CN115490728B - 一种烯丙基膦衍生物的合成方法 - Google Patents
一种烯丙基膦衍生物的合成方法 Download PDFInfo
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- QHJWOSHIGFDANE-UHFFFAOYSA-N prop-2-enylphosphane Chemical class PCC=C QHJWOSHIGFDANE-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 238000001308 synthesis method Methods 0.000 title claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 64
- -1 alkenyl carbonate Chemical compound 0.000 claims abstract description 35
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 18
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 18
- 239000003054 catalyst Substances 0.000 claims abstract description 13
- 239000002184 metal Substances 0.000 claims abstract description 10
- 229910052751 metal Inorganic materials 0.000 claims abstract description 10
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 238000004073 vulcanization Methods 0.000 claims abstract description 5
- 238000005859 coupling reaction Methods 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 69
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 50
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 48
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 26
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 26
- 239000001257 hydrogen Substances 0.000 abstract description 26
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 abstract description 6
- 238000002360 preparation method Methods 0.000 abstract description 5
- 239000006227 byproduct Substances 0.000 abstract description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 abstract description 3
- 239000001569 carbon dioxide Substances 0.000 abstract description 3
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 84
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 44
- 239000012043 crude product Substances 0.000 description 42
- 239000000047 product Substances 0.000 description 26
- 239000002904 solvent Substances 0.000 description 23
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 22
- 239000000203 mixture Substances 0.000 description 22
- 239000003208 petroleum Substances 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 21
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 239000007787 solid Substances 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000007788 liquid Substances 0.000 description 5
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 150000001879 copper Chemical class 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 150000002940 palladium Chemical class 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000012271 agricultural production Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
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- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
- C07F9/5333—Arylalkane phosphine oxides or thioxides
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- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
- C07F9/5325—Aromatic phosphine oxides or thioxides (P-C aromatic linkage)
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
- C07F9/65517—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring
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Abstract
本发明公开一种烯丙基膦衍生物的合成方法,以烯基碳酸酯为原料,以二芳基膦氢为膦源,同时加入金属催化剂、碱、有机溶剂,在一定温度下进行偶联反应和硫化处理,得到烯丙基膦衍生物。本发明方法涉及的反应原料廉价易得,反应条件温和,在室温下即可进行,制备工艺简单,适用底物范围广,官能团兼容性强,污染少(反应副产物只有二氧化碳),对环境友好。
Description
技术领域
本发明属于有机中间体合成的技术领域,具体的是一种烯丙基膦衍生物的合成方法。
背景技术
有机膦化合物因其具有独特的生物和理化性质,不仅是生命体的重要组成部分,而且在有机合成、生物医药、工农业生产、材料科学等多个领域中均有着广泛的应用。烯丙基膦衍生物作为一类重要的有机膦化合物,在工业生产和科学研究中有着重要的意义,其结构式如下:
合成烯丙基膦的传统方法,可归纳为以下二种:
方法一(直接法):以二芳基膦氢为膦源,在催化作用下,与含有离去基团的烯丙基烷烃反应生成烯丙基膦衍生物(Angew.Chem.Int.Ed.2008,47,4878–4881;J.Am.Chem.Soc.2021,143,9912–9921),如下列反应式(1)中所示:
此方法虽然可以合成烯丙基膦衍生物,但往往存在反应产物收率低,副产物多,选择性差,或者反应底物受限制等缺点。
方法二(间接法):以氧化(或硫化)膦氢等为膦源,与烯丙基烷烃、1,3-丁二烯、联烯等试剂反应,生成氧化(或硫化)的烯丙基膦化合物,再还原得到烯丙基膦衍生物(J.Am.Chem.Soc.2019,141,16584–16589;Chem.Soc.Jpn.1982,55,909-913;Chem.Sci.,2022,13,1390;TetrahedronLett.2001,42,297-299;J.Am.Chem.Soc.2018,140,16450-16454;Angew.Chem.Int.Ed.2021,60,27288-27292),如下列反应式(2)中所示:
此方法合成的产物,需要脱保护(还原过程)才能得到烯丙基膦衍生物。脱保护工艺不但增加了生产成本,而且还增加了三废排放,污染环境严重。
发明内容
本发明的目的是针对现有技术中的不足,提供一种烯丙基膦衍生物的制备方法。该方法以烯基碳酸酯为原料,以二芳基膦氢为膦源,在金属钯催化剂作用下,通过偶联反应得到烯丙基膦衍生物。该制备方法所涉及的反应条件温和、反应活性高、选择性高、操作方便、污染少(反应副产物只有二氧化碳)、对环境友好。
本发明采用如下技术方案:
以烯基碳酸酯1为原料,以二芳基膦氢2为膦源,同时加入金属催化剂、碱、有机溶剂至反应容器,在一定温度下进行偶联反应,生成化工中间体烯丙基膦3’,再进行硫化处理,得到烯丙基膦衍生物3,其合成路线如下:
其中,R1为芳基、杂芳基和萘基中的一种;Ar1,Ar2为芳基。
烯丙基膦3’中的磷为三价磷,在惰性环境中是稳定的,但对空气敏感,在空气易被氧化。为了方便对产物进行表征,本发明对产物进行了硫化处理,得到更为稳定的烯丙基膦衍生物3。
作为优选,所述金属催化剂包括铜盐催化剂和钯盐催化剂。其中铜盐为氯化亚铜、碘化亚铜中的一种;钯盐为Pd(OAc)2、Pd2(dba)3、[Pd(C2H5)Cl]2、Pd(PPh3)4中的一种;更为优选地,所述金属催化剂为Pd(OAc)2。
作为优选,所述碱包括有机碱和无机碱,其中有机碱为三乙胺、DBU、TMEDA、Barton碱中的一种;无机碱为Cs2CO3、K2CO3中的至少一种;更为优选地,所述碱为三乙胺。
作为优选,所述有机溶剂为四氢呋喃、甲基叔丁基醚、乙醚、甲苯、二氯甲烷、二氯乙烷的至少一种,更为优选地,所述溶剂为四氢呋喃。
作为优选,所述烯基碳酸酯1、二芳基膦氢2、碱和金属催化剂的摩尔比为1:1~10:1~10:0.001~1,更为优选地,为1:1~5:1~10:0.001~0.5。
作为优选,反应温度为0~100℃,更为优选为25℃。
作为优选,反应时间为0.5~12小时,更为优选为5小时。
本发明的有益效果是:
本发明提供了一种以烯基碳酸酯和二芳基膦氢为反应原料,在金属催化剂催化作用下,经反应得到烯丙基膦衍生物的新方法(新工艺)。本发明涉及的反应原料廉价易得,反应条件温和,在室温下即可进行,制备工艺简单,适用底物范围广,官能团兼容性强,污染少(反应副产物只有二氧化碳),对环境友好。
具体实施方式
下面结合具体实施例对本发明进行详细说明。
以下实施例将有助于本领域的技术人员进一步理解本发明,但不以任何形式限制本发明。应当指出的是,对本领域的普通技术人员来说,在不脱离本发明构思的前提下,还可以做出若干变形和改进。
本发明烯丙基膦衍生物的制备方法在具体实施例操作,按照以下执行:
S1:在室温(25℃)条件下,将烯基碳酸酯1、二芳基膦氢2、催化剂、碱、有机溶剂分别置于反应容器中。将混合物在室温下搅拌5-12小时,TLC检测反应进展。
S2:反应结束后,加入硫粉,室温下搅拌20分钟进行硫化。
S3:反应结束后,除去溶剂,粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物。
实施例1:
分别将烯基碳酸酯1a(22.8mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3a(淡黄色固体,34.9mg,产率为80%)。
NMR分析数据(Z)-3a:
1H NMR(500MHz,CDCl3):δ7.81-7.77(m,4H),7.46-7.39(m,6H),7.27(d,J=7.3Hz,2H),7.21-7.16(m,3H),5.49(td,J1=8.4Hz,J2=5.9Hz,1H),4.36(d,J=2.1Hz,2H),3.55(dd,J1=14.5Hz,J2=8.5Hz,2H),2.38(brs,1H).13C NMR(126MHz,CDCl3):δ146.0(d,J=12.8Hz),140.9(d,J=4.1Hz),132.0(d,J=80.4Hz),131.9(d,J=3.0Hz),131.4(d,J=10.0Hz),128.8(d,J=12.1Hz),128.4,127.6,126.5(d,J=2.7Hz),118.4(d,J=9.9Hz),60.0(d,J=3.1Hz),34.4(d,J=51.8Hz).31P NMR(202MHz,CDCl3):δ40.5.HRMS(ESI-TOF)m/z:[M+H]+calculated for C22H21OPS 365.11129,Found 365.1122.
实施例2:
分别将烯基碳酸酯1b(24.9mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品通过柱色谱法(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3b(淡黄色固体,38.1mg,产率为83%)。
NMR分析数据(Z)-3b:
1H NMR(500MHz,CDCl3):δ7.89-7.85(m,4H),7.56-7.48(m,6H),7.34-7.31(m,2H),6.97-6.94(m,2H),5.49(td,J1=8.4Hz,J2=5.7Hz,1H),4.41(d,J=1.7Hz,2H),3.61(dd,J1=14.5Hz,J2=8.5Hz,2H),2.89(brs,1H).13C NMR(126MHz,CDCl3):δ162.4(d,J=247.4Hz),145.1(d,J=12.7Hz),137.1(dd,J1=3.6Hz,J2=3.6Hz),132.0(d,J=80.5Hz),131.9(d,J=2.9Hz),131.3(d,J=10.0Hz),128.9(d,J=12.1Hz),128.1(dd,J1=7.9Hz,J2=2.7Hz),118.2(d,J=10.7Hz),115.2(d,J=21.4Hz),59.9(d,J=3.0Hz),34.3(d,J=51.6Hz).31P NMR(202MHz,CDCl3):δ40.5.HRMS(ESI-TOF)m/z:[M+H]+calculated forC22H20FOPS 383.1035,Found 383.1031.
实施例3:
分别将烯基碳酸酯1c(26.9mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3c(淡黄色固体,38.8mg,总产率为81%)。
NMR分析数据(Z)-3c:
1H NMR(500MHz,CDCl3):δ7.81-7.77(m,4H),7.49-7.41(m,6H),7.22(d,J=8.5Hz,2H),7.16(d,J=8.3Hz,2H),5.44(td,J1=8.1Hz,J2=6.1Hz,1H),4.34(s,2H),3.53(dd,J1=14.5Hz,J2=8.5Hz,2H),2.81(brs,1H).13C NMR(126MHz,CDCl3):δ145.1(d,J=12.7Hz),139.4(d,J=4.2Hz),133.5,132.0(d,J=2.9Hz),131.9(d,J=80.6Hz),131.3(d,J=10.0Hz),128.9(d,J=12.2Hz),128.5,127.8(d,J=2.7Hz),118.8(d,J=10.0Hz),59.8(d,J=3.0Hz),34.4(d,J=51.4Hz).31P NMR(202MHz,CDCl3):δ40.4.HRMS(ESI-TOF)m/z:[M+H]+calculated for C22H20ClOPS 399.0739,Found 399.0732.
实施例4:
分别将烯基碳酸酯1d(32.2mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3d(淡黄色固体,50.0mg,总产率为94%)。
NMR分析数据(Z)-3d:
1H NMR(500MHz,CDCl3):δ7.88-7.84(m,4H),7.55-7.48(m,6H),7.39(d,J=8.6Hz,2H),7.23(d,J=8.3Hz,2H),5.53(td,J1=8.5Hz,J2=5.7Hz,1H),4.40(d,J=4.1Hz,2H),3.60(dd,J1=14.5Hz,J2=8.5Hz,2H),2.88(brs,1H).13C NMR(126MHz,CDCl3):δ145.1(d,J=12.7Hz),139.9(d,J=4.2Hz),132.0(d,J=3.0Hz),131.9(d,J=80.6Hz),131.4,131.3(d,J=10.0Hz),128.9(d,J=12.1Hz),128.1(d,J=2.7Hz),121.6(d,J=1.0Hz),118.8(d,J=9.9Hz),59.7(d,J=3.0Hz),34.4(d,J=51.4Hz).31P NMR(202MHz,CDCl3):δ40.3.HRMS(ESI-TOF)m/z:[M+H]+calculated for C22H20BrOPS433.0234,Found 433.0232.
实施例5:
分别将烯基碳酸酯1a(30.9mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3e(无色液体,50.8mg,总产率为98%)。
NMR分析数据(Z)-3e:
1H NMR(500MHz,CDCl3):δ7.90-7.85(m,4H),7.57-7.46(m,10H),5.59(td,J1=8.5Hz,J2=5.6Hz,1H),4.45(d,J=4.0Hz,2H),3.64(dd,J1=14.6Hz,J2=8.5Hz,2H),2.95(brs,1H).13C NMR(126MHz,CDCl3):δ145.1(d,J=12.6Hz),144.6-144.5(m),132.0(d,J=3.0Hz),131.8(d,J=80.8Hz),131.3(d,J=10.1Hz),129.5(q,J=32.9Hz),128.9(d,J=12.2Hz),126.8(d,J=2.7Hz),125.3(q,J=3.7Hz),124.2(q,J=272.1Hz),120.3(d,J=9.7Hz),59.7(d,J=3.1Hz),34.4(d,J=51.2Hz).31P NMR(202MHz,CDCl3):δ40.4.HRMS(ESI-TOF)m/z:[M+H]+calculated for C23H20F3OPS433.1003,Found 433.0996.
实施例6:
分别将烯基碳酸酯1f(26.4mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3f(淡黄色固体,38.3mg,总产率为81%)。
NMR分析数据(Z)-3f:
1H NMR(500MHz,CDCl3):δ7.88-7.84(m,4H),7.55-7.47(m,6H),7.30(d,J=8.5Hz,2H),6.81(d,J=8.8Hz,2H),5.49(td,J1=8.5Hz,J2=5.8Hz,1H),4.42(d,J=1.8Hz,2H),3.78(s,3H),3.60(dd,J1=14.5Hz,J2=8.5Hz,2H),2.79(brs,1H).13C NMR(126MHz,CDCl3):δ159.2,145.4(d,J=12.8Hz),133.4(d,J=4.2Hz),132.1(d,J=80.2Hz),131.9(d,J=3.0Hz),131.4(d,J=10.0Hz),128.8(d,J=12.1Hz),127.6(d,J=2.7Hz),116.6(d,J=9.9Hz),113.8,59.9(d,J=3.2Hz),55.3,34.3(d,J=51.8Hz).31P NMR(202MHz,CDCl3):δ40.5.HRMS(ESI-TOF)m/z:[M+H]+calculated for C23H23O2PS 395.1235,Found 395.1228.
实施例7:
分别将烯基碳酸酯1g(28.4mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3g(淡黄色固体,40.4mg,总产率为82%)。
NMR分析数据(Z)-3g:
1H NMR(500MHz,CDCl3):δ7.88-7.84(m,4H),7.56-7.47(m,6H),7.29(d,J=8.3Hz,2H),7.16(d,J=8.5Hz,2H),5.53(td,J1=8.5Hz,J2=5.8Hz,1H),4.41(d,J=1.3Hz,2H),3,61(dd,J1=14.5Hz,J2=8.5Hz,2H),2.85(brs,1H),2.45(s,3H).13C NMR(126MHz,CDCl3):δ145.3(d,J=12.8Hz),137.9,137.7(d,J=4.1Hz),132.0(d,J=80.4Hz),131.9(d,J=3.0Hz),131.3(d,J=10.0Hz),128.8(d,J=12.1Hz),126.8(d,J=2.7Hz),126.5,117.8(d,J=9.9Hz),59.7(d,J=3.1Hz),34.4(d,J=51.6Hz),15.9.31P NMR(202MHz,CDCl3):δ40.4.HRMS(ESI-TOF)m/z:[M+H]+calculated for C23H23OPS2411.1006,Found 411.1002.
实施例8:
分别将烯基碳酸酯1h(31.9mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3h(淡黄色固体,51.3mg,总产率为97%)。
NMR分析数据(Z)-3h:
1H NMR(500MHz,CDCl3):δ7.90-7.85(m,4H),7.56-7.48(m,10H),7.45-7.40(m,4H),7.31(t,J=7.3Hz,1H),5.62(td,J1=8.4Hz,J2=5.9Hz,1H),4.48(s,2H),3.64(dd,J1=14.5Hz,J2=8.5Hz,2H),2.89(brs,1H).13C NMR(126MHz,CDCl3):δ145.6(d,J=12.8Hz),140.7,140.5,139.8(d,J=4.0Hz),132.0(d,J=80.3Hz),131.9(d,J=2.9Hz),131.4(d,J=10.0Hz),128.8(d,J=12.2Hz),128.8,127.3,127.1,127.0,126.8(d,J=2.6Hz),118.2(d,J=9.9Hz),59.9(d,J=3.2Hz),34.5(d,J=51.6Hz).31P NMR(202MHz,CDCl3):δ40.5.HRMS(ESI-TOF)m/z:[M+H]+calculated for C28H25OPS441.1442,Found 441.1432.
实施例9:
分别将烯基碳酸酯1i(35.5mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3i(淡黄色固体,53.0mg,总产率为94%)。
NMR分析数据(Z)-3i:
1H NMR(500MHz,CDCl3):δ7.81-7.77(m,4H),7.48-7.40(m,6H),7.34-7.28(m,4H),7.25-7.22(m,3H),6.81(d,J=8.8Hz,2H),5.42(td,J1=8.4Hz,J2=5.8Hz,1H),4.97(s,2H),4.34(s,2H),3.52(dd,J1=14.5Hz,J2=8.4Hz,2H),2.70(brs,1H).13C NMR(126MHz,CDCl3):δ158.4,145.4(d,J=12.8Hz),137.0,133.6(d,J=4.2Hz),132.1(d,J=80.2Hz),131.9(d,J=2.9Hz),131.4(d,J=9.9Hz),128.8(d,J=12.1Hz),128.6,128.0,127.6(d,J=2.6Hz),127.4,116.7(d,J=9.9Hz),114.7,70.0,59.9(d,J=3.1Hz),34.4(d,J=51.8Hz).31P NMR(202MHz,CDCl3):δ40.5.HRMS(ESI-TOF)m/z:[M+H]+calculated forC29H27O2PS471.1548,Found 471.1545.
