CN116478210A - Chiral selenium/sulfur catalyst based on PHOX ligand skeleton and synthesis method and application thereof - Google Patents
Chiral selenium/sulfur catalyst based on PHOX ligand skeleton and synthesis method and application thereof Download PDFInfo
- Publication number
- CN116478210A CN116478210A CN202310247904.3A CN202310247904A CN116478210A CN 116478210 A CN116478210 A CN 116478210A CN 202310247904 A CN202310247904 A CN 202310247904A CN 116478210 A CN116478210 A CN 116478210A
- Authority
- CN
- China
- Prior art keywords
- sulfur
- selenium
- chiral
- catalyst
- phox
- 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.)
- Pending
Links
- 239000003446 ligand Substances 0.000 title claims abstract description 58
- 239000003054 catalyst Substances 0.000 title claims abstract description 52
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 title claims abstract description 46
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 title claims abstract description 44
- 229910052717 sulfur Inorganic materials 0.000 title claims abstract description 44
- 239000011593 sulfur Substances 0.000 title claims abstract description 44
- 229910052711 selenium Inorganic materials 0.000 title claims abstract description 38
- 239000011669 selenium Substances 0.000 title claims abstract description 38
- 238000001308 synthesis method Methods 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- 239000000758 substrate Substances 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 17
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 125000005110 aryl thio group Chemical group 0.000 claims abstract description 5
- 238000001212 derivatisation Methods 0.000 claims abstract description 5
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 17
- -1 2-diazo-2-phenyl ethyl Chemical group 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 7
- 238000006467 substitution reaction Methods 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- 238000012544 monitoring process Methods 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 3
- 239000012298 atmosphere Substances 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 239000012043 crude product Substances 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 230000003197 catalytic effect Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000003748 selenium group Chemical group *[Se]* 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 229940126062 Compound A Drugs 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 2
- 229910052741 iridium Inorganic materials 0.000 description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000000746 allylic group Chemical group 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000006717 asymmetric allylation reaction Methods 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- POSICDHOUBKJKP-UHFFFAOYSA-N prop-2-enoxybenzene Chemical compound C=CCOC1=CC=CC=C1 POSICDHOUBKJKP-UHFFFAOYSA-N 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
- C07F9/653—Five-membered rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0255—Phosphorus containing compounds
- B01J31/0257—Phosphorus acids or phosphorus acid esters
- B01J31/0262—Phosphorus acids or phosphorus acid esters comprising phosphinous acid (-ester) groups (R2P(OR')) or the isomeric phosphine oxide groups (R3P=O), i.e. R= C, R'= C, H
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
-
- 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
- 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
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
- C07F9/653—Five-membered rings
- C07F9/65324—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a chiral selenium/sulfur catalyst based on PHOX ligand skeleton, and a synthesis method and application thereof. The catalyst is based on PHOX ligand skeleton selenium or sulfide, and the synthesis method is that the PHOX ligand skeleton substrate is used as a raw material, and is subjected to one-step derivatization, separation and purification to obtain different chiral selenium/sulfur catalysts based on PHOX ligand skeleton. The catalyst is applied to organic chiral catalytic reactions, and is particularly used for generating aryl thio products with quaternary carbon centers. Compared with the prior art, the method has the advantages of simple reaction steps, mild conditions, easy purchase of the used raw materials, high yield, rich product types, good economy and the like.
Description
Technical Field
The invention relates to the technical field of organic chemical synthesis, in particular to a chiral selenium/sulfur catalyst based on PHOX ligand skeleton, and a synthesis method and application thereof.
Background
The David Crich group synthesized the PHOX ligand backbone molecule for the first time in 1989 (Tetrahedron letters 1989,30,475.) in which the synthesis of the PHOX ligand backbone molecule remained on the racemic product and was synthesized as an intermediate for lower yield reactions. The glonter Helmchen group (Tetrahedron Letters,1993,34,1769.) in 2019 used the PHOX ligand backbone molecule as a chiral catalyst for the first time, and was able to increase the ee value of the asymmetric allylation reaction product to 99% as a catalyst. The Jonathan M.J.Williams group improved the synthesis yield of chiral PHOX ligand backbone molecules to 92% in 1994.
In 2003, richard c.bunt group of topics (Organic Letters,2003,5,2279.) applied chiral PHOX ligand backbone molecules to palladium-catalyzed allylic substitution reactions, corresponding to products with ee values as high as 93%. Christoph Schneider group in 2013 (J.org.chem.2012, 77,1477) catalyzed hydrogenation of this PHOX ligand with metallic iridium. In the same year, fan Qinghua subject group (chem. Asian J.2013,8,1101.) re-uses this PHOX ligand and metallic iridium as ligands to catalyze asymmetric hydrogenation reaction, and the ee value of the corresponding product is as high as 97%. Scott e.denmark synthesized a range of PHOX ligand backbone molecules (j.am. Chem. Soc.2021,143, 13408) by 1, 2-oxyalkylation of olefins with ee values up to 96% and a range of derivatizations of this range of PHOX ligand backbone molecule products.
The PHOX ligand is not well applied to chiral sulfur or selenium-containing compound construction at present, so that the application combines the understanding of chiral construction of sulfur or selenium-containing compounds, tries to construct a new sulfur or selenium-oxidized PHOX catalyst, and applies the catalyst to construction of sulfur-containing chiral compounds, thereby expanding the catalytic range of the PHOX ligand.
Disclosure of Invention
The invention aims to overcome at least one of the defects in the prior art and provide the chiral selenium/sulfur catalyst based on the PHOX ligand skeleton, which has the advantages of simple reaction steps, mild conditions, easily purchased raw materials, high yield, rich product types and good economy, and the synthesis method and application thereof.
The aim of the invention can be achieved by the following technical scheme:
in the application, PHOX ligand molecules are taken as basic frameworks, chiral catalysts of different selenium/sulfur oxidized PHOX ligand framework molecules are further constructed, the ligand is applied to small organic molecule catalytic reaction, and certain catalytic activity is shown, and the specific scheme is as follows:
chiral selenium/sulfur catalyst based on PHOX ligand skeleton, which is selenium or sulfide based on PHOX ligand skeleton, comprising the following structural formula:
further, the structural formula of the catalyst is as follows:
the synthetic method of the chiral selenium/sulfur catalyst based on the PHOX ligand skeleton comprises the steps of taking a PHOX ligand skeleton substrate as a raw material, carrying out one-step derivatization, separating and purifying to obtain different chiral selenium/sulfur catalysts based on the PHOX ligand skeleton, wherein the specific preparation route is as follows:
further, the method comprises the following specific steps: dissolving different PHOX ligand substrates in a solvent, adding selenium powder or sulfur powder for reaction, monitoring whether the reaction is completed by TLC during the reaction, and purifying by reduced pressure distillation and column chromatography to obtain different derivatized selenium/sulfur catalysts based on PHOX ligand skeleton.
Further, the mol ratio of PHOX ligand substrate to selenium powder or sulfur powder is 1 (2.5-3.5), the reaction time is 40-50h, and the solvent is DCM.
Further, the molar ratio of PHOX ligand substrate to selenium or sulfur powder was 1:3 and the reaction time was 2 days.
The use of a chiral selenium/sulfur based catalyst based on a PHOX ligand backbone as described above, for use in organic chiral catalytic reactions.
Further, the catalyst is applied to the formation of aryl thio products with quaternary carbon centers, and the synthetic route is as follows:
further, the synthesis method specifically comprises the following steps: adding a substrate of 2-diazo-2-phenyl ethyl acetate, an aryl sulfur reagent, a catalyst and tetraethyl cyanohexafluorophosphate into a reaction tube, adding a solvent, reacting in an inert atmosphere, monitoring the reaction by using a TLC plate during the reaction, and separating and purifying to obtain the chiral compound with a quaternary carbon center and aryl sulfur substitution.
Further, the molar ratio of the substrate, the aryl sulfur reagent, the catalyst and the tetraethyl cyanide copper hexafluorophosphate is 0.05 (0.05-0.07): 0.005-0.006): 0.004-0.006; the solvent is toluene.
Compared with the prior art, the invention has the following characteristics:
(1) According to the method, through PHOX ligand substrates of the same type, the synthesis of selenium/sulfur catalysts based on PHOX ligand frameworks with different selenium/sulfur substitutions is realized for the first time;
(2) The method adopts a simple and easy-to-operate one-step method to prepare the chiral selenium/sulfur catalyst based on the PHOX ligand skeleton, thereby avoiding a complex synthetic route;
(3) The product of the method has universality, and can synthesize various derivative chiral catalysts with selenium/sulfur substitution according to different substituted PHOX ligand substrates, and has certain catalytic activity.
Detailed Description
The following describes in detail the examples of the present invention, which are implemented on the premise of the technical solution of the present invention, and detailed embodiments and specific operation procedures are given, but the scope of protection of the present invention is not limited to the following examples.
The method for synthesizing the selenium/sulfur catalyst based on the PHOX ligand skeleton is characterized in that different chiral selenium/sulfur catalysts based on the PHOX ligand skeleton are generated by further derivatization from PHOX ligand skeleton substrates.
The hydrogen nuclear magnetic resonance spectrum (1H NMR, 13C NMR) of the compound was determined by Bruker AVANCE III HD400, and the solvent was deuterated chloroform. Chemical shift (δ) is referenced in ppm with tetramethylsilane as an internal standard, the multiplicity is as follows: s=singlet, d=doublet, t=triplet, q=quadruple, m=multiplet.
The catalyst in the synthesis method of the invention comprises the following components:
for catalytic applications of such PHOX ligands, a synthetic method for preparing an aryl sulfur substituted product having a quaternary carbon center comprises the steps of:
the synthetic route of the method is as follows:
the method applied to the catalyst is designed by taking economic and commercially available 2-diazo-2-phenyl ethyl acetate and aryl sulfur reagent as raw materials, reacting for a period of time in an argon atmosphere at room temperature under the action of the catalyst and tetraethyl copper hexafluorophosphate, and separating and purifying to obtain an aryl thio product with a quaternary carbon center.
The invention is further illustrated by the following examples, which are only intended to provide a better understanding of the invention. Accordingly, the scope of protection of this patent is not limited to these embodiments.
Example 1: preparation of Compound A
Under anhydrous and anaerobic conditions, 0.12mmol of A-0 (cas No. 148461-15-8) was dissolved in ultra-dry DCM (0.5 mL), 0.36mmol of selenium powder was added thereto at room temperature, the reaction was stirred at room temperature for 2 days, the completion of the reaction was monitored by TLC plates, filtered through celite after completion, concentrated by rotary evaporator, and dried by rotary evaporator. The crude product was purified on silica gel (1:3 EtOAc: petroleum ether) to give compound A as a white solid in 99% yield.
1 H NMR(400MHz,Chloroform-d)δ7.99(dd,J＝7.7,4.3Hz,1H),7.92–7.69(m,4H),7.58–7.35(m,8H),7.35–7.25(m,3H),7.25–7.15(m,3H),4.98(t,J＝9.8Hz,1H),4.21(dd,J＝10.2,8.2Hz,1H),4.02–3.70(m,1H)； 13 C NMR(101MHz,CDCl 3 )δ164.64,164.61,141.66,134.34,134.24,132.85,132.73,132.60,132.50,132.32,132.27,132.21,132.17,132.14,132.09,132.07,131.95,131.43,131.40,131.26,131.23,131.19,131.16,130.43,130.31,128.45,128.43,128.39,128.30,128.26,127.34,126.89,74.39,69.89.
Example 2: preparation of Compound B
Under anhydrous and anaerobic conditions, 0.12mmol of A-0 (cas No. 148461-15-8) was dissolved in ultra-dry DCM (0.5 mL), 0.36mmol of sulfur powder was added thereto at room temperature, the reaction was stirred at room temperature for 2 days, the completion of the reaction was monitored by TLC plates, filtered through celite after completion, concentrated by rotary evaporator, and dried by rotary evaporator. The crude product was purified on silica gel (1:3 EtOAc: petroleum ether) to give compound B as a white solid in 99% yield.
1 H NMR(400MHz,Chloroform-d)δ7.98(dd,J＝7.8,4.2Hz,1H),7.86–7.75(m,4H),7.58–7.36(m,9H),7.35–7.26(m,2H),7.23(m,3H),4.99(t,J＝9.8Hz,1H),4.20(dd,J＝10.2,8.2Hz,1H),3.96–3.74(m,1H)； 13 C NMR(101MHz,CDCl 3 )δ164.97,164.93,141.71,134.26,134.15,134.05,133.97,133.45,133.19,133.11,132.64,132.15,132.13,132.10,132.06,131.99,131.86,131.81,131.75,131.71,131.41,131.38,131.24,131.21,131.17,131.14,130.39,130.27,128.47,128.44,128.39,128.31,128.26,127.38,126.95,74.59,69.98.
Example 3: preparation of Compound C
Under anhydrous and anaerobic conditions, 0.12mmol of C-0 (cas No. 201409-47-4) was dissolved in ultra-dry DCM (0.5 mL), 0.36mmol of selenium powder was added thereto at room temperature, the reaction was stirred at room temperature for 2 days, the completion of the reaction was monitored by TLC plates, filtered through celite after completion, concentrated by rotary evaporator, and dried by rotary evaporator. The crude product was purified on silica gel (1:2 EtOAc: petroleum ether) to give compound C as a white solid in 99% yield.
1 H NMR(400MHz,Chloroform-d)δ7.88–7.69(m,5H),7.53–7.26(m,10H),7.19(dt,J＝7.3,3.8Hz,2H),7.13(m,1H),5.30(d,J＝8.0Hz,1H),4.90(t,J＝7.3Hz,1H),3.13(dd,J＝18.0,6.8Hz,1H),2.84(d,J＝18.0Hz,1H)； 13 CNMR(101MHz,CDCl 3 )δ163.92,163.89,141.47,140.03,134.38,134.28,132.97,132.91,132.70,132.59,132.44,132.33,132.19,132.14,132.12,132.07,131.98,131.96,131.30,131.27,131.26,131.24,131.22,131.15,131.12,130.28,130.16,128.42,128.29,128.24,128.16,127.22,125.45,125.20,83.59,76.59,38.6
Example 4: preparation of Compound D
Under anhydrous and anaerobic conditions, 0.12mmol of C-0 (cas No. 201409-47-4) was dissolved in ultra-dry DCM (0.5 mL), 0.36mmol of sulfur powder was added thereto at room temperature, the reaction was stirred at room temperature for 2 days, the completion of the reaction was monitored by TLC plates, filtered through celite after completion, concentrated by rotary evaporator, and dried by rotary evaporator. The crude product was purified on silica gel (1:2 EtOAc: petroleum ether) to give compound D as a white solid in 99% yield.
1 H NMR(400MHz,Chloroform-d)δ7.89–7.66(m,5H),7.58–7.28(m,10H),7.24–7.07(m,3H),5.29(d,J＝8.0Hz,1H),4.87(t,J＝7.2Hz,1H),3.13(dd,J＝18.0,6.8Hz,1H),2.88(d,J＝17.9Hz,1H)； 13 C NMR(101MHz,CDCl 3 )δ164.09,164.06,141.43,140.02,134.21,134.20,134.11,134.04,133.33,133.22,133.18,132.41,132.18,132.12,132.02,131.89,131.79,131.23,131.20,131.17,131.09,131.06,130.18,130.06,128.38,128.38,128.25,128.24,128.21,128.11,127.16,125.41,125.16,83.64,76.63,38.67.
Example 5: preparation of Compound E
Under anhydrous and anaerobic conditions, 0.13mmol E-0 (cas No. 148461-14-7) was dissolved in ultra-dry DCM (0.5 mL), 0.39mmol selenium powder was added thereto at room temperature, the reaction was stirred at room temperature for 2 days, the TLC plate monitored the completion of the reaction, filtered through celite after completion, concentrated by rotary evaporator, and dried by rotary evaporator. The crude product was purified on silica gel (1:2 EtOAc: petroleum ether) to give compound E as a white solid in 99% yield.
1 H NMR(400MHz,Chloroform-d)δ8.35–7.63(m,5H),7.61–6.91(m,9H),3.80(dd,J＝9.8,8.2Hz,1H),3.66(t,J＝8.6Hz,1H),3.51(q,J＝9.1Hz,1H),1.59(m,1H),0.79(dd,J＝33.5,6.7Hz,6H)； 13 C NMR(101MHz,CDCl 3 )δ163.00,162.97,134.46,134.35,132.90,132.76,132.59,132.51,132.48,132.21,132.13,132.10,131.98,131.79,131.70,131.61,131.32,131.29,131.14,131.11,131.06,131.04,131.01,130.11,129.99,128.32,128.29,128.19,128.17,73.06,70.73,32.51,19.34,18.79.
Example 6: preparation of Compound F
Under anhydrous and anaerobic conditions, 0.13mmol E-0 (cas No. 148461-14-7) was dissolved in ultra-dry DCM (0.5 mL), 0.39mmol sulfur powder was added thereto at room temperature, the reaction was stirred at room temperature for 2 days, the completion of the reaction was monitored by TLC plates, filtered through celite after completion, concentrated by rotary evaporator, and dried by rotary evaporator. The crude product was purified on silica gel (1:2 EtOAc: petroleum ether) to give compound F as a white solid in 99% yield.
1 H NMR(400MHz,Chloroform-d)δ7.89–7.69(m,5H),7.58–7.27(m,9H),3.78(dd,J＝9.8,8.1Hz,1H),3.66(t,J＝8.6Hz,1H),3.52(td,J＝9.3,7.4Hz,1H),1.59(h,J＝6.8Hz,1H),0.86(d,J＝6.7Hz,3H),0.76(d,J＝6.7Hz,3H)； 13 C NMR(101MHz,CDCl 3 )δ163.26,163.22,134.28,134.17,134.06,133.98,133.20,133.11,133.09,132.52,132.45,132.28,132.06,132.04,131.93,131.68,131.57,131.48,131.28,131.25,131.10,131.06,131.00,130.97,130.94,130.07,129.95,128.30,128.28,128.18,128.15,72.99,70.76,32.52,19.31,18.72.
Example 7: preparation of Compound G
Under anhydrous and anaerobic conditions, 0.13mmol of G-0 (cas No. 148461-16-9) was dissolved in ultra-dry DCM (0.5 mL), 0.39mmol of selenium powder was added thereto at room temperature, the reaction was stirred at room temperature for 2 days, the completion of the reaction was monitored by TLC plates, filtered through celite after completion, concentrated by rotary evaporator, and dried by rotary evaporator. The crude product was purified on silica gel (1:3 EtOAc: petroleum ether) to give compound G as a white solid in 99% yield.
1 H NMR(400MHz,Chloroform-d)δ7.92–7.68(m,5H),7.61–7.33(m,9H),3.82(t,J＝8.5Hz,1H),3.60(dd,J＝10.3,8.3Hz,1H),3.47(dd,J＝10.3,8.6Hz,1H),0.78(s,9H)； 13 C NMR(101MHz,CDCl 3 )δ163.03,163.00,134.87,134.76,132.99,132.96,132.77,132.66,132.46,132.39,132.22,132.18,132.16,132.05,131.82,131.68,131.59,131.43,131.41,131.19,131.16,131.09,131.05,131.02,130.28,130.16,128.36,128.34,128.23,128.21,76.13,68.71,33.68,26.08.
Example 8: preparation of Compound H
Under anhydrous and anaerobic conditions, 0.13mmol of G-0 (cas No. 148461-16-9) was dissolved in ultra-dry DCM (0.5 mL), 0.39mmol of sulfur powder was added thereto at room temperature, the reaction was stirred at room temperature for 2 days, the completion of the reaction was monitored by TLC plates, filtered through celite after completion, concentrated by rotary evaporator, and dried by rotary evaporator. The crude product was purified on silica gel (1:3 EtOAc: petroleum ether) to give compound H as a white solid in 99% yield.
1 H NMR(400MHz,Chloroform-d)δ8.07–7.61(m,5H),7.61–7.20(m,9H),3.83(td,J＝8.3,2.3Hz,1H),3.57(dd,J＝10.3,8.2Hz,1H),3.47(ddd,J＝10.0,8.2,1.3Hz,1H),0.79(s,9H)； 13 C NMR(101MHz,CDCl 3 )δ163.25,163.22,134.47,134.36,134.05,133.18,133.05,132.32,132.25,132.12,132.01,131.55,131.53,131.44,131.30,131.27,131.07,131.04,130.94,130.91,130.17,130.04,128.27,128.24,128.14,128.11,76.01,68.71,33.61,25.99.
Application example
0.05mmol of substrate I (cas No. 22065-57-2,1.0 equiv), 0.06mmol of allyloxybenzene thiophenol J (cas No. 5296-64-0,1.2 equiv), 0.0055mmol of catalyst H (0.11 equiv) and 0.005mmol of tetraethylcopper hexafluorophosphate (cas No. 64443-05-6,0.1 equiv) were added to a reaction tube at room temperature, a solvent (toluene, 0.5 mL) was added, and after reacting in an argon atmosphere for a while, the TLC plate was monitored for reaction, and then purified by column chromatography under reduced pressure to give a chiral compound K having a quaternary carbon center and an arylthio substitution (yield: 47%, ee value: 4%).
The nuclear magnetic data of product K can be found in literature (Journal of Organic Chemistry,2020,85,11882. The present invention uses different catalytic methods to construct a catalyst that, although known chiral, demonstrates the catalytic activity of the catalyst of the present invention). Separation of enantiomers by HPLC the number of the individual pieces of the plastic,Column AD-H,30℃,n-hexane:i-PrOH＝99:1,1mL/min,minor retention time:8.60min,major retention time:7.61min,er＝48:52.
according to the invention, a new sulfur or selenium oxidized PHOX catalyst is prepared through one-step oxidation, a new action site between the PHOX catalyst and a substrate is added on the basis of the existing PHOX ligand, and further, the construction of chiral compounds containing sulfur or selenium can be further controlled through weak interaction between sulfur atoms and selenium atoms.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the invention in any way, and any person skilled in the art may make modifications or alterations to the disclosed technical content to the equivalent embodiments. However, any simple modification, equivalent variation and variation of the above embodiments according to the technical substance of the present invention still fall within the protection scope of the technical solution of the present invention.
Claims (10)
1. The chiral selenium/sulfur catalyst based on PHOX ligand skeleton is characterized by comprising the following structural formula:
2. the chiral selenium/sulfur based catalyst based on a PHOX ligand framework of claim 1, wherein the catalyst has the structural formula:
3. the method for synthesizing chiral selenium/sulfur catalyst based on PHOX ligand skeleton according to claim 1 or 2, wherein the method is characterized in that the chiral selenium/sulfur catalyst based on PHOX ligand skeleton is obtained by taking PHOX ligand skeleton substrate as raw material, carrying out one-step derivatization, separating and purifying, and the specific preparation route is as follows:
4. a method for synthesizing chiral selenium/sulfur based catalyst based on a PHOX ligand framework according to claim 3, wherein the method comprises the following specific steps: dissolving different PHOX ligand substrates in a solvent, adding selenium powder or sulfur powder for reaction, monitoring whether the reaction is completed by TLC during the reaction, and purifying by reduced pressure distillation and column chromatography to obtain different derivatized selenium/sulfur catalysts based on PHOX ligand skeleton.
5. The method for synthesizing chiral selenium/sulfur catalyst based on PHOX ligand skeleton according to claim 3, wherein the molar ratio of PHOX ligand substrate to selenium powder or sulfur powder is 1 (2.5-3.5), the reaction time is 40-50h, and the solvent is DCM.
6. The method for synthesizing chiral selenium/sulfur catalyst based on a PHOX ligand backbone according to claim 5, wherein the molar ratio of PHOX ligand substrate to selenium or sulfur powder is 1:3 and the reaction time is 2 days.
7. Use of a chiral selenium/sulfur based catalyst based on a PHOX ligand framework according to claim 1 or 2, characterized in that the catalyst is used in an organic chiral catalytic reaction.
8. Use of a chiral selenium/sulfur based catalyst based on a PHOX ligand backbone according to claim 7, wherein the catalyst is used to produce an arylthio product with a quaternary carbon center, the synthetic route being as follows:
9. the application of chiral selenium/sulfur catalyst based on PHOX ligand skeleton as claimed in claim 8, wherein the synthesis method comprises the following steps: adding a substrate of 2-diazo-2-phenyl ethyl acetate, an aryl sulfur reagent, a catalyst and tetraethyl cyanohexafluorophosphate into a reaction tube, adding a solvent, reacting in an inert atmosphere, monitoring the reaction by using a TLC plate during the reaction, and separating and purifying to obtain the chiral compound with a quaternary carbon center and aryl sulfur substitution.
10. The use of a chiral selenium/sulfur based catalyst based on a PHOX ligand backbone according to claim 9, wherein the molar ratio of substrate, aryl sulfur reagent, catalyst and tetraethyl copper hexafluorophosphate is 0.05 (0.05-0.07): 0.005-0.006): 0.004-0.006; the solvent is toluene.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310247904.3A CN116478210A (en) | 2023-03-15 | 2023-03-15 | Chiral selenium/sulfur catalyst based on PHOX ligand skeleton and synthesis method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310247904.3A CN116478210A (en) | 2023-03-15 | 2023-03-15 | Chiral selenium/sulfur catalyst based on PHOX ligand skeleton and synthesis method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116478210A true CN116478210A (en) | 2023-07-25 |
Family
ID=87212777
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310247904.3A Pending CN116478210A (en) | 2023-03-15 | 2023-03-15 | Chiral selenium/sulfur catalyst based on PHOX ligand skeleton and synthesis method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116478210A (en) |
-
2023
- 2023-03-15 CN CN202310247904.3A patent/CN116478210A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gorla et al. | Synthesis of an optically active platinum (II) complex containing a new terdentate PCP ligand and its catalytic activity in the asymmetric aldol reaction of methyl isocyanoacetate. X-ray crystal structure of [2, 6-bis [(1'S, 2'S)-1'-(diphenylphosphino)-2', 3'-O-isopropylidene-2', 3'-dihydroxypropyl] phenyl](. eta. 1-nitrato) platinum (II) | |
| CN111777637B (en) | Axial chiral oxindole-derived styrene phosphine oxide catalyst and preparation method and application thereof | |
| EP0916637B1 (en) | Process for preparating optically active compounds | |
| CN107602382B (en) | Method for synthesizing chiral aryl allyl ether compound through organic catalysis | |
| CN110204468B (en) | Asymmetric synthesis method of chiral alpha-thiocyano cyclic ketonic acid ester compound | |
| CN116478210A (en) | Chiral selenium/sulfur catalyst based on PHOX ligand skeleton and synthesis method and application thereof | |
| CN115108937A (en) | Synthesis method of alpha-azidoketone containing three-level stereocenter | |
| CN104860911B (en) | Synthesis method of chiral 3,4-dihydrocoumarin derivative compound | |
| CN112209947A (en) | Chiral indoxazinone compound and synthesis method thereof | |
| CN112552343A (en) | Axial chiral naphthalene-indole phosphine catalyst and preparation method and application thereof | |
| CN117720537B (en) | Axial chiral indole-furan catalyst and preparation method and application thereof | |
| US6054065A (en) | Chiral ligand and method for preparing cyanohydrins from aldehydes | |
| Fan et al. | Rhodium catalyzed asymmetric Pauson-Khand reaction using SDP ligands | |
| CN115466288B (en) | Method for synthesizing selenium/sulfur ligand based on chiral diphosphine ligand | |
| CN116041393B (en) | N-N axis chiral bisindolyl phosphine ligand and synthetic method and application thereof | |
| CN111018869B (en) | Preparation method of chiral fused ring pyrano-dihydropyrrole compound | |
| CN115155658B (en) | Synthetic method for synthesizing selenium-sulfur compounds based on VAPOL | |
| CN115057848B (en) | Axis chiral isopyranone-indole derivative and synthesis method thereof | |
| CN111848673A (en) | Cyclohexyl fused ring spiroindane diphosphine ligand | |
| CN115650824B (en) | Chiral diol and preparation method thereof, prepared catalyst and preparation method and application thereof | |
| CN112300220B (en) | Chiral ferrocene P, N ligand derivative and preparation method and application thereof | |
| CN117720537A (en) | Axial chiral indole-furan catalyst and preparation method and application thereof | |
| JP4373933B2 (en) | (1S, 2S)-or (1R, 2R) -cis-1-arylphosphorane-2-carboxylic acid / borane complex and method for producing the same | |
| CN116283931A (en) | (Z) -azacycloalkenyl chlorine compound and preparation method and application thereof | |
| Sugiyama et al. | Preparation of New Chiral Building Blocks by a Mukaiyama–Michael Reaction of 2-(Phenylsulfonyl) cyclopent-2-en-1-one |
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 |