CN114573472B - α-高烯丙基酰胺衍生物及其合成方法 - Google Patents

α-高烯丙基酰胺衍生物及其合成方法 Download PDF

Info

Publication number
CN114573472B
CN114573472B CN202210111333.6A CN202210111333A CN114573472B CN 114573472 B CN114573472 B CN 114573472B CN 202210111333 A CN202210111333 A CN 202210111333A CN 114573472 B CN114573472 B CN 114573472B
Authority
CN
China
Prior art keywords
mmol
cdcl
reaction
glove box
nmr
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
CN202210111333.6A
Other languages
English (en)
Other versions
CN114573472A (zh
Inventor
邢栋
王上
项云菲
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.)
East China Normal University
Original Assignee
East 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 East China Normal University filed Critical East China Normal University
Priority to CN202210111333.6A priority Critical patent/CN114573472B/zh
Publication of CN114573472A publication Critical patent/CN114573472A/zh
Application granted granted Critical
Publication of CN114573472B publication Critical patent/CN114573472B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
    • C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
    • C07D207/06—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32—Oxygen atoms
    • C07D209/34—Oxygen atoms in position 2
    • 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
    • C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—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 one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D211/74—Oxygen atoms
    • C07D211/76—Oxygen atoms attached in position 2 or 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D223/08—Oxygen atoms
    • C07D223/10—Oxygen atoms attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
    • 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
    • C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

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

Abstract

本发明公开了一种α‑高烯丙基取代酰胺衍生物的制备方法，以γ‑内酰胺等环状酰胺或直链酰胺和共轭1,3‑二烯化合物为原料，在有机溶剂和添加剂存在的条件下，以高收率、高区域选择性得到目标产物。本发明具有高原子经济性、高区域选择性等优势，可实现酰胺化合物的α‑高烯丙基化反应。本发明合成的α‑高烯丙基酰胺衍生物是一种潜在的合成中间体，在医药化工等领域具有潜在应用前景。

Description

α-高烯丙基酰胺衍生物及其合成方法
技术领域
本发明属于化学合成领域，具体涉及一种α-高烯丙基酰胺衍生物及其合成方法。
背景技术
构建C-C键是有机合成最主要的目标之一，羰基化合物α-烷基化反应是构建C-C键最直接有效的方法。近些年，有机合成化学家尝试开发更加绿色高效和原子经济性更好的转化方法，而过渡金属催化的羰基化合物与不饱和碳氢化合物的α-烯丙基化反应成为研究的重点领域(Chem.Rev.2017,117,9333-9403)。这其中，共轭1,3-丁二烯在与各种羰基化合物发生α-烯丙基烷基化反应显示出了良好的底物适用性。
在传统的过渡金属催化羰基化合物与共轭1,3-二烯发生α-烯丙基烷基化反应过程中，首先会生成一类金属氢物种，它可以活化共轭1,3-二烯从而生成一类金属-π-烯丙基物种，然后羰基化合物做为亲核试剂选择性进攻金属-π-烯丙基物种发生1,2-加成生成相应的支链选择性产物(J.Am.Chem.Soc.,2018,140,11627-11630)。另一方面，羰基化合物与取代的1,3-二烯选择性2,1-加成生成相应的直链选择性α-高烯丙基烷基化产物还没有报导。因此，从容易获得的简单酰胺和共轭1,3-二烯开发原子经济性和无副产物的α-高烯基化反应生成直链选择性产物具有高度重要性。
发明内容
本发明的目的是克服现有技术存在的上述缺陷，公开一种经济、绿色、高效、选择性好、底物范围广的酰胺与共轭1,3-二烯的α-高烯丙基烷基化反应，通过使用碱作为添加剂，以92％的产率获得所需的α-高烯丙基化目标产物3a即所述α-高烯丙基酰胺衍生物，并具有优异的区域选择性和原子经济性。
本发明提出一种α-高烯丙基酰胺衍生物的合成方法，在有机溶剂、添加剂存在的条件下，以式(1a)所示的酰胺、式(2a)所示的共轭1,3-二烯为反应原料，进行反应，得到式(3a)所示的α-高烯丙基酰胺衍生物；所述反应如下反应式(A)所示：
其中：
R1为以下所列基团中的一种，包括链状烷烃，苯基，苄基，烷基取代的苯基，烷氧基取代的苯基，烷氧基取代的苄基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代基的苯基；
R2为以下所列基团中的一种，包括链状烷烃，苯基，苄基，烷基取代的苯基；
R3为氢；或当R3不是氢时，式(1a)为包括γ-内酰胺、δ-内酰胺在内，碳个数在4-6的各种环状酰胺；
R4为以下所列基团中的一种，包括链状烷烃，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的链状烷烃，环烷基，苯基，苄基，烷基取代的苯基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的苯基，芳环或芳杂环取代的苯基，芳杂环；
R5为以下所列基团中的一种，包括氢，烷基，苯基；
R6为以下所列基团中的一种，包括苯基，烷基取代的苯基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的苯基，芳环或芳杂环取代的苯基，芳杂环。
优选地，
R1为甲基，苯基，苄基，对甲氧基苯基，对甲氧基苄基，烯丙基；
R2为甲基，苄基，烷基取代的苯基；
R3为氢；或当R3不是氢时，式(1a)为包括γ-内酰胺、δ-内酰胺在内，碳个数在4-6的各种环状酰胺；
R4为C1-C6烷基，含有氧原子取代的链状烷烃，苯基，苄基，C1-C6烷基取代的苯基，卤素原子取代的苯基；
R5为以下所列基团中的一种，包括氢，甲基，苯基；
R6为苯基，C1-C6烷基取代的苯基，卤素原子取代的苯基，N，N-二甲基取代的苯基，萘基，呋喃基。
进一步优选地，
R1苯基，苄基；
R2为甲基，苄基；
R3为氢；
R4为甲基，乙基，异丙基，正丁基，苯基，苄基；
R5为氢，甲基，苯基；
R6为苯基，对甲基苯基，对氯苯基，对甲氧基苯基，萘基，呋喃基。
本发明中，所述酰胺包括γ-内酰胺，δ-内酰胺，直链烷基酰胺等。
本发明中，所述有机溶剂为1，2-二氯乙烷，甲苯，乙腈，四氢呋喃，1，4-二氧六环，甲基叔丁基醚，CPME，乙二醇二甲醚，二甲亚砜中的一种或多种；优选地，为CPME。
本发明中，所述添加剂为叔丁醇钾，叔丁醇钠，叔丁醇锂，氢氧化钾，六甲基二硅基胺基钾中一种或多种；优选地，为叔丁醇钾。
本发明中，当所述酰胺:共轭1,3-二烯:添加剂的摩尔比为：1:(1-3):(0.1-1.2)；优选地，为1:1.2:0.2。
本发明中，以酰胺的用量为基准，所述有机溶剂的加入量为1mL/mmol酰胺；
本发明中，所述反应温度为25–100℃；优选地，为50℃。
本发明中，所述反应的时间为12-48h；优选地，为24h。
本发明合成方法，还包括后处理步骤：将反应得到的粗反应液用体积比为乙醚:石油醚＝1:10～1:5的溶液进行柱层析，高收率、高区域选择性得到α-高烯丙基酰胺衍生物。
本发明方法中粗产物分离纯化的方法为将粗反应液用体积比为乙醚:石油醚＝1:10～1:5的流动相进行柱层析。
在一个具体的实施方案中，本发明α-高烯丙基酰胺衍生物的合成过程包括:向装有搅拌子的4mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。
本发明还提出一种α-高烯丙基酰胺衍生物，其结构如式(3a)所示：
其中：R1为以下所列基团中的一种，包括链状烷烃，苯基，苄基，烷基取代的苯基，烷氧基取代的苯基，烷氧基取代的苄基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代基的苯基；
R2为以下所列基团中的一种，包括链状烷烃，苯基，苄基，烷基取代的苯基；
R3为氢；或当R3不是氢时，式(1a)为包括γ-内酰胺、δ-内酰胺在内，碳个数在4-6的各种环状酰胺；
R4为以下所列基团中的一种，包括链状烷烃，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的链状烷烃，环烷基，苯基，苄基，烷基取代的苯基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的苯基，芳环或芳杂环取代的苯基，芳杂环；
R5为以下所列基团中的一种，包括氢，烷基，苯基；
R6为以下所列基团中的一种，包括苯基，烷基取代的苯基，含有氧原子、氮原子、硼原子、硅原子、卤素原子取代的苯基，芳环或芳杂环取代的苯基，芳杂环。
优选地，
R1为甲基，苯基，苄基，对甲氧基苯基，对甲氧基苄基，烯丙基；
R2为甲基，苄基，烷基取代的苯基；
R3为氢；或当R3不是氢时，式(1a)为包括γ-内酰胺、δ-内酰胺在内，碳个数在4-6的各种环状酰胺；
R4为C1-C6烷基，含有氧原子取代的链状烷烃，苯基，苄基，C1-C6烷基取代的苯基，卤素原子取代的苯基；
R5为以下所列基团中的一种，包括氢，甲基，苯基；
R6为苯基，C1-C6烷基取代的苯基，卤素原子取代的苯基，N，N-二甲基取代的苯基，萘基，呋喃基。
本发明还提出按如上方法合成制备得到的如式(3a)所示的α-高烯丙基酰胺衍生物。
本发明还提供了所述α-高烯丙基酰胺衍生物在合成药物中间体等中的应用。
本发明所述的合成方法可以用于很多生物活性物质的结构优化及合成。
本发明具有高原子经济性、高区域选择性等优势，可实现廉价基础的有机化学品到高附加值α-高烯丙基酰胺衍生物的高效转化。本发明合成的α-高烯丙基酰胺衍生物是一种潜在的合成中间体，在精细化学品合成和药物中间体合成中具有潜在应用前景。
本发明有益效果还包括：采用共轭1,3-二烯作为烯丙基烷基化试剂，可替代传统方法中通常所需要的带离去基团的烯丙基化试剂，反应步骤得到简化，原子经济性高，不产生副产物；同时，采用催化量的叔丁醇钾做为添加剂，有效克服了传统方法中需要用到当量的金属强碱，如LDA、LiHMDS、KHMDS等，反应条件温和、收率高、选择性好、底物适用性广、操作安全简单。同时，本发明所得到的α-高烯丙基酰胺衍生物可以发生进一步转化，得到其他方法较难合成化合物或者药物分子，在精细化学品的合成中具有潜在的应用前景。
具体实施方式
结合以下具体实施例，对本发明作进一步的详细说明，本发明的保护内容不局限于以下实施例。在不背离发明构思的精神和范围下，本领域技术人员能够想到的变化和优点都被包括在本发明中，并且以所附的权利要求书为保护范围。实施本发明的过程、条件、试剂、实验方法等，除以下专门提及的内容之外，均为本领域的普遍知识和公知常识，本发明没有特别限制内容。
实施例1：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为92％。1HNMR(400MHz,CDCl3)δ7.47(d,J＝7.6Hz,2H),7.25-7.18(m,4H),7.12-7.09(m,1H),6.82(d,J＝8.0Hz,2H),6.33(d,J＝15.6Hz,1H),6.18-6.10(m,1H),3.72(s,3H),3.69-3.64(m,2H),2.31-2.25(m,1H),2.18-2.04(m,2H),1.90-1.84(m,1H),1.72-1.67(m,2H),1.19(s,3H).13C NMR(101MHz,CDCl3)δ177.76,156.47,136.16,132.92,132.43,130.99,128.92,128.60,127.15,121.48,114.00,55.50,45.56,44.99,37.39,30.82,28.14,23.24.IR(v/cm-1):3732,3448,2945,2830,2171,2016,1121,1028cm-1.HRMS(ESI):calcd.C22H26NO2[M+H]+:336.1964.Found:336.1959.
实施例2：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的甲苯，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为91％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.21(d,J＝8.0Hz,2H),7.09(d,J＝8.0Hz,2H),6.89(d,J＝9.2Hz,2H),6.37(d,J＝16.0Hz,1H),6.19-6.12(m,1H),3.80(s,3H),3.75-3.71(m,2H),2.32(s,3H),2.24-2.12(m,2H),1.96-1.90(m,1H),1.79-1.74(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ178.01,156.54,136.75,134.99,133.08,130.02,129.30,125.95,121.63,114.11,55.61,45.72,45.16,37.65,30.98,28.25,23.29,21.27.IR(V/cm-1):3732,3448,2945,2830,2171,2016,1121,1023cm-1.HRMS(ESI):calcd.C23H28NO2[M+H]+:350.2120.Found:350.2133.
实施例3：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钠(1.0eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为82％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.24(d,J＝8.0Hz,2H),6.89(d,J＝9.2Hz,2H),6.82(d,J＝8.4Hz,2H),6.35(d,J＝16.0Hz,1H),6.10-6.03(m,1H),3.80(s,6H),3.74(t,J＝7.2Hz,2H),2.36-2.28(m,1H),2.23-2.12(m,2H),1.97-1.90(m,1H),1.81-1.72(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ178.00,158.84,156.55,133.11,130.65,129.56,128.18,127.14,121.62,114.12,114.04,55.60,55.40,45.70,45.14,37.76,30.97,28.23,23.32.IR(V/cm-1):3749,3724,3569,3376,2843,2832,2339,1973,1126,1022cm-1.HRMS(ESI):calcd.C23H28NO3[M+H]+:366.2069.Found:336.2045.
实施例4：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为90％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.37(dd,J＝7.6,1.6Hz,1H),7.19-7.15(m,1H),6.91-6.87(m,3H),6.83(d,J＝8.0Hz,1H),6.73(d,J＝16.0Hz,1H),6.24-6.16(m,1H),3.81(s,3H),3.79(s,3H),3.73(t,J＝7.2Hz,2H),2.43-2.31(m,1H),2.30-2.20(m,1H),2.21-2.11(m,1H),1.97-1.88(m,1H),1.83-1.74(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ178.04,156.52,156.38,133.11,131.03,128.03,126.84,126.55,124.82,121.63,120.74,114.09,110.85,55.59,55.52,45.71,45.15,37.66,30.92,28.70,23.33.IR(V/cm-1):3749,3647,3563,3376,2843,2839,2027,1512,1126,1022cm-1.HRMS(ESI):calcd.C23H28NO3[M+H]+:366.2069.Found:366.2045.
实施例5：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的四氢呋喃，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为82％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.21(d,J＝8.4Hz,2H),6.89(d,J＝9.2Hz,2H),6.66(d,J＝8.8Hz,2H),6.32(d,J＝16.0Hz,1H),6.03-5.96(m,1H),3.80(s,3H),3.73(t,J＝7.2Hz,2H),2.93(s,6H),2.37-2.25(m,1H),2.24-2.12(m,2H),1.98-1.88(m,1H),1.78-1.73(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ178.10,156.51,149.84,133.14,129.93,126.90,126.14,121.62,114.10,112.73,55.60,45.72,45.18,40.75,37.91,30.99,28.28,23.30.IR(V/cm-1):3820,3750,3446,2996,2829,2108,1997,1120,1022cm-1.HRMS(ESI):calcd.C24H31N2O2[M+H]+:379.2386.Found:379.2359.
实施例6：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的1,4-二氧六环，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为89％。1HNMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.30-7.22(m,2H),6.96(t,J＝8.4Hz,2H),6.89(d,J＝9.2Hz,2H),6.36(d,J＝16.0Hz,1H),6.15-6.08(m,1H),3.79(s,3H),3.75-3.71(m,2H),2.40-2.28(m,1H),2.27-2.10(m,2H),1.96-1.90(m,1H),1.84-1.74(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ177.91,163.24,160.80,156.56,133.93,133.90,133.03,130.09,130.07,129.01,127.49,127.41,121.60,115.52,115.31,114.10,55.59,45.68,45.10,37.58,30.92,28.19,23.33.IR(V/cm-1):3709,3610,2941,2830,2271,2046,1515,1124,1023cm-1.HRMS(ESI):calcd.C22H25FNO2[M+H]+:354.1869.Found:354.1898.
实施例7：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的二甲亚砜，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为89％。1H NMR(400MHz,CDCl3)δ7.53(d,J＝9.2Hz,2H),7.27-7.21(m,4H),6.89(d,J＝9.2Hz,2H),6.35(d,J＝15.6Hz,1H),6.23-6.15(m,1H),3.80(s,3H),3.76-3.72(m,2H),2.42-2.29(m,1H),2.29-2.09(m,2H),2.00-1.88(m,1H),1.84-1.70(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ177.87,156.58,136.28,133.04,132.55,131.11,129.04,128.72,127.26,121.60,114.12,55.61,45.68,45.10,37.51,30.94,28.26,23.36.IR(V/cm-1):3751,3660,3486,2941,2830,2271,2046,1516,1124,1022cm-1.HRMS(ESI):calcd.C22H25ClNO2[M+H]+:370.1574.Found:370.1572.
实施例8：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的1,2-二氯乙烷，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为87％。1HNMR(400MHz,CDCl3)δ7.53(d,J＝9.2Hz,2H),7.38(d,J＝8.4Hz,2H),7.16(d,J＝8.4Hz,2H),6.89(d,J＝9.2Hz,2H),6.34(d,J＝16.0Hz,1H),6.24-6.16(m,1H),3.80(s,3H),3.76-3.71(m,2H),2.40-2.28(m,1H),2.27-2.10(m,2H),1.97-1.90(m,1H),1.80-1.74(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ177.88,156.61,136.73,133.04,131.66,131.27,129.10,127.62,121.63,120.66,114.14,55.63,45.70,45.10,37.48,30.95,28.28,23.37.IR(V/cm-1):3868,3651,3552,2946,2889,2169,1513,1125,1022cm-1.HRMS(ESI):calcd.C22H25BrNO2[M+H]+:414.1069.Found:414.1088.
实施例9：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇锂(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为91％。1HNMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.22-7.08(m,3H),7.00(d,J＝7.2Hz,1H),6.89(d,J＝9.2Hz,2H),6.38(d,J＝15.6Hz,1H),6.23-6.19(m,1H),3.80(s,3H),3.73(d,J＝7.2Hz,2H),2.32(s,4H),2.28-2.10(m,2H),1.99-1.89(m,1H),1.84-1.71(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ177.94,156.54,138.10,137.72,133.10,130.26,130.15,128.50,127.82,126.80,123.21,121.65,121.60,114.11,55.60,45.69,45.13,37.63,30.98,28.28,23.31,21.52.IR(V/cm-1):3732,3448,2945,2830,2171,2016,1121,1023cm-1.HRMS(ESI):calcd.C23H28NO2[M+H]+:350.2120.Found:350.2133.
实施例10：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和氢氧化钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为56％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.28(s,1H),7.21-7.12(m,3H),6.89(d,J＝9.2Hz,2H),6.34(d,J＝16.0Hz,1H),6.26-6.18(m,1H),3.79(s,3H),3.76-3.72(m,2H),2.41-2.30(m,1H),2.29-2.09(m,2H),1.96-1.90(m,1H),1.80-1.74(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ177.82,156.57,139.67,134.51,133.04,132.01,129.80,128.97,126.95,126.00,124.28,121.59,114.12,55.60,45.66,45.09,37.45,30.96,28.24,23.34.IR(V/cm-1):3709,3660,3486,2841,2630,2170,2046,1516,1124,1022cm-1.HRMS(ESI):calcd.C22H25ClNO2[M+H]+:370.1574.Found:370.1572.
实施例11：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和六甲基二硅基胺基钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为63％。1H NMR(400MHz,CDCl3)δ7.82-7.72(m,3H),7.64(s,1H),7.55(d,J＝9.2Hz,3H),7.48-7.37(m,2H),6.88(d,J＝9.2Hz,2H),6.57(d,J＝16.0Hz,1H),6.38-6.31(m,1H),3.79(s,3H),3.75(t,J＝7.2Hz,2H),2.47-2.36(m,1H),2.34-2.14(m,2H),2.01-1.92(m,1H),1.85-1.79(m,2H),1.29(s,3H).13C NMR(101MHz,CDCl3)δ177.95,156.56,135.26,133.80,133.10,132.82,130.87,130.35,128.20,127.97,127.74,126.25,125.62,125.55,123.65,121.62,114.12,55.61,45.71,45.17,37.65,31.00,28.43,23.39.IR(V/cm-1):3732,3448,2945,2830,2171,2016,1121,1022cm-1.HRMS(ESI):calcd.C26H27NO2Na[M+Na]+:408.1939.Found:408.1938.
实施例12：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热12小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为92％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.30(d,J＝2.0Hz,1H),6.90(d,J＝9.2Hz,2H),6.33(dd,J＝3.6,2.0Hz,1H),6.27-6.09(m,3H),3.80(s,3H),3.75-3.71(m,2H),2.37-2.26(m,1H),2.25-2.09(m,2H),1.95-1.91(m,1H),1.80-1.72(m,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ177.87,156.57,153.21,141.44,133.06,129.32,121.64,118.93,114.12,111.18,106.31,55.60,45.68,45.08,37.45,31.02,27.97,23.20.IR(V/cm-1):3863,3647,3252,2947,2831,2215,2013,1514,1120,1022cm-1.HRMS(ESI):calcd.C20H24NO3[M+H]+:326.1756.Found:326.1746.
实施例13：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热48小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为38％。1.4:1dr.1H NMR(400MHz,Chloroform-d)δ7.49(d,J＝3.6Hz,2H),7.32-6.97(m,10H),6.89(d,J＝8.4Hz,2H),6.29(d,J＝15.6Hz,1H),5.98-5.91(m,1H),3.80(s,3H),3.61(q,J＝8.4Hz,1H),3.49-3.30(m,1H),3.22-3.08(m,1H),2.80-2.72(m,1H),2.69-2.43(m,2H),2.24-1.98(m,1H),1.83-1.75(m,1H),1.41(s,1H),1.13(s,2H).13C NMR(101MHz,CDCl3)δ177.39,176.35,156.66,142.50,141.85,140.99,138.83,137.80,132.98,132.90,131.25,129.75,129.25,128.96,128.80,128.41,128.36,128.25,128.07,127.96,126.97,126.90,126.86,126.09,125.82,121.87,114.10,114.09,55.62,55.60,52.46,51.54,49.48,45.80,45.67,35.96,35.18,32.04,31.27,28.33,24.06,23.52.IR(V/cm-1):3691,3667,2947,2832,2146,1515,1119,1022cm-1.HRMS(ESI):calcd.C28H30NO2[M+H]+:412.2277.Found:412.2245.
实施例14：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热48小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为52％。1.4:1dr.1HNMR(400MHz,CDCl3)δ7.54(d,J＝8.8Hz,2H),7.35-7.27(m,4H),7.20(t,J＝7.2Hz,1H),6.89(dd,J＝8.8,5.6Hz,2H),6.39(t,J＝16.0Hz,1H),6.23-6.16(m,1H),3.80(s,3H),3.77-3.66(m,2H),2.66-2.57(m,1H),2.64-2.59(m,0.6H),2.38-2.33(m,0.4H),2.23-2.15(m,1H),2.09-1.88(m,2H),1.81-1.74(m,1H),1.28(s,3H),0.97(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ178.15,178.06,156.63,137.82,133.05,131.46,131.40,129.76,129.53,128.65,128.60,127.08,127.01,126.12,126.09,121.80,121.78,114.16,114.14,55.64,49.18,48.82,45.94,45.85,39.10,38.91,36.69,34.95,27.23,26.80,22.91,22.26,15.20,13.86.IR(V/cm-1):3773,3667,2947,2832,2146,1515,1119,1022cm-1.HRMS(ESI):calcd.C23H28NO2[M+H]+:350.2120.Found:350.2133.
实施例15：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的甲基叔丁基醚，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为78％。1HNMR(400MHz,CDCl3)δ7.66(d,J＝8.0Hz,2H),7.41-7.25(m,6H),7.22-7.10(m,2H),6.41(d,J＝16.0Hz,1H),6.25-6.17(m,1H),3.80-3.76(m,2H),2.41-2.30(m,1H),2.28-2.11(m,2H),1.98-1.92(m,1H),1.81-1.76(m,2H),1.28(s,3H).13C NMR(101MHz,CDCl3)δ178.33,139.81,137.76,130.29,130.25,128.92,128.60,127.04,126.06,124.48,119.84,45.37,45.30,37.55,30.92,28.23,23.23.IR(V/cm-1):3648,3463,2944,2829,2167,1980,1472,1118,1022cm- 1.HRMS(ESI):calcd.C21H24NO[M+H]+:306.1858.Found:306.1877.
实施例16：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的乙二醇二甲醚，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为69％。1HNMR(400MHz,CDCl3)δ7.35-7.26(m,7H),7.25-7.16(m,3H),6.39(d,J＝16.0,1H),6.24-6.17(m,1H),4.45(d,J＝3.2Hz,2H),3.15(t,J＝7.2Hz,2H),2.33-2.25(m,1H),2.22-2.12(m,1H),2.05-1.95(m,1H),1.83-1.68(m,3H),1.20(s,3H).13C NMR(101MHz,CDCl3)δ178.85,137.80,136.83,130.47,130.10,128.78,128.76,128.60,128.20,127.63,127.02,126.04,46.89,44.03,43.44,37.49,31.16,28.26,23.32.IR(V/cm-1):3684,3347,2943,2830,2336,2043,1472,1120,1022cm-1.HRMS(ESI):calcd.C22H26NO2[M+OH]+:336.1964.Found:336.1959.
实施例17：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的乙腈，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为92％。1H NMR(400MHz,CDCl3)δ7.34-7.26(m,4H),7.21-7.14(m,3H),6.85(d,J＝9.2Hz,2H),6.38(d,J＝16.0Hz,1H),6.24-6.16(m,1H),4.38(d,J＝5.6Hz,2H),3.79(s,3H),3.13(t,J＝6.4Hz,2H),2.34-2.22(m,1H),2.21-2.10(m,1H),2.03-1.93(m,1H),1.79-1.68(m,3H),1.18(s,3H).13C NMR(101MHz,CDCl3)δ178.73,159.14,137.83,130.52,130.09,129.57,128.94,128.62,127.03,126.06,114.15,55.39,46.29,44.11,43.33,37.49,31.15,28.28,23.32.IR(V/cm-1):3690,3456,2946,2830,2193,2002,1516,1126,1023cm-1.HRMS(ESI):calcd.C23H28NO2[M+H]+:350.2120.Found:350.2133.
实施例18：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为87％。1H NMR(400MHz,CDCl3)δ7.35-7.24(m,5H),7.22-7.14(m,1H),6.88(dd,J＝19.6,2.4Hz,1H),6.39(d,J＝16.0Hz,1H),6.22-6.12(m,1H),5.02-4.90(m,1H),3.41(t,J＝9.6Hz,2H),2.36-2.05(m,3H),1.95-1.81(m,1H),1.78-1.66(m,5H),1.20(s,3H).13C NMR(101MHz,CDCl3)δ176.68,137.74,130.21,130.18,128.58,127.02,126.04,124.86,106.88,44.67,42.34,37.67,30.96,28.25,23.55,15.33.IR(V/cm-1):3750,3464,3051,2828,2196,1506,1125,1023cm-1.HRMS(ESI):calcd.C18H24NO[M+H]+:270.1858.Found:270.1855.
实施例19：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的甲苯，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为93％。1HNMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.35-7.24(m,4H),7.22-7.14(m,1H),6.89(d,J＝9.2Hz,2H),6.39(d,J＝16.0Hz,1H),6.24-6.16(m,1H),3.79(s,3H),3.72(t,J＝7.2Hz,2H),2.37-2.15(m,2H),2.12-2.04(m,2H),1.83-1.71(m,2H),1.65-1.56(m,2H),1.49-1.38(m,1H),1.35-1.24(m,1H),0.93(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ177.34,156.57,137.77,132.97,130.39,130.16,128.57,126.99,126.03,121.74,114.10,55.59,48.75,46.13,39.79,36.89,28.13,17.68,14.73.IR(V/cm-1):3711,3567,2946,2828,2365,1996,1669,1183,1023cm-1.HRMS(ESI):calcd.C24H30NO2[M+H]+:364.2277.Found:364.2291.
实施例20：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为89％。1HNMR(400MHz,CDCl3)δ7.55(d,J＝9.2Hz,2H),7.33-7.24(m,4H),7.21-7.14(m,1H),6.89(d,J＝9.2Hz,2H),6.39(d,J＝16.0Hz,1H),6.24-6.16(m,1H),3.79(s,3H),3.72(t,J＝7.2Hz,2H),2.38-2.27(m,1H),2.27-2.16(m,1H),2.11-2.04(m,2H),1.86-1.71(m,2H),1.65-1.60(m,2H),1.42-1.26(m,4H),0.90(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ177.28,156.49,137.69,132.91,130.31,130.07,128.48,126.91,125.95,121.66,114.02,55.51,48.58,46.03,37.12,36.78,28.05,26.45,23.29,14.07.IR(V/cm-1):3751,3690,2943,2830,2339,2148,1514,1120,1023cm-1.HRMS(ESI):calcd.C25H32NO2[M+H]+:378.2433.Found:378.2408.
实施例21：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热48小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为91％。柱层析法分离粗产物(硅胶，PE/Et2O＝100:1～60:1)，得到纯产品。产物为无色液体，产率为72％。1H NMR(400MHz,CDCl3)δ7.55(d,J＝9.2Hz,2H),7.33-7.25(m,4H),7.21-7.16(m,1H),6.90(d,J＝9.2Hz,2H),6.38(d,J＝16.0Hz,1H),6.23-6.17(m,1H),3.80(s,3H),3.78-3.64(m,2H),2.35-2.20(m,2H),2.19-2.09(m,2H),1.92-1.69(m,3H),0.93(t,J＝6.8Hz,6H).13C NMR(101MHz,CDCl3)δ177.18,156.68,137.77,132.84,130.43,130.21,128.58,127.00,126.04,121.97,114.15,114.12,55.61,52.49,46.56,36.90,33.55,28.31,23.52,18.42,16.96.IR(V/cm-1):3751,3690,3417,2943,2830,2389,1514,1120,1024cm-1.HRMS(ESI):calcd.C24H30NO2[M+H]+:364.2277.Found:364.2291.
实施例22：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为89％。1H NMR(400MHz,CDCl3)δ7.34-7.27(m,5H),7.26-7.15(m,7H),6.84(d,J＝9.2Hz,2H),6.42(d,J＝16.0Hz,1H),6.26-6.19(m,1H),3.77(s,3H),3.40-3.34(m,1H),3.14(d,J＝12.8Hz,1H),2.82-2.78(m,1H),2.71(d,J＝13.6Hz,1H),2.43-2.24(m,2H),2.14-1.92(m,3H),1.79-1.75(m,1H).13C NMR(101MHz,CDCl3)δ176.53,156.72,137.73,137.61,132.61,130.31,130.19,130.15,128.58,128.30,127.03,126.79,126.05,122.19,114.02,55.53,50.33,46.02,43.71,37.98,28.22,26.73.IR(V/cm-1):3709,3647,3436,2944,2832,2371,1983,1558,1119,1023cm-1.HRMS(ESI):calcd.C28H30NO2[M+H]+:412.2277.Found:412.2245.
实施例23：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的1,4-二氧六环，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为86％。1HNMR(400MHz,CDCl3)δ7.54(d,J＝9.2Hz,2H),7.33-7.26(m,4H),7.22-7.15(m,1H),6.90(d,J＝9.2Hz,2H),6.40(d,J＝16.0Hz,1H),6.24-6.16(m,1H),3.80(s,3H),3.76-3.72(m,2H),3.54-3.49(m,2H),3.31(s,3H),2.41-2.29(m,1H),2.27-2.16(m,2H),2.14-2.07(m,1H),2.02-1.87(m,2H),1.86-1.74(m,2H).13CNMR(101MHz,CDCl3)δ176.86,156.68,137.73,132.94,130.32,130.18,128.61,127.06,126.07,121.86,114.15,69.45,58.85,55.63,47.58,46.13,36.96,36.37,28.52,28.06.IR(V/cm-1):3735,3647,2944,2832,2371,1983,1119,1023cm-1.HRMS(ESI):calcd.C24H30NO3[M+H]+:380.2226.Found:380.2251.
实施例24：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为87％。1H NMR(400MHz,CDCl3)δ7.53(d,J＝9.2Hz,2H),7.33-7.24(m,4H),7.21-7.15(m,1H),6.89(d,J＝9.2Hz,2H),6.39(d,J＝16.0Hz,1H),6.23-6.15(m,1H),5.86-5.75(m,1H),5.20-5.08(m,2H),3.79(s,3H),3.74-3.65(m,2H),2.49-2.43(m,1H),2.38-2.18(m,3H),2.15-2.01(m,2H),1.88-1.80(m,1H),1.78-1.72(m,1H).13CNMR(101MHz,CDCl3)δ176.69,156.65,137.71,133.90,132.85,130.28,130.17,128.57,127.02,126.04,121.82,118.78,114.11,55.58,48.70,46.11,41.94,36.89,28.10,27.34.IR(V/cm-1):3608,3509,3297,2944,2830,2338,1115,1022cm-1.HRMS(ESI):calcd.C24H28NO2[M+H]+:362.2120.Found:362.2100.
实施例25：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为68％。1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.4Hz,4H),7.36(t,J＝7.6Hz,2H),7.31-7.26(m,5H),7.19-7.17(m,1H),6.89(d,J＝8.8Hz,2H),6.35(d,J＝16.0Hz,1H),6.20-6.13(m,1H),3.79(s,3H),3.75-3.69(m,2H),2.70-2.65(m,1H),2.43-2.34(m,1H),2.33-2.02(m,4H).13C NMR(101MHz,CDCl3)δ175.46,156.67,140.89,137.79,132.95,130.26,130.16,128.75,128.60,127.15,127.02,126.71,126.05,121.74,114.13,55.63,53.28,45.89,38.93,31.13,28.48.IR(V/cm-1):3614,3466,3335,3048,2950,2137,1646,1224,952cm-1.HRMS(ESI):calcd.C27H28NO2[M+H]+:398.2120.Found:398.2148.
实施例26：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为83％。1H NMR(400MHz,CDCl3)δ7.35-7.26(m,4H),7.21-7.17(m,1H),7.09(d,J＝8.8Hz,2H),6.87(d,J＝8.8Hz,2H),6.42(d,J＝16.0Hz,1H),6.26-6.19(m,1H),3.79(s,3H),3.67-3.59(m,1H),3.59-3.54(m,1H),2.39-2.17(m,2H),2.07-1.93(m,4H),1.73-1.66(m,2H),1.33(s,3H).13C NMR(101MHz,CDCl3)δ175.67,158.02,137.91,136.89,130.94,129.98,128.59,127.53,126.95,126.07,114.42,55.58,52.60,42.11,39.85,33.18,28.35,26.70,20.30.IR(V/cm-1):3712,3460,2944,2826,2380,1540,1199,1029cm-1.HRMS(ESI):calcd.C23H27NO2Na[M+Na]+:372.1939.Found:372.1912.
实施例27：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为77％。1H NMR(400MHz,CDCl3)δ7.37-7.27(m,4H),7.22-7.18(m,1H),7.03(d,J＝8.8Hz,2H),6.87(d,J＝8.8Hz,2H),6.43(d,J＝16.0Hz,1H),6.30-6.23(m,1H),3.92-3.83(m,1H),3.79(s,3H),3.64-3.56(m,1H),2.42-2.18(m,2H),2.01-1.93(m,1H),1.91-1.69(m,7H),1.33(s,3H).13C NMR(101MHz,CDCl3)δ177.73,157.83,140.01,137.78,130.86,129.90,128.50,127.63,126.88,125.96,114.43,55.49,51.12,46.31,35.80,28.36,28.24,26.64,23.30.IR(V/cm-1):3566,3249,2943,2899,2228,1558,1123,1021cm-1.HRMS(ESI):calcd.C24H30NO2[M+H]+:364.2277.Found:364.2291.
实施例28：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为58％。1H NMR(400MHz,CDCl3)δ7.33-7.27(m,4H),7.25-7.12(m,8H),7.09-7.03(m,1H),6.71(d,J＝7.6Hz,1H),6.15(d,J＝16.0Hz,1H),6.17-6.00(m,1H),4.91(d,J＝15.6Hz,1H),4.78(d,J＝15.6Hz,1H),2.24-2.15(m,1H),2.03-1.93(m,2H),1.90-1.80(m,1H),1.44(s,3H).13C NMR(101MHz,CDCl3)δ180.75,142.65,137.68,136.30,133.85,130.36,129.65,128.89,128.57,127.84,127.68,127.42,127.07,126.08,122.80,122.67,109.23,48.37,43.82,37.91,28.67,24.67.IR(V/cm-1):3522,3419,2945,2860,2143,1521,1122,1020cm-1.HRMS(ESI):calcd.C26H26NO[M+H]+:368.2014.Found:368.1994.
实施例29：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的1,4-二氧六环，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热12小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为68％。1HNMR(400MHz,CDCl3)δ7.38-7.25(m,9H),7.24-7.09(m,6H),6.29(d,J＝16.0Hz,1H),6.11(m,1H),4.64(d,J＝4.8Hz,2H),4.45(s,2H),2.76(m,1H),2.28-2.13(m,2H),1.99(m,1H),1.60(m,1H),1.18(d,J＝6.4Hz,3H).13C NMR(101MHz,CDCl3)δ177.16,137.74,137.60,136.90,130.50,130.10,128.92,128.65,128.47,128.30,127.57,127.41,126.94,126.34,125.94,49.76,48.40,35.13,34.01,30.78,18.11.IR(V/cm-1):3405,2973,2900,1378,1153,1087,1046,880cm- 1.HRMS(ESI):calcd.C27H30NO[M+H]+:384.2327.Found:384.2310.
实施例30：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的1,4-二氧六环，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热12小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为82％。1HNMR(400MHz,CDCl3)δ7.30(m,12H),7.16(m,3H),6.29(d,J＝15.6Hz,1H),6.10(m,1H),4.66(q,J＝14.4Hz,2H),4.47(s,2H),2.62(m,1H),2.30-2.07(m,2H),1.91(m,1H),1.69(m,3H),0.88(t,J＝7.2Hz,3H).13CNMR(101MHz,CDCl3)δ176.44,137.83,137.61,136.98,130.43,130.18,128.88,128.63,128.48,128.46,127.57,127.41,126.94,126.48,125.95,49.75,48.48,42.21,32.08,30.81,25.75,12.03.IR(V/cm-1):3393,2972,2897,2062,1379,1081,1048,880cm- 1.HRMS(ESI):calcd.C28H32NO[M+H]+:398.2484.Found:398.2515.
