CN112851469A - 一种合成手性氘代伯醇的方法 - Google Patents
一种合成手性氘代伯醇的方法 Download PDFInfo
- Publication number
- CN112851469A CN112851469A CN202110070828.4A CN202110070828A CN112851469A CN 112851469 A CN112851469 A CN 112851469A CN 202110070828 A CN202110070828 A CN 202110070828A CN 112851469 A CN112851469 A CN 112851469A
- Authority
- CN
- China
- Prior art keywords
- compound
- chiral
- deuterated
- primary alcohol
- synthesizing
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/14—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of a —CHO group
-
- 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
- B01J31/16—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/001—Acyclic or carbocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/42—Singly bound oxygen atoms
- C07D307/44—Furfuryl alcohol
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
-
- 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
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
- B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (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
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
-
- 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
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
-
- 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
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/845—Cobalt
-
- 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
- C07B2200/05—Isotopically modified compounds, e.g. labelled
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种合成手性氘代伯醇的方法,该方法包含:将醛类化合物在手性钴催化剂作用下,以联硼酸频那醇酯和氘代试剂的组合为还原剂,以NaBHEt3作为激活剂,于非质子性有机溶剂中,在室温下反应,获得手性氘代伯醇。本发明的方法以廉价易得的醛类化合物为原料,联硼酸频那醇酯和氘代试剂的组合为还原剂,于非质子性有机溶剂中,在手性钴催化剂的作用下,高效地合成相应的手性氘代伯醇化合物。该方法采用的手性钴催化剂中,手性配体为PAOR1,激活剂为NaBHEt3,不仅提高了反应的产率,产率在80%以上,而且光学纯度在90%以上。
Description
技术领域
本发明属于有机合成领域,具体涉及一种合成手性氘代伯醇的方法。
背景技术
手性氘代伯醇是一类重要的有机化合物,被广泛应用与化学和生物化学反应的机理研究中。同时,手性氘代苯甲醇是合成手性(H,D,T)-乙酸的重要前体,其合成路线如下:
该化合物在生物酶蛋白质催化机制研究中发挥着十分重要的作用。
目前,现有的合成手性伯醇的方法主要有两种:
(1)氘代醛和手性硼烷的不对称硼氢化反应,合成路线如下:
(2)醛和氘代硼烷的不对称硼氢化反应,合成路线如下:
然而,手性Alpine borane试剂活泼不易保存,价格昂贵;氘代醛或者氘代Alpineborane试剂尚未商业化,实验室合成复杂需要多步操作。而且,这两个方法的反应效率低,操作复杂。因此,这两个方法无法大规模应用,难以产业化。
发明内容
本发明的目的是提供一种合成手性氘代伯醇的方法,解决现有方法采用的试剂昂贵而且反应效率低的问题,该方法采用的联硼酸频那醇酯和氘代甲醇廉价易得,反应高效,条件温和,操作简便,提高了反应产率和光学纯度。
为了达到上述目的,本发明提供了一种合成手性氘代伯醇的方法,该方法的合成路线为:
将化合物A在手性钴催化剂作用下,以联硼酸频那醇酯和氘代试剂的组合为还原剂,以NaBHEt3作为激活剂,于非质子性有机溶剂中,在室温下反应,获得手性氘代伯醇。
其中,所述化合物A的化学结构式中,R选自芳香环、C1-C10的链烷烃、C3-C8的环烷烃或n为1-3;所述氘代试剂选自MeOD、EtOD或D2O;所述非质子性有机溶剂选自四氢呋喃、甲苯或二氧六环;所述手性钴催化剂为CoCl2和手性配体PAOR1;其中,所述手性配体PAOR1的化学结构式为:
式中,R1选自异丙基、正丁基、苯基或苄基。
优选地,所述芳香环选自无取代或取代的苯基、联苯、萘、富电子五元环、六元芳杂环;所述取代为吸电子基取代或供电子基取代。
优选地,所述吸电子基取代选自甲基、甲氧基、甲硫基;所述吸电子基选自氟、氯、溴、碘、三氟甲基、酯基。
优选地,所述富电子五元环选自呋喃、噻吩。
优选地,所述六元芳杂环选自吡啶。
优选地,所述化合物A选自以下任意一种:
优选地,所述化合物A选自以下任意一种:
优选地,所述化合物A、联硼酸频那醇酯、氘代甲醇、CoCl2、手性配体PAOR1的摩尔比为1:1.1:2:0.001~0.01:0.001~0.01。
优选地,所述化合物A与NaBHEt3的摩尔比为1:0.003~0.03。
本发明的合成手性氘代伯醇的方法,解决了现有方法采用的试剂昂贵而且反应效率低的问题,具有以下优点:
本发明的合成手性氘代伯醇的方法,以廉价易得的醛类化合物为原料,联硼酸频那醇酯和氘代试剂的组合为还原剂,于非质子性有机溶剂中,在手性钴催化剂的作用下,高效地合成相应的手性氘代伯醇化合物。该方法采用的手性钴催化剂中,手性配体为PAOR1,激活剂为NaBHEt3,不仅提高了反应的产率,产率在80%以上,而且光学纯度在90%以上。
具体实施方式
下面将对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
实施例1
一种合成手性氘代伯醇的方法,其合成路线如下:
该方法的具体步骤,如下:
25℃,氮气氛下,在一干燥的反应管中依次加入氯化钴(0.01mmol)、PAOiPr配体(0.01mmol)、苯甲醛(1mmol,化合物1a)、联硼酸频那醇酯(1.1equiv.)、氘代甲醇(2equiv.)、四氢呋喃(THF)(1mL),注射入三乙基硼氢化钠(0.03mmol),反应混合物搅拌1h。
待反应结束后,柱层析分离得到手性氘代伯醇,即化合物1b,为无色油状液体,产率为95%,ee值为98%。
化合物1b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.28-7.49(m,5H),4.67(br,1H)。
实施例2
与实施例1基本相同,区别在于:采用的醛为2-甲氧基苯甲醛(化合物2a),制备得到化合物2b,为无色油状液体,产率为92%,ee值为92%。
化合物2b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.11-7.20(m,2H),6.75-6.84(m,2H),4.60(br,1H),3.77(s,3H)。
实施例3
与实施例1基本相同,区别在于:采用的醛为3-甲氧基苯甲醛(化合物3a),制备得到化合物3b,为无色油状液体,产率为95%,ee值为98%。
化合物3b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.26(dd,J=8.4Hz,3.2Hz,2H),6.82(dd,J=6.0Hz,1.2Hz,1H),4.63(br,1H),3.80(s,3H)。
实施例4
与实施例1基本相同,区别在于:采用的醛为4-甲氧基苯甲醛(化合物4a),制备得到化合物4b,为无色油状液体,产率为96%,ee值为98%。
化合物4b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.29(d,J=8.2Hz,2H),6.89(d,J=8.2Hz,2H),4.58(br,1H),3.81(s,3H)。
实施例5
与实施例1基本相同,区别在于:采用的醛为4-甲基苯甲醛(化合物5a),制备得到化合物5b,为白色固体,产率为95%,ee值为98%。
化合物5b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.22(d,J=8.2Hz,2H),7.12(d,J=8.2Hz,2H),4.79(br,1H),2.35(s,3H)。
实施例6
与实施例1基本相同,区别在于:采用的醛为4-联苯甲醛(化合物6a),制备得到化合物6b,为白色固体,产率为96%,ee值为97%。
化合物6b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.55-7.65(m,4H),7.38-7.48(m,4H),7.31-7.39(m,1H),4.74(br,1H)。
实施例7
与实施例1基本相同,区别在于:采用的醛为4-甲硫基苯甲醛(化合物7a),制备得到化合物7b,为黄色固体,产率为90%,ee值为97%。
化合物7b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.32(d,J=8.6Hz,2H),7.28(d,J=8.6Hz,2H),4.66(br,1H)。
实施例8
与实施例1基本相同,区别在于:采用的醛为4-氟苯甲醛(化合物8a),制备得到化合物8b,为淡黄色油状液体,产率为90%,ee值为97%。
化合物8b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.27-7.36(m,2H),7.03-7.10(m,2H),4.69(br,1H)。
实施例9
与实施例1基本相同,区别在于:采用的醛为4-氯苯甲醛(化合物9a),制备得到化合物9b,为白色固体,产率为91%,ee值为98%。
化合物9b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.26-7.32(m,4H),4.64(s,br,1H)。
实施例10
与实施例1基本相同,区别在于:采用的醛为4-溴苯甲醛(化合物10a),制备得到化合物10b,为白色固体,产率为92%,ee值为97%。
化合物10b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.45-7.50(d,J=8.0Hz,2H),7.27(d,J=8.0Hz,2H),4.62(br,1H)。
实施例11
与实施例1基本相同,区别在于:采用的醛为4-碘苯甲醛(化合物11a),制备得到化合物11b,为白色固体,产率为85%,ee值为96%。
化合物11b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.62(d,2H,J=8.2Hz),7.03(d,2H,J=8.0Hz),4.55(br,1H)。
实施例12
与实施例1基本相同,区别在于:采用的醛为4-三氟甲基苯甲醛(化合物12a),制备得到化合物12b,为淡黄色油状液体,产率为82%,ee值为94%。
化合物12b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ8.28(d,J=8.8Hz,2H),7.59(d,J=8.8Hz,2H),4.58(br,1H)。
实施例13
与实施例1基本相同,区别在于:采用的醛为4-甲酰基苯甲酸(化合物13a),制备得到化合物13b,为白色固体,产率为77%,ee值为95%。
化合物13b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ8.04(d,J=8.2Hz,2H),7.43(d,J=8.2Hz,2H),4.72(br,1H),3.88(s,3H)。
实施例14
与实施例1基本相同,区别在于:采用的醛为2-萘甲醛(化合物14a),制备得到化合物14b,为白色固体,产率为96%,ee值为98%。
化合物14b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.81-7.87(m,4H),7.46-7.52(m,3H),4.89(br,1H)。
实施例15
与实施例1基本相同,区别在于:采用的醛为1-萘甲醛(化合物15a),制备得到化合物15b,为白色固体,产率为88%,ee值为92%。
化合物15b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ8.19(d,J=8.0Hz,1H),8.03-7.73(m,2H),7.64-7.54(m,3H),7.51(t,J=7.4Hz,1H),5.21(br,1H)。
实施例16
与实施例1基本相同,区别在于:采用的醛为4-吡啶甲醛(化合物16a),制备得到化合物16b,为淡黄色固体,产率为87%,ee值为94%。
化合物16b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ8.33-8.42(m,2H),7.24-7.31(m,2H),4.70(br,1H)。
实施例17
与实施例1基本相同,区别在于:采用的醛为2-呋喃甲醛(化合物17a),制备得到化合物17b,为淡黄色油状液体,产率为85%,ee值为90%。
化合物17b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.35(s,1H),6.33(s,1H),6.27(d,J=3.2Hz,1H),4.55(br,1H)。
实施例18
与实施例1基本相同,区别在于:采用的醛为2-噻吩甲醛(化合物18a),制备得到化合物18b,为淡黄色油状液体,产率为88%,ee值为92%。
化合物18b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.31(dd,J=4.9Hz,1.4Hz,1H),6.92-7.00(m,2H),4.81(br,1H)。
实施例19
与实施例1基本相同,区别在于:采用的醛为环己基甲醛(化合物19a),制备得到化合物19b,为无色油状液体,产率为72%,ee值为82%。
化合物19b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ3.42-3.50(m,1H),1.81-1.60(m,5H),1.42-1.52(m,1H),1.35-1.10(m,3H),0.86-0.94(m,2H)。
实施例20
与实施例1基本相同,区别在于:采用的醛为苯乙醛(化合物20a),制备得到化合物20b,为无色油状液体,产率为78%,ee值为80%。
化合物20b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ7.40-7.32(m,2H),7.34-7.25(m,3H),3.92-3.85(m,1H),2.93-2.84(d,J=7.6Hz,2H)。
实施例21
与实施例1基本相同,区别在于:采用的醛为庚醛(化合物21a),制备得到化合物21b,为无色油状液体,产率为70%,ee值为77%。
化合物21b的核磁表征数据如下:
1H NMR(400MHz,CDCl3):δ3.64-3.57(m,1H),1.60-1.52(t,J=8.0Hz,3H),1.33-1.24(m,8H),0.91-0.82(m,3H)。
实施例22
与实施例1基本相同,区别在于:采用的配体为PAOBu,化合物1b的产率为90%,ee值为90%。
实施例23
与实施例1基本相同,区别在于:采用的配体为PAOPh,化合物1b的产率为88%,ee值为92%。
实施例24
与实施例1基本相同,区别在于:采用的配体为PAOBn,化合物1b的产率为92%,ee值为95%。
实施例25
与实施例1基本相同,区别在于:采用的氘代试剂为EtOD,化合物1b的产率为92%,ee值为98%。
实施例26
与实施例1基本相同,区别在于:采用的氘代试剂为D2O,化合物1b的产率为82%,ee值为95%。
实施例27
与实施例1基本相同,区别在于:采用的溶剂为甲苯,化合物1b的产率为80%,ee值为90%。
实施例28
与实施例1基本相同,区别在于:采用的溶剂为二氧六环,化合物1b的产率为88%,ee值为93%。
实施例29
与实施例4基本相同,区别在于:反应量在十克级,化合物4a的用量为11g,氯化钴的量为0.1mol%,PAOiPr配体的量为0.1mol%,NaBHEt3的量为0.3mol%,制备得到10.96g化合物4b,产率为98%,ee值为98%。
对比例1
与实施例1基本相同,区别在于:未加任何配体,仅以CoCl2催化,化合物1b的产率为10%,ee值为0。
对比例2
与实施例1基本相同,区别在于:采用的配体为PAOMe,化合物1b的产率为96%,ee值为77%。
对比例3
与实施例1基本相同,区别在于:采用的配体为PAOEt,化合物1b的产率为95%,ee值为83%。
对比例4
与实施例1基本相同,区别在于:采用的配体为PAOPr,化合物1b的产率为93%,ee值为88%。
对比例5
与实施例1基本相同,区别在于:采用的配体为PAOtBu,化合物1b的产率为43%,ee值为98%。
对比例6
与实施例1基本相同,区别在于:采用NaOtBu替代NaBHEt3,化合物1b的产率为57%,ee值为92%。
尽管本发明的内容已经通过上述优选实施例作了详细介绍,但应当认识到上述的描述不应被认为是对本发明的限制。在本领域技术人员阅读了上述内容后,对于本发明的多种修改和替代都将是显而易见的。因此,本发明的保护范围应由所附的权利要求来限定。
Claims (9)
2.根据权利要求1所述的合成手性氘代伯醇的方法,其特征在于,所述芳香环选自无取代或取代的苯基、联苯、萘、富电子五元环、六元芳杂环;所述取代为吸电子基取代或供电子基取代。
3.根据权利要求2所述的合成手性氘代伯醇的方法,其特征在于,所述供电子基取代选自甲基、甲氧基、甲硫基;所述吸电子基选自氟、氯、溴、碘、三氟甲基、酯基。
4.根据权利要求2所述的合成手性氘代伯醇的方法,其特征在于,所述富电子五元环选自呋喃、噻吩。
5.根据权利要求2所述的合成手性氘代伯醇的方法,其特征在于,所述六元芳杂环选自吡啶。
8.根据权利要求1所述的合成手性氘代伯醇的方法,其特征在于,所述化合物A、联硼酸频那醇酯、氘代甲醇、CoCl2、手性配体PAOR1的摩尔比为1:1.1:2:0.001~0.01:0.001~0.01。
9.根据权利要求1所述的合成手性氘代伯醇的方法,其特征在于,所述化合物A与NaBHEt3的摩尔比为1:0.003~0.03。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110070828.4A CN112851469B (zh) | 2021-01-19 | 2021-01-19 | 一种合成手性氘代伯醇的方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110070828.4A CN112851469B (zh) | 2021-01-19 | 2021-01-19 | 一种合成手性氘代伯醇的方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN112851469A true CN112851469A (zh) | 2021-05-28 |
CN112851469B CN112851469B (zh) | 2022-05-20 |
Family
ID=76007334
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110070828.4A Active CN112851469B (zh) | 2021-01-19 | 2021-01-19 | 一种合成手性氘代伯醇的方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN112851469B (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007246481A (ja) * | 2006-03-17 | 2007-09-27 | Japan Science & Technology Agency | 位置・立体選択的安定同位体標識セリン、シスチン並びにアラニンの合成方法 |
WO2014006433A2 (en) * | 2012-07-06 | 2014-01-09 | Debreceni Egyetem | Process for the activation of the c-h bond of organic compounds and a reactions system serving the process |
CN108349974A (zh) * | 2016-02-02 | 2018-07-31 | 深圳市塔吉瑞生物医药有限公司 | 一种取代的吡啶酰胺类化合物及其应用 |
CN109529940A (zh) * | 2018-12-11 | 2019-03-29 | 温州大学 | 二苯胺-膦-噁唑啉配体、其合成方法及其金属配合物和用途 |
CN110128233A (zh) * | 2019-05-21 | 2019-08-16 | 南京工业大学 | 一种氘代醇类或胺类化合物的制备方法 |
-
2021
- 2021-01-19 CN CN202110070828.4A patent/CN112851469B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007246481A (ja) * | 2006-03-17 | 2007-09-27 | Japan Science & Technology Agency | 位置・立体選択的安定同位体標識セリン、シスチン並びにアラニンの合成方法 |
WO2014006433A2 (en) * | 2012-07-06 | 2014-01-09 | Debreceni Egyetem | Process for the activation of the c-h bond of organic compounds and a reactions system serving the process |
CN108349974A (zh) * | 2016-02-02 | 2018-07-31 | 深圳市塔吉瑞生物医药有限公司 | 一种取代的吡啶酰胺类化合物及其应用 |
CN109529940A (zh) * | 2018-12-11 | 2019-03-29 | 温州大学 | 二苯胺-膦-噁唑啉配体、其合成方法及其金属配合物和用途 |
CN110128233A (zh) * | 2019-05-21 | 2019-08-16 | 南京工业大学 | 一种氘代醇类或胺类化合物的制备方法 |
Non-Patent Citations (4)
Title |
---|
ABOO, AHMED H.ET AL: "Methanol as hydrogen source: transfer hydrogenation of aromatic aldehydes with a rhodacycle", 《CHEMICAL COMMUNICATIONS (CAMBRIDGE, UNITED KINGDOM)》 * |
CHEN, ZHENYU ET AL: "Methanol as Hydrogen Source: Transfer Hydrogenation of Aldehydes near Room Temperature", 《ASIAN JOURNAL OF ORGANIC CHEMISTRY》 * |
JIANG, BIAO-LIN ET AL: "Cobalt-Catalyzed Chemoselective Transfer Hydrogenation of C=C and C=O Bonds with Alkanols", 《CHEMCATCHEM》 * |
LIN, XIAO ET AL: "Diboron-Mediated Rhodium-Catalyzed Transfer Hydrogenation of Alkenes and Carbonyls", 《EUROPEAN JOURNAL OF ORGANIC CHEMISTRY》 * |
Also Published As
Publication number | Publication date |
---|---|
CN112851469B (zh) | 2022-05-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Zeng et al. | Facile synthesis of benzofurans via copper-catalyzed aerobic oxidative cyclization of phenols and alkynes | |
WO2021169359A1 (zh) | 一种苯并二氢呋喃并杂环类化合物及其制备方法 | |
CN112142694A (zh) | 一种多取代四氢呋喃与四氢吡喃双烯体类化合物及其制备方法 | |
CN112851469B (zh) | 一种合成手性氘代伯醇的方法 | |
CN112442008B (zh) | 一种温度调控单质硫与活泼内炔制备1,4-二噻烯和噻吩类化合物的方法及其转化反应 | |
CN109704914A (zh) | 一种1,1-二氟乙基芳香化合物的简易合成新方法 | |
CN109336794B (zh) | 一种芳乙烯基三氟甲硫醚类化合物的合成方法 | |
JP5170382B2 (ja) | 不斉触媒アルドール反応生成物の製造方法 | |
CN104045596B (zh) | 制备依托考昔中间体1‑(6‑甲基吡啶‑3‑基)‑2‑[4‑(甲磺酰基)苯基]乙酮的方法 | |
CN101967075A (zh) | 一种利用3-芳基-2,3-二溴丙酸合成端炔化合物的方法 | |
Yu et al. | A convenient approach to difluoromethylated all-carbon quaternary centers via Ni (II)-catalyzed enantioselective Michael addition | |
CN104447521B (zh) | 一种制备高选择性单氟烯烃的试剂 | |
Tamura et al. | Highly stereoselective reduction of chiral α-keto-β, γ-unsaturated acetals: Synthesis of both epimeric allyl alcohols by proper choice of additive | |
CN110294758B (zh) | 2-取代5,6-二氢吡唑并[5,1-α]异喹啉、衍生物及其合成方法 | |
CN109942553B (zh) | 一种手性3,4,6-三取代四氢2h-吡喃-2-酮化合物的合成及其转化方法 | |
CN106349125A (zh) | 利用锰盐选择性合成(e)‑乙烯基砜化合物的方法 | |
CN113200899A (zh) | 一种芳基硒醚类化合物及其合成方法 | |
JP5608636B2 (ja) | 光学活性アルコールを製造する方法 | |
CN106854125B (zh) | 一种制备含有两个手性中心α-氟-β-乙炔基酮化合物的方法 | |
CN111732552A (zh) | 一种钯催化合成1,3-噁唑-2-硫酮的方法 | |
CN114213298B (zh) | 一种由硫酚直接氧化制备硫代磺酸酯类化合物的方法 | |
CN109096336A (zh) | 一种苯并磷杂萘衍生物的制备方法及应用 | |
CN101041648B (zh) | 反式-1,2-环丙烷衍生物及其制备方法 | |
CN112851470B (zh) | 一种合成手性二级醇化合物的方法 | |
CN103819396B (zh) | 一种手性的1-(3,5-二氯吡啶-4-基)-乙醇的合成方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |