甲酸酯基)外，其余均同实施例29，制备得到的化合物Ⅱ-14(结构式详见下文)，产率：87％；ee值：90％。
(S)-10-(1-(benzyloxy)but-3-yn-2-yl)anthracen-9(10H)-one
实施例48：
具体实施方式，参考实施例29，除改变相应的炔丙醇酯底物中的离去基团(将离去基团由乙酸酯基改为五氟苯甲酸酯基)外，其余均同实施例29，制备得到的化合物Ⅱ-15(结构式详见下文)，产率：92％；ee值：89％。
(S)-10-(5-(methylthio)pent-1-yn-3-yl)anthracen-9(10H)-one
实施例49：
具体实施方式，参考实施例29，除改变相应的炔丙醇酯底物中的离去基团(将离去基团由乙酸酯基改为五氟苯甲酸酯基)外，其余均同实施例29，制备得到的化合物Ⅱ-16(结构式详见下文)，产率：92％；ee值：86％。
(S)-tert-butyl-4-(2-(10-oxo-9,10-dihydroanthracen-9-yl)but-3-yn-1-yl)piperidine-1-carboxylate
实施例50：
具体实施方式，参考实施例29，除改变相应的炔丙醇酯底物中的离去基团(将离去基团由乙酸酯基改为五氟苯甲酸酯基)外，其余均同实施例29，制备得到的化合物Ⅱ-17(结构式详见下文)，产率：95％；ee值：88％。
(S)-10-(7-chlorohept-1-yn-3-yl)anthracen-9(10H)-one
实施例51：
具体实施方式，参考实施例29，除改变相应的炔丙醇酯底物和蒽酮类底物外，其余均同实施例29，制备得到的化合物Ⅱ-18(结构式详见下文)，产率：85％；ee值：92％。
(S)-1,8-dihydroxy-10-(1-phenylprop-2-yn-1-yl)anthracen-9(10H)-one
实施例52：
具体实施方式，参考实施例29，除改变相应的炔丙醇酯底物和蒽酮类底物外，其余均同实施例29，制备得到的化合物Ⅱ-19(结构式详见下文)，产率：88％；ee值：88％。
(S)-1,8-dichloro-10-(1-phenylprop-2-yn-1-yl)anthracen-9(10H)-one
实施例53：
具体实施方式，参考实施例29，除改变相应的炔丙醇酯底物和蒽酮类底物外，其余均同实施例29，制备得到的化合物Ⅱ-20(结构式详见下文)，产率：87％；ee值：84％。
(S)-4,5-dichloro-10-(1-phenylprop-2-yn-1-yl)anthracen-9(10H)-one
实施例54：
具体实施方式，参考实施例29，除改变相应的炔丙醇酯底物和蒽酮类底物外，其余均同实施例29，制备得到的化合物Ⅱ-21(结构式详见下文)，产率：90％；ee值：92％。
(S)-1,8-dihydroxy-10-(5-phenylpent-1-yn-3-yl)anthracen-9(10H)-one
实施例55：
具体实施方式，参考实施例29，除改变相应的炔丙醇酯底物和蒽酮类底物外，其余均同实施例29，制备得到的化合物Ⅱ-22(结构式详见下文)，产率：88％；ee值：80％。
(S)-1,8-dihydroxy-10-(1-(4-methoxyphenyl)prop-2-yn-1-yl)anthracen-9(10H)-one
实施例56：
具体实施方式，参考实施例29，除改变相应的炔丙醇酯底物和蒽酮类底物外，其余均同实施例29，制备得到的化合物Ⅱ-23(结构式详见下文)，产率：90％；ee值：92％。
(S)-methyl-4-(1-(4,5-dihydroxy-10-oxo-9,10-dihydroanthracen-9-yl)prop-2-yn-1-yl)benzoate
Figure GDA0003621746060000281
Figure GDA0003621746060000291
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本发明的保护范围之内。

Claims (9)

1.一种手性10-炔丙基蒽酮类化合物的合成方法，其特征在于，所述合成方法包括：
在碱性添加剂存在下，以手性铜催化剂在第一反应介质中催化炔丙基类化合物与蒽酮类化合物发生不对称炔丙基烷基化反应，得到手性10-炔丙基蒽酮类化合物，所述手性10-炔丙基蒽酮类化合物具有以下两种结构之一：
Figure FDA0003621746050000011
所述式Ⅰ和所述式Ⅱ互为对映异构体，在所述式Ⅰ和所述式Ⅱ中，R1选自C1-C40的烷基、C3-C12的环烷基、带有取代基的C3-C12的环烷基、苯基、取代苯基、苄基、取代苄基、含一个或二个以上杂原子取代的五元或者六元杂环芳香基团或者酯基中的任意一种；R2、R3分别独立地为氢、卤素、羟基、氰基、含有1-20个碳原子的饱和或不饱和烷基、取代或未取代C6-C60芳基、或者含有一个或二个以上杂原子取代或未取代的五元至六十元杂环芳香基团；所述杂原子为氧原子、硫原子、或者氮原子；
其中，控制所述不对称炔丙基烷基化反应的反应温度为-40℃～25℃；
其中，制备所述手性铜催化剂的方法包括：在惰性气体保护下，将铜盐和手性P,N,N-配体混合于第二反应介质中，在室温下搅拌0.5～2h；
所述手性P,N,N-配体的结构式如式L具有如下结构式之一：
Figure FDA0003621746050000012
所述反应介质为甲醇、乙醇、二氯甲烷、甲苯、乙腈、二甲苯、氟苯、氯苯、四氢呋喃中的任意一种或者多种的组合；
所述碱性添加剂为N,N-二异丙基乙胺；
所述炔丙基类化合物的结构式如式Ⅲ中所示：
Figure FDA0003621746050000021
所述式Ⅲ中，R1选自C1-C40的烷基、C3-C12的环烷基、带有取代基的C3-C12的环烷基、苯基、取代苯基、苄基、取代苄基、含一个或二个以上杂原子取代的五元或者六元杂环芳香基团或者酯基中的任意一种，LG选自F、Cl、Br、I、烷基羧酸酯、烷基碳酸酯、烷基磺酸酯、烷基磷酸酯、苯基、取代苯基碳酸酯、取代苯基羧酸酯、取代苯基磺酸酯或者取代苯基磷酸酯；所述烷基羧酸酯、所述烷基碳酸酯、所述烷基磺酸酯以及所述烷基磷酸酯中的烷基为C1-C40烷基或C3-C12的环烷基；所述取代苯基羧酸酯、所述取代苯基碳酸酯、所述取代苯基磺酸酯以及所述取代苯基磷酸酯中苯基上的取代基为C1-C40烷基、C1-C40的烷氧基、卤素、硝基、酯基或氰基中的至少一种；
所述蒽酮类化合物的结构式如式Ⅳ中所示：
Figure FDA0003621746050000022
所述式Ⅳ中，R2和R3分别独立地为氢、卤素、羟基、氰基、含有1-20个碳原子的饱和或不饱和烷基、取代或未取代C6-C60芳基、或者含有一个或二个以上杂原子取代或未取代的五元至六十元杂环芳香基团；所述杂原子为氧原子、硫原子、或者氮原子。
2.根据权利要求1所述的合成方法，其特征在于，所述C3-C12的环烷基上的取代基、所述苯基上的取代基及所述苄基上的取代基选自C1-C40的烷基、C1-C40的烷氧基、卤素、硝基、酯基、氰基中的至少一种。
3.根据权利要求1所述的合成方法，其特征在于，所述手性10-炔丙基蒽酮类化合物具有以下结构之一：
Figure FDA0003621746050000031
Figure FDA0003621746050000041
Figure FDA0003621746050000051
4.根据权利要求1所述的合成方法，其特征在于，所述铜盐选自水合醋酸铜、水合硫酸铜、无水醋酸铜、无水硫酸铜、三氟甲磺酸铜、氯化铜、氯化亚铜、碘化亚铜、醋酸亚铜、六水合高氯酸铜、三氟甲磺酸亚铜合苯、六氟磷酸四乙腈铜、四氟硼酸四乙腈铜、或者高氯酸四乙腈铜中的任意一种或者多种的组合。
5.根据权利要求1所述的合成方法，其特征在于，所述铜盐和所述手性P,N,N-配体的摩尔比为1:0.1～1:10。
6.根据权利要求1所述的合成方法，其特征在于，所述第一反应介质为包含无水甲醇和无水甲苯的混合溶液，所述混合溶液中，所述无水甲醇和所述无水甲苯的体积比为2:1～5:1。
7.根据权利要求1所述的合成方法，其特征在于，所述碱性添加剂的摩尔用量为所述炔丙基类化合物的摩尔用量的0.01～10倍；和/或
所述手性铜催化剂的摩尔用量为所述炔丙基类化合物的摩尔用量的0.01～100倍。
8.根据权利要求4所述的合成方法，其特征在于，控制所述不对称炔丙基烷基化反应的反应温度为-20℃～0℃。
9.根据权利要求1所述的合成方法，其特征在于，所述合成方法还包括：在不对称炔丙基烷基化反应结束后，减压去除反应介质，然后采用硅胶柱层析分离技术进行提纯。
CN202110381524.XA 2021-04-09 2021-04-09 一种手性10-炔丙基蒽酮类化合物及其合成方法 Active CN113214069B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110381524.XA CN113214069B (zh) 2021-04-09 2021-04-09 一种手性10-炔丙基蒽酮类化合物及其合成方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110381524.XA CN113214069B (zh) 2021-04-09 2021-04-09 一种手性10-炔丙基蒽酮类化合物及其合成方法

Publications (2)

Publication Number Publication Date
CN113214069A CN113214069A (zh) 2021-08-06
CN113214069B true CN113214069B (zh) 2022-07-08

Family

ID=77086801

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110381524.XA Active CN113214069B (zh) 2021-04-09 2021-04-09 一种手性10-炔丙基蒽酮类化合物及其合成方法

Country Status (1)