实施例31：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为80％。1H NMR(400MHz,CDCl3)δ7.38-7.22(m,12H),7.16(m,3H),6.28(d,J＝16.0Hz,1H),6.09(m,1H),4.67(s,2H),4.46(s,2H),2.75-2.57(m,1H),2.16(m,2H),1.97-1.83(m,1H),1.66(m,2H),1.54-1.45(m,1H),1.24(m,4H),0.90-0.78(t,J＝6.8Hz,3H).13C NMR(101MHz,CDCl3)δ176.66,137.85,137.63,137.04,130.47,130.19,128.89,128.63,128.49,127.58,127.44,126.95,126.48,125.96,49.83,48.62,40.69,32.52,32.38,30.85,29.74,22.88,14.01.IR(V/cm-1):3407,2970,2885,2017,1941,1450,1086,1047,880cm-1.HRMS(ESI):calcd.C30H36NO[M+H]+:426.2797.Found:426.2789.
实施例32：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为91％。1H NMR(400MHz,CDCl3)δ7.40-7.26(m,10H),7.17(m,5H),6.28(d,J＝16.0Hz,1H),6.13(m,1H),4.88(d,J＝14.4Hz,1H),4.55(d,J＝17.2Hz,1H),4.42(m,2H),2.52(m,1H),2.25(m,1H),2.04-1.93(m,3H),0.94(m,6H).13C NMR(101MHz,CDCl3)δ175.83,137.88,137.71,136.97,130.51,130.19,128.89,128.79,128.63,128.58,128.53,128.47,127.62,127.41,126.89,126.71,125.94,49.87,48.21,47.01,31.01,30.64,28.63,21.52,19.09.IR(V/cm-1):3370,2971,2872,2164,1992,1456,1087,1047,880cm-1.HRMS(ESI):calcd.C29H34NO[M+H]+:412.2640.Found:412.2619.
实施例33：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为74％。1H NMR(400MHz,CDCl3)δ7.38-7.24(m,12H),7.17(d,J＝7.7Hz,3H),6.26(d,J＝15.9Hz,1H),6.18-6.05(m,1H),4.73(d,J＝14.5Hz,1H),4.64-4.44(m,3H),2.62(d,J＝8.6Hz,1H),2.32-1.90(m,5H),1.86-1.73(m,2H),1.53(p,J＝11.6Hz,5H),1.12(dt,J＝30.6,10.0Hz,2H).13C NMR(101MHz,CDCl3)δ176.35,137.85,137.68,136.96,130.45,130.20,128.89,128.74,128.58,128.50,127.63,127.44,126.92,126.76,126.43,125.94,49.92,48.28,45.61,43.38,32.73,31.65,31.21,30.75,30.25,25.04,24.98,24.91.IR(V/cm-1):3305,2973,2935,1382,1086,1047,880cm-1.HRMS(ESI):calcd.C31H36NO[M+H]+:438.2797.Found:438.2787.
实施例34：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为92％。1H NMR(400MHz,CDCl3)δ7.37-7.25(m,12H),7.18(t,J＝6.8Hz,1H),7.12(d,J＝7.6Hz,2H),6.28(d,J＝16.0Hz,1H),6.17-6.04(m,1H),4.78(d,J＝14.8Hz,1H),4.56(d,J＝14.8Hz,1H),4.42(s,2H),2.24(m,2H),2.07(m,2H),1.89-1.77(m,1H),1.21-1.10(m,1H),0.61-0.41(m,2H),0.15-0.01(m,2H).13CNMR(101MHz,CDCl3)δ176.23,137.74,137.62,136.94,130.49,130.23,128.90,128.65,128.50,128.44,127.64,127.46,126.97,126.45,125.95,49.83,48.42,44.81,33.24,30.67,14.14,4.19,3.15.IR(V/cm-1):3563,3377,2055,1975,1558,1055,1047,880cm- 1.HRMS(ESI):calcd.C29H32NO[M+H]+:410.2484.Found:410.2477.
实施例35：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为79％。1H NMR(400MHz,CDCl3)δ7.29-7.16(m,14H),7.13(m,2H),7.06(m,2H),6.91-6.83(m,2H),6.26(d,J＝15.6Hz,1H),6.03(m,1H),4.58(s,2H),4.31-4.10(m,2H),2.98(m,2H),2.79(dd,J＝12.0,4.8Hz,1H),2.30-2.06(m,2H),1.92(m,1H),1.76-1.68(m,1H).13C NMR(101MHz,CDCl3)δ175.85,139.82,137.54,137.44,136.81,130.59,129.83,129.28,128.87,128.54,128.49,128.46,127.46,127.38,127.00,126.39,126.30,125.98,49.69,48.80,43.41,39.09,32.70,30.67.IR(V/cm-1):3503,3075,2105,1992,1456,1087,1047,880cm-1.HRMS(ESI):calcd.C33H34NO[M+H]+:460.2640.Found:460.2650.
实施例36：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的甲苯，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为68％。1H NMR(400MHz,CDCl3)δ7.32-7.21(m,17H),7.11(d,J＝7.2Hz,2H),7.00(d,J＝6.8Hz,2H),6.31(d,J＝15.6Hz,1H),6.11(m,1H),5.02(d,J＝14.8Hz,1H),4.53(d,J＝17.2Hz,1H),4.20(t,J＝13.6Hz,2H),3.78(t,J＝7.2Hz,1H),2.37(m,1H),2.18(m,2H),1.91(m,1H).13C NMR(101MHz,CDCl3)δ173.49,139.99,137.68,137.47,136.70,130.59,130.02,128.90,128.87,128.52,128.45,128.11,127.97,127.54,127.28,127.12,126.90,126.38,125.98,49.65,48.53,48.31,34.97,30.99.IR(V/cm-1):3517,2982,2104,1997,1446,1089,1047,880cm-1.HRMS(ESI):calcd.C33H32NO[M+H]+:446.2484.Found:446.2468.
实施例37：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的甲苯，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为84％。1H NMR(400MHz,CDCl3)δ7.36-7.15(m,13H),7.11(d,J＝7.2Hz,2H),7.02(d,J＝6.8Hz,2H),6.84(d,J＝8.0Hz,2H),6.30(d,J＝16.0Hz,1H),6.10(m,1H),5.01(d,J＝14.8Hz,1H),4.54(d,J＝17.2Hz,1H),4.20(t,J＝14.6Hz,2H),3.79(s,3H),3.72(t,J＝7.2Hz,1H),2.31(m,1H),2.16(m,2H),1.88(m,1H).13C NMR(101MHz,CDCl3)δ173.84,158.68,137.70,137.52,136.79,132.01,130.52,130.09,129.00,128.90,128.53,128.49,128.45,128.11,127.52,127.28,126.89,126.36,125.98,114.23,55.31,49.67,48.55,47.36,34.97,30.93,26.94.IR(V/cm-1):3404,2978,2148,2020,1456,1087,1047,879cm-1.HRMS(ESI):calcd.C33H34NO[M+H]+:476.2590.Found:476.2563.
实施例38：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为72％。1HNMR(400MHz,CDCl3)δ7.58(d,J＝7.6Hz,1H),7.30-7.09(m,16H),7.04-6.95(m,2H),6.35(d,J＝16.0Hz,1H),6.16(m,1H),5.02(d,J＝14.8Hz,1H),4.51-4.31(m,2H),4.19(dd,J＝20.8,14.8Hz,2H),2.34(m,2H),2.15(m,1H),1.84(m,1H).13C NMR(101MHz,CDCl3)δ172.94,137.88,137.76,137.36,136.44,133.09,130.55,129.95,129.63,128.79,128.75,128.53,128.44,128.40,128.12,127.51,127.46,127.33,126.85,126.50,126.00,49.45,48.31,44.07,34.25,31.11.IR(V/cm-1):3392,2973,2897,2180,1975,1380,1086,1045,879cm-1.HRMS(ESI):calcd.C32H31ClNO[M+H]+:480.2094.Found:480.2062.
实施例39：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为58％。1H NMR(400MHz,CDCl3)δ7.27(m,15H),7.13(m,2H),7.07-6.97(m,4H),6.94(m,1H),6.30(d,J＝16.0Hz,1H),6.10(m,1H),4.96(d,J＝14.8Hz,1H),4.50(d,J＝17.2Hz,1H),4.26(dd,J＝27.2,14.8Hz,2H),3.78(t,J＝7.2Hz,1H),2.34(m,1H),2.17(m,2H),1.91(m,1H).13C NMR(101MHz,CDCl3)δ173.03,142.42,137.54,137.33,136.53,130.81,130.28,130.19,129.66,128.95,128.60,128.47,128.15,127.64,127.42,126.99,126.26,125.99,123.73,115.00,114.20,113.99,49.74,48.79,47.86,34.89,30.89.IR(V/cm-1):3342,2980,2887,2150,1540,1392,1080,1047,878cm-1.HRMS(ESI):calcd.C32H31FNO[M+H]+:464.2390.Found:464.2431.
实施例40：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的四氢呋喃，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为69％。1H NMR(400MHz,CDCl3)δ7.36-7.18(m,10H),6.36(d,J＝15.6Hz,1H),6.19(m,1H),3.77(t,J＝7.2Hz,1H),2.93(s,3H),2.90(s,3H),2.37-2.09(m,3H),1.88(m,1H).13C NMR(101MHz,CDCl3)δ172.91,140.02,137.74,130.50,130.27,128.77,128.51,128.00,126.93,126.91,125.96,47.96,37.16,35.95,34.44,31.10.IR(V/cm-1):3503,3327,2014,1507,1050,1047,880cm-1.HRMS(ESI):calcd.C20H24NO[M+H]+:294.1858.Found:294.1871.
实施例41：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(1eq,0.2mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为87％。1H NMR(400MHz,CDCl3)δ7.38-7.16(m,10H),6.37(d,J＝15.6Hz,1H),6.20(m,1H),3.77(t,J＝7.8Hz,1H),3.68(m,1H),3.42(m,1H),3.32(t,J＝5.6Hz,2H),2.24(m,3H),1.88(m,1H),1.55-1.27(m,6H),0.96(m,1H).13C NMR(101MHz,CDCl3)δ170.93,140.55,137.78,130.47,130.35,128.76,128.70,128.50,127.89,126.90,126.78,125.96,47.82,46.61,43.21,34.36,31.10,26.03,25.57,24.54.IR(V/cm-1):3514,3304,2068,1976,1553,1097,1047,880cm-1.HRMS(ESI):calcd.C23H27NO[M+H]+:334.2171.Found:334.2159.
实施例42：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为95％。1H NMR(400MHz,CDCl3)δ7.26(m,13H),7.17-7.03(m,6H),7.00(m,2H),6.28(d,J＝15.6Hz,1H),6.05(m,1H),5.00(d,J＝14.4Hz,1H),4.52(d,J＝16.8Hz,1H),4.21(t,J＝15.2Hz,2H),3.78(t,J＝7.2Hz,1H),2.43-2.29(m,4H),2.16(m,2H),1.91(m,1H).13C NMR(101MHz,CDCl3)δ173.53,140.04,137.50,136.72,136.61,134.93,130.45,129.16,128.97,128.91,128.87,128.53,128.13,127.99,127.55,127.29,127.11,126.42,125.89,49.67,48.52,48.30,35.06,31.00,21.17.IR(V/cm-1):3350,2973,2887,2338,1381,1087,1047,880cm-1.HRMS(ESI):calcd.C33H34NO[M+H]+:460.2640.Found:460.2650.
实施例43：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为82％。1H NMR(400MHz,CDCl3)δ7.35-7.20(m,12H),7.17(d,J＝7.6Hz,2H),7.11(d,J＝6.8Hz,2H),7.00(d,J＝6.4Hz,2H),6.81(d,J＝7.6Hz,2H),6.25(d,J＝15.6Hz,1H),6.04-5.88(m,1H),5.00(d,J＝14.8Hz,1H),4.52(d,J＝16.8Hz,1H),4.21(t,J＝15.2Hz,2H),3.79(s,4H),2.35(m,1H),2.16(m,2H),1.89(m,1H).13C NMR(101MHz,CDCl3)δ173.54,158.73,140.06,137.50,136.73,130.57,129.96,128.90,128.86,128.53,128.13,127.99,127.84,127.55,127.29,127.10,127.07,126.42,113.90,55.31,49.66,48.52,48.29,35.14,30.98.IR(V/cm-1):3361,2970,2879,2150,1989,1457,1087,1048,878cm-1.HRMS(ESI):calcd.C33H34NO2[M+H]+:476.2590.Found:476.2563.
实施例44：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为71％。1H NMR(400MHz,CDCl3)δ7.40-7.18(m,13H),7.17-7.07(m,4H),6.99(d,J＝6.8Hz,2H),6.74-6.59(m,2H),6.23(d,J＝16.0Hz,1H),5.91(m,1H),4.95(d,J＝14.8Hz,1H),4.51(d,J＝16.8Hz,1H),4.23(dd,J＝23.2,14.8Hz,2H),3.80(t,J＝7.6Hz,1H),2.93(s,6H),2.36(m,1H),2.15(m,2H),1.89(m,1H).13CNMR(101MHz,CDCl3)δ173.62,149.77,140.16,137.54,136.73,130.41,128.89,128.82,128.52,128.15,128.03,127.53,127.27,127.04,126.86,126.50,125.79,112.62,49.68,48.45,48.24,40.68,35.32,31.06.IR(V/cm-1):3393,2971,2899,2173,1455,1087,1045,879cm-1.HRMS(ESI):calcd.C34H37N2O[M+H]+:489.2906.Found:489.2933.
实施例45：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为64％。1H NMR(400MHz,CDCl3)δ7.38-7.18(m,13H),7.18-7.07(m,4H),7.01(d,J＝6.8Hz,2H),6.25(d,J＝15.6Hz,1H),6.07(m,1H),5.05(d,J＝14.8Hz,1H),4.53(d,J＝17.2Hz,1H),4.18(m,2H),3.75(t,J＝7.2Hz,1H),2.35(m,1H),2.16(m,2H),1.90(m,1H).13C NMR(101MHz,CDCl3)δ173.43,139.92,137.45,136.73,136.19,132.44,130.81,129.37,128.92,128.58,128.54,128.12,127.98,127.94,127.58,127.32,127.18,126.33,49.65,48.61,48.37,34.88,30.97.IR(V/cm-1):3393,2971,2899,2029,1453,1089,1048,881cm-1.HRMS(ESI):calcd.C32H31ClNO[M+H]+:480.2094.Found:480.2062.
实施例46：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为69％。1HNMR(400MHz,CDCl3)δ7.37(d,J＝8.8Hz,2H),7.34-7.20(m,13H),7.09(m,4H),7.01(d,J＝6.8Hz,2H),6.23(d,J＝16.0Hz,1H),6.09(m,1H),5.05(d,J＝14.4Hz,1H),4.53(d,J＝17.2Hz,1H),4.18(m,2H),3.74(t,J＝7.2Hz,1H),2.36(m,1H),2.16(m,2H),1.89(m,1H).13C NMR(101MHz,CDCl3)δ173.43,139.91,137.44,136.73,136.63,131.52,130.96,129.41,128.92,128.54,128.11,127.98,127.93,127.58,127.53,127.32,127.19,126.32,120.54,49.65,48.62,48.37,34.84,30.98.IR(V/cm-1):3325,2980,2900,2015,1558,1075,1048,879cm-1.HRMS(ESI):calcd.C32H31BrNO[M+H]+:524.1589.Found:524.1581.
实施例47：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为60％。1H NMR(400MHz,CDCl3)δ7.36-7.06(m,17H),7.01(d,J＝6.8Hz,2H),6.23(d,J＝16.0Hz,1H),6.09(m,1H),5.06(d,J＝14.8Hz,1H),4.53(d,J＝17.2Hz,1H),4.19(dd,J＝16.0,8.8Hz,2H),3.74(t,J＝7.2Hz,1H),2.35(m,1H),2.17(m,2H),1.90(m,1H).13C NMR(101MHz,CDCl3)δ173.42,139.87,139.54,137.44,136.72,134.38,131.63,129.65,129.33,128.93,128.91,128.53,128.10,127.94,127.61,127.31,127.18,126.83,126.28,125.88,124.21,49.66,48.67,48.27,34.77,30.89.IR(V/cm-1):3361,2981,2885,2331,1970,1558,1080,1041,878cm-1.HRMS(ESI):calcd.C32H31ClNO[M+H]+:480.2094.Found:480.2062.
实施例48：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的甲苯，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在100℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为72％。1H NMR(400MHz,CDCl3)δ7.84-7.69(m,3H),7.56(s,1H),7.43(m,3H),7.35-7.29(s,4H),7.24(m,7H),7.12(d,J＝6.8Hz,2H),7.01(d,J＝7.2Hz,2H),6.47(d,J＝16.0Hz,1H),6.24(m,1H),5.03(d,J＝14.4Hz,1H),4.53(d,J＝17.2Hz,1H),4.21(t,J＝15.2Hz,2H),3.80(t,J＝7.2Hz,1H),2.41(m,1H),2.24(m,2H),1.95(m,1H).13C NMR(101MHz,CDCl3)δ173.51,140.00,137.49,136.72,135.14,133.68,132.72,130.73,130.51,128.90,128.54,128.14,128.03,127.99,127.84,127.64,127.55,127.30,127.15,126.37,126.14,125.51,125.44,123.59,49.67,48.58,48.31,35.00,31.13.IR(V/cm-1):3343,2973,2889,2331,2150,2032,1448,1085,1046,879cm- 1.HRMS(ESI):calcd.C36H34NO[M+H]+:496.2640.Found:496.2670.
实施例49：
向装有搅拌子的4-mL高温预处理过的小瓶中转移进手套箱中，加入0.2mL的CPME，然后依次加入1a(1eq,0.2mmol)和叔丁醇钾(20mol％,0.04mmol)，随后再加入2a(1.2eq,0.24mmol)。将小瓶盖紧，从手套箱中取出并在50℃下加热24小时。反应结束后，将混合产物冷却至室温，TLC检测，原料完全转化。减压旋蒸除去溶剂，柱层析法分离粗产物(硅胶，PE/EA＝10:1)，得到纯产品。产物为无色液体，产率为82％。1H NMR(400MHz,CDCl3)δ7.38-7.18(m,14H),7.10(d,J＝7.2Hz,2H),7.00(d,J＝6.8Hz,2H),6.32(s,1H),6.21-6.01(m,3H),4.99(d,J＝14.8Hz,1H),4.52(d,J＝16.8Hz,1H),4.21(t,J＝17.2Hz,2H),3.77(t,J＝8.0Hz,1H),2.34(m,1H),2.15(m,2H),1.89(m,1H).13C NMR(101MHz,CDCl3)δ173.42,153.13,141.28,139.96,137.48,136.69,128.97,128.88,128.83,128.52,128.12,127.97,127.54,127.28,127.12,126.44,126.41,119.30,111.08,106.19,49.68,48.51,48.26,34.85,30.72.IR(V/cm-1):3377,2971,2879,2143,1635,1558,1379,1082,1047,879cm- 1.HRMS(ESI):calcd.C30H29NO2[M+H]+:436.2277.Found:436.2249.
基于以上本发明各实施例中的γ-烯基酮，本发明进一步针对其主要结构，对部分产品进行应用性的衍生化，以证明本发明实施例制备的α-高烯丙基酰胺衍生物的实用性，具体结构和合成步骤如下：
衍生实施例1:
化合物3a(200mg,0.59mmol)溶于4mL乙腈中，降温至0℃，硝酸铈铵(654mg,1.19mmol)溶于4mL去离子水中，滴加至上述反应液中，反应在0℃下搅拌1小时。乙酸乙酯和水萃取洗涤，无水硫酸钠干燥。过滤，减压旋蒸除去溶剂，柱层析法分离纯化，最终得到产物7。
无色液体，产率70％。1HNMR(400MHz,CDCl3)δ7.33-7.28(m,4H),7.18(t,J＝7.2Hz,1H),6.41(d,J＝15.2Hz,2H),6.24-6.17(m,1H),3.31(t,J＝7.2Hz,2H),2.35-2.27(m,1H),2.25-2.10(m,2H),1.94-1.87(m,1H),1.69(t,J＝8.4Hz,2H),1.20(s,3H).13C NMR(101MHz,CDCl3)δ182.85,137.83,130.42,130.14,128.61,127.03,126.05,42.93,38.96,37.17,33.74,28.24,23.01.IR(V/cm-1):3711,3577,3046,2829,2123,1735,1513,1368,1237,965,734cm-1.HRMS(ESI):calcd.C15H20NO[M+H]+:230.1545.Found:230.1528.
衍生实施例2:
化合物3a(200mg，0.59mmol)溶于2mL四氢呋喃中，降温至0℃，分批加入四氢铝锂(68mg，1.79mmol)，反应在70℃下搅拌3h。降温至0℃，加饱和硫酸钠溶液淬灭，二氯甲烷萃取，饱和食盐水洗，无水硫酸钠干燥。过滤，减压旋蒸除去溶剂，柱层析法分离纯化，最终得到产物8。
无色液体，产率84％。1HNMR(400MHz,CDCl3)δ7.37-7.26(m,4H),7.19(t,J＝7.2Hz,1H),6.84(d,J＝8.4Hz,2H),6.48(d,J＝8.4Hz,2H),6.41(d,J＝16.0Hz,1H),6.26-6.19(m,1H),3.75(s,3H),3.36-3.31(m,2H),3.10(d,J＝8.8Hz,1H),3.01(d,J＝8.8Hz,1H),2.31-2.24(m,2H),1.88-1.76(m,2H),1.63(t,J＝8.4Hz,2H),1.13(s,3H).13C NMR(101MHz,CDCl3)δ150.73,143.23,137.88,131.07,129.90,128.63,127.01,126.03,115.22,112.15,60.37,56.19,47.38,41.58,40.21,38.15,29.01,24.31.IR(V/cm-1):3675,3463,2942,2199,1732,1514,1264,733cm-1.HRMS(ESI):calcd.C22H28NO[M+H]+:322.2171.Found:322.2139.
衍生实施例3:
化合物3a(100mg，0.30mmol)溶于5mL甲醇中，加入10mg Pd/C催化剂，反应在H2球氛围下室温搅拌过夜。过滤出去Pd/C,减压蒸馏，柱层析分离得到产物9。
无色液体，产率92％。1H NMR(400MHz,CDCl3)δ7.53(d,J＝7.6Hz,2H),7.27-7.23(m,2H),7.16(m,3H),6.89(d,J＝7.2Hz,2H),3.79(s,3H),3.69(m,2H),2.62(t,J＝8.0Hz,2H),2.06(m,1H),1.87(m,1H),1.68-1.55(m,4H),1.46(m,1H),1.37-1.28(m,1H),1.21(s,3H).13C NMR(101MHz,CDCl3)δ178.22,156.43,142.58,133.06,128.40,128.29,125.67,121.51,114.02,55.51,45.64,45.15,37.84,35.83,31.97,30.76,24.13,23.18.IR(V/cm-1):3392,3259,2971,2162,1964,1676,1514,1249,1089,1046,879cm-1.HRMS(ESI):calcd.C22H27NO2Na[M+Na]+:360.1939.Found:360.1965.
衍生实施例4:
化合物3a(200mg，0.59mmol)溶于5mL二氯甲烷中，加入间氯过氧苯甲酸(152mg，0.88mmol)，反应在室温下搅拌过夜。加饱和硫代硫酸钠溶液淬灭，乙酸乙酯萃取，无水硫酸钠干燥。过滤，减压旋蒸除去溶剂，柱层析法分离纯化，最终得到产物10。
无色液体，产率92％。dr＝1.4:1.1HNMR(400MHz,CDCl3)δ7.53(d,J＝7.6Hz,2H),7.31(m,3H),7.26-7.19(m,2H),6.89(d,J＝6.8Hz,2H),3.79(s,3H),3.77-3.68(m,2H),3.64(s,1H),2.98(s,1H),2.10(m,1H),1.99-1.89(m,1H),1.89-1.64(m,4H),1.25(s,3H).13C NMR(101MHz,CDCl3)δ177.50,156.54,137.58,137.56,132.85,128.46,128.08,125.57,121.58,121.56,114.05,62.90,62.86,58.63,58.51,55.50,45.57,45.55,44.80,44.66,33.92,33.61,31.04,30.75,27.61,27.47,23.27,22.66.IR(V/cm-1):3355,2975,2888,1675,1514,1456,1251,1088,1047,879cm-1.HRMS(ESI):calcd.C22H26NO3[M+H]+:352.1913.Found:352.1918.
衍生实施例5:
化合物3a(200mg，0.59mmol)溶于5mL乙醇中，依次加入苯硅烷(128mg，1.2mmol)和三氯化铁(2.8mg，3mol％)。反应敞口搅拌过夜，粗产品直接浓缩，柱层析分离纯化得到产物11。
无色液体，产率83％。1H NMR(400MHz,CDCl3)δ7.95(d,J＝7.6Hz,2H),7.62-7.50(m,3H),7.46(t,J＝7.6Hz,2H),6.89(d,J＝8.4Hz,2H),3.80(s,3H),3.78-3.69(m,2H),3.01(t,J＝6.5Hz,2H),2.21(m,1H),1.92(m,2H),1.78-1.64(m,3H),1.25(s,3H).13C NMR(101MHz,CDCl3)δ200.01,178.01,156.47,137.00,133.03,132.98,128.61,128.01,121.56,114.02,55.50,45.68,45.23,38.65,37.45,30.47,23.06,19.08.IR(V/cm-1):3687,2993,2209,1738,1514,1372,1236,1095,1045,879cm-1.HRMS(ESI):calcd.C22H26NO3[M+H]+:352.1913.Found:352.1918.
本发明保护内容不局限于以上实施例。在不背离发明构思的精神和范围下，本领域技术人员能够想到的变化和优点都被包括在本发明中，并且以所附的权利要求书为保护范围。

Claims (3)

1.一种α-高烯丙基酰胺衍生物的合成方法，其特征在于，在有机溶剂、添加剂存在的条件下，以式1a所示的酰胺、式2a所示的共轭1,3-二烯为反应原料，进行反应，得到式3a所示的α-高烯丙基酰胺衍生物；所述添加剂为叔丁醇钾，叔丁醇钠，叔丁醇锂，氢氧化钾，六甲基二硅基胺基钾中的一种或多种；所述有机溶剂为CPME；所述反应如下反应式(A)所示：
其中：
R1为苄基；
R2为苄基；
R3为氢；
R4为C1-C6烷基，苯基，苄基，C1-C6烷基取代的苯基，卤素原子取代的苯基，环烷基；
R5为氢，甲基，苯基；
R6为苯基，C1-C6烷基取代的苯基，卤素原子取代的苯基，萘基，呋喃基；
所述酰胺:共轭1,3-二烯:添加剂的摩尔比为1:1.2：0.2；和/或，以所述酰胺的用量为基准，所述有机溶剂的加入量为1mL/mmol酰胺。
2.根据权利要求1所述的合成方法，其特征在于，所述反应温度为25–100oC；所述反应的时间为12-48小时。
3.根据权利要求1所述的合成方法，其特征在于，进一步包括后处理步骤，将反应得到的粗反应液用体积比为乙酸乙酯:石油醚＝1:10～1:5的溶液进行柱层析，高收率、高区域选择性得到α-高烯丙基酰胺衍生物。
CN202210111333.6A 2022-01-29 2022-01-29 α-高烯丙基酰胺衍生物及其合成方法 Active CN114573472B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210111333.6A CN114573472B (zh) 2022-01-29 2022-01-29 α-高烯丙基酰胺衍生物及其合成方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210111333.6A CN114573472B (zh) 2022-01-29 2022-01-29 α-高烯丙基酰胺衍生物及其合成方法

Publications (2)

Publication Number Publication Date
CN114573472A CN114573472A (zh) 2022-06-03
CN114573472B true CN114573472B (zh) 2024-03-26

Family

ID=81769073

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210111333.6A Active CN114573472B (zh) 2022-01-29 2022-01-29 α-高烯丙基酰胺衍生物及其合成方法

Country Status (1)

Country Link
CN (1) CN114573472B (zh)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5599975A (en) * 1993-10-28 1997-02-04 Adir Et Compagnie Cyclised analogues of fatty acid metabolites
US6867297B1 (en) * 1993-02-12 2005-03-15 Daiichi Suntory Pharma Co., Ltd. Process for synthesizing 4-substituted azetidinone derivatives
WO2005077885A1 (en) * 2004-02-06 2005-08-25 Yale University Ruthenium-catalyzed hydroamination of olefins
CN110776407A (zh) * 2019-09-29 2020-02-11 华东师范大学 γ-烯基酮及其制备方法
WO2020114025A1 (zh) * 2018-12-06 2020-06-11 苏州大学 β-内酰胺衍生物的制备方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6867297B1 (en) * 1993-02-12 2005-03-15 Daiichi Suntory Pharma Co., Ltd. Process for synthesizing 4-substituted azetidinone derivatives
US5599975A (en) * 1993-10-28 1997-02-04 Adir Et Compagnie Cyclised analogues of fatty acid metabolites
WO2005077885A1 (en) * 2004-02-06 2005-08-25 Yale University Ruthenium-catalyzed hydroamination of olefins
WO2020114025A1 (zh) * 2018-12-06 2020-06-11 苏州大学 β-内酰胺衍生物的制备方法
CN110776407A (zh) * 2019-09-29 2020-02-11 华东师范大学 γ-烯基酮及其制备方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Big conductance calcium-activated potassium channel openers control spasticity without sedation;David Baker等;British Journal of Pharmacology;第174卷;第2662-2681页 *
Synthesis and Lateral Root-Inducing Activity of N-Benzyl-3-Substituted-2-Piperidones;Hidetaka Tsukada等;J. Fat. Agr. Kyushu. Univ.;第44卷(第1-2期);第119-126页 *
重氮化合物参与的不对称催化多组分反应;唐敏 等;有机化学;第34卷;第1268-1276页 *

Also Published As

Publication number Publication date
CN114573472A (zh) 2022-06-03

Similar Documents

Publication Publication Date Title
Gao et al. Asymmetric synthesis of both enantiomers of tomoxetine and fluoxetine. Selective reduction of 2, 3-epoxycinnamyl alcohol with Red-Al
Stadtmüller et al. Stereoselective Preparation of Polyfunctional Cyclopentane Derivatives by Radical Nickel‐or Palladium‐Catalyzed Carbozincations
Bonadies et al. Use of pyridinium chlorochromate as methylene oxidant in 5, 6-dihydropyrans: a practical one-step preparation of the anhydromevalonolactone
Chen et al. l-Threonine-catalysed asymmetric α-hydroxymethylation of cyclohexanone: application to the synthesis of pharmaceutical compounds and natural products
Barluenga et al. Enantioselective Synthesis of Highly Functionalized 4‐Piperidones by the Asymmetric Imino‐Diels–Alder Reaction of Chiral 2‐Amino‐1, 3‐Butadienes
Annunziata et al. Synthesis of optically active 3-(1-hydroxyalkyl) phthalides by stereoselective pinacol cross-coupling
HUT68255A (en) Process for the preparation of beta-phenylisoserine derivatives and use thereof
CN114573472B (zh) α-高烯丙基酰胺衍生物及其合成方法
Austad et al. Halichondrin B: synthesis of the C (37)–C (54) subunit
Schwarz et al. Chiral bicyclic Lactams as homoenolate equivalents: An asymmetric route to 5-substituted cyclohexenones
Lee et al. Efficient synthesis of 3-hydroxyprolines and 3-hydroxyprolinols from sugars
Hernández-Guadarrama et al. Synthesis of β-mono-and β, γ-di-substituted α-methylene-γ-lactams
WO2022206399A1 (zh) 一种铜催化的以氧气为氧化剂氧化醇制备羧酸化合物的方法
Seto et al. Preparation of (±)-2-(2, 3-2H2) jasmonic acid and its methyl ester, methyl (±)-2-(2, 3-2H2) jasmonate
Battaglia et al. 1′-Azido-and 1′-amino-1, 3-dioxolan-4-ones
Kamimura et al. A convenient stereoselective synthesis of β-lactams from β-hydroxy-α-thioalkylesters prepared from Michael/aldol tandem reaction or stereoselective addition of thiols to the Baylis–Hillman adducts
Hénin et al. Fluorinated ketene dithioacetals: 6. Synthesis of α-trifluoromethyl-γ-lactams from bis (ethylsulfanyl)(tetrafluoroethylidene) methane
WO2009011551A2 (en) Process for the efficient preparation of 3-hydroxy pyrrolidine and derivatives thereof
Díaz et al. Enantioselective synthesis of novel homochiral α-substituted (S)-isoserine derivatives. Incorporation of this amino acid in a highly conformationally constrained dipeptide surrogate
Couche The Synthesis of Highly Functionalized Enantiomerically Enriched Cyclohexanes. An Approach to Carba-Sugars and Aminocarba-Sugars
US5380849A (en) Process for optically pure decahydroisoqiunolines
CN115448865B (zh) 一种不对称合成塞曲西坦中间体的方法
AU2001266208A1 (en) Cyclic ketones, their preparation and their use in the synthesis of amino acids
WO2002000584A1 (en) Cyclic ketones, their preparation and their use in the synthesis of amino acids
Ivšić et al. Synthesis of GABOB and GABOB‐Based Chiral Units Possessing Distinct Protecting Groups

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