CN110746272B - 一种含开链手性季碳中心类化合物及其制备方法 - Google Patents

一种含开链手性季碳中心类化合物及其制备方法 Download PDF

Info

Publication number
CN110746272B
CN110746272B CN201911154534.9A CN201911154534A CN110746272B CN 110746272 B CN110746272 B CN 110746272B CN 201911154534 A CN201911154534 A CN 201911154534A CN 110746272 B CN110746272 B CN 110746272B
Authority
CN
China
Prior art keywords
nmr
cdcl3
alkyl
chain
yield
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
CN201911154534.9A
Other languages
English (en)
Other versions
CN110746272A (zh
Inventor
余达刚
陈小旺
李静
蓝宇
朱磊
贵永远
敬科
蒋元旭
伯知豫
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.)
Sichuan University
Original Assignee
Sichuan 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 Sichuan University filed Critical Sichuan University
Publication of CN110746272A publication Critical patent/CN110746272A/zh
Application granted granted Critical
Publication of CN110746272B publication Critical patent/CN110746272B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/44—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by addition reactions, i.e. reactions involving at least one carbon-to-carbon double or triple bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/02—Formation or introduction of functional groups containing oxygen of hydroxy or O-metal groups
    • 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
    • C07C323/10—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 singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C323/18—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 singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
    • C07C323/19—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 singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton with singly-bound oxygen atoms bound to acyclic carbon atoms of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/02—Acyclic alcohols with carbon-to-carbon double bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/02—Acyclic alcohols with carbon-to-carbon double bonds
    • C07C33/025—Acyclic alcohols with carbon-to-carbon double bonds with only one double bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/02—Acyclic alcohols with carbon-to-carbon double bonds
    • C07C33/025—Acyclic alcohols with carbon-to-carbon double bonds with only one double bond
    • C07C33/035—Alkenediols
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/05—Alcohols containing rings other than six-membered aromatic rings
    • C07C33/14—Alcohols containing rings other than six-membered aromatic rings containing six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/28—Alcohols containing only six-membered aromatic rings as cyclic part with unsaturation outside the aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/34—Monohydroxylic alcohols containing six-membered aromatic rings and other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/40—Halogenated unsaturated alcohols
    • C07C33/46—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts
    • C07C33/48—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts with unsaturation outside the aromatic rings
    • C07C33/483—Monocyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
    • C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
    • 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
    • C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
    • 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
    • C07C69/84—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of monocyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of a six-membered aromatic ring
    • 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
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • 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
    • C07D295/04—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/096—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/54—Radicals substituted by oxygen atoms
    • 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
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F17/00—Metallocenes
    • C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
    • 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
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/56—Ring systems containing bridged rings
    • C07C2603/58—Ring systems containing bridged rings containing three rings
    • C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
    • C07C2603/74—Adamantanes

Landscapes

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

Abstract

本发明公开了一种含开链手性季碳中心类化合物及其制备方法，本发明利用二氧化碳参与1,1‑二取代1,3二烯的催化不对称官能化来实现开链手性季碳中心的高效高选择性构建。本发明方法原料易得、条件温和、得到的产物易于衍生转化。为手性药物创制提供可供选择的新途径，也为二氧化碳的高效利用提供新思路。