实施例10:
分别将烯基碳酸酯1j(24.9mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3j(淡黄色固体,38.5mg,产率为84%)。
NMR分析数据(Z)-3j:
1H NMR(500MHz,CDCl3):δ7.89-7.85(m,4H),7.56-7.48(m,6H),7.23-7.19(m,2H),7.07-7.04(m,1H),7.00-6.96(m,1H),5.52(td,J1=8.3Hz,J2=6.2Hz,1H),4.37(s,2H),3.64(dd,J1=14.5Hz,J2=8.4Hz,1H),2.68(brs,1H).13C NMR(126MHz,CDCl3):δ159.7(dd,J1=247.0Hz,J2=2.6Hz),142.1(d,J1=14.4Hz,J2=1.4Hz),132.1(d,J=80.6Hz),131.9(d,J=3.0Hz),131.3(d,J=10.1Hz),130.8(dd,J1=3.6Hz,J2=3.6Hz),129.2(dd,J1=14.3Hz,J2=3.8Hz),129.1(d,J=8.3Hz),128.8(d,J=12.2Hz),124.2(d,J=3.5Hz),122.0(dd,J1=9.1Hz,J2=1.7Hz),115.5(d,J=22.7Hz),60.7(dd,J1=3.2Hz,J2=3.2Hz),34.0(d,J=51.8Hz).31P NMR(202MHz,CDCl3):δ40.5.HRMS(ESI-TOF)m/z:[M+H]+calculated for C22H20FOPS 383.1035,Found 383.1028.
实施例11:
分别将烯基碳酸酯1k(26.4mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3k(淡黄色固体,24.1mg,总产率为54%)。
NMR分析数据(Z)-3k:
1H NMR(500MHz,CDCl3):δ7.90-7.86(m,4H),7.54-7.46(m,6H),7.25-7.21(m,1H),7.04(dd,J1=7.4Hz,J2=1.7Hz,1H),6.90-6.87(m,1H),6.83(d,J=8.2Hz,1H),5.55(td,J1=8.1Hz,J2=7.2Hz,1H),4.25(d,J=4.4Hz,2H),3.79(s,3H),3.62(dd,J1=14.4Hz,J2=8.1Hz,2H),2.66(brs,1H).13C NMR(126MHz,CDCl3):δ156.2(d,J=2.2Hz),145.2(d,J=13.2Hz),132.4(d,J=80.3Hz),131.7(d,J=2.9Hz),131.4(d,J=10.0Hz),131.3(d,J=3.6Hz),130.7(d,J=3.3Hz),128.9,128.7(d,J=12.1Hz),121.6(d,J=9.0Hz),121.0,110.5,60.9(d,J=2.7Hz),55.6,33.7(d,J=52.9Hz).31P NMR(202MHz,CDCl3):δ40.8.HRMS(ESI-TOF)m/z:[M+H]+calculated for C23H23O2PS 395.1235,Found 395.1229.
实施例12:
分别将烯基碳酸酯1l(26.4mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3l(淡黄色液体,39.3mg,总产率为83%)。
NMR分析数据(Z)-3l:
1H NMR(500MHz,CDCl3):δ7.89-7.84(m,4H),7.54-7.48(m,6H),7.20-7.18(m,1H),6.94(d,J=7.7Hz,1H),6.90-6.89(m,1H),6.79(dd,J1=8.2Hz,J2=2.5Hz,1H),5.55(td,J1=8.5Hz,J2=5.8Hz,1H),4.43(d,J=2.1Hz,2H),3.77(s,3H),3.62(dd,J1=14.5Hz,J2=8.5Hz,2H),2.83(brs,1H).13C NMR(126MHz,CDCl3):δ159.6,146.1(d,J=12.7Hz),142.5(d,J=4.1Hz),132.0(d,J=80.4Hz),131.9(d,J=3.0Hz),131.4(d,J=10.0Hz),129.3,128.8(d,J=12.1Hz),118.9(d,J=2.7Hz),118.5(d,J=9.9Hz),113.1,112.2(d,J=2.8Hz),60.1(d,J=3.0Hz),55.2,34.4(d,J=51.7Hz).31P NMR(202MHz,CDCl3):δ40.5.HRMS(ESI-TOF)m/z:[M+H]+calculated for C23H23O2PS 395.1235,Found 395.1227.
实施例13:
分别将烯基碳酸酯1m(26.9mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3m(淡黄色固体,42.6mg,总产率为89%)。
NMR分析数据(Z)-3m:
1H NMR(500MHz,CDCl3):δ7.89-7.84(m,4H),7.57-7.49(m,6H),7.33(s,1H),7.26(s,1H),7.22-7.19(m,2H),5.52(td,J1=8.5Hz,J2=5.6Hz,1H),4.41(d,J=1.5Hz,2H),3.61(dd,J1=14.6Hz,J2=8.5Hz,2H),2.94(brs,1H).13C NMR(126MHz,CDCl3):δ145.1(d,J=12.7Hz),142.9(d,J=4.2Hz),134.2,132.0(d,J=2.9Hz),131.8(d,J=80.6Hz),131.3(d,J=10.0Hz),129.6,128.9(d,J=12.2Hz),127.6,126.7(d,J=2.8Hz),124.7(d,J=2.7Hz),119.4(d,J=10.0Hz),59.8(d,J=3.0Hz),34.4(d,J=51.3Hz).31P NMR(202MHz,CDCl3):δ40.4.HRMS(ESI-TOF)m/z:[M+H]+calculated for C22H20ClOPS 399.0739,Found399.0732.
实施例14:
分别将烯基碳酸酯1n(31.1mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3n(淡黄色固体,48.4mg,总产率为93%)。
NMR分析数据(Z)-3n:
1H NMR(400MHz,CDCl3):δ7.81-7.76(m,4H),7.51-7.41(m,6H),7.37(d,J=1.9Hz,1H),7.26(d,J=8.4Hz,1H),7.15(dd,J1=8.4Hz,J2=1.8Hz,1H),5.43(td,J1=8.5Hz,J2=5.5Hz,1H),4.32(s,2H),3.53(dd,J1=14.6Hz,J2=8.5Hz,2H),2.97(brs,1H).13C NMR(101MHz,CDCl3):δ144.2(d,J=12.7Hz),141.1(d,J=4.3Hz),132.4,132.1(d,J=3.0Hz),131.6(d,J=81.2Hz),131.5,131.3(d,J=10.0Hz),130.2,128.9(d,J=12.2Hz),128.4(d,J=2.9Hz),125.8(d,J=2.8Hz),119.8(d,J=9.9Hz),59.5(d,J=3.2Hz),34.4(d,J=51.2Hz).31P NMR(202MHz,CDCl3):δ40.3.HRMS(ESI-TOF)m/z:[M+H]+calculated forC22H19Cl2OPS 433.0350,Found 433.0331.
实施例15:
分别将烯基碳酸酯1o(27.1mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3o(淡黄色固体,40.4mg,总产率为84%)。
NMR分析数据(Z)-3o:
1H NMR(500MHz,CDCl3):δ7.82-7.77(m,4H),7.49-7.41(m,6H),7.15-7.11(m,1H),6.74-6.64(m,2H),5.39(td,J1=8.3Hz,J2=5.9Hz,1H),4.27(s,2H),3.55(dd,J1=14.5Hz,J2=8.4Hz,2H),2.67(brs,1H).13C NMR(126MHz,CDCl3):δ162.3(dd,J1=249.8Hz,J2=12.5Hz),161.4-158.6(m,1C),141.2(dd,J1=13.0Hz,J2=1.8Hz),131.9(d,J=2.9Hz),131.9(d,J=80.7Hz),131.6-131.4(m,1C),131.3(d,J=10.1Hz),128.8(d,J=12.2Hz),125.4-125.2(m,1C),122.1(dd,J1=9.3Hz,J2=1.9Hz),111.2(dd,J1=21.0Hz,J2=3.7Hz),103.9(dd,J1=26.1Hz,J2=26.1Hz),60.3(dd,J1=3.0Hz,J2=3.0Hz),33.9(d,J=51.5Hz).31P NMR(202MHz,CDCl3):δ40.5.HRMS(ESI-TOF)m/z:[M+H]+calculated forC22H19F2OPS 401.0941,Found 401.0928.
实施例16:
分别将烯基碳酸酯1p(28.1mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3p(白色固体,57.5mg,总产率为89%)。
NMR分析数据(Z)-3p:
1H NMR(500MHz,CDCl3):δ7.88-7.83(m,4H),7.55-7.47(m,6H),6.85(d,J=8.2Hz,1H),6.84(s,1H),6.71(d,J=7.9Hz,1H),5.91(s,2H),5.45(td,J1=8.5Hz,J2=5.8Hz,1H),4.37(d,J=1.8Hz,2H),3.58(dd,J1=14.4Hz,J2=8.5Hz,2H),2.86(brs,1H).13C NMR(126MHz,CDCl3):δ147.7,147.1,145.6(d,J=12.8Hz),135.2(d,J=4.1Hz),132.0(d,J=80.3Hz),131.9(d,J=2.9Hz),131.3(d,J=10.0Hz),128.8(d,J=12.1Hz),120.1(d,J=3.0Hz),117.3(d,J=10.0Hz),108.1,107.1(d,J=2.7Hz),101.0,60.0(d,J=3.0Hz),34.3(d,J=51.7Hz).31P NMR(202MHz,CDCl3):δ40.4.HRMS(ESI-TOF)m/z:[M+H]+calculatedfor C23H21O3PS 409.1027,Found 409.1011.
实施例17:
分别将烯基碳酸酯1q(21.6mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3q(淡黄色固体,42.1mg,总产率为90%)。
NMR分析数据(Z)-3q:
1H NMR(500MHz,CDCl3):δ7.81-7.77(m,4H),7.49-7.41(m,6H),7.21(s,1H),6.36(s,1H),6.30-6.29(m,1H),5.79(td,J1=8.6Hz,J2=6.3Hz,1H),4.33(s,2H),3.54(dd,J1=14.8Hz,J2=8.7Hz,2H),2.88(brs,1H).13C NMR(126MHz,CDCl3):δ153.5(d,J=5.7Hz),142.1(d,J=1.7Hz),135.5(d,J=12.9Hz),132.0(d,J=80.2Hz),131.9(d,J=3.0Hz),131.3(d,J=10.0Hz),128.8(d,J=12.2Hz),114.4(d,J=10.9Hz),111.4(d,J=1.5Hz),107.1(d,J=3.2Hz),57.9(d,J=3.1Hz),34.0(d,J=51.6Hz).31P NMR(202MHz,CDCl3):δ40.5.HRMS(ESI-TOF)m/z:[M+H]+calculated for C20H19O2PS 355.0922,Found 355.0912.
实施例18:
分别将烯基碳酸酯1r(23.5mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3r(淡黄色液体,32.9mg,总产率为74%)。
NMR分析数据(Z)-3r:
1H NMR(500MHz,CDCl3):δ7.80-7.75(m,4H),7.49-7.40(m,6H),7.05-7.04(m,2H),6.89-6.87(m,1H),5.56(td,J1=8.5Hz,J2=5.9Hz,1H),4.38(dd,J1=6.7Hz,J2=1.9Hz,2H),3.51(dd,J1=14.6Hz,J2=8.5Hz,2H),2.94(brs,1H).13C NMR(126MHz,CDCl3):δ143.2(d,J=5.2Hz),138.7(d,J=12.9Hz),131.9(d,J=2.9Hz),130.7(d,J=80.4Hz),130.3(d,J=10.0Hz),127.8(d,J=12.2Hz),126.5(d,J=1.2Hz),123.4(d,J=1.6Hz),123.3(d,J=3.0Hz),115.3(d,J=10.7Hz),58.7(d,J=3.1Hz),33.3(d,J=51.3Hz).31P NMR(202MHz,CDCl3):δ40.4.HRMS(ESI-TOF)m/z:[M+H]+calculated for C20H19OPS2 371.0693,Found371.0683.
实施例19:
分别将烯基碳酸酯1s(28.8mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3s(淡黄色固体,37.3mg,总产率为75%,区域选择性大于20:1)。
NMR分析数据(Z)-3s:
1H NMR(500MHz,CDCl3):δ7.90-7.84(m,5H),7.78-7.75(m,2H),7.73(d,J=8.6Hz,1H),7.55-7.46(m,7H),7.45-7.40(m,2H),5.68(td,J1=8.4Hz,J2=5.8Hz,1H),4.54(d,J=1.8Hz,2H),3.66(dd,J1=14.5Hz,J2=8.5Hz,2H),2.96(brs,1H).13C NMR(126MHz,CDCl3):δ146.0(d,J=12.7Hz),138.2(d,J=4.2Hz),133.4,132.8,132.0(d,J=80.4Hz),131.9(d,J=2.9Hz),131.4(d,J=10.0Hz),128.9(d,J=12.1Hz),128.3,127.9,127.5,126.2,126.0,125.4(d,J=3.2Hz),124.6(d,J=2.3Hz),118.9(d,J=10.0Hz),60.0(d,J=3.1Hz),34.6(d,J=51.5Hz).31P NMR(202MHz,CDCl3):δ40.5.HRMS(ESI-TOF)m/z:[M+H]+calculatedfor C26H23OPS 415.1285,Found 415.1272.
实施例20:
分别将烯基碳酸酯1t(15.4mg,0.12mmol)、二苯基膦氢2a(67.0mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3t(淡黄色液体,20.5mg,总产率为72%)。
NMR分析数据(Z)-3t:
1H NMR(500MHz,CDCl3):δ7.84-7.80(m,4H),7.53-7.44(m,6H),5.56-5.51(m,1H),3.96(d,J=3.7Hz,2H),3.31(dd,J1=14.5Hz,J2=7.7Hz,2H),1.57(brs,1H),1.50(d,J=3.3Hz,3H).13C NMR(126MHz,CDCl3):δ141.1(d,J=12.9Hz),132.6(d,J=80.0Hz),131.6(d,J=2.9Hz),131.3(d,J=10.0Hz),128.6(d,J=12.0Hz),114.2(d,J=8.0Hz),68.3(d,J=2.7Hz),33.5(d,J=55.3Hz),14.2(d,J=2.6Hz).31P NMR(202MHz,CDCl3):δ41.4.HRMS(ESI-TOF)m/z:[M+H]+calculated for C17H19OPS 303.0972,Found303.0964.
实施例21:
分别将烯基碳酸酯1a(22.8mg,0.12mmol)、二苯基膦氢2b(86.4mg,0.36mmol)、Pd(OAc)2(1.3mg,5.0mol%)、Et3N(24.2mg,0.24mmol)置于反应瓶中,加入四氢呋喃(1.0mL),将混合物在25℃下搅拌5小时后。反应结后将硫粉(11.5mg,0.36mmol)加入到反应混合物中,并继续在室温下搅拌20分钟,然后除去溶剂得到粗品。粗品用硅胶柱色谱(石油醚:二氯甲烷:丙酮=20:4:1)分离得到目标产物3u(淡黄色液体,36.8mg,总产率为73%)。
NMR分析数据(Z)-3u:
1H NMR(500MHz,CDCl3):δ7.37(d,J=13.2Hz,4H),7.29(d,J=7.2Hz,2H),7.22-7.14(m,3H),7.07(s,2H),5.47(td,J1=8.5Hz,J2=5.7Hz,1H),4.37(d,J=4.4Hz,2H),3.50(dd,J1=14.5Hz,J2=8.5Hz,2H),2.28(s,12H),2.80(brs,1H).13C NMR(126MHz,CDCl3):δ145.7(d,J=12.6Hz),141.1(d,J=4.1Hz),138.5(d,J=12.8Hz),133.6(d,J=3.0Hz),131.8(d,J=79.7Hz),128.9(d,J=10.0Hz),128.3,127.5,126.5(d,J=2.7Hz),118.8(d,J=9.8Hz),60.0(d,J=3.0Hz),34.3(d,J=51.4Hz),21.4.31P NMR(202MHz,CDCl3):δ40.4.HRMS(ESI-TOF)m/z:[M+H]+calculated for C26H29OPS 421.1755,Found 421.1773.
Claims (5)
1.一种烯丙基膦衍生物的合成方法,其特征在于,所述方法具体是:
以烯基碳酸酯1为原料,以二芳基膦氢2为膦源,同时加入金属催化剂、碱、有机溶剂至反应容器,在一定温度下进行偶联反应,生成化工中间体烯丙基膦3’,再进行硫化处理,得到烯丙基膦衍生物3;
其合成路线如下:
其中,R1为芳基或杂芳基中的一种;Ar1,Ar2为芳基;所述金属催化剂为Pd(OAc)2,所述碱为三乙胺。
2.根据权利要求1所述的一种烯丙基膦衍生物的合成方法,其特征在于,所述有机溶剂为四氢呋喃、甲基叔丁基醚、乙醚、甲苯、二氯甲烷、二氯乙烷中的一种。
3.根据权利要求2所述的一种烯丙基膦衍生物的合成方法,其特征在于,所述有机溶剂为四氢呋喃。
4.根据权利要求1所述的一种烯丙基膦衍生物的合成方法,其特征在于,烯基碳酸酯1、二芳基膦氢2、碱和金属催化剂的摩尔比为1:1~10:1~10:0.001~1。
5.根据权利要求1所述的一种烯丙基膦衍生物的合成方法,其特征在于,反应温度为0~100℃,反应时间为0.5~12小时。
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Asymmetric epoxidation and kinetic resolution of allylic phosphine oxides;Clayden, Jonathan et al;ournal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999);第19卷;2811-23 * |
Asymmetric epoxidations and kinetic resolutions of δ-hydroxy allylic phosphine oxides;Clayden, Jonathan et al;Tetrahedron Letters;第33卷;7043-6 * |
The synthesis of δ-hydroxy allylic phosphine oxides by palladium(II)-catalyzed allylic acetate transposition;Clayden, Jonathan et al;Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry;第23卷;2913-23 * |
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