Country Link
CN (1) CN113214069B (zh)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104513146A (zh) * 2013-10-08 2015-04-15 中国科学院大连化学物理研究所 一种由β-酮酸不对称合成手性β-乙炔基酮的方法
CN104761660A (zh) * 2015-01-22 2015-07-08 河南金誉包装科技股份有限公司 含助引发剂胺的可聚合硫杂蒽酮咔唑类可见光引发剂及其制备方法
CN106866389A (zh) * 2015-12-10 2017-06-20 中国科学院大连化学物理研究所 一种制备手性炔丙基芳基醚类化合物的方法
CN108101755A (zh) * 2016-11-24 2018-06-01 中国科学院大连化学物理研究所 一种制备手性4-(2-炔丙基)苯酚类化合物的方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104513146A (zh) * 2013-10-08 2015-04-15 中国科学院大连化学物理研究所 一种由β-酮酸不对称合成手性β-乙炔基酮的方法
CN104761660A (zh) * 2015-01-22 2015-07-08 河南金誉包装科技股份有限公司 含助引发剂胺的可聚合硫杂蒽酮咔唑类可见光引发剂及其制备方法
CN106866389A (zh) * 2015-12-10 2017-06-20 中国科学院大连化学物理研究所 一种制备手性炔丙基芳基醚类化合物的方法
CN108101755A (zh) * 2016-11-24 2018-06-01 中国科学院大连化学物理研究所 一种制备手性4-(2-炔丙基)苯酚类化合物的方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Highly Enantioselective Copper-Catalyzed Propargylic Substitution of Propargylic Acetates with 1,3-Dicarbonyl Compounds;Fu-Zhong Han et al.;《Organic Letters》;20131227;第16卷(第2期);第588-591页 *
Phase-Transfer-Catalyzed Alkylation of Anthrone and 10-Propargylanthrone;Majumdar, K. C. et al.;《Synthesis》;19880731(第7期);第552-553页 *

Also Published As

Publication number Publication date
CN113214069A (zh) 2021-08-06

Similar Documents

Publication Publication Date Title
Holder et al. Synthesis of diverse β-quaternary ketones via palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic enones
CN108640869B (zh) 过渡金属催化的c-h偶联高效制备邻酰胺化芳基杂环类衍生物
Ren et al. C (sp2)–H Functionalization of Imidazole at the C2-and C4-Position via Palladium-Catalyzed Isocyanide Insertion Leading to Indeno [1, 2-d] imidazole and Imidazo [1, 2-a] indole Derivatives
Karataş et al. N-heterocyclic carbene palladium complexes with different N-coordinated ligands: Comparison of their catalytic activities in Suzuki-Miyaura and Mizoroki-Heck reactions
KR20080027794A (ko) 교차결합반응용 Ｐｄ(ａｃａｃ)2의 친핵 복소환식 카르벤유도체
Nawaz et al. Direct arylation (hetero-coupling) of heteroarenes via unsymmetrical palladium-PEPPSI-NHC type complexes
Ge et al. Palladium-catalyzed domino aminocarbonylation of alkynols: direct and selective synthesis of itaconimides
CN113214069B (zh) 一种手性10-炔丙基蒽酮类化合物及其合成方法
Li et al. Synthesis and structure of an air-stable bis (pentamethylcyclopentadienyl) zirconium pentafluorbezenesulfonate and its application in catalytic epoxide ring-opening reactions
CN108101755B (zh) 一种制备手性4-(2-炔丙基)苯酚类化合物的方法
TWI642658B (zh) 茚並異喹啉衍生物的製備方法
CN108440373B (zh) 一种铁催化的氰烷基吲哚啉及其制备方法
Karthik et al. Dibenzofuran and dibenzothiophene based palladium (ii)/NHC catalysts–synthesis and applications in C–C bond formation
CN112824412B (zh) 手性1′H-螺[吲哚啉-3,4′-吡喃并[2,3-c]吡唑]-2-酮类化合物
Niedballa et al. Consecutive Three‐Component Coupling‐Addition Synthesis of β‐Amino Enoates and 3‐Hydroxypyrazoles via Ethyl 3‐Arylpropiolates
CN111825509B (zh) 一种手性3,4,4-三取代吡咯烷酮类化合物的催化不对称合成方法
CN108752213B (zh) 一种可见光激发二硫醚催化制备α-羟甲基-β-二羰基化合物的方法
CN113105401A (zh) 一种1，2，3-三氮唑衍生物及其制备方法与应用
CN107382782B (zh) 一种多芳基取代萘酚衍生物的合成方法
CN108976186B (zh) 一种基于碳-氢键活化的制备四取代呋喃类化合物的方法
Siah et al. Preparation and Catalytic Activity of Novel σ, π‐Dual Gold (I) Acetylide Complexes
CN113461690B (zh) 一种手性4,6-二氧八氢吡咯并[3,4-c]吡咯-1-羧酸酯类化合物的合成方法
CN112661700B (zh) 一种3-(1h-吡唑-1-基)丙烯酸乙酯类化合物的制备方法
CN109438439A (zh) 四氢异喹啉并1,2,4-三唑类衍生物及其制备方法
CN114426521B (zh) 一种含氟烷硫基取代的吡唑衍生物及其合成方法

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant