CN116947580A - 一种铑催化的蒽的氢化去对称化构建轴手性化合物的方法 - Google Patents
一种铑催化的蒽的氢化去对称化构建轴手性化合物的方法 Download PDFInfo
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- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 238000000034 method Methods 0.000 title claims abstract description 21
- 150000001875 compounds Chemical class 0.000 title claims abstract description 16
- 238000005984 hydrogenation reaction Methods 0.000 title claims abstract description 12
- -1 anthracene compound Chemical class 0.000 claims abstract description 30
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- 239000003054 catalyst Substances 0.000 claims abstract description 21
- 239000003446 ligand Substances 0.000 claims abstract description 18
- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 16
- 239000010948 rhodium Substances 0.000 claims abstract description 16
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 239000000758 substrate Substances 0.000 claims description 10
- 239000002243 precursor Substances 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 150000002790 naphthalenes Chemical class 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- MNCMBBIFTVWHIP-UHFFFAOYSA-N 1-anthracen-9-yl-2,2,2-trifluoroethanone Chemical group C1=CC=C2C(C(=O)C(F)(F)F)=C(C=CC=C3)C3=CC2=C1 MNCMBBIFTVWHIP-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 2
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims 2
- 229910052786 argon Inorganic materials 0.000 claims 1
- 238000011049 filling Methods 0.000 claims 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 abstract description 9
- 150000001454 anthracenes Chemical class 0.000 abstract description 8
- 238000010276 construction Methods 0.000 abstract description 2
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 16
- 239000002994 raw material Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 150000001601 aromatic carbocyclic compounds Chemical class 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- 239000012018 catalyst precursor Substances 0.000 description 2
- 238000010596 desymmetrization reaction Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 229910052707 ruthenium Inorganic materials 0.000 description 2
- GTPDHYQKBSCXAP-ZETCQYMHSA-N (2s)-4-methylsulfanyl-2-(thiophene-2-carbonylamino)butanoic acid Chemical compound CSCC[C@@H](C(O)=O)NC(=O)C1=CC=CS1 GTPDHYQKBSCXAP-ZETCQYMHSA-N 0.000 description 1
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- RSNQVABHABAKEZ-UHFFFAOYSA-N 2,3-diphenylquinoxaline Chemical class C1=CC=CC=C1C1=NC2=CC=CC=C2N=C1C1=CC=CC=C1 RSNQVABHABAKEZ-UHFFFAOYSA-N 0.000 description 1
- BWRRWBIBNBVHQF-UHFFFAOYSA-N 4-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)butanoic acid Chemical compound O1C(CCCC(=O)O)=NC(C=2N=CC=CC=2)=N1 BWRRWBIBNBVHQF-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 241001562081 Ikeda Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000010597 enzymatic desymmetrization reaction Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000006362 organocatalysis Methods 0.000 description 1
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical class [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- KIHQWOBUUIPWAN-UHFFFAOYSA-N phenanthren-9-amine Chemical compound C1=CC=C2C(N)=CC3=CC=CC=C3C2=C1 KIHQWOBUUIPWAN-UHFFFAOYSA-N 0.000 description 1
- RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
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- C07B35/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving a change in the type of bonding between two carbon atoms already directly linked
- C07B35/02—Reduction
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- C07C231/00—Preparation of carboxylic acid amides
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Abstract
本发明公开了一种铑催化的蒽类化合物的氢化去对称化构建轴手性化合物的方法。该方法通过2%‑6%的铑和双膦配体催化9‑芳基取代蒽的氢化去对称化实现了轴手性化合物的构建,以高收率和高对映选择性得到碳环氢化的轴手性化合物。氢化产物经过简单转化可以得到具有轴手性的单膦配体。本发明使用的催化剂廉价易得,并且反应条件较温和,可以取得优秀的产率和对映选择性,具有潜在的实用价值。
Description
技术领域
本发明属于不对称催化合成领域,涉及一种铑催化的蒽的氢化去对称化构建轴手性化合物的方法,提供了一种高对映选择性合成轴手性化合物的方法。
技术背景
芳香化合物的不对称氢化为手性环状化合物的合成提供了简洁且高效的途径。虽然芳香杂环化合物不对称氢化取得了一系列优秀的研究成果,但是芳香碳环化合物不对称氢化的发展却非常缓慢,目前仅有少数芳香碳环化合物不对称氢化的报道。2011年,德国明斯特大学Glorius教授利用富电子的手性卡宾作为配体,实现了钌催化区域选择性2,3-二苯基喹喔啉的芳香碳环不对称氢化。2012年,日本九州大学Kuwano课题组采用反式螯合配位的二茂铁双膦配体Ph-TRAP与过渡金属钌的配合物作为催化剂实现2-萘醚化合物的不对称氢化。随后,又将该催化体系拓展到8-取代喹啉和6-取代异喹啉的高区域选择性芳香碳环不对称氢化。最近,大连化物所周永贵研究员采用钌的手性双膦配合物催化剂,实现了9-菲胺的不对称氢化。该催化体系不仅对单取代的菲胺底物有效,也适用于9,10-二取代菲胺的不对称氢化,构建相邻两个手性中心的烷基胺化合物。(参考文献一:(a)Urban,S.;Ortega,N.;Glorius,F.Angew.Chem.Int.Ed.2011,50,3803-3806.(b)Kuwano,R.;Morioka,R.;Kashiwabara,M.;Kameyama,N.Angew.Chem.Int.Ed.2012,51,4136-4139.(c)Kuwano,R.;Ikeda,R.;Hirasada,K.Chem.Commun.2015,51,7558-7561.(d)Jin,Y.;Makida,Y.;Uchida,T.;Kuwano,R.J.Org.Chem.2018,83,3829-3839.(e)Yan,Z.;Xie,H.-P.;Shen,H.-Q.;Zhou,Y.-G.Org.Lett.2018,20,1094-1097.)。
轴手性联芳基化合物广泛存在于天然产物、药物和材料中,并作为轴手性配体或催化剂广泛用于不对称反应中。(参考文献二:(a)Bringmann,G.;Gulder,T.;Gulder,T.A.M.;Breuning,M.Chem.Rev.2011,111,563-639.(b)Tang,W.;Zhang,X.Chem.Rev.2003,103,3029-3069.(c)Terada,M.Synthesis 2010,12,1929-1982.(d)Rueping,M.;Kuenkel,A.;Atodiresei,L.Chem.Soc.Rev.2011,40,4539-4549.(e)Chen,Y.;Yekta,S.;Yudin,A.K.Chem.Rev.2003,103,3155-3212.)。去对称化是高效构建手性化合物的策略之一。(参考文献三:(a)Willis,M.C.Enantioselective desymmetrisation.J.Chem.Soc.,PerkinTrans.1999,1,1765.(b)García-Urdiales,E.;Alfonso,I.;Gotor,V.Enantioselectiveenzymatic desymmetrizations in organic synthesis.Chem.Rev.2005,105,313.(c)Borissov,A.;Davies,T.Q.;Ellis,S.R.;Fleming,T.A.;Richardson,M.S.W.;Dixon,D.J.Organocatalytic enantioselective desymmetrisation.Chem.Soc.Rev.2016,45,5474.)。因此,发展高效催化体系实现芳香碳环化合物不对称氢化仍然是合成化学面临的具有挑战性的前沿科学问题之一。基于此,本发明提供了第一个铑和手性双膦配体催化的9-芳基取代蒽化合物的不对称氢化,通过去对称化策略合成提供了具有高对映选择性的轴向手性联芳基化合物。
发明内容
本发明提供了一种铑催化的蒽的氢化去对称化构建轴手性化合物的方法,本发明操作简便实用,原料易得,对映选择性好,产率高,且反应具有绿色原子经济性,环境友好且具有潜在的实用价值等优点。
本发明的技术方案如下:
一种铑催化的蒽的氢化去对称化构建轴手性化合物的方法,其特征在于,所述方法以铑的手性双膦配合物为催化剂,9-芳基取代蒽化合物为底物,氢化去对称化合成具有轴手性的1-芳基取代萘类衍生物;
反应式如下:
式中:
R为C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
或R=N(R1)SO2R2,其中,R1、R2分别独立为氢,或者C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
或R=N(R1)COR2,其中,R1、R2分别独立为氢,或者C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
或R=OR1,其中,R1为氢,或者C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
或R=OSO2R1,其中,R1为C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
或R=OCOR1,其中,R1为C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
或R=PR1 2,其中,R1为C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
Ar为苯环或含有取代基的芳环,所述的取代基为C1-C10的烷基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
所述催化剂为金属铑前体和手性双膦配体的配合物。
基于以上技术方案,优选的,反应溶剂为有机溶剂,所述有机溶剂为1,2-二氯乙烷、二氯甲烷、四氢呋喃、甲苯、氯仿的一种或两种以上;优选为二氯甲烷。
基于以上技术方案,优选的,反应温度:25-70℃,优选为30℃;反应时间:45分钟-60小时,优选为5小时;氢气压力:400-1000psi,优选为600psi。
基于以上技术方案,优选的,9-芳基取代蒽化合物、金属铑前体与手性双膦配体摩尔比为1:0.01:0.011-1:0.1:0.11,优选为1:0.05:0.055或1:0.02:0.022;有机溶剂的用量为0.5-6mL,优选为6mL;9-芳基取代蒽化合物的用量为0.05-0.4mmol,优选为0.15mmol。
基于以上技术方案,优选的,所述金属铑前体为双(1,5-环辛二烯)铑(I)六氟化锑盐、双(双环戊二烯)四氟硼酸铑中的一种;优选为双(1,5-环辛二烯)铑(I)六氟化锑盐。
基于以上技术方案,优选的,所述手性双膦配体为(S)-(-)-[(5,6),(5',6')-双(乙烯二氧)联苯-2,2'-基]二苯基磷、(R)-(+)-(6,6'-二甲氧基联苯-2,2'-基)双(二苯基膦)、(+)-1,2-双((2S,5S)-2,5-二甲基磷烷)苯、(S,S,Rax)-C3*-TunePhos、[(2S,2'S,3S,3'S)-3,3'-二叔丁基-2,2',3,3'-四氢-4,4'-二甲氧基-2,2'-双-1,3-苯并氧磷杂环戊二烯]、(2R,2'R,3R,3'R)-4,4'-双(2,6-二甲氧基苯基)-3,3'-二叔丁基-2,2',3,3'-四氢-2,2'-双-1,3-苯并氧磷杂环戊二烯、(2R,2'R,3R,3'R)-4,4'-二(9-蒽基)-3,3'-二(叔丁基)-2,2',3,3'-四氢-2,2'-二苯并[D][1,3]氧,膦戊轭中的一种,优选为(2R,2'R,3R,3'R)-4,4'-二(9-蒽基)-3,3'-二(叔丁基)-2,2',3,3'-四氢-2,2'-二苯并[D][1,3]氧,膦戊轭。
基于以上技术方案,优选的,所述催化剂的制备方法为:氮气保护下,将金属铑前体和手性双膦配体在溶剂中室温搅拌10分钟-60分钟,催化剂的制备所用溶剂选自三氟乙醇、1,2-二氯乙烷、二氯甲烷、乙酸乙酯、四氢呋喃、1,4-二氧六环、甲苯、苯、三氟甲苯、氯苯、甲醇的一种或两种以上,优选为二氯甲烷。
基于以上技术方案,优选的,所述方法的具体反应步骤为:将9-芳基取代蒽化合物、原位制备的催化剂和溶剂加入到反应瓶中,将反应瓶装入高压釜中,通入H2反应得到氢化的产物,纯化后得到纯的产物。
基于以上技术方案,优选的,所述纯化的步骤为:所述纯化的步骤为:释放氢气后,旋干溶剂,柱层析分离得到纯的产物。
通过本发明方法可以实现铑催化的9-芳基取代蒽的氢化去对称化反应,以及高收率和高对映选择性的得到具有轴手性化合物(对映体过量可达89%)。本发明具有高度的对映选择性,操作简便实用,原料易得,催化剂商业可得,反应条件温和,能耗低,环境友好且具有潜在的实用价值。
有益效果
1.原料简单易得,催化剂制备方便,反应操作简便实用。
2.反应活性高,原料转化完全,分离方便,能获得高纯度的产物。
3.立体选择性好,能高对映选择性地得到对映异构体。
4.反应条件温和,环境友好绿色。
具体实施方式
下面通过实施例详述本发明,但本发明并不限于下述的实施例。
下述实施例中9-芳基取代蒽合成参考文献:(a)Bartoszek,M.;Beller,M.;Deutsch,J.;Klawonn,M.;Kockritz,A.;Nemati,N.;Pews-Davtyan,A.Tetrahedron 2008,64,1316-1322.(b)St-Gelais,A.;Alsarraf,J.;Legault,J.;Gauthier,C.;Pichette,A.Org.Lett.2018,20,7424-7428.(c)Han,B.;Ma,P.;Cong,X.;Chen,H.;Zeng,X.J.Am.Chem.Soc.2019,141,9018-9026.(d)Zhang,A.;RajanBabu,T.V.J.Am.Chem.Soc.2006,128,54-55.(e)Hu,R.-B.;Zhang,H;Zhang,X.-Y;Yang,S.-D.Chem.Commun.2014,50,2193-2195.(f)Xie,J.-H.;Wang,L.-X.;Fu,Y.;Zhu,S.-F;Fan,B.-M.;Duan,H.-F;Zhou,Q.-L.J.Am.Chem.Soc.2003,125,4404-4405.(g)Agrawal,T.;Cook,S.P.Org.Lett.2014,16,5080-5083.
实施例1-14
条件优化:改变有机溶剂、催化剂前体和手性配体的种类
在反应瓶中投入铑前体(5.0mol%)和手性配体(5.5mol%),氮气置换后加入1mL溶剂,室温搅拌10分钟,原位制备催化剂。手套箱中将预先放有底物9-芳基取代蒽1a(0.05mmol)反应瓶中加入原为制备的催化剂和1mL溶剂,放入高压反应釜中,通入氢气(600psi),30℃反应22小时。慢慢释放氢气,旋蒸除去溶剂,柱层析分离得到纯的产物。
有机溶剂、催化剂前体和手性配体的种类,具体结果如表1;ee为对映选择性。
表1. 9-芳基取代蒽1a的不对称氢化反应条件的优化
实施例15-42
9-芳基取代蒽的不对称氢化。
在反应瓶中投入双(1,5-环辛二烯)铑(I)六氟化锑盐(5.0mol%)和(2R,2'R,3R,3'R)-4,4'-二(9-蒽基)-3,3'-二(叔丁基)-2,2',3,3'-四氢-2,2'-二苯并[D][1,3]氧,膦戊轭(5.5mol%),氮气置换后加入1mL二氯甲烷,室温搅拌10分钟,原位制备催化剂。手套箱中将预先放有底物9-芳基取代蒽(0.15mmol)反应瓶中加入原为制备的催化剂和5mL二氯甲烷,放入高压反应釜中,通入氢气(600psi),30℃反应5小时。慢慢释放氢气,旋蒸除去溶剂,柱层析分离得到纯的产物。
含有氮原子的9-芳基取代蒽类化合物为1,仅改变反应中1的种类得到14个不同1-芳基取代萘类衍生物2的实施例,改变的种类具体如下:
其中2b的反应时间都为12小时,2c-n的反应时间都为45分钟。
其中2a的绝对构型通过X衍射测定为R。CCDC号为2095168。
为扩大9-芳基取代蒽化合物的不对称氢化底物适用范围,底物中含有酯基、磺酰基,烷基的原料也能以高收率和高对映选择性得到1-芳基取代萘类衍合物,该类化合物为3,仅改变反应中3的种类得到12个不同1-芳基取代萘类衍生物4的实施例,改变的种类具体如下:
其中4i-k的催化剂用量为5mol%。
其中4c的绝对构型通过X衍射测定为R。CCDC号为2080871。
为进一步扩大9-芳基取代蒽化合物的不对称氢化底物适用范围且发掘其应用价值,底物中磷的原料也能以高收率和高对映选择性得到轴手性膦氧化合物,该类化合物为5,仅改变反应中5的种类得到2个不同轴手性膦氧化合物6,化合物6经过简单处理可以得到具有轴手性的单膦配体7,改变的种类具体如下:
其中6a的反应时间为5小时,6b的反应时间为48小时,。
其中6a的绝对构型通过X衍射测定为R。CCDC号为2044557。产物6经过简单还原后得到的化合物7,可以作为具有轴手性的单膦配体用于有机合成。
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Claims (7)
1.一种铑催化的蒽类化合物的氢化去对称化构建轴手性化合物的方法,其特征在于,所述方法以铑的手性双膦配合物为催化剂,9-芳基取代蒽化合物为底物,氢化去对称化合成具有轴手性的1-芳基取代萘类衍生物;
反应式如下:
式中:
R为C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
或R=N(R1)SO2R2,其中,R1、R2分别独立为氢,或者C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
或R=N(R1)COR2,其中,R1、R2分别独立为氢,或者C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
或R=OR1,其中,R1为氢,或者C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
或R=OSO2R1,其中,R1为C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
或R=OCOR1,其中,R1为C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
或R=PR1 2,其中,R1为C1-C10的烷基或者芳基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
Ar为苯环或含有取代基的芳环,所述的取代基为C1-C10的烷基,C1-C10烷基包括甲氧基、卤素中一种或多种取代基;
所述催化剂为金属铑前体和手性双膦配体的配合物。
2.根据权利要求1所述的方法,其特征在于,反应溶剂为有机溶剂,所述有机溶剂为1,2-二氯乙烷、二氯甲烷、四氢呋喃、甲苯、氯仿的一种或两种以上;反应温度:25-70℃;反应时间:45分钟-60小时;氢气压力:400-1000psi。
3.根据权利要求1所述的方法,其特征在于:9-芳基取代蒽化合物、金属铑前体与手性双膦配体摩尔比为1:0.01:0.011-1:0.1:0.11,有机溶剂的用量为每0.05-0.4mmol 9- 芳基取代蒽化合物0.5-6mL。
4.根据权利要求1所述的方法,其特征在于:所述金属铑前体为双(1,5-环辛二烯)铑(I)六氟化锑盐、双(双环戊二烯)四氟硼酸铑中的一种;手性双膦配体为(S)-(-)-[(5,6),(5',6')-双(乙烯二氧)联苯-2,2'-基]二苯基磷、(R)-(+)-(6,6'-二甲氧基联苯-2,2'-基)双(二苯基膦)、(+)-1,2-双((2S,5S)-2,5-二甲基磷烷)苯、(S,S,Rax)-C3*-TunePhos、[(2S,2'S,3S,3'S)-3,3'-二叔丁基-2,2',3,3'-四氢-4,4'-二甲氧基-2,2'-双-1,3-苯并氧磷杂环戊二烯]、(2R,2'R,3R,3'R)-4,4'-双(2,6-二甲氧基苯基)-3,3'-二叔丁基-2,2',3,3'-四氢-2,2'-双-1,3-苯并氧磷杂环戊二烯、(2R,2'R,3R,3'R)-4,4'-二(9-蒽基)-3,3'-二(叔丁基)-2,2',3,3'-四氢-2,2'-二苯并[D][1,3]氧,膦戊轭中的一种。
5.根据权利要求1所述的方法,其特征在于:所述催化剂的制备方法为:氮气或氩气保护下,将金属铑前体和手性双膦配体在溶剂中室温搅拌10分钟-60分钟,催化剂的制备所用溶剂选自三氟乙醇、1,2-二氯乙烷、二氯甲烷、乙酸乙酯、四氢呋喃、1,4-二氧六环、甲苯、苯、三氟甲苯、氯苯、甲醇的一种或两种以上。
6.根据权利要求1所述的方法,其特征在于,所述方法的具体反应步骤为:将9-芳基取代蒽化合物、原位制备的催化剂和溶剂加入到反应瓶中,将反应瓶装入高压釜中,通入H2反应得到氢化的产物,纯化后得到纯的产物。
7.根据权利要求1所述的方法,其特征在于,所述纯化的步骤为:释放氢气后,旋干溶剂,柱层析分离得到纯的产物。
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