CN116199716A - 一种手性p,n,n配体及其制备与应用 - Google Patents
一种手性p,n,n配体及其制备与应用 Download PDFInfo
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- 229910052757 nitrogen Inorganic materials 0.000 title claims abstract description 78
- 239000003446 ligand Substances 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 229910052698 phosphorus Inorganic materials 0.000 claims abstract description 38
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 claims abstract description 26
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 12
- WIJJGRVJLNMTCI-UHFFFAOYSA-N 2-diphenylphosphanylaniline Chemical compound NC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 WIJJGRVJLNMTCI-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000001816 cooling Methods 0.000 claims abstract description 8
- 239000011259 mixed solution Substances 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000010992 reflux Methods 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims abstract description 4
- 238000000605 extraction Methods 0.000 claims abstract description 3
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 7
- -1 2-diphenylphosphinophenylethylamine Chemical compound 0.000 claims description 6
- PVZMGWZOXQPFLS-UHFFFAOYSA-N 6-phenylpyridine-2-carbaldehyde Chemical compound O=CC1=CC=CC(C=2C=CC=CC=2)=N1 PVZMGWZOXQPFLS-UHFFFAOYSA-N 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 abstract description 11
- 239000003054 catalyst Substances 0.000 abstract description 6
- 229910052748 manganese Inorganic materials 0.000 abstract description 6
- 239000002243 precursor Substances 0.000 abstract description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 4
- 229910052751 metal Inorganic materials 0.000 abstract description 4
- 239000002184 metal Substances 0.000 abstract description 4
- 238000004440 column chromatography Methods 0.000 abstract description 2
- 238000001035 drying Methods 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract description 2
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 abstract 1
- 238000011049 filling Methods 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 17
- 239000011572 manganese Substances 0.000 description 12
- 150000002576 ketones Chemical class 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- GCHFIBIMNGTFFG-UHFFFAOYSA-N 2-phenylethanamine pyridine Chemical compound c1ccncc1.NCCc1ccccc1 GCHFIBIMNGTFFG-UHFFFAOYSA-N 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 238000004896 high resolution mass spectrometry Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical group [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 4
- 150000002431 hydrogen Chemical group 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- TWKVYXRFUZNRSH-OUKQBFOZSA-N (e)-1,3-diphenylbut-2-en-1-ol Chemical compound C=1C=CC=CC=1C(/C)=C/C(O)C1=CC=CC=C1 TWKVYXRFUZNRSH-OUKQBFOZSA-N 0.000 description 2
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 2
- 150000001335 aliphatic alkanes Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- SAXHIDRUJXPDOD-UHFFFAOYSA-N ethyl hydroxy(phenyl)acetate Chemical compound CCOC(=O)C(O)C1=CC=CC=C1 SAXHIDRUJXPDOD-UHFFFAOYSA-N 0.000 description 2
- HZEGZGIYWZMCQN-UHFFFAOYSA-N n-[2-[hydroxy(phenyl)methyl]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1C(O)C1=CC=CC=C1 HZEGZGIYWZMCQN-UHFFFAOYSA-N 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- PLELHVCQAULGBH-OUKQBFOZSA-N (e)-1,3-diphenylbut-2-en-1-one Chemical compound C=1C=CC=CC=1C(/C)=C/C(=O)C1=CC=CC=C1 PLELHVCQAULGBH-OUKQBFOZSA-N 0.000 description 1
- MZYVNRHFOZMNQR-UHFFFAOYSA-N 2-diphenylphosphanyl-N-phenylaniline Chemical compound C1(=CC=CC=C1)NC1=C(C=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1 MZYVNRHFOZMNQR-UHFFFAOYSA-N 0.000 description 1
- GKKZMYDNDDMXSE-UHFFFAOYSA-N Ethyl 3-oxo-3-phenylpropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC=C1 GKKZMYDNDDMXSE-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical group [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 150000004705 aldimines Chemical class 0.000 description 1
- 150000008365 aromatic ketones Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 150000002466 imines Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- MRXZRJQRQWTKIX-UHFFFAOYSA-N n-(2-benzoylphenyl)acetamide Chemical compound CC(=O)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MRXZRJQRQWTKIX-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- FAQJJMHZNSSFSM-UHFFFAOYSA-N phenylglyoxylic acid Chemical class OC(=O)C(=O)C1=CC=CC=C1 FAQJJMHZNSSFSM-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
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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
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
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- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
- B01J31/2447—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring
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Abstract
本发明提供一种手性P,N,N配体及其制备方法与在不对称氢化反应中的应用。将2‑二苯基膦基苯乙胺与6‑苯基吡啶‑2‑甲醛,充入氮气后,加入甲醇,所形成的混合液回流反应,冷却后,加入NaBH4。随后,混合液再次于回流。冷却,加水(,二氯甲烷萃取,无水硫酸钠干燥,脱去溶剂后,经柱层析得到所需的手性P,N,N配体。本发明所述手性配体与Mn、Ir‑、Ru‑等金属前体形成的催化剂对C=C、C=N、C=O双键的催化不对称氢化反应具有优异的催化活性和立体选择性,对映选择性高达99%ee,TON高达100000。
Description
技术领域
本发明涉及一类新型手性P,N,N配体的制备方法。本发明还涉及上述配体在C=C、C=N、C=O双键的不对称氢化反应中的应用。
背景技术
近年来,具有稳定的八面体的Mn(I)络合物已被证明是C=O键的不对称氢化中贵金属的潜在替代品。Mn(CO)5Br是目前不对称氢化的唯一实用的Mn(I)前体,因此设计与合成新的手性三齿配体是提升锰催化不对称氢化反应效果的关键。2017年,Kirchner报道了一类含有二茂铁骨架的P,N,P三齿醛亚胺配体,该配体与Mn(CO)5Br的络合物能够应用于一些酮的不对称氢化,并具有较好的对映选择性[[a]A. Zirakzadeh,S.R.M.M.de Aguiar,B.Sto¨ger,M.Widhalm and K.Kirchner, ChemCatChem,2017,9,1744–1748.]。同年,Clarke报道了一类含有二茂铁骨架P,N(H),N三齿配体,这个不具有亚胺结构的配体与 Mn(CO)5Br的络合物在催化酮的不对称氢化体系中也显示出较好的反应活性以及对映选择性[(b)M.B.Widegren,G.J.Harkness,A.M.Z. Slawin,D.B.Cordes and M.L.Clarke,Angew.Chem.,Int.Ed.,2017,56, 5825–5828.(c)M.B.Widegren and M.L.Clarke,Catal.Sci.Technol., 2019,9,6047–6058.]。在锰催化酮的不对称氢化体系所使用的配体中,具有平面手性的二茂铁骨架并不是必要的。Beller报道的一类非二茂铁骨架的P,N,P三齿配体与Mn(CO)5Br的络合物,尽管在芳香族酮的不对称氢化中未能得到良好的结果,但在脂肪族的酮的不对称氢化中具有优异的选择性和反应活性,就很好的证明了这一点[(d)M.Garbe, K.Junge,S.Walker,Z.Wei,H.Jiao,A.Spannenberg,S.Bachmann,M. Scaloneand M.Beller,Angew.Chem.,Int.Ed.,2017,56,11237–11241.(e) M.Garbe,Z.Wei,B.Tannert,A.Spannenberg,H.Jiao,S.Bachmann,M. Scalone,K.Junge and M.Beller,Adv.Synth.Catal.,2019,361,1913– 1920.]。然而,在这些开创性的实验中虽然已成功实现了多种简单的酮的不对称氢化,但所获得的具有高ee值的产物的底物范围相对狭窄。
尽管锰催化酮的不对称氢化反应中已取得了较大的进展,然而对于一些其他类型的酮类化合物如酰基吡啶、α,β-不饱和酮、α-卤素取代的酮的不对称氢化至今未曾报道过;另外,在C=N双键的不对称氢化中也有很大的进展空间;在C=C双键的不对称氢化也存在着很大的挑战。因此设计与合成新的手性二齿、三齿或四齿配体或者寻找其它锰催化前体以改善Mn(I)络合物的催化活性,仍然有极大的研究意义。
发明内容
本发明公开了一类手性P,N,N配体及其制备方法。
为实现上述目的,本发明提供的手性P,N,N配体,结构如下式:
式中:
Ar为苯基、2-取代、3-取代、4-取代、2,6-二取代、2,4,6-三取代的芳基等芳环上碳数为C6-C60(优选为C6-C30,更优选为C6-C24)的芳香基团;所述取代基为C1-C40(优选为C1-C30,更优选为C1-C6)烷烃基、C1-C40(优选为C1-C30,更优选为C1-C6)烷氧基、卤素、硝基、酯基或氰基中的一种或多种。
R为氢、C1-C40(优选为C1-C30,更优选为C1-C6)烷烃基;芳环上碳数为C6-C60(优选为C6-C30,更优选为C6-C24)的芳香基团,芳环上含有一个或多个N、S、O、P杂原子的芳环上碳数为C3-C60芳香基团(优选为C3-C30,更优选为C3-C24)。
所述的手性P,N,N配体,其优势绝对构型为S或R
所述的手性P,N,N配体,上述R基团中芳环上碳数为C6-C60(优选为C6-C30,更优选为C6-C24)的芳香基团,优选为菲I-4b。
本发明提供了手性P,N,N配体的制备方法:手性P,N,N配体按以下路线合成:
式中:
Ar为苯基、2-取代、3-取代、4-取代、2,6-二取代、2,4,6-三取代的芳基等芳环上碳数为C6-C60(优选为C6-C30,更优选为C6-C24)的芳香基团;所述取代基为C1-C40(优选为C1-C30,更优选为C1-C6)烷烃基、C1-C40(优选为C1-C30,更优选为C1-C6)烷氧基、卤素、硝基、酯基或氰基中的一种或多种。
R为氢、C1-C40(优选为C1-C30,更优选为C1-C6)烷烃基;芳环上碳数为C6-C60(优选为C6-C30,更优选为C6-C24)的芳香基团,芳环上含有一个或多个N、S、O、P杂原子的芳环上碳数为C3-C60芳香基团(优选为C3-C30,更优选为C3-C24)。
在氮气氛围下,向装有2-二苯基膦基苯乙胺与6-苯基吡啶-2-甲醛的容器中加入甲醇溶液(2-二苯基膦基苯乙胺终浓度为0.2-1.0M),所形成的混合液于70-80℃回流反应1-2小时,待冷却至室温后,加入2-3 equiv.(相对于2-二苯基膦基苯乙胺的量)NaBH4;随后,混合液再次于70-80℃回流反应3-4小时;冷却至室温后,向反应液中加入水(水与混合液的体积比为3:1-5:1),再以二氯甲烷萃取(体积为10-50mL x 3),无水硫酸钠干燥,脱去溶剂后,分离得到所需的手性P,N,N配体。
所述2-二苯基膦基苯乙胺:6-苯基吡啶-2-甲醛摩尔比为1: 1.2-1:2.0.
本发明所述手性P,N,N配体与Mn、Ir-、Ru-等金属前体形成的催化剂对C=C、C=N、C=O双键的催化不对称氢化反应具有优异的催化活性和立体选择性,对映选择性高达99%ee,TON高达100000。
本发明还涉及上述配体在含有C=C、C=N、C=O反应底物中的一种或二种以上的不对称氢化反应中的应用。
本发明提供的手性P,N,N配体,其可用于C=C、C=N、C=O键中的一种或二种以上不对称氢化反应中,将手性P,N,N配体与Mn、Ir、Ru 或Rh中的一种或二种以上按其与金属摩尔比1.1∶1-2.2∶1组成催化剂,反应底物与催化剂的比例为100-10000(优选为100-1000,更优选为100-500),反应时间0.1-24小时。
所述的不对称氢化反应为以下几类底物的催化不对称氢化反应:
(1)α-芳基酮的催化不对称氢化反应;
(2)α,β-不饱和酮的催化不对称氢化反应;
(3)苯或取代苯甲酰基甲酸酯类的催化不对称氢化;
本发明的有益效果:
本发明的手性P,N,N配体,其在空气下稳定、制备方法简单、催化反应活性高,与Mn、Ir、Ru或Rh等金属前体形成的催化剂性质稳定,对空气和湿度具有很好的忍耐力,其参与的不对称氢化反应条件温和,可以在室温下反应,氢气的压力适用范围广,从常压到高压均不影响催化剂的活性和立体选择性。
附图说明
为了更清楚地说明本发明实施例的技术方案,下面将对实施例中所需要使用的附图作简单地介绍,应当理解,以下附图仅示出了本发明的某些实施例,因此不应被看作是对范围的限定,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他相关的附图。
图1手性吡啶-苯乙胺的P,N,N配体化合物I-2a的核磁氢谱图;
图2手性吡啶-苯乙胺的P,N,N配体化合物I-2a的核磁磷谱图;
图3手性吡啶-苯乙胺的P,N,N配体化合物I-4a的核磁氢谱图;
图4手性吡啶-苯乙胺的P,N,N配体化合物I-4a的核磁磷谱图;
图5手性吡啶-苯乙胺的P,N,N配体化合物I-4b的核磁氢谱图;
图6手性吡啶-苯乙胺的P,N,N配体化合物I-4b的核磁磷谱图;
图7N-(2-(羟基(苯基)甲基)苯基)乙酰胺IV-A的核磁氢谱图;
图8手性(E)-1,3-二苯基丁-2-烯-1-醇IV-B的核磁氢谱图;
图9手性2-羟基-2-苯基乙酸乙酯IV-C的核磁氢谱图。
具体实施方式
本发明设计的手性配体是以2-二苯基膦基苯乙胺与6-苯基吡啶-2-甲醛得到手性P,N,N配体。
下面通过实施例详述本发明,但本发明并不限于下述实施例。核磁共振是通过Bruker核磁共振仪测定,高分辨质谱(HRMS)是通过 Agilent 1260系列质谱仪测定。
一、手性配体的合成
实施例1
在氮气氛围下,向装有2-二苯基膦基苯乙胺(1.0mmol)和6-苯基 -2-吡啶基甲醛(1.2mmol)的休朗克瓶中加入5mL无水甲醇(0.2M),混合液于80℃回流反应1小时,待冷却至室温后,加入2equiv(相对于 2-二苯基膦基苯乙胺).NaBH4。随后,再次升温至80℃回流反应3小时。冷却至室温后,向反应液中加入水(15mL),再以二氯甲烷萃取(10mL x 3),无水硫酸钠干燥,脱去溶剂后,经柱层析得到所需的手性P,N,N配体I-2a。
1H NMR(400MHz,CDCl3)δ8.00–6.87(m,22H),4.82–4.75(m, 1H),3.67(dd,J=14.0Hz,J=8.0Hz,2H),2.26(s,1H),1.29(d,J=6.4Hz, 2H).31P NMR(162MHz,CDCl3):δ-17.4;HRMS cal.for C42H36N2P+[M+H]+: 473.2141,found:473.2146.产率为93%。
实施例2
将实施例1中2-二苯基膦基苯乙胺改为下所示的中间体(III-4a),其余过程和条件同实施例1,得到下所示手性P,N,N配体I-4a,1H NMR(400MHz,CDCl3)δ7.98–6.86(m,21H),4.60–4.57(m,1H),4.04 (s,2H),2.95–2.75(m,2H),2.24–2.07(m,2H),1.86(s,1H),1.74–1.58 (m,2H).31P NMR(162MHz,CDCl3):δ-16.4.HRMS cal.for C39H42N2P+ [M+H]+:499.2298,found:499.2300.产率88%。
实施例3
将实施例2中6-苯基-2-吡啶基甲醛改为下所示的中间体(III-1b),其余过程和条件同实施例2,得到下所示手性P,N,N配体I-4b,1H NMR(400MHz,CDCl3)δ8.71–6.94(m,25H),4.63(t,J=2.8Hz,1H), 4.12(s,2H),2.91–2.71(m,2H),2.24–2.08(m,2H),1.84(t,J=4.8Hz, 1H),1.71–1.57(m,2H).31P NMR(162MHz,CDCl3):δ-16.4;HRMS cal. for C42H36N2P+[M+H]+:599.2611,found:599.2610.产率为92%。
二、不对称加氢反应
实施例4
氮气保护下,将Mn(CO)5Br(0.002mmol,1mol%),手性P,N,N配体(I-4b)(0.0022mmol,1.1mol%)溶于乙醇(1.0ml)中,室温(25℃)下搅拌1小时,加入底物2-乙酰胺基二苯甲酮(0.2mmol)的乙醇(1.0ml)溶液,将其置于高压反应釜中,氢气置换3次,然后通入30bar氢气,室温(25℃)下反应12小时。慢慢释放氢气,除去溶剂后用硅胶柱分离得到产物N-(2-(羟基(苯基)甲基)苯基)乙酰胺IV-A。转化率99%,98%ee 的对映选择性1H NMR(400MHz,CDCl3)δ8.53(d,J=3.6Hz,1H),7.94– 7.07(m,9H),5.85(s,1H),3.82(d,J=22.0Hz,1H),1.8(d,J=2.4Hz,1H).。
实施例4
将实施例3中底物换为(E)-1,3-二苯基丁-2-烯-1-酮,其余过程和条件同实施例3,反应得手性(E)-1,3-二苯基丁-2-烯-1-醇IV-B,转化率为99%,98%ee的对映选择性,1HNMR(400MHz,CDCl3)δ7.44–7.21 (m,10H),6.00–5.98(m,1H),5.61(d,J=8.4Hz,1H),2.17(d,J=1.2Hz, 3H).。
实施例5
将实施例3中底物换成苯甲酰基乙酸乙酯,其余过程和条件同实施例3,反应得产物得手性2-羟基-2-苯基乙酸乙酯IV-C,转化率为99%, 98%ee的对映选择性1H NMR(400MHz,CDCl3)δ7.43–7.29(m,5H), 5.15(s,1H),4.29–4.12(m,2H),3.47(s,1H),1.22(t,J=6.8Hz,3H)。
Claims (6)
1.一种手性P,N,N配体,其特征在于:结构式如下:
式中:
Ar为苯基,2-取代、3-取代、4-取代、2,6-二取代或2,4,6-三取代的芳基等芳环上碳数为C6-C60(优选为C6-C30,更优选为C6-C24)的芳香基团;所述取代基为C1-C40(优选为C1-C30,更优选为C1-C6)烷烃基、C1-C40(优选为C1-C30,更优选为C1-C6)烷氧基、卤素、硝基、酯基或氰基中的一种或多种;
R为氢、C1-C40(优选为C1-C30,更优选为C1-C6)烷烃基、芳环上碳数为C6-C60(优选为C6-C30,更优选为C6-C24)的芳香基团、或芳环上含有一个或多个N、S、O、P杂原子的芳环上碳数为C3-C60芳香基团(优选为C3-C30,更优选为C3-C24)。
2.根据权利要求1的手性P,N,N配体,其特征在于:所述配体的优势绝对构型为S或R。
5.一种权利要求1-3任一所述手性P,N,N配体的合成方法,具体如下:
在氮气氛围下,向装有2-二苯基膦基苯乙胺与6-苯基吡啶-2-甲醛的容器中加入甲醇溶液(2-二苯基膦基苯乙胺终浓度为0.2-1.0M),所形成的混合液于70-80℃回流反应1-2小时,待冷却至室温后,加入2-3equiv.(相对于2-二苯基膦基苯乙胺的量)NaBH4;随后,混合液再次于70-80℃回流反应3-4小时;冷却至室温后,向反应液中加入水(水与混合液的体积比为3:1-5:1),再以二氯甲烷萃取,无水硫酸钠干燥,脱去溶剂后,分离得到所需的手性P,N,N配体;所述2-二苯基膦基苯乙胺:6-苯基吡啶-2-甲醛摩尔比为1:1.2-1:2.0。
6.一种权利要求1-3任一所述手性P,N,N配体在不对称氢化反应中的应用。
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