Description

一种含开链手性季碳中心类化合物及其制备方法
技术领域
本发明属于有机化学技术领域，具体涉及一种含开链手性季碳中心类化合物及其制备方法。
背景技术
手性季碳中心广泛存在于天然产物和药物分子中，它对天然产物的生理活性和药物分子的代谢稳定性都具有重要影响。迄今为止，虽然已经有众多不对称催化方法被建立起来，但是通过直接的的碳-碳成键方式来进行多官能团取代的手性季碳中心的构建，仍然是有机合成领域的热点和难点。究其原因，在合成季碳手性中心时，空间位阻的急剧增大使得反应需要克服更高的能垒。同时，生成的四个碳原子取代的碳原子中心在空间上高度拥挤，这使得季碳中心的构建在动力学和热力学上都是不利的过程。另一方面，对于开链的手性季碳中心，四个不同的碳原子取代基在空间上具有更高的自由度，这使得开链手性季碳中心的构建更为困难。此外，已经发展起来的手性季碳中心的构建方法大多完全依赖于精细化学品的使用。因此，亟需探索发展一类利用廉价易得的非加工的工业原材料来进行手性季碳中心的高原子经济、高步骤经济的合成方法。
近年来，1,3-二烯由于其原料易得且反应多样性受到有机合成学术界和工业界的极大关注。最近，通过1,3-二烯的不对称官能化来构建三级手性中心被广泛研究。但是通过1,3-二烯的不对称官能化来进行开链手性季碳中心的构建，只有1例通过铱催化1,3-二烯与原位生成的高活性的甲醛进行不对称官能化来成功实现开链手性季碳中心的构建。但对于其他惰性碳一化合物与1,3二烯进行不对称官能化来构建开链手性季碳中心却未取得进展。
二氧化碳是一种常见的温室气体，它作为一种储量丰富、廉价易得、无毒可再生的碳一资源被广泛应用于多种高附加值的化学品的合成。但是，由于二氧化碳自身的高稳定性使得它的高效利用特别是在二氧化碳参与的手性分子的合成仍然具有很大的挑战。二氧化碳参与的不对称转化尤其是二氧化碳参与的催化不对称碳-碳成键更是化学化工合成领域的巨大难点。
发明内容
本发明的目的在于：针对现有技术中存在的不足，提供一种含开链手性季碳中心类化合物及其制备方法。
本发明采用的技术方案如下：
一种含开链手性季碳中心类化合物的制备方法，包括：将1,1-二取代1,3-二烯类化合物与CO2在铜催化剂、手性配体、硅烷的存在下于溶剂中发生反应，制得；其中，反应温度为50-65℃，反应时间为8-12h。
进一步地，具体为：将1-芳基-1烷基取代的1,3-二烯类化合物或1,1-二烷基取代的1,3-二烯与CO2在铜催化剂、手性配体、硅烷的存在下于溶剂中发生反应，制得；反应式如下：
Figure GDA0003170389860000021
其中，R1为芳基、氢、烷基、卤素、甲氧基、三氟甲基、三氟甲氧基、甲巯基、吗啉、酯基及其衍生物；R2为烷基、苯并环烷基及其衍生物；R3为H、甲基；R4为杂芳基、烷基、烯基及其衍生物。
进一步地，烷基为具有1-41个碳原子的直链烷基、支链烷基、环烷基、含烯基的长链烷基；芳基为具有6-20个碳原子的芳基；杂芳基为具有6-20个碳原子的杂芳基；烯基为含有6-41个碳原子的烯基。优选烷基为具有1-15个碳原子的直链烷基、支链烷基、环烷基、含烯基的长链烷基；芳基为具有6-15个碳原子的芳基；杂芳基为具有6-15个碳原子的杂芳基；烯基为含有6-15个碳原子的烯基。
进一步地，1,1-二取代1,3-二烯类化合物与铜催化剂的摩尔比为18-22:1，1,1-二取代1,3-二烯类化合物与配体的摩尔比为15-18:1，1,1-二取代1,3-二烯类化合物与硅烷的摩尔比为1:6-9。
进一步地，1,1-二取代1,3-二烯类化合物与铜催化剂的摩尔比为20:1，所述1,1-二取代1,3-二烯类化合物与配体的摩尔比为16.6:1，所述1,1-二取代1,3-二烯类化合物与硅烷的摩尔比为1:8。
进一步地，铜催化剂为醋酸铜、醋酸亚铜、均三甲苯基亚铜、噻吩-2-甲酸亚铜或四氟硼酸四乙腈铜；优选为醋酸铜。
进一步地，手性配体为(R)-(-)-5,5'-双[二(3,5-二叔丁基-4-甲氧基苯基)磷]-4,4'-二-1,3-苯并二氧烷、(S)-联萘(3,5-二甲苯基)膦、(R)-(+)-(6,6'-二甲氧基联苯-2,2'-基)双(二苯基膦)、Josiphos-SL-J007-1、(+)-1,13-双(二苯基)膦(5aR,8aR,14aR)-5a,6,7,8,8a,9-六氢-5H-[1]苯并吡喃并[3,2-D]氧杂蒽、(+)-1,2-双((2S,5S)-2,5-二苯基膦)乙烷或(-)-1,2-双((2R,5R)-2,5-二甲基磷)苯；优选为(+)-1,2-双((2S,5S)-2,5-二苯基膦)乙烷。
进一步地，硅烷为甲基二甲氧基硅烷、甲基二乙氧基硅烷、三乙氧基硅烷、聚甲基聚硅氧烷，优选为甲基二甲氧基硅烷；溶剂为环己烷、四氢呋喃、甲基叔丁基醚、乙酸乙酯或N,N-二甲基甲酰胺，优选为环己烷。
上述的方法制备得到的含开链手性季碳中心类化合物，结构通式为：
Figure GDA0003170389860000031
其中，R1为芳基、氢、烷基、卤素、甲氧基、三氟甲基、三氟甲氧基、甲巯基、吗啉、酯基及其衍生物；R2为烷基、苯并环烷基及其衍生物；R3为H、甲基；R4为杂芳基、烷基、烯基及其衍生物；烷基为具有1-41个碳原子的直链烷基、支链烷基、环烷基、含烯基的长链烷基；芳基为具有6-20个碳原子的芳基；杂芳基为具有6-20个碳原子的杂芳基；烯基为含有6-41个碳原子的烯基。
进一步地，含开链手性季碳中心类化合物的具体结构式为：
Figure GDA0003170389860000032
Figure GDA0003170389860000041
上述的含开链手性季碳中心类化合物在制备手性药物中的应用。
在制备化合物
Figure GDA0003170389860000042
时，当底物中苯环上存在取代基时，苯基、烷基、甲氧基、三氟甲基、三氟甲氧基、甲巯基、吗啉、酯基以及卤素取代的邻、间、对的各种电性取代的底物都可以以良好的收率和非常高的对映选择性得到相应产物。对于萘环取代1,3-二烯类化合物，不论是1位还是2位，反应都可以顺利地进行。当把R2替换成位阻更大的乙基、正丁基、异丁基或者刚性骨架的四氢萘、茚满等底物时，也表现出了良好的反应性。另外，杂芳环的底物：二茂铁、胡椒基、噻吩、吡啶、吲哚也可以较好的收率和优异的对映选择性得到目标产物。当使用1,1,4-三取代分子内1,3-二烯作为底物时，也能以优秀的收率和非常高的对映选择性得到相应产物。
Figure GDA0003170389860000051
化合物
Figure GDA0003170389860000052
的制备方法与上述的制备方法相同。只是将反应原料从1芳基-1-烷基取代的1,3二烯更换为1，1-二烷基取代的1,3二烯。
在制备该化合物时，当底物中R4为苄基时，苯环上取代基为甲氧基、三氟甲基、卤素时，都能以较好到优秀的收率、反式选择性以及优异的对映选择性得到含有开链手性季碳中心的高烯丙醇类化合物。当R4为更加柔性的取代基，例如苯乙基、甲基环己烷、直链羟基等也能很好的进行反应。当R4为杂环，如胡椒基以及吲哚的时候，也能以优秀的手性控制得到产物。当R4为大位阻基团，例如二苯甲基、金刚烷时，也能以极其优异的产率，反式选择性以及对应选择性得到对应产物。此外，当R4为与1,3二烯共轭的环己烯的时候，也得到了不错的结果。显示出该反应具有优秀的区域选择性。一系列从天然开链萜类化合物(香叶醇、橙花醇、法尼醇、茄尼醇等)简单衍生得到的1，1-二烷基取代的1,3二烯也能取得非常优异的结果。
本发明的方法机理如下：
通过铜氢物质INT1对1，1-二取代1，3二烯进行高对映选择性的1,2加成得到二级烯丙基铜中间体INT2。然后烯丙基铜中间体INT2与二氧化碳通过六元环过渡态得到羧酸铜中间体INT3。随后硅烷与羧酸铜中间体INT3进行转金属化得到羧酸硅酯中间体INT4并再生铜氢物质INT1完成第一个催化循环。
铜氢物质INT1对羧酸硅酯中间体INT4进行加成得到烷氧基铜中间体INT5。然后烷氧基铜中间体INT5发生铜的β-O消除得到醛中间体INT7和硅氧基铜中间体INT6。然后硅氧基铜中间体INT6与硅烷发生转金属化得到二硅醚并且再生铜氢物质完成第二个催化循环。
铜氢物质INT1与醛中间体INT7进行加成得到烷氧基铜中间体INT8。随后烷氧基铜中间体INT8与硅烷转金属化得到高烯丙醇硅醚中间体INT9并且再生铜氢物质完成第三个催化循环。最后利用饱和氟化铵的甲醇溶液对中间体INT9进行脱硅得到含有手性季碳中心的高烯丙醇产物。具体反应过程如下：
Figure GDA0003170389860000061
综上所述，由于采用了上述技术方案，本发明的有益效果是：
1、本发明在温和条件下，实现了含有开链手性季碳中心类化合物的高效构建；
2、本发明合成方法中利用了惰性二氧化碳作为碳一合成子，有一定的学术价值和经济环境意义；
3、本发明对于手性季碳中心类化合物的合成具有高化学、区域、顺反、对映选择性，底物范围广泛、官能团兼容性好以及易于放大和后期衍生转化等优点，为其在手性药物创制、材料领域的潜在应用打下坚实的基础。
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，以下结合实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅用以解释本发明，并不用于限定本发明，即所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。
实施例
(S,E)-2-(4-苯基)-苯基-2-甲基-3-烯-戊醇(以下称为化合物2a)的制备：
将1,1-二取代-1,3二烯类化合物(1a，0.5mmol)、铜催化剂(0.025mmol)和配体(0.03mmol)混合，然后充入CO2(1个大气压)，在CO2气氛下加入有机溶剂，在室温下搅拌30min，在CO2气氛下加入硅烷(4mmol)，在60℃搅拌反应10h，最后冷却至室温，用饱和氟化铵的甲醇溶液和乙酸乙酯淬灭反应液，在室温下搅拌30min。用硅藻土或少量硅胶过滤后浓缩旋干，纯化，制得最终纯的目标产物。具体反应原料见下表，反应式如下：
Figure GDA0003170389860000062
Figure GDA0003170389860000071
上表中，b本表中产率是在柱色谱纯化后得到的。且所有产物的1,4加成(2a)与1,2加成(2a’)的比例均大于95:5。c对映体过量(ee值)是由具有手性固定相的手性HPLC分析确定的。d没有确定。e无铜催化剂。f无配体。g无硅烷。CyH＝环己烷,THF＝四氢呋喃,MTBE＝甲基叔丁基醚.EA＝乙酸乙酯,DMF＝N,N-二甲基甲酰胺,PMHS＝聚甲基氢硅氧烷。Trace＝痕量。N.R.＝没有反应。
由上表可知，序号为6，所得目标产物的产率较大同时ee值最高。其具体操作过程如下：向含有磁子的干燥的史莱克(Schlenk)管(25mL)中加入反应底物(110mg，0.5mmol，1equiv)，然后将史莱克管转入手套箱中，再加入醋酸铜(Cu(OAc)2)(4.5mg，0.025mmol，5mol％)，(+)-1,2-双((2S,5S)-2,5-二苯基膦)乙烷((S,S)-Ph-BPE)(15.2mg，0.03mmol，5mol％)。将Schlenk管封死后从手套箱中取出并连接到连有CO2钢瓶的双排管上，拧松盖子并在双排管上抽充置换CO2 3次，使其管中充满CO2气体，然后在CO2气氛下加入超干环己烷(CyH)(2.5mL)。室温下搅拌30min后，在CO2气氛下加入甲基二甲氧基硅烷(Me(MeO)2SiH)(0.5mL，8当量)最后，将反应管封死置于金属浴上，于60℃下搅拌反应10h。冷却至室温后用饱和氟化铵的甲醇溶液和乙酸乙酯淬灭反应液，在室温下搅拌30min。用硅藻土或少量硅胶过滤后浓缩旋干。残余物通过快速柱层析纯化(PE/EA＝20:1)，最终得到纯的所需产物，产物为无色液体，质量为93.8mg，产率为74％，Rf(PE/EA＝10:1)：0.2；1H NMR(400MHz,CDCl3)δ7.56(td,J＝8.6,8.1,1.8Hz,4H),7.46–7.38(m,4H),7.36–7.28(m,1H),5.70(dq,J＝15.6,1.5Hz,1H),5.58(dq,J＝15.7,6.2Hz,1H),3.77(m,J＝2.4Hz,2H),1.77(dd,J＝6.2,1.4Hz,3H),1.51(brs,J＝11.2Hz,1H),1.44(s,3H)；13C NMR(101MHz,CDCl3)δ139.20,136.32,128.74,127.34,127.17,127.07,127.02,125.36,125.36,70.35,46.05,23.22,18.39；HRMS(ESI+,m/z)：calcd for C18H20O[M+Na]+275.1406,Found 275.1401；ee值＝96％,；[α]D 25＝+8.86°(c＝1.0,CHCl3)。
所有的消旋样品均由与上述流程相似的步骤合成。此法可得到具有高区域选择性(1,4加成：1,2加成>95:5)以及高反/顺选择性(>98:2)的消旋化合物。
不同1-芳基-1-烷基类开链手性季碳中心化合物(化合物2b-2ak)的制备：
该类化合物的合成步骤与化合物2a的合成步骤一致，仅为原料不同，具体反应式和化合物具体结构如下：
Figure GDA0003170389860000091
不同1，1-二烷基类开链手性季碳中心化合物(化合物4a-4p)的制备：
该类化合物的合成步骤与化合物2a的合成步骤一致，仅为原料不同，具体反应式和化合物具体结构如下：
Figure GDA0003170389860000101
所得含有手性季碳中心的高烯丙醇(化合物2a-4p)的结构式和参数如下：
(S,E)-2-(4-苯基)-苯基-2-甲基-3-烯-戊醇(2a)：
Figure GDA0003170389860000102
其为无色油状液体，质量为93.8mg,收率为74％，Rf(PE/EA＝10:1)：0.2；.1H NMR(400MHz,CDCl3)δ7.56(td,J＝8.6,8.1,1.8Hz,4H),7.46–7.38(m,4H),7.36–7.28(m,1H),5.70(dq,J＝15.6,1.5Hz,1H),5.58(dq,J＝15.7,6.2Hz,1H),3.77(m,J＝2.4Hz,2H),1.77(dd,J＝6.2,1.4Hz,3H),1.51(brs,J＝11.2Hz,1H),1.44(s,3H)；13C NMR(101MHz,CDCl3)δ139.20,136.32,128.74,127.34,127.17,127.07,127.02,125.36,125.36,70.35,46.05,23.22,18.39；HRMS(ESI+,m/z)：calcd for C18H20O[M+Na]+275.1406,Found 275.1401；ee值＝96％,determined by HPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝95:5,flow rate 1.0mL/min,T＝30℃,λ＝254nm):tR＝12.14min(major),tR＝14.06min(minor)；[α]D 25＝+8.86°(c＝1.0,CHCl3)。
(R,E)-2-(4-苯基)-苯基-2-甲基-3-烯-戊醇(2a”)：
Figure GDA0003170389860000111
其为无色油状液体，质量为113.6mg，收率为90％，ee值＝96％,determined byHPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝95:5,flow rate 1.0mL/min,T＝30℃,λ＝254nm):tR＝11.8min(minor),tR＝13.4min(major)；[α]D 25＝-6.58°(c＝1.0,CHCl3)。
(S,E)-2-对氟苯基-2-甲基-3-烯-戊醇(2b)：
Figure GDA0003170389860000112
其为无色油状液体，质量为76.7mg，收率为79％，Rf(PE/EA＝10:1)：0.3；1H NMR(400MHz,CDCl3)δ7.24–7.12(m,2H),6.92–6.80(m,2H),5.50(dq,J＝15.8,1.5Hz,1H),5.38(dq,J＝15.7,6.2Hz,1H),3.57(m,2H),1.61(dd,J＝6.1,1.4Hz,3H),1.52–1.34(brs,1H),1.23(s,3H)；13C NMR(101MHz,CDCl3)δ161.32(d,J＝244.9Hz),140.97(d,J＝3.1Hz),136.20,128.50(d,J＝7.9Hz),125.44,114.97(d,J＝21.0Hz),70.26,45.78,23.44,18.30；19F NMR(376MHz,CDCl3)δ-117.07；HRMS(ESI+,m/z)：calcd for C12H15FO[M+H]+195.1180,Found195.1184；ee值＝94％,determined by HPLC(Daicel Chiralpak OJ Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝13.95min(minor),tR＝20.95min(major)；[α]D 25＝-11.2°(c＝0.75,CHCl3)。
(S,E)-2-苯基-2-甲基-3-烯-戊醇(2c)：
Figure GDA0003170389860000113
其为无色油状液体，质量为54.64mg，收率为62％，Rf(PE/EA＝20:1)：0.2；1H NMR(400MHz,CDCl3)δ7.36–7.29(m,4H),7.26–7.18(m,1H),5.67(dq,J＝15.7,1.4Hz,1H),5.54(dq,J＝15.7,6.2Hz,1H),3.73(m,J＝2.7Hz,2H),1.76(dd,J＝6.2,1.5Hz,3H),1.48(brs,1H),1.40(s,3H)；13C NMR(101MHz,CDCl3)δ145.32,136.44,128.39,126.93,126.36,125.25,70.36,46.23,23.23,18.40；HRMS(ESI+,m/z)：calcd for C12H16O[M+H-H2O]+159.1168,Found 159.1167；ee值＝97％,determined by HPLC(Daicel Chiralpak OD-HColumn,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝9.42min(minor),tR＝10.56min(major)；[α]D 25＝-2.67°(c＝1.1,CHCl3)。
(S,E)-2-对甲苯基-2-甲基-3-烯-戊醇(2d)：
Figure GDA0003170389860000121
其为无色油状液体，质量为75.3mg，收率为79％，Rf(PE/EA＝20:1)：0.2；1H NMR(400MHz,CDCl3)δ7.24–7.12(m,2H),6.92–6.80(m,2H),5.50(dq,J＝15.8,1.5Hz,1H),5.38(dq,J＝15.7,6.2Hz,1H),3.57(m,2H),1.61(dd,J＝6.1,1.4Hz,3H),1.52–1.34(m,1H),1.23(s,3H)；13C NMR(101MHz,CDCl3)δ142.27,136.64,135.87,129.10,126.80,124.99,70.43,45.88,23.23,20.90,18.35；HRMS(ESI+,m/z)：calcd for C13H18O[M+Na]+213.1250,Found213.1252；ee值＝94％,determined by HPLC(Daicel Chiralpak IDColumn,n-Hexane:i-PrOH＝99:1,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝9.27min(minor),tR＝10.30min(major)；[α]D 25＝+5.86°(c＝1.0,CHCl3)。
(S,E)-2-甲基-2-(4-三氟甲氧基苯基)-3-烯-戊醇(2e)：
Figure GDA0003170389860000122
其为无色油状液体，质量为81mg，收率为62％，Rf(PE/EA＝10:1)：0.3；1H NMR(400MHz,CDCl3)δ7.39–7.34(m,2H),7.16(dq,J＝8.9,1.0Hz,2H),5.65(dq,J＝15.8,1.3Hz,1H),5.54(dq,J＝15.8,6.1Hz,1H),3.74(s,2H),1.76(dd,J＝6.1,1.3Hz,3H),1.45(s,1H),1.39(s,3H).；13C NMR(101MHz,CDCl3)δ147.62,144.14,135.96,128.40,125.84,121.77,120.67,119.22,70.17,45.98,23.41,18.31：19F NMR(376MHz,CDCl3)δ-57.87；HRMS(ESI+,m/z)calcd for C13H15F3O2[M+H-H2O]+：243.0991,Found243.0992；ee值＝94％,determined by HPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝98:2,flowrate 1.0mL/min,T＝30℃,λ＝210nm):tR＝8.07min(major),tR＝8.63min(minor)；[α]D 25＝-0.4°(c＝1.05,CHCl3)。
(S,E)-2-(4-甲氧基苯基)-2-甲基-3-烯-戊醇(2f)：
Figure GDA0003170389860000123
其为无色油状液体，质量为83.55mg，收率为81％，Rf(PE/EA＝10:1)：0.25；1H NMR(400MHz,CDCl3)δ7.14–7.08(m,2H),6.75–6.69(m,2H),5.51(dq,J＝15.6,1.4Hz,1H),5.38(dq,J＝15.7,6.2Hz,1H),3.64(s,3H),3.56(d,J＝2.5Hz,2H),1.61(dd,J＝6.2,1.4Hz,3H),1.38(brs,1H),1.23(s,3H)；13C NMR(101MHz,CDCl3)δ157.94,137.20,136.63,127.93,124.94,113.68,70.42,55.21,45.54,23.31,18.32；HRMS(ESI+,m/z)calcd for C13H18O2[M+Na]+：229.1199,Found229.1201；ee值＝96％,determined by HPLC(Daicel Chiralpak OJColumn,n-Hexane:i-PrOH＝90:10,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝10.59min(minor),tR＝12.3min(major)；[α]D 25＝-0.76°(c＝1.0,CHCl3)。
(S,E)-2-(4-甲硫基苯基)-2-甲基-3-烯-戊醇(2g)：
Figure GDA0003170389860000131
其为无色油状液体，质量为81.3mg，收率为73％，Rf(PE/EA＝10:1)：0.3；1H NMR(400MHz,CDCl3)δ7.29–7.19(m,4H),5.64(dq,J＝15.7,1.4Hz,1H),5.53(dq,J＝15.7,6.2Hz,1H),3.71(d,J＝1.5Hz,2H),2.46(s,3H),1.75(dd,J＝6.2,1.4Hz,3H),1.46(brs,1H),1.37(s,3H)；13C NMR(101MHz,CDCl3)δ142.28,136.25,136.13,127.48,126.76,125.36,70.25,45.87,23.20,18.34,15.98；HRMS(ESI+,m/z)calcd for C13H18OS[M+H-H2O]+：205.1045,Found205.1046；ee值＝94％,determined by HPLC(Daicel Chiralpak OD-HColumn,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝13.15min(major),tR＝13.87min(minor)；[α]D 25＝+6.38°(c＝1.09,CHCl3)。
(S,E)-2-(4-吗啉基苯基)-2-甲基-3-烯-戊醇(2h)：
Figure GDA0003170389860000132
其为无色油状液体，质量为104.5mg收率为80％，Rf(PE/EA＝5:1)：0.15，1H NMR(400MHz,CDCl3)δ7.29–7.22(m,2H),6.92–6.83(m,2H),5.65(dq,J＝15.7,1.5Hz,1H),5.53(dq,J＝15.7,6.2Hz,1H),3.85(t,4H),3.71(d,J＝4.4Hz,2H),3.14(t,4H),1.75(dd,J＝6.2,1.4Hz,3H),1.38(s,4H)，13C NMR(101MHz,CDCl3)δ149.58,136.65,136.45,127.69,124.94,115.53,70.44,66.95,49.30,45.53,23.22,18.36，HRMS(ESI+,m/z)calcd forC16H23NO2[M+Na]+：284.1621,Found284.1623，ee值＝98％,determined by HPLC(DaicelChiralpak OD-H Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝35.01min(minor),tR＝35.99min(major)，[α]D 25＝+7.9°(c＝1.06,CHCl3)。
(S,E)-2-(4-三氟甲基苯基)-2-甲基-3-烯-戊醇(2i)：
Figure GDA0003170389860000133
其为无色油状液体，质量为78.5mg，收率为70％，Rf(PE/EA＝10:1)：0.32，1H NMR(400MHz,CDCl3)δ7.43(d,J＝8.3Hz,2H),7.32(d,J＝8.3Hz,2H),5.51(dq,J＝15.7,1.4Hz,1H),5.40(dq,J＝15.7,6.1Hz,1H),3.62(s,2H),1.62(dd,J＝6.1,1.4Hz,3H),1.45(brs,1H),1.27(s,3H)，13C NMR(101MHz,CDCl3)δ149.63(d,J＝1.3Hz),135.62,127.36,126.14,125.14(q,J＝3.8Hz),69.98,46.37,23.27,18.30，19F NMR(376MHz,CDCl3)δ-62.46，HRMS(ESI+,m/z)calcd for C13H15F3O[M+H-H2O]+：227.1042,Found227.1040，ee值＝98％,determined by HPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝99:1,flowrate 1.0mL/min,T＝30℃,λ＝210nm):tR＝16.87min(minor),tR＝19.59min(major)，[α]D 25＝-3.17°(c＝1.08,CHCl3)。
(S,E)-2-间甲苯基-2-甲基-3-烯-戊醇(2j)：
Figure GDA0003170389860000141
其为无色油状液体，质量为78mg，收率为82％，Rf(PE/EA＝20:1)：0.2，1H NMR(400MHz,CDCl3)δ7.12–7.03(m,1H),7.02–6.96(m,2H),6.92–6.86(m,1H),5.52(dq,J＝15.8,1.4Hz,1H),5.40(dq,J＝15.7,6.2Hz,1H),3.64–3.53(m,2H),2.20(s,3H),1.62(dd,J＝6.2,1.5Hz,3H),1.36(brs,1H),1.24(s,3H)，13C NMR(101MHz,CDCl3)δ145.23,137.90,136.51,128.28,127.60,127.12,125.06,123.90,70.40,46.12,23.21,21.66,18.35，HRMS(ESI+,m/z)：calcd for C13H18O[M+Na]+213.1250,Found213.1253，ee值＝96％,determined by HPLC(Daicel Chiralpak ID Column,n-Hexane:i-PrOH＝99:1,flow rate1.0mL/min,T＝30℃,λ＝210nm):tR＝8.22min(minor),tR＝9.94min(major)，[α]D 25＝-2.32°(c＝0.68,CHCl3)。
(S,E)-2-(3-甲氧基苯基)-2-甲基-3-烯-戊醇(2k)：
Figure GDA0003170389860000142
其为无色油状液体，质量为75.2mg，收率为73％，Rf(PE/EA＝10:1)：0.3，1H NMR(400MHz,CDCl3)δ7.11(t,J＝8.0Hz,1H),6.82–6.74(m,2H),6.62(ddd,J＝8.2,2.6,0.9Hz,1H),5.52(dq,J＝15.7,1.4Hz,1H),5.41(dq,J＝15.8,6.2Hz,1H),3.65(s,3H),3.62–3.54(m,2H),1.61(dd,J＝6.1,1.4Hz,3H),1.41(brs,1H),1.25(s,3H)，13C NMR(101MHz,CDCl3)δ159.60,147.12,136.27,129.33,125.20,119.25,113.67,110.92,70.36,55.18,46.25,23.17,18.39，HRMS(ESI+,m/z)calcd for C13H18O2[M+Na]+：229.1199,Found229.1201，ee值＝94％,determined by HPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝21.24min(minor),tR＝23.56min(major)，[α]D 25＝-1.39°(c＝1.14,CHCl3)。
(S,E)-2-间氯苯基-2-甲基-3-烯-戊醇(2l)：
Figure GDA0003170389860000143
其为无色油状液体，质量为69mg，收率为65％，Rf(PE/EA＝10:1)：0.2，1H NMR(400MHz,CDCl3)δ7.32(t,J＝1.8Hz,1H),7.25–7.17(m,3H),5.66–5.60(m,1H),5.55(dq,J＝15.7,5.9Hz,1H),3.72(s,2H),1.77(dd,J＝6.0,1.2Hz,3H),1.48(brs,1H),1.38(s,3H)，13C NMR(101MHz,CDCl3)δ147.64,135.65,134.23,129.54,127.34,126.49,125.91,125.10,70.08,46.26,23.21,18.38，HRMS(ESI+,m/z)calcd for C12H15ClO[M+H-H2O]+：193.0778,Found193.0777，ee值＝92％,determined by HPLC(Daicel Chiralpak OD-HColumn,n-Hexane:i-PrOH＝99:1,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝14.22min(minor),tR＝14.92min(major)，[α]D 25＝-0.83°(c＝0.89,CHCl3)。
(S,E)-2-间溴苯基-2-甲基-3-烯-戊醇(2m)：
Figure GDA0003170389860000151
其为无色油状液体，质量为68mg收率为53％，Rf(PE/EA＝10:1)：0.2，1H NMR(400MHz,CDCl3)δ7.47(t,J＝1.9Hz,1H),7.35(ddd,J＝7.8,2.0,1.1Hz,1H),7.28(ddd,J＝7.9,1.8,1.2Hz,1H),7.19(t,J＝7.8Hz,1H),5.63(dd,J＝15.8,1.2Hz,1H),5.55(dq,J＝15.7,5.8Hz,1H),3.72(s,2H),1.77(dd,J＝5.9,1.1Hz,3H),1.50(brs,1H),1.38(s,3H)，13CNMR(101MHz,CDCl3)δ147.94,135.63,130.22,129.86,129.43,125.96,125.59,122.63,70.07,46.27,23.22,18.39，HRMS(ESI+,m/z)calcd for C12H15BrO[M+H-H2O]+：237.0273,Found237.0274，ee值＝96％,determined by HPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝99:1,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝15.00min(minor),tR＝15.78min(major)，[α]D 25＝-3.87°(c＝0.9,CHCl3)。
(S,E)-2-(3-三氟甲基苯基)-2-甲基-3-烯-戊醇(2n)：
Figure GDA0003170389860000152
其为无色油状液体，质量为77mg，收率为63％，Rf(PE/EA＝10:1)：0.2，1H NMR(400MHz,CDCl3)δ7.59(tt,J＝1.7,0.8Hz,1H),7.57–7.52(m,1H),7.50–7.41(m,2H),5.65(dq,J＝15.6,1.3Hz,1H),5.55(dq,J＝15.8,6.1Hz,1H),3.76(s,2H),1.77(dd,J＝6.1,1.3Hz,3H),1.51(brs,1H),1.42(s,3H)，13C NMR(101MHz,CDCl3)δ146.52,135.56,130.68,130.47(q,J＝1.5Hz),128.69,126.28,125.60,123.71(q,J＝3.9Hz),123.19(q,J＝3.7Hz),69.99,46.32,23.30,18.37，19F NMR(376MHz,CDCl3)δ-62.43，HRMS(ESI+,m/z)calcd for C13H15F3O[M+H-H2O]+：227.1042,Found227.1040，ee值＝77.5％,determined byHPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝7.80min(major),tR＝8.36min(minor)，[α]D 25＝+0.58°(c＝1.0,CHCl3)。
(S,E)-2-((3-甲酸甲酯基)苯基)-2-甲基-3-烯-戊醇(2o)：
Figure GDA0003170389860000153
其为无色油状液体，质量为62.5mg，收率为53％，Rf(PE/EA＝5:1)：0.2，1H NMR(400MHz,Chloroform-d)δ8.03–7.98(m,1H),7.87(dt,J＝7.7,1.4Hz,1H),7.53(ddd,J＝7.8,2.0,1.2Hz,1H),7.42–7.34(m,1H),5.65(dq,J＝15.7,1.5Hz,1H),5.52(dq,J＝15.8,6.2Hz,1H),3.89(s,3H),3.75(d,J＝0.8Hz,2H),1.74(dd,J＝6.2,1.5Hz,3H),1.61(brs,1H),1.41(s,3H).13C NMR(101MHz,Chloroform-d)δ167.23,145.87,135.89,131.73,130.12,128.35,128.00,127.57,125.89,70.10,52.12,46.24,23.25,18.34.GC-MS(EI+,m/z)for C14H18O3:Calcd.234.1,Found:234.1.ee值＝96％,determined by HPLC(DaicelChiralpak OD-H Column,n-Hexane:i-PrOH＝95:5,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝19.1min(minor),tR＝27.3min(major).[α]D 25＝+3.86°(c＝1.0,CHCl3)。
(S,E)-2-邻甲苯基-2-甲基-3-烯-戊醇(2p)：
Figure GDA0003170389860000161
其为无色油状液体，质量为62mg，收率为65％，Rf(PE/EA＝10:1)：0.3，1H NMR(400MHz,CDCl3)δ7.36–7.31(m,1H),7.17(dd,J＝6.4,2.2Hz,1H),7.15–7.12(m,2H),5.61(dq,J＝15.8,1.6Hz,1H),5.37(dq,J＝15.8,6.4Hz,1H),3.81(q,J＝11.6,8.6Hz,2H),2.37(s,3H),1.73(dd,J＝6.4,1.6Hz,3H),1.55(brs,1H),1.41(s,3H)，13C NMR(101MHz,CDCl3)δ142.78,137.21,136.78,132.62,127.02,126.49,125.77,125.67,68.84,46.75,23.57,22.58,18.16，HRMS(ESI+,m/z)：calcd for C13H18O[M+Na]+213.1250,Found213.1252，ee值＝94％,determined by HPLC(Daicel Chiralpak OJ Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝9.62min(minor),tR＝11.17min(major)，[α]D 25＝+9.23°(c＝1.06,CHCl3)。
(S,E)-2-邻氯苯基-2-甲基-3-烯-戊醇(2q)：
Figure GDA0003170389860000162
其为无色油状液体，质量为83.1mg，收率为78％，Rf(PE/EA＝10:1)：0.35，1H NMR(400MHz,CDCl3)δ7.47(dd,J＝7.9,1.7Hz,1H),7.34(dd,J＝7.8,1.6Hz,1H),7.22(td,J＝7.6,1.6Hz,1H),7.16(td,J＝7.5,1.7Hz,1H),5.68(dq,J＝15.7,1.6Hz,1H),5.35(dq,J＝15.8,6.4Hz,1H),3.91(d,J＝2.4Hz,2H),1.74(dd,J＝6.5,1.7Hz,3H),1.60(brs,1H),1.50(s,3H)，13C NMR(101MHz,CDCl3)δ142.07,135.43,133.98,131.84,129.58,127.78,126.64,125.82,68.24,47.12,22.81,18.18，HRMS(ESI+,m/z)calcd for C12H15ClO[M+H-H2O]+：193.0778,Found193.0777，ee值＝94％,determined by HPLC(Daicel Chiralpak OD-HColumn,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝8.56min(minor),tR＝9.50min(major)，[α]D 25＝-5.36°(c＝1.0,CHCl3)。
(S,E)-2-(β-萘基)-2-甲基-3-烯-戊醇(2r)：
Figure GDA0003170389860000163
其为白色液体，质量为80mg，收率为71％，Rf(PE/EA＝10:1)：0.2，1H NMR(400MHz,CDCl3)δ7.85–7.74(m,4H),7.52–7.40(m,3H),5.75(dq,J＝15.6,1.5Hz,1H),5.58(dq,J＝15.7,6.3Hz,1H),3.92–3.79(m,2H),1.78(dd,J＝6.4,1.6Hz,3H),1.50(s,3H),1.46(brs,1H)，13C NMR(101MHz,CDCl3)δ142.63,136.37,133.36,132.07,128.00,127.97,127.42,126.02,125.73,125.68,125.55,125.44,70.24,46.45,23.36,18.45，HRMS(ESI+,m/z)calcd for C16H18O[M+Na]+：249.1250,Found249.1250，ee值＝97％,determined by HPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝254nm):tR＝14.75min(major),tR＝16.16min(minor)，[α]D 25＝+7.84°(c＝1.0,CHCl3)。
(S,E)-2-(α-萘基)-2-甲基-3-烯-戊醇(2s)：
Figure GDA0003170389860000171
其为无色油状液体，质量为96.2mg收率为85％，Rf(PE/EA＝10:1)：0.25，1H NMR(400MHz,CDCl3)δ8.32–8.25(m,1H),7.85–7.81(m,1H),7.75(dd,J＝8.1,1.2Hz,1H),7.54(dd,J＝7.4,1.2Hz,1H),7.48–7.35(m,3H),5.84(dq,J＝15.9,1.7Hz,1H),5.40(dq,J＝15.8,6.4Hz,1H),4.09–3.89(m,2H),1.72(dd,J＝6.5,1.7Hz,3H),1.60(s,4H)，13C NMR(101MHz,CDCl3)δ140.76,137.64,135.01,131.45,129.24,128.00,127.51,126.57,125.18,124.92,124.87,124.58,69.39,47.00,25.24,18.25，HRMS(ESI+,m/z)calcd forC16H18O[M+Na]+：249.1250,Found249.1250，ee值＝88％,determined by HPLC(DaicelChiralpak OD-H Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝254nm):tR＝12.67min(minor),tR＝15.41min(major)，[α]D 25＝+9.02°(c＝1.0,CHCl3)。
(S,E)-2-(3-氟-4-甲氧基苯基)-2-甲基-3-烯-戊醇(2t)：
Figure GDA0003170389860000172
其为无色油状液体，质量为88mg，收率为78％，Rf(PE/EA＝5:1)：0.25，1H NMR(400MHz,CDCl3)δ6.93–6.83(m,1H),6.74(t,J＝8.7Hz,0H),5.44(dd,J＝15.8,1.4Hz,0H),5.35(dq,J＝15.7,5.9Hz,0H),3.69(s,1H),3.51(s,1H),1.58(dd,J＝6.0,1.2Hz,1H),1.19(s,1H)，13C NMR(101MHz,CDCl3)δ152.20(d,J＝244.9Hz),145.89(d,J＝10.8Hz),138.63(d,J＝5.4Hz),136.09,125.49,122.40(d,J＝3.4Hz),115.09(d,J＝18.9Hz),113.24(d,J＝2.2Hz),70.29,56.32,45.65,23.31,18.29，19F NMR(376MHz,CDCl3)δ-134.95，GC-MS(EI+,m/z)calcd for C13H17FO2：224.1,found:224.1，ee值＝96％,determined by HPLC(Daicel Chiralpak ID Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝12.69min(major),tR＝15.18min(minor)，[α]D 25＝+4.26°(c＝1.0,CHCl3)。
(S,E)-2-(3-溴-4-甲氧基苯基)-2-甲基-3-烯-戊醇(2u)：
Figure GDA0003170389860000173
其为无色油状液体，质量为96mg收率为68％，Rf(PE/EA＝5:1)：0.27，1H NMR(400MHz,CDCl3)δ7.50(d,J＝2.3Hz,1H),7.25(dd,J＝8.6,2.4Hz,1H),6.86(d,J＝8.6Hz,1H),5.65–5.58(m,1H),5.53(dq,J＝15.7,5.9Hz,1H),3.87(s,3H),3.69(s,2H),1.76(dd,J＝6.0,1.2Hz,3H),1.36(s,3H)，13C NMR(101MHz,CDCl3)δ154.28,139.11,136.07,132.03,126.98,125.58,111.71,111.62,70.28,56.26,45.57,23.36,18.33，GC-MS(EI+,m/z)calcdfor C13H17BrO2：284.0,found284.0，ee值＝90％,determined by HPLC(Daicel ChiralpakID Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝11.53min(major),tR＝12.95min(minor)，[α]D 25＝+2.88°(c＝1.0,CHCl3)。
(S,E)-2-(2,4-二氟苯基)-2-甲基-3-烯-戊醇(2v)：
Figure GDA0003170389860000181
其为无色油状液体，质量为64mg，收率为60％，Rf(PE/EA＝10:1)：0.3，1H NMR(400MHz,CDCl3)δ7.31(td,J＝8.9,6.5Hz,1H),6.85–6.79(m,1H),6.79–6.72(m,1H),5.67(dp,J＝15.6,1.5Hz,1H),5.46(dqd,J＝15.7,6.4,0.8Hz,1H),3.80(s,2H),1.74(dd,J＝6.4,1.6Hz,3H),1.57(brs,1H),1.41(d,J＝0.9Hz,3H)，13C NMR(101MHz,CDCl3)δ162.77(dd,J＝43.2,11.9Hz),160.29(dd),134.82(d,J＝1.5Hz),130.12(dd,J＝9.3,7.0Hz),127.80(dd,J＝11.7,3.9Hz),125.84(d,J＝1.5Hz),110.69(dd,J＝20.2,3.6Hz),104.62(dd,J＝28.0,25.0Hz),68.57(d,J＝4.3Hz),45.35(d,J＝3.4Hz),22.38(d,J＝2.8Hz),18.24，19F NMR(376MHz,CDCl3)δ-104.58,-113.35，GC-MS(EI+,m/z)calcd for C12H14F2O：212.1,found:212.1，ee值＝99.8％,determined by HPLC(Daicel Chiralpak AD-HColumn,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝7.83min(major),tR＝8.72min(minor)，[α]D 25＝+2.32°(c＝1.0,CHCl3)
(S,E)-2-(3,4,5-三甲氧基苯基)-2-甲基-3-烯-戊醇(2w)：
Figure GDA0003170389860000182
其为无色油状液体，质量为79mg，收率为74％，Rf(PE/EA＝3:1)：0.3，1H NMR(400MHz,CDCl3)δ6.56(s,2H),5.66(dd,J＝15.8,1.5Hz,1H),5.57(dq,J＝15.8,6.0Hz,1H),3.85(d,J＝9.4Hz,9H),3.76–3.69(m,2H),1.77(dd,J＝6.1,1.2Hz,3H),1.40(s,4H)，13C NMR(101MHz,CDCl3)δ152.98,140.98,136.55,136.25,125.25,104.31,70.47,60.81,56.16,46.42,23.36,18.37，HRMS(ESI+,m/z)calcd for C15H22O4[M+Na]+：289.1410,Found289.1415，ee值＝98％,determined by HPLC(Daicel Chiralpak ID Column,n-Hexane:i-PrOH＝90:10,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝22.57min(minor),tR＝24.47min(major)，[α]D 25＝+4.6°(c＝1.0,CHCl3)。
(S,E)-2-(4-甲氧基苯基)-2-乙基-3-烯-戊醇(2x)：
Figure GDA0003170389860000191
其为无色油状液体，质量为82mg，收率为74％，Rf(PE/EA＝10:1)：0.18，1H NMR(400MHz,CDCl3)δ7.25–7.15(m,2H),6.94–6.81(m,2H),5.55(d,J＝4.3Hz,2H),3.79(s,3H),3.76(s,2H),1.86–1.75(m,5H),1.44(brs,1H),0.74(t,J＝7.4Hz,3H)，13C NMR(101MHz,CDCl3)δ157.90,135.73,135.46,128.70,125.84,113.59,67.56,55.21,49.22,28.63,18.54,8.49，HRMS(ESI+,m/z)calcd for C14H20O2[M+Na]+：243.1356,Found243.1351，ee值＝94％,determined by HPLC(Daicel Chiralpak AD-H Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝25.10min(major),tR＝27.96min(minor)，[α]D 25＝+7.36°(c＝1.0,CHCl3)。
(S,E)-2-苯基-2-乙基-3-烯-戊醇(2y)：
Figure GDA0003170389860000192
其为无色油状液体，质量为67.3mg，收率为71％，Rf(PE/EA＝20:1)：0.2，1H NMR(400MHz,CDCl3)δ7.35–7.27(m,4H),7.20(tt,J＝5.7,2.1Hz,1H),5.66–5.44(m,2H),3.80(s,2H),1.86–1.81(m,2H),1.79(d,J＝4.8Hz,3H),1.36(s,1H),0.74(t,J＝7.4Hz,3H)，13CNMR(101MHz,CDCl3)δ143.89,135.28,128.23,127.68,126.25,126.03,67.48,49.86,28.56,18.52,8.48，HRMS(ESI+,m/z)：calcd for C13H18O[M+Na]+213.1250,Found213.1249，ee值＝95.5％,determined by HPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝7.63min(minor),tR＝8.65min(major)，[α]D 25＝-2.38°(c＝1.0,CHCl3)。
(S,E)-2-(3-甲氧基苯基)-2-乙基-3-烯-戊醇(2z)：
Figure GDA0003170389860000193
其为无色油状液体，质量为68.5mg，收率为62％，Rf(PE/EA＝10:1)：0.3，1H NMR(400MHz,CDCl3)δ7.24(t,J＝8.0Hz,1H),6.89(dt,J＝7.8,1.3Hz,1H),6.86(t,J＝2.2Hz,1H),6.76(dt,J＝8.2,1.6Hz,1H),5.64–5.50(m,2H),3.79(d,J＝4.0Hz,5H),1.85–1.80(m,2H),1.78(dd,3H),1.37(s,1H),0.75(t,J＝7.4Hz,3H)，13C NMR(101MHz,CDCl3)δ159.57,145.73,135.08,129.13,125.97,120.01,114.42,110.83,67.52,55.15,49.88,28.52,18.52,8.50，HRMS(ESI+,m/z)calcd for C14H20O2[M+Na]+：243.1356,Found243.1355，ee值＝98％,determined by HPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝13.48min(minor),tR＝14.77min(major)，[α]D 25＝-11.28°(c＝1.0,CHCl3)。
(S,E)-2-间氯苯基-2-乙基-3-烯-戊醇(2aa)：
Figure GDA0003170389860000201
其为无色油状液体，质量为73.7mg，收率为66％，Rf(PE/EA＝10:1)：0.35，1H NMR(400MHz,CDCl3)δ7.30–7.22(m,2H),7.19(dt,J＝7.1,2.0Hz,2H),5.66–5.40(m,2H),3.88–3.69(m,2H),1.87–1.71(m,5H),1.41(s,1H),0.74(t,J＝7.4Hz,3H)，13C NMR(101MHz,CDCl3)δ146.28,134.57,134.16,129.37,128.04,126.70,126.41,125.86,67.17,49.89,28.59,18.56,8.41，GC-MS(EI+,m/z)calcd for C13H17ClO：224.1,found224.1，ee值＝97％,determined by HPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝7.98min(minor),tR＝9.35min(major)，[α]D 25＝-5.12°(c＝1.0,CHCl3)。
(S,E)-2-对氟苯基-2-(1-丙烯基)-己醇(2ab)：
Figure GDA0003170389860000202
其为无色油状液体，质量为100mg，收率为85％，Rf(PE/EA＝10:1)：0.25，1H NMR(400MHz,CDCl3)δ7.31–7.21(m,2H),7.06–6.92(m,2H),5.65–5.45(m,2H),3.77(d,J＝2.0Hz,2H),1.79(d,J＝4.7Hz,3H),1.74(t,J＝8.3Hz,2H),1.37(brs,1H),1.31–1.20(m,2H),1.16–0.98(m,2H),0.84(t,J＝7.3Hz,3H)，13C NMR(101MHz,CDCl3)δ161.28(d,J＝244.8Hz),139.79(d,J＝3.4Hz),135.42,129.16(d,J＝7.7Hz),126.20,114.91(d,J＝20.9Hz),67.88,49.21,36.30,26.13,23.37,18.50,14.01，19F NMR(376MHz,CDCl3)δ-117.13，GC-MS(EI+,m/z)calcd for C15H21FO：236.2,found236.1，ee值＝96％,determinedby HPLC(Daicel Chiralpak OJ Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝6.11min(major),tR＝6.58min(minor)，[α]D 25＝-2.32°(c＝1.0,CHCl3)。
(S,E)-2-苯基-2-异丁基-3-烯-戊醇(2ac)：
Figure GDA0003170389860000203
其为无色油状液体，质量为84.4mg，收率为77％，Rf(PE/EA＝20:1)：0.3，1H NMR(400MHz,CDCl3)δ7.36–7.29(m,4H),7.25–7.18(m,1H),5.67–5.51(m,2H),3.83(s,2H),1.83–1.78(m,3H),1.71(dd,J＝5.5,2.4Hz,2H),1.60–1.52(m,1H),1.34(s,1H),0.74(dd,J＝6.6,1.7Hz,6H)，13C NMR(101MHz,CDCl3)δ144.19,135.85,128.17,127.71,126.26,125.76,67.97,50.02,45.44,24.90,24.88,24.19,18.54，GC-MS(EI+,m/z)calcd forC15H22O：218.2,found218.2，ee值＝93％,determined by HPLC(Daicel Chiralpak OD-HColumn,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝200nm):tR＝6.24min(major),tR＝7.42min(minor)，[α]D 25＝+6.52°(c＝1.0,CHCl3)。
(S,E)-(6-甲氧基-1-(1-丙烯基)-2,3-二氢-1H-茚基)甲醇(2ad)：
Figure GDA0003170389860000211
其为无色油状液体，质量为73.5mg，收率为67％，Rf(PE/EA＝10:1)：0.2，1H NMR(400MHz,CDCl3)δ7.12(dt,J＝8.9,1.1Hz,1H),6.78–6.69(m,2H),5.63(dq,J＝15.6,1.6Hz,1H),5.44(dq,J＝15.6,6.3Hz,1H),3.82–3.76(m,3H),3.69–3.59(m,2H),2.81(t,J＝7.0Hz,2H),2.22(dt,J＝12.6,7.2Hz,1H),2.04(dt,J＝12.6,7.2Hz,1H),1.70(dd,J＝6.3,1.4Hz,3H),1.51(s,1H)，13C NMR(101MHz,CDCl3)δ158.72,147.36,136.39,134.62,125.44,125.32,112.80,109.73,68.09,56.07,55.48,35.24,29.29,18.23，HRMS(ESI+,m/z)for C14H18O2[M+Na]+:calcd.241.1199,Found241.1195，ee值＝98％,determined byHPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝99:1,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝17.54min(major),tR＝22.29min(minor)，[α]D 25＝+68.1°(c＝1.0,CHCl3)。
(S,E)-(1-(1-丙烯基)-1,2,3,4-四氢萘基)甲醇(2ae)：
Figure GDA0003170389860000212
其为无色油状液体，质量为74.8mg，收率为74％，Rf(PE/EA＝10:1)：0.3，1H NMR(400MHz,CDCl3)δ7.29–7.26(m,1H),7.19–7.09(m,3H),5.52(dq,J＝15.6,1.6Hz,1H),5.24(dq,J＝15.7,6.4Hz,1H),3.85(d,J＝11.1Hz,1H),3.64(d,J＝11.1Hz,1H),2.82–2.71(m,2H),2.03(ddd,J＝12.9,9.6,3.6Hz,1H),1.87–1.70(m,4H),1.68(dd,J＝6.4,1.6Hz,3H)，13C NMR(101MHz,CDCl3)δ138.71,138.54,137.28,129.55,127.81,126.16,126.04,125.80,69.64,46.15,31.61,30.38,18.91,18.28，HRMS(ESI+,m/z)calcd for C14H18O[M+Na]+：225.1250,Found225.1249，ee值＝97.5％,determined by HPLC(Daicel Chiralpak OD-HColumn,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝200nm):tR＝8.68min(minor),tR＝9.84min(major)，[α]D 25＝-2.07°(c＝1.0,CHCl3)。
(S,E)-2-(3,4,-笨并[1,3]二氧五环)-2-甲基-3-烯-戊醇(2af)：
Figure GDA0003170389860000213
其为无色油状液体，质量为89.2mg，收率为81％，Rf(PE/EA＝10:1)：0.2，1H NMR(400MHz,CDCl3)δ6.69(d,J＝1.8Hz,1H),6.66–6.57(m,2H),5.76(s,2H),5.46(dd,J＝15.8,1.4Hz,1H),5.37(dq,J＝15.7,6.0Hz,1H),3.52(d,J＝2.0Hz,2H),1.59(dd,J＝6.0,1.3Hz,3H),1.36(brs,1H),1.20(s,3H)，13C NMR(101MHz,CDCl3)δ147.69,145.88,139.28,136.49,125.07,119.85,107.97,107.78,100.93,70.44,46.04,23.50,18.36，HRMS(ESI+,m/z)calcd for C13H16O3[M+Na]+：243.0992,Found243.0986，ee值＝99％,determined byHPLC(Daicel Chiralpak ID Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝9.97min(major),tR＝11.96min(minor)，[α]D 25＝-1.58°(c＝1.0,CHCl3)
(S,E)-2-二茂铁基-2-甲基-3-烯-戊醇(2ag)：
Figure GDA0003170389860000221
其为无色油状液体，质量为79.5mg，收率为56％，Rf(PE/EA＝10:1)：0.2，1H NMR(400MHz,CDCl3)δ5.68(dq,J＝15.7,1.6Hz,1H),5.48(dq,J＝15.6,6.3Hz,1H),4.19–4.12(m,7H),4.05(ddt,J＝15.7,2.6,1.3Hz,2H),3.52(t,J＝8.4Hz,2H),1.75(dd,J＝6.4,1.6Hz,3H),1.34(s,3H)，13C NMR(101MHz,CDCl3)δ136.58,124.01,95.15,71.18,68.55,67.75,67.39,66.01,65.94,41.36,22.65,18.30，HRMS(ESI+,m/z)calcd for C16H20FeO[M+Na]+：307.0756,Found307.0753，ee值＝91％,determined by HPLC(Daicel ChiralpakOD-H Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝10.63min(minor),tR＝12.03min(major)，[α]D 25＝+35.58°(c＝1.0,CHCl3)。
(R,E)-2-(2-噻吩基)-2-甲基-3-烯-戊醇(2ah)：
Figure GDA0003170389860000222
其为无色油状液体，质量为61.2mg，收率为67％，Rf(PE/EA＝10:1)：0.25，1H NMR(400MHz,CDCl3)δ7.02(dd,J＝5.1,1.2Hz,1H),6.80(dd,J＝5.2,3.6Hz,1H),6.72(dd,J＝3.5,1.2Hz,1H),5.54(dq,J＝15.6,1.4Hz,1H),5.41(dq,J＝15.6,6.3Hz,1H),3.49(t,J＝7.1Hz,2H),1.57(dd,J＝6.3,1.5Hz,3H),1.44(brs,1H),1.31(s,3H)，13C NMR(101MHz,CDCl3)δ150.47,135.83,126.73,125.53,123.84,123.70,71.43,45.23,24.12,18.22，GC-MS(EI+,m/z)calcd for C10H14OS182.1,found182.0，ee值＝81％,determined by HPLC(Daicel Chiralpak OD-H Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝11.78min(minor),tR＝13.23min(major)，[α]D 25＝+0.9°(c＝1.0,CHCl3)。
(S,E)-2-(3-[6-甲氧基吡啶])-2-甲基-3-烯-戊醇(2ai)：
Figure GDA0003170389860000223
其为无色油状液体，质量为70mg，收率为67％，Rf(PE/EA＝5:1)：0.2，1H NMR(400MHz,CDCl3)δ8.13(dd,J＝2.6,0.8Hz,1H),7.56(dd,J＝8.7,2.6Hz,1H),6.70(dd,J＝8.7,0.7Hz,1H),5.63(dq,J＝15.7,1.3Hz,1H),5.52(dq,J＝15.7,6.1Hz,1H),3.91(s,3H),3.71(s,2H),1.75(dd,J＝6.1,1.4Hz,3H),1.39(s,3H)，13C NMR(101MHz,CDCl3)δ162.63,145.24,137.85,135.80,133.34,125.81,110.29,70.03,53.34,44.32,23.16,18.28，HRMS(ESI+,m/z)calcd for C12H17NO2[M+Na]+：230.1151,Found230.1152，ee值＝91％,determined by HPLC(Daicel Chiralpak OJ Column,n-Hexane:i-PrOH＝92:8,flow rate1.0mL/min,T＝30℃,λ＝210nm):tR＝7.12min(minor),tR＝7.56min(major)，[α]D 25＝-0.71°(c＝1.0,CHCl3)。
(S,E)-3-(2-[1-羟基-2-甲基-3-烯戊基])-1H-吲哚-1-羧酸酯(2aj)：
Figure GDA0003170389860000231
其为无色油状液体，质量为81mg，收率为51％，Rf(PE/EA＝10:1)：0.25，1H NMR(400MHz,CDCl3)δ8.19–8.07(m,1H),7.61(dq,J＝7.9,1.1Hz,1H),7.46(s,1H),7.36–7.23(m,1H),7.18(ddt,J＝8.3,7.2,1.2Hz,1H),5.71(dt,J＝15.7,1.5Hz,1H),5.52(dqd,J＝15.6,6.4,1.3Hz,1H),3.89(dd,J＝10.6,1.4Hz,1H),3.81(dd,J＝10.7,1.4Hz,1H),1.75(brs,1H),1.72(dt,J＝6.4,1.5Hz,3H),1.67(d,J＝1.4Hz,9H),1.48(d,J＝1.3Hz,3H)，13CNMR(101MHz,CDCl3)δ134.72,128.96,126.33,124.12,124.03,123.30,122.05,121.62,115.39,83.67,69.09,43.06,28.21,23.06,18.24，HRMS(ESI+,m/z)calcd for C19H25NO3[M+Na]+：338.1727,found338.1724，ee值＝91％,determined by HPLC(Daicel Chiralpak IDColumn,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝8.46min(minor),tR＝9.60min(major)，[α]D 25＝+6.56°(c＝1.0,CHCl3)。
(S,E)-2-(4-苯基)-苯基-2-甲基-3-烯-己醇(2ak)：
Figure GDA0003170389860000232
其为白色固体，质量为112.2mg，收率为84％，Rf(PE/EA＝10:1)：0.25，1H NMR(400MHz,Chloroform-d)δ7.61–7.52(m,4H),7.48–7.37(m,4H),7.37–7.28(m,1H),5.72–5.56(m,2H),3.78(d,J＝1.6Hz,2H),2.18–2.05(m,2H),1.44(s,3H),1.41(s,1H),1.03(t,J＝7.4Hz,3H).13C NMR(101MHz,Chloroform-d)δ144.42,140.76,139.18,134.02,132.51,128.72,127.32,127.15,127.06,127.01,70.30,45.88,25.97,23.32,13.94.GC-MS(EI+,m/z)for C19H22O:Calcd.266.2,found 266.2.ee值＝95％,determined by HPLC(DaicelChiralpak OD-H Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝254nm):tR＝19.4min(major),tR＝21.3min(minor).[α]D 25＝+23.26°(c＝1.0,CHCl3)。
(R,E)-2-(4-氟苄基)-2-甲基-3-烯-戊醇(4a)：
Figure GDA0003170389860000233
其为无色油状液体，质量为80.9mg，收率为78％，Rf(PE/EA＝10:1)：0.25，1H NMR(400MHz,CDCl3)δ7.11–7.04(m,2H),6.97–6.89(m,2H),5.47–5.33(m,2H),3.32(q,J＝10.6Hz,2H),2.61(q,2H),1.70(dd,3H),1.41(brs,1H),0.91(s,3H)，13C NMR(101MHz,CDCl3)δ161.46(d,J＝243.7Hz),136.23,133.63(d,J＝3.4Hz),131.87(d,J＝7.7Hz),125.47,114.43(d,J＝21.0Hz),69.16,42.61,42.24(d,J＝1.1Hz),20.66,18.34，19F NMR(376MHz,CDCl3)δ-117.57，HRMS(ESI+,m/z)calcd for C13H17FO[M+H-H2O]+：191.1230,Found191.1228，ee值＝96％,determined by HPLC(Daicel Chiralpak IG Column,n-Hexane:i-PrOH＝95:5,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝5.20min(major),tR＝5.46min(minor)，[α]D 25＝-17.32°(c＝1.0,CHCl3)。
(R,E)-2-(2-溴苄基)-2-甲基-3-烯-戊醇(4b)：
Figure GDA0003170389860000241
其为无色油状液体，质量为85.5mg，收率为64％，Rf(PE/EA＝10:1)：0.3，1H NMR(400MHz,CDCl3)δ7.53(dd,J＝8.0,1.2Hz,1H),7.25–7.17(m,2H),7.04(ddd,J＝8.0,6.9,2.2Hz,1H),5.51–5.45(m,1H),5.38(dq,J＝15.8,5.9Hz,1H),3.49–3.35(m,2H),2.87(q,J＝13.4Hz,2H),1.70(dd,J＝6.0,1.2Hz,3H),1.57(brs,1H),1.01(s,3H)，13C NMR(101MHz,CDCl3)δ137.83,136.18,132.86,132.57,127.69,126.61,126.07,125.23,69.44,43.39,41.98,20.37,18.35，HRMS(ESI+,m/z)calcd for C13H17BrO[M+H-H2O]+：251.0430,Found251.0421，ee值＝97.5％,determined by HPLC(Daicel Chiralpak IG Column,n-Hexane:i-PrOH＝95:5,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝7.71min(major),tR＝11.90min(minor)，[α]D 25＝-27.38°(c＝1.0,CHCl3)。
(R,E)-2-(3,4-二甲氧基苄基)-2-甲基-3-烯-戊醇(4c)：
Figure GDA0003170389860000242
其为无色油状液体，质量为101.9mg，收率为81％，Rf(PE/EA＝5:1)：0.2，1H NMR(400MHz,CDCl3)δ6.76(d,J＝8.6Hz,1H),6.69–6.63(m,2H),5.46–5.35(m,2H),3.84(d,J＝4.4Hz,6H),3.36(q,2H),2.59(q,2H),1.71(dd,3H),1.46(brs,1H),0.92(s,3H)，13C NMR(101MHz,CDCl3)δ148.05,147.28,136.65,130.59,125.11,122.57,113.88,110.51,69.37,55.80,55.74,43.25,42.37,20.79,18.38，HRMS(ESI+,m/z)calcd for C15H22O3[M+Na]+：273.1461,found 273.1457，ee值＝94％,determined by HPLC(Daicel Chiralpak IGColumn,n-Hexane:i-PrOH＝90:10,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝10.02min(major),tR＝11.15min(minor)，[α]D 25＝-6.74°(c＝1.0,CHCl3)。
(R,E)-2-(3-三氟甲基苄基)-2-甲基-3-烯-戊醇(4d)：
Figure GDA0003170389860000251
其为无色油状液体，质量为76.7mg，收率为79％，Rf(PE/EA＝10:1)：0.28，1H NMR(400MHz,CDCl3)δ7.46(d,J＝7.6Hz,1H),7.40–7.29(m,3H),5.51–5.23(m,2H),3.36(q,2H),2.71(q,2H),1.70(d,J＝4.8Hz,3H),1.57(brs,1H),0.92(s,3H)，13C NMR(101MHz,CDCl3)δ139.01,135.74,133.91(q,J＝1.3Hz),129.91(q,J＝31.9Hz),128.00,127.21(q,J＝3.9Hz),125.84,125.62,122.83(q,J＝3.9Hz),69.30,43.23,42.34,20.52,18.21，19FNMR(376MHz,CDCl3)δ-62.58，HRMS(ESI+,m/z)calcd for C14H17F3O[M+H-H2O]+241.1198,Found241.1197，ee值＝89％,determined by HPLC(Daicel Chiralpak IG Column,n-Hexane:i-PrOH＝99:1,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝8.29min(minor),tR＝9.74min(major)，[α]D 25＝-20.72°(c＝1.0,CHCl3)。
(R,E)-叔丁基-3-(2-(羟甲基)-2-甲基-3-烯戊基)-1H-吲哚-1-羧酸酯(4e)：
Figure GDA0003170389860000252
其为无色油状液体，质量为100.9mg，收率为61％，Rf(PE/EA＝10:1)：0.18，1H NMR(400MHz,CDCl3)δ8.10(d,J＝8.1Hz,1H),7.55(dt,J＝7.8,0.9Hz,1H),7.36(s,1H),7.29(ddd,J＝8.4,7.1,1.4Hz,1H),7.22(td,J＝7.5,1.2Hz,1H),5.56–5.42(m,2H),3.49–3.36(m,2H),2.72(q,2H),1.70(d,J＝4.6Hz,3H),1.67(s,9H),1.48(brs,1H),1.02(s,3H)，13CNMR(101MHz,CDCl3)δ149.79,136.70,135.03,131.90,125.26,124.57,123.96,122.24,119.63,116.86,114.99,83.40,69.57,42.28,32.33,28.23,21.24,18.33，HRMS(ESI+,m/z)calcd for C20H27NO3[M+Na]+：352.1883,found 352.1887，ee值＝96％,determined byHPLC(Daicel Chiralpak IG Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝17.05min(major),tR＝18.35min(minor)，[α]D 25＝-5.54°(c＝1.0,CHCl3)。
(S,E)-2-二苯甲基-2-甲基-3-烯-戊醇(4f)：
Figure GDA0003170389860000253
其为无色油状液体，质量为120mg，收率为90％，Rf(PE/EA＝10:1)：0.3，1H NMR(400MHz,CDCl3)δ7.42–7.37(m,2H),7.37–7.32(m,2H),7.24(t,J＝7.5Hz,4H),7.19–7.12(m,2H),5.62(dq,J＝15.8,1.6Hz,1H),5.45(dq,J＝15.8,6.3Hz,1H),4.07(s,1H),3.40–3.22(m,2H),1.76(dd,J＝6.3,1.6Hz,3H),1.45(s,1H),1.08(s,3H)，13C NMR(101MHz,CDCl3)δ142.35,141.62,134.06,130.10,129.97,128.00,127.96,126.55,126.25,126.22,69.59,58.38,44.91,21.00,18.64，HRMS(ESI+,m/z)calcd for C19H22O[M+H-H2O]+：249.1637,Found249.1635，ee值＝99.3％,determined by HPLC(Daicel Chiralpak IDColumn,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝8.80min(minor),tR＝10.40min(major)，[α]D 25＝-44.68°(c＝1.0,CHCl3)。
(R,E)-2-甲基-2-苯乙基-3-烯-戊醇(4g)：
Figure GDA0003170389860000261
其为无色油状液体，质量为79.1mg，收率为77％，Rf(PE/EA＝10:1)：0.35，1H NMR(400MHz,CDCl3)δ7.30–7.23(m,3H),7.17(d,J＝7.2Hz,3H),5.53(dq,J＝15.8,6.3Hz,1H),5.37(dq,J＝15.8,1.6Hz,1H),3.37(q,J＝10.6Hz,2H),2.64–2.46(m,2H),1.75(dd,J＝6.3,1.5Hz,3H),1.61(t,J＝8.7Hz,2H),1.35(brs,1H),1.07(s,3H)，13C NMR(101MHz,CDCl3)δ143.01,136.35,128.33,128.28,125.65,125.59,70.56,41.65,39.77,30.43,20.38,18.39，HRMS(ESI+,m/z)calcd for C14H20O[M+H-H2O]+：187.1481,Found187.1479，ee值＝89％,determined by HPLC(Daicel Chiralpak IG Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝200nm):tR＝8.93min(minor),tR＝9.52min(major)，[α]D 25＝+26.2°(c＝1.0,CHCl3)。
(R,E)-2-(2-(3,4-苯并[1,3]二氧五环)乙基)-2-甲基-3-烯-戊醇(4h)：
Figure GDA0003170389860000262
其为无色油状液体，质量为97.7mg，收率为79％，Rf(PE/EA＝10:1)：0.2，1H NMR(400MHz,CDCl3)δ6.71(d,J＝7.9Hz,1H),6.68–6.65(m,1H),6.63–6.59(m,1H),5.90(s,1H),5.52(dq,J＝15.8,6.3Hz,1H),5.34(dq,J＝15.7,1.5Hz,2H),3.35(q,J＝10.6Hz,2H),2.55–2.37(m,2H),1.74(dd,J＝6.3,1.5Hz,3H),1.61–1.48(m,2H),1.43(s,1H),1.05(s,3H)，13C NMR(101MHz,CDCl3)δ147.47,145.41,136.86,136.25,125.62,120.85,108.80,108.11,100.71,70.51,41.61,40.03,30.16,20.28,18.42，HRMS(ESI+,m/z)calcd forC15H20O3[M+H-H2O]+：231.1379,Found231.1373，ee值＝92％,determined by HPLC(DaicelChiralpak IG Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝200nm):tR＝30.91min(minor),tR＝36.40min(major)，[α]D 25＝+21.58°(c＝1.0,CHCl3)。
(R,E)-2-甲基-2-(1-丙烯基)-1,5-戊二醇(4i)：
Figure GDA0003170389860000263
其为无色油状液体，质量为49.3mg，收率为63％，Rf(PE/EA＝1:1)：0.25，1H NMR(400MHz,CDCl3)δ5.48(dq,J＝15.7,6.3Hz,1H),5.30(dq,J＝15.7,1.6Hz,1H),3.63(t,J＝6.5Hz,2H),3.35(q,2H),1.71(dd,J＝6.3,1.5Hz,3H),1.58–1.45(m,4H),1.40–1.31(m,2H),0.99(s,3H)，13C NMR(101MHz,CDCl3)δ136.42,125.34,70.41,63.58,41.17,33.42,27.14,20.47,18.38，HRMS(ESI+,m/z)calcd for C9H18O2[M+H-H2O]+：141.1274,Found141.1270，ee值＝87.5％,determined by HPLC(Daicel Chiralpak IAColumn,n-Hexane:i-PrOH＝95:5,flow rate 1.0mL/min,T＝30℃,λ＝200nm):tR＝16.62min(minor),tR＝17.25min(major)，[α]D 25＝-0.76°(c＝1.0,CHCl3)。
(R,E)-2-(环己基甲基)-2-甲基-3-烯-戊醇(4j)：
Figure GDA0003170389860000271
其为无色油状液体，质量为60mg，收率为61％，Rf(PE/EA＝20:1)：0.22，1H NMR(400MHz,CDCl3)δ5.44(dq,J＝15.7,6.2Hz,1H),5.30(dq,J＝15.7,1.5Hz,1H),3.31–3.17(m,2H),1.70(dd,J＝6.2,1.5Hz,3H),1.67–1.59(m,5H),1.34(brs,1H),1.31–1.04(m,6H),1.00(s,3H),0.98–0.81(m,2H)，13C NMR(101MHz,CDCl3)δ137.36,124.75,70.94,45.47,41.97,35.74,35.35,33.57,26.51,26.47,26.29,20.38,18.35，HRMS(ESI+,m/z)calcd forC13H24O[M+H-H2O]+：179.1794,Found179.1794，ee值＝76％,determined by HPLC(DaicelChiralpak IG Column,n-Hexane:i-PrOH＝95:5,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝7.71min(major),tR＝11.90min(minor)，[α]D 25＝-8.3°(c＝1.0,CHCl3)。
(S,E)-2-(2-(1S,3S,5S,7S)-金刚烷基)-2-甲基-3-烯-戊醇(4k)：
Figure GDA0003170389860000272
其为无色油状液体，质量为85.8mg，收率为73％Rf(PE/EA＝10:1)：0.2，1H NMR(400MHz,CDCl3)δ5.53–5.41(m,2H),3.65(d,J＝10.3Hz,1H),3.42(d,J＝10.3Hz,1H),1.99–1.92(m,3H),1.76(dd,3H),1.71–1.54(m,12H),1.16(brs,1H),0.97(s,3H)，13C NMR(101MHz,CDCl3)δ133.74,126.63,65.61,46.72,37.21,36.94,36.85,28.79,18.60,14.67，HRMS(ESI+,m/z)calcd for C16H26O[M+H-H2O]+：217.1950,Found217.1950，ee值＝94％,determined by HPLC(Daicel Chiralpak IG Column,n-Hexane:i-PrOH＝95:5,flow rate1.0mL/min,T＝30℃,λ＝200nm):tR＝5.75min(major),tR＝7.45min(minor)，[α]D 25＝-8.66°(c＝1.0,CHCl3)。
(S,E)-2-(1-环己烯基)-2-甲基-3-烯-戊醇(4l)：
Figure GDA0003170389860000273
其为无色油状液体，质量为75mg，收率为83％，Rf(PE/EA＝10:1)：0.2，1H NMR(400MHz,CDCl3)δ5.57(tt,J＝3.7,1.6Hz,1H),5.46(dq,J＝15.8,5.9Hz,1H),5.41–5.34(m,1H),3.59–3.51(m,1H),3.44(d,J＝10.5Hz,1H),2.06(tdt,J＝6.0,4.4,2.5Hz,2H),1.93(ddp,J＝5.7,3.6,1.9Hz,2H),1.71(dd,J＝6.0,1.2Hz,3H),1.65–1.50(m,4H),1.32(brs,1H),1.11(s,3H)，13C NMR(101MHz,CDCl3)δ140.11,135.86,124.32,122.81,67.85,47.05,25.58,24.99,23.27,22.40,21.08,18.33，HRMS(ESI+,m/z)calcd for C12H20O[M+H-H2O]+：163.1481,Found163.1478，ee值＝86％,determined by HPLC(Daicel Chiralpak IGColumn,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝200nm):tR＝6.75min(major),tR＝7.13min(minor)，[α]D 25＝+5.7°(c＝1.0,CHCl3)。
(R,E)-2,6-二甲基-2-(1-丙烯基)-5-烯-己醇(4m)：
Figure GDA0003170389860000281
其为无色油状液体，质量为78.2mg，收率为85％，Rf(PE/EA＝20:1)：0.25，1H NMR(400MHz,CDCl3)δ5.47(dq,J＝15.8,6.3Hz,1H),5.30(dq,J＝15.7,1.6Hz,1H),5.08(dddd,J＝7.1,5.7,2.9,1.5Hz,1H),3.31(q,J＝10.6Hz,2H),1.97–1.81(m,2H),1.71(dd,J＝6.3,1.5Hz,3H),1.67(d,3H),1.58(d,J＝1.3Hz,3H),1.35(brs,1H),1.32–1.25(m,2H),0.99(s,3H)，13C NMR(101MHz,CDCl3)δ136.52,131.29,125.26,124.79,70.50,41.50,37.69,25.68,22.50,20.21,18.36,17.58，HRMS(ESI+,m/z)calcd for C12H22O[M+NH4]+：200.2009,Found200.2005，ee值＝92％,determined by HPLC(Daicel Chiralpak IG Column,n-Hexane:i-PrOH＝98:2,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝5.87min(major),tR＝6.30min(minor)，[α]D 25＝+8.78°(c＝1.0,CHCl3)。
(S,E)-2,6-二甲基-2-(1-丙烯基)-5-烯-己醇(4n)：
Figure GDA0003170389860000282
其为无色油状液体，质量为57.1mg，收率为63％，Rf(PE/EA＝20:1)：0.25，HRMS(ESI+,m/z)calcd for C12H22O[M+NH4]+：200.2009,Found200.2005，ee值＝84.5％,determined by HPLC(Daicel Chiralpak IG Column,n-Hexane:i-PrOH＝98:2,flow rate1.0mL/min,T＝30℃,λ＝200nm):tR＝6.20min(minor),tR＝6.54min(major)，[α]D 25＝-7.2°(c＝1.0,CHCl3)。
(R,E)-2,6,10-三甲基-2-((E)-1-丙烯基)-5,9-二烯-十一醇(4o)：
Figure GDA0003170389860000283
其为无色油状液体，质量为117.7mg，收率为87％，Rf(PE/EA＝20:1)：0.2，1H NMR(400MHz,CDCl3)δ5.47(dq,J＝15.7,6.3Hz,1H),5.30(dq,J＝15.7,1.5Hz,1H),5.09(dddd,J＝8.3,6.9,5.6,1.4Hz,2H),3.31(q,J＝10.6Hz,2H),2.10–2.01(m,2H),1.99–1.81(m,4H),1.71(dd,J＝6.3,1.6Hz,3H),1.69–1.66(m,6H),1.58(dd,J＝6.2,1.3Hz,6H),1.35(s,1H),1.34–1.27(m,2H),1.00(s,3H)，13C NMR(101MHz,CDCl3)δ136.55,134.91,131.33,125.26,124.63,124.31,70.51,41.53,39.68,37.68,26.70,25.70,22.41,20.23,18.38,17.68,15.92，HRMS(ESI+,m/z)calcd for C17H30O[M+Na]+：251.2369,found251.2365；[M+H-H2O]+：calcd.233.2263,Found233.2259，ee值＝92％,determined by HPLC(DaicelChiralpak OD-H Column,n-Hexane:i-PrOH＝99:1,flow rate 1.0mL/min,T＝30℃,λ＝210nm):tR＝6.27min(major),tR＝6.66min(minor)，[α]D 25＝+9.44°(c＝1.0,CHCl3)。
(R,5E,9E,13E,17E,21E,25E,29E)-2,6,10,14,18,22,26,30,34-九甲基-2-((E)-1-丙烯基)-5,9,13,17,21,25,29,33-八烯-三十五醇(4p)：
Figure GDA0003170389860000291
其为无色油状液体，质量为285mg，收率为86％，Rf(PE/EA＝20:1)：0.2，1H NMR(400MHz,CDCl3)δ5.47(dq,J＝15.7,6.3Hz,1H),5.30(dq,J＝15.8,1.5Hz,1H),5.16–5.05(m,8H),3.31(q,J＝10.6Hz,2H),2.06(td,J＝8.7,8.1,4.5Hz,14H),1.98(dd,J＝9.5,5.4Hz,14H),1.90(q,J＝7.4Hz,2H),1.72(dd,J＝6.3,1.6Hz,3H),1.68(d,J＝1.3Hz,3H),1.62–1.56(m,24H),1.30(t,J＝8.2Hz,2H),1.00(s,3H)，13C NMR(101MHz,CDCl3)δ136.54,134.98,134.95,134.93,134.90,134.87,70.51,41.54,39.74,39.72,39.70,37.72,26.75,26.69,26.65,26.63,25.71,22.42,20.22,18.38,17.69,16.03,16.00,15.95，HRMS(ESI+,m/z)calcd for C47H78O[M+Na]+：681.5945,found 681.5950，ee值＝95％,determined byWaters ACQUITY UPC2(Daicel Chiralpak ID-3Column,CO2:MeOH＝80:20,flow rate1.5mL/min,T＝30℃,λ＝210nm):tR＝8.51min(minor),tR＝9.61min(major)，[α]D 25＝+2.34°(c＝1.0,CHCl3)。
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 (2)

1.一种含开链手性季碳中心类化合物的制备方法，其特征在于，具体为：将1,1-二取代1,3-二烯类化合物与CO2在铜催化剂、手性配体、硅烷的存在下于溶剂中发生反应，反应温度为60℃，反应时间为10h，反应后冷却至室温，用饱和氟化铵的甲醇溶液和乙酸乙酯淬灭反应液，制得含开链手性季碳中心类化合物；其中，所述1,1-二取代1,3-二烯类化合物为1-芳基-1烷基取代的1,3-二烯类化合物或1,1-二烷基取代的1,3-二烯；
所述1-芳基-1烷基取代的1,3-二烯类化合物的结构通式如下：
Figure FDA0003176045690000011
所述1，1-二烷基取代的1,3二烯的结构通式如下：
Figure FDA0003176045690000012
所述含开链手性季碳中心类化合物的结构通式如下：
Figure FDA0003176045690000013
R1为芳基、氢、烷基、卤素、甲氧基、三氟甲基、三氟甲氧基、甲巯基、吗啉或酯基；R2为烷基；R3为H或甲基；R4为杂芳基、烷基或烯基；
所述1,1-二取代1,3-二烯类化合物与铜催化剂的摩尔比为20:1，所述1,1-二取代1,3-二烯类化合物与配体的摩尔比为16.6:1，所述1,1-二取代1,3-二烯类化合物与硅烷的摩尔比为1:8；
所述铜催化剂为醋酸铜，所述配体为(+)-1,2-双((2S,5S)-2,5-二苯基膦)乙烷，所述硅烷为甲基二甲氧基硅烷，所述溶剂为环己烷。
2.根据权利要求1所述的含开链手性季碳中心类化合物的制备方法，其特征在于：所述烷基为具有1-41个碳原子的直链烷基、支链烷基或环烷基；所述芳基为具有6-20个碳原子的芳基；所述杂芳基为具有6-20个碳原子的杂芳基；所述烯基为含有6-41个碳原子的烯基。
CN201911154534.9A 2019-10-25 2019-11-21 一种含开链手性季碳中心类化合物及其制备方法 Active CN110746272B (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201911022818 2019-10-25
CN2019110228182 2019-10-25

Publications (2)

Publication Number Publication Date
CN110746272A CN110746272A (zh) 2020-02-04
CN110746272B true CN110746272B (zh) 2021-09-14

Family

ID=69284208

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201911154534.9A Active CN110746272B (zh) 2019-10-25 2019-11-21 一种含开链手性季碳中心类化合物及其制备方法

Country Status (1)

Country Link
CN (1) CN110746272B (zh)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104744394A (zh) * 2015-02-16 2015-07-01 中国农业大学 一种不对称合成含三氟甲基手性季碳化合物的方法
CN110078652A (zh) * 2019-04-12 2019-08-02 香港科技大学深圳研究院 手性四芳基取代甲烷及其制备方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104744394A (zh) * 2015-02-16 2015-07-01 中国农业大学 一种不对称合成含三氟甲基手性季碳化合物的方法
CN110078652A (zh) * 2019-04-12 2019-08-02 香港科技大学深圳研究院 手性四芳基取代甲烷及其制备方法

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Construction of All-Carbon Chiral Quaternary Centers through CuI-Catalyzed Enantioselective Reductive Hydroymethylation of 1,1-Disubstituted Allenes with CO2;Jia Qiu等;《Chemistry-A European Journal》;20190828;第25卷(第61期);第13876页右栏第2段、表2、Scheme 2 *
Copper-catalyzed C–C bond-forming transformation of CO2 to alcohol oxidation level:selective synthesis of homoallylic alcohols from allenes, CO2, and hydrosilanes;Yosuke Tani等;《Chem. Commun.》;20151231;第51卷(第65期);全文 *
Highly Regio- and Enantioselective Copper-Catalyzed Reductive Hydroxymethylation of Styrenes and 1,3-Dienes with CO2;Yong-Yuan Gui等;《Journal of the American Chemical Society》;20171231;第139卷(第47期);摘要、表3、图1、第17012页左栏最后一段、Supporting Information第S3页第II部分、第S5页通用步骤B *
Highly Selective and Catalytic Generation of Acyclic Quaternary Carbon Stereocenters via Functionalization of 1,3-Dienes with CO2;Xiao-Wang Chen等;《Journal of the American Chemical Society》;20191108;第141卷(第47期);第18826页右栏第2段-第18829页左栏第2段、表1-3、式1-2 *

Also Published As

Publication number Publication date
CN110746272A (zh) 2020-02-04

Similar Documents

Publication Publication Date Title
JP4676617B2 (ja) イソプレゴールの製造方法
CN114478337B (zh) 一种轴手性含硫双芳基衍生物及其合成方法
Liu et al. Developments in the Construction of Cyclopropanols
CN113087691A (zh) 一种基于动力学拆分策略合成手性芳基叔醇和苯并吡喃类化合物的方法
Shimizu et al. Stereoselective generation of cis-2-lithio-3-CF3-oxirane via CF3-substituted β-oxido carbenoids. Highly stereoselective synthesis of CF3-substituted tri-and tetrasubstituted oxiranes and tetrasubstituted alkenes
CN110746272B (zh) 一种含开链手性季碳中心类化合物及其制备方法
Tanaka et al. Chiral amplification and the catalytic process in the enantioselective conjugate addition of chiral alkoxydimethylcuprate to (E)-cyclopentadec-2-en-l-one
Klumpp et al. Lithiation of cyclopropylcarbinols
KR850000925B1 (ko) 비대칭 에폭시화의 방법
WO2006003795A1 (ja) 光学活性なアジリジン化合物及びアミン化合物の製造方法、並びに該方法に用いる錯体及びその中間体
Jayaraman et al. New access to chiral syn-α-Chlorohydrins and cis-vinyloxiranes through chloroallyboration
Rudler et al. A Major Breakthrough in the Use of Alkoxycarbene Complexes of Chromium and Tungsten for the Synthesis of Elaborate Organic Compounds: Dihydropyridine Induced Reductions and Cascade Insertion Reactions
CN112679290B (zh) 一种镍催化的烯烃不对称氢炔基化方法及在制备amg837中的应用
Xianming et al. Acid catalyzed ring-opening reactions of optically pure 2-aryl-3, 3-dimethyloxetanes
Ukaji et al. Control of Enantiofacial Differentiation in the Addition Reaction of Organometallics to a Nitrone in the Presence of an External Chiral Auxiliary.
JP2003520274A (ja) 反応触媒としてのイミダゾリジノンの酸付加塩
Kündig et al. Synthesis of [6, n] cis-fused ring compounds via Cr-mediated dearomatisation–ring-closing metathesis
Mori et al. Utilization of the Stannyl Anionic Species Generated from Me3SiSnBu3 and X-in Organic Synthesis
Wakamatsu et al. Preparation of (triphenylsilyl) allyl anion and (triphenylgermyl) allyl anion from 1-propenyltriphenylsilane and 1-propenyltriphenylgermane and their reactions with electrophiles
CN116354995A (zh) 一种含硼手性烯丙基酯类化合物及高立体选择性合成的方法
Smith Aliphatic compounds. Part (ii) other aliphatic compounds
Zhang Enantioselective and Diastereodivergent Conversion of Nitriles to Homoallylic Amines and Alcohols
Dian et al. Oxenoids as Homologation Partners
Meng Synthesis of organoboron compounds by difunctionalization of alkenes
Siemiaszko Pushing the limits of the organometallic chemistry of titanium: carboxylation of alkynes using carbon dioxide and cyclotrimerization reactions

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