CN110669073A - 一种磷杂菲类叔膦衍生物、其合成方法及应用 - Google Patents

一种磷杂菲类叔膦衍生物、其合成方法及应用 Download PDF

Info

Publication number
CN110669073A
CN110669073A CN201911080219.6A CN201911080219A CN110669073A CN 110669073 A CN110669073 A CN 110669073A CN 201911080219 A CN201911080219 A CN 201911080219A CN 110669073 A CN110669073 A CN 110669073A
Authority
CN
China
Prior art keywords
compound
formula
menthyl
chiral
preparation
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
Application number
CN201911080219.6A
Other languages
English (en)
Other versions
CN110669073B (zh
Inventor
赵长秋
颜丙霞
张宇
李强
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Liaocheng University
Original Assignee
Liaocheng University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Liaocheng University filed Critical Liaocheng University
Priority to CN201911080219.6A priority Critical patent/CN110669073B/zh
Publication of CN110669073A publication Critical patent/CN110669073A/zh
Application granted granted Critical
Publication of CN110669073B publication Critical patent/CN110669073B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

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 System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6568—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus atoms as the only ring hetero atoms
    • C07F9/65683—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus atoms as the only ring hetero atoms the ring phosphorus atom being part of a phosphine
    • 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
    • B01J31/0267—Phosphines or phosphonium compounds, i.e. phosphorus bonded to at least one carbon atom, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, the other atoms bonded to phosphorus being either carbon or hydrogen
    • B01J31/0268—Phosphonium compounds, i.e. phosphine with an additional hydrogen or carbon atom bonded to phosphorous so as to result in a formal positive charge on phosphorous
    • 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
    • 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
    • B01J31/2461—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 ring members in the condensed ring system or in a further ring
    • B01J31/2466—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 ring members in the condensed ring system or in a further ring comprising aliphatic or saturated rings
    • 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
    • C07C29/143—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 ketones
    • C07C29/145—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 ketones with hydrogen or hydrogen-containing gases
    • 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 System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6568—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus atoms as the only ring hetero atoms
    • C07F9/65685—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus atoms as the only ring hetero atoms the ring phosphorus atom being part of a phosphine oxide or thioxide
    • 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 System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6568—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus atoms as the only ring hetero atoms
    • C07F9/65688—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus atoms as the only ring hetero atoms the ring phosphorus atom being part of a phosphonium compound
    • 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)

Abstract

本公开属于手性三羟基磷合成技术领域，具体涉及一种磷杂菲类叔膦衍生物、其合成方法及应用。手性的三烃基膦化合物的手性中心靠近反应活性中心，因此通常能够表现良好的催化活性，是手性药物、化工中间体的重要合成原料。环状手性叔膦化合物具有良好的稳定型及配位能力，但相关研究较为空白。本公开提供了一种系列碳、磷、轴手性的9‑薄荷基‑9,10‑二氢磷杂菲类叔膦衍生物及合成方法，采用CDOP作为起始产物，向磷原子上引入薄荷基，再进行分子内环化反应得到了一系列具有10‑位含有不同取代基的环状9‑薄荷基二氢磷杂菲化合物，具有良好的催化活性。

Description

一种磷杂菲类叔膦衍生物、其合成方法及应用
技术领域
本公开属于手性三烃基膦合成技术领域，具体涉及一种磷杂菲类叔膦衍生物、其合成方法及应用。
背景技术
公开该背景技术部分的信息仅仅旨在增加对本公开的总体背景的理解，而不必然被视为承认或以任何形式暗示该信息构成已经成为本领域一般技术人员所公知的现有技术。
三烃基膦具有还原性和配位性，作为络合催化剂配体和的基础原料，在化工、石油化工中有广阔的用途。例如，三苯基膦可应用于医药工业、有机合成、分析等领域，作为染料工艺的增光剂、高分子聚合，彩色胶卷显象的抗氧剂，聚环氧化的稳定剂，还可作为分析试剂。
手性的三烃基膦化合物，可以单独催化不对称反应，也可作为配体和金属结合形成手性催化剂，应用于不对称合成，是很多手性药物、药物中间体、生物活性物质等的生产过程中必不可少的关键材料。目前工业生产中应用的手性膦化合物，多为碳骨架手性的配体，例如二(二苯基膦基)联萘，英文缩写为BINAP，广泛应用于不对称合成领域及工业生产中。
但是，繁琐冗长的合成路线，导致手性的三烃基膦化合物价格昂贵。工业上常用的手性催化剂，往往由手性配体和贵金属钯铑铂铱等组成，其中，手性叔膦配体的价格所占比例，超过了这些贵金属。例如从简单原料到BINAP合成步骤，不少于5步，BINAP已经作为商品出售，其价格为￥958/克(百灵威公司参考价)。类似市售手性叔膦化合物(1R,2R)-二[(2-甲氧基苯基)苯基膦基]乙烷，缩写为(R,R)-DIPAMP，其合成步骤不少于7步，价格为￥6327/克(百灵威公司参考价)。
由于磷原子手性的膦化合物的手性中心更加靠近反应活性中心，通常能够表现出更加优良的催化性能。但是，由于磷原子手性的化合物获取不易，常常需要繁琐的拆分过程，并且形成手性磷原子的反应立体选择性不高，其后续转化或应用过程中，手性容易发生变化或者损减，所以，磷原子手性的膦化合物的研究和应用，一直受到限制。
通常的叔膦化合物多为开链结构，其手性磷原子容易在高温等条件下发生消旋，而处于环内的手性磷原子，因为环结构的稳定作用，构型比较稳定。同时，因为环的约束，磷原子上的孤对电子，具有更强的配位能力，因此，环状手性叔膦化合物，具有优良的配位和催化性能。
复合多手性的叔膦化合物，因为含有多个种类的手性中心，通过其协同作用，可望提供卓越的不对称环境，有效提高不对称催化反应的对映选择性，因而在不对称合成领域，具有广阔的应用前景。
目前，环状的手性叔膦化合物，无论其种类还是应用，研究报道的都很少，含有多种手性因素的该类化合物，研究开发的更加稀少。已经报道的环状的手性叔膦化合物，都是通过多步化学反应，同时，还必须经过化学拆分过程，其合成方法繁琐，效率低下，即使这样繁琐的方法，也没有关于包含碳磷轴多种手性因素的类似叔膦化合物的报道。
发明内容
依据上述研究背景，本公开提供了一系列碳、磷、轴手性的9-薄荷基-9,10-二氢磷杂菲类叔膦衍生物及合成方法。本公开采用工业阻燃剂原料CDOP(6-Chloro-6H-dibenzo[c,e][1,2]oxaphosphinine)作为起始物，通过在磷原子上引入薄荷基，然后对所得中间化合物进行分子内环化反应，获得一系列10-位含有不同取代基的环状9-薄荷基二氢磷杂菲化合物，该过程中，利用薄荷基的手性，通过一系列反应，诱导形成碳、磷原子和联苯轴等的手性。其中，10-位取代基为氢的化合物，经过进一步转化，可得到鳌合型双膦手性配体。
基于上述研究结果，本公开提供以下技术方案：
本公开第一方面，提供一种化合物，或所述化合物的异构体或溶剂化物，所述化合物具有下式1或式2所示的结构：
Figure BDA0002263732120000021
Figure BDA0002263732120000031
其中，所述R1＝H，Ph，p-MeC6H4,o-MeC6H4，p-tBuC6H4或m-MeO6H4。
本公开第二方面，提供如式1所述化合物的制备方法，所述制备方法工艺流程如下：
Figure BDA0002263732120000032
优选的，所述R1＝H，Ph，p-MeC6H4，o-MeC6H4，p-tBuC6H4或m-MeO6H4时，所述制备方法包括以下步骤：
(1)将薄荷基卤化镁或薄荷基锂加入化合物1的醚溶剂的溶液中，加热得到化合物2/2’的RP和SP构型的混合物；
(2)向步骤(1)得到的混合物中加入盐酸得到化合物3/3’的RP和SP构型的混合物；
(3)将化合物3/3’溶于碱性醇溶液中，加入碘甲烷，室温搅拌，得到化合物4/4’的RP和SP构型的混合物；
(4)将化合物4/4’加入醚类溶剂中，室温下滴加草酰氯，然后低温下加入格氏试剂，搅拌的同时，温度缓慢升至室温，得到化合物RP-5；
(5)优选的，R2＝H时，所述制备方法包括以下步骤：RP-5a的醚类溶剂的溶液中，低温下滴加丁基锂，形成分子内取代的环化产物RP-6a，得到式1所述化合物(即SP,RA-6，化合物的R1＝H)。
(6)优选的，当R1＝Ph，p-MeC6H4,o-MeC6H4，p-tBuC6H4或m-MeO6H4时，向RP-5b到RP-5f所示化合物的醚类溶剂的溶液中，低温下滴加丁基锂，加入碘化亚铜，低温下淬灭得到所述式1化合物6b到6f。
本公开第三方面，提供如式2所示化合物的制备方法，所述制备方法如下：将式1化合物加入醚类溶剂的溶液中，低温下滴加丁基锂，然后加入无水氯化铜，低温淬灭后得到所述式2化合物。
本公开第四方面，提供一种化合物，或所述化合物的异构体、溶剂化物或可药用盐，所述化合物具有下式3或式4所示的结构：
Figure BDA0002263732120000041
所述R2＝H，Ph，p-MeC6H4,，p-tBuC6H4，m-MeOC6H4或ClC6H4。
本公开第五方面，提供所述式3化合物的制备方法，所述制备方法流程如下：
Figure BDA0002263732120000042
优选的，R2＝H时，所述制备方法包括以下步骤：向RP-8所示化合物的醚类溶剂的溶液中，低温下滴加丁基锂，低温下淬灭得到所述式3化合物。
优选的，当R2＝H，Ph，p-MeC6H4,，p-tBuC6H4，m-MeOC6H4或ClC6H4时，向RP-8所示化合物的醚类溶剂的溶液中，低温下滴加丁基锂，加入碘化亚铜，低温下淬灭得到所述式3化合物。
本公开第六方面，提供所述式4化合物的制备方法，所述制备方法如下：
向所述RP-9a的醚类溶剂的溶液中，低温下滴加丁基锂，然后加入无水氯化铜，低温淬灭后，得到所述式4化合物。
本公开第七方面，提供第二、三方面和/或第五、六方面所述制备方法得到的化合物作为催化剂的应用。
优选的，所述催化剂应用于苯乙醇的生产。
与现有技术相比，本公开的有益效果是：
1.本公开提供的手性叔膦化合物，采用工业原料作为起始原料，经过转化，获得在不对称合成中发挥着关键作用的手性叔膦化合物。薄荷基除了作为手性源，诱导后续一系列手性中心的形成外，还作为叔膦的三个烃基之一，避免了额外移除手性助剂的步骤，简化了手性叔膦化合物的合成步骤。
2.采用手性薄荷基可稳定手性磷原子的构型，使产物的后续转化和应用的反应条件放宽，因而扩大了其应用范围。同时，手性薄荷基体积大，能强化手性磷原子的不对称诱导效果。
3.产物的环状结构，能进一步稳定磷原子的构型，并且，有利于立体选择性的后续转化反应。
4.产物含有包括碳、磷和联苯轴三种手性因素在内的多个手性中心，该类化合物结构新颖，在不对称催化中，可望发挥重要的作用，取得优良的不对称选择性。
5.合理利用薄荷基的存在，可以使用非对映异构体的混合物做原料，通过草酰氯以及随后的格氏反应，以高的收率和立体选择性，获得单一立体异构体的产物，避免了繁琐的拆分过程。
附图说明
构成本公开的一部分的说明书附图用来提供对本公开的进一步理解，本公开的示意性实施例及其说明用于解释本公开，并不构成对本公开的不当限定。
图1为实施例1中SP,RA-6a结构示意图；
图2为实施例1中RP,RP,RC,RC',RA,RA'-7结构示意图；
图3为实施例1中RP,SA-9a结构示意图；
图4为实施例1中SP,RA-9a’结构示意图；
图5为实施例1中SP,SC,SA-9c结构示意图；
图6为实施例1中SP,SC,SA-9d结构示意图。
具体实施方式
应该指出，以下详细说明都是例示性的，旨在对本公开提供进一步的说明。除非另有指明，本文使用的所有技术和科学术语具有与本公开所属技术领域的普通技术人员通常理解的相同含义。
需要注意的是，这里所使用的术语仅是为了描述具体实施方式，而非意图限制根据本公开的示例性实施方式。如在这里所使用的，除非上下文另外明确指出，否则单数形式也意图包括复数形式，此外，还应当理解的是，当在本说明书中使用术语“包含”和/或“包括”时，其指明存在特征、步骤、操作、器件、组件和/或它们的组合。
正如背景技术所介绍的，手性叔膦化合物具有良好的催化活性，但是制备较为困难，产率低，且产物不稳定；为了弥补现有技术中的空白，本公开提供了一系列包含碳磷轴多种手性因素的类似叔膦化合物及其制备方法。
为了使得本领域技术人员能够更加清楚地了解本公开的技术方案，以下将结合具体的实施例与对比例详细说明本公开的技术方案。
以下实施例中出现的试剂均为市售产品，未标明具体条件的实验方法，通常按照常规条件或按照制造厂商所建议的条件。
术语解释：
本公开文件的化学式标识中，因为手性磷原子不同构型，有时会形成两个非对映异构体的混合物，例如第一步，形成2和2’两个异构体，用2/2’表示，第二步反应中，生成了3和3’两个异构体，用3/3’表示，以此类推。
旋光性标识：斜体的R和S表示手性原子或其他手性位点的构型，其附带的大写非斜体下标，“P”表示的手性磷原子(phosphorus)，“A”表示手性轴(axis)，“C”表示手性碳原子(carbon)，下同；如“RP/SP-3/3’”表示生成的磷原子R构型和S构型的混合物，“SP,RA-6”表示生成的是磷原子的S构型化合物或轴的R型化合物。
实施例1
本实施例提供二氢9-薄荷基-9-磷杂菲的膦硼烷络合物和二氢9-薄荷基-9-磷杂菲膦氧化物，以及通过偶联形成的双膦配体。上述化合物的结构及制备方法如下：
Figure BDA0002263732120000071
步骤1-1：二氢9-薄荷基-9,10-磷氧杂菲2的制备
上述反应流程中的化合物1依据现有报道方法进行制备:将薄荷基卤化镁或者薄荷基锂溶液滴到1的溶液中，搅拌、加热回流，得到化合物2/2’的RP和SP构型的混合物。
其中，薄荷基卤化镁或薄荷基锂溶液依照发明人公开专利(CN103665038A-一种碳磷手性二烃基氧膦及其合成方法)中的方法制备：将(L)-(-)-薄荷基氯或(L)-(-)-薄荷基溴与金属镁或者金属锂，在醚类溶剂中反应，得到薄荷基氯化镁或者薄荷基溴化镁溶液；使用(L)-(-)-薄荷基氯与金属锂，在醚类溶剂或烃类溶剂中反应，制得薄荷基锂溶液。
步骤1-2：2’-羟基2-联苯基薄荷基氧膦3/3’的制备
将步骤1-1中得到的二氢9-薄荷基-9,10-磷氧杂菲2的粗产物在醚类或烃类溶剂形成的溶液中，加入盐酸室温下水解12小时，获得化合物3/3’的RP和SP构型的混合物。
步骤1-3：2’-甲氧基-2-联苯基薄荷基氧膦4/4’的制备
在氮气保护下，在RP-3/SP-3’(1.00g,2.79mmol)和KOH(0.18g,2.79mmol)在乙醇(10ml)中的溶液中，加入碘甲烷(1.03mL,16.7mmol),室温下搅拌，反应完成后，减压除去溶剂，向溶液中加入饱和氯化铵溶液(20mL),混合物用二氯甲烷(3x 20mL)萃取，用水洗涤，无水硫酸镁干燥，得到化合物RP-4/SP-4’。
步骤1-4：RP-2’-甲氧基-2-联苯基烃基薄荷基膦硼烷络合物RP-5的制备
本实施例中通过化合物4/4’发生氯代-格式反应得到所述RP-5，其中格氏试剂溶液按照本领域常规制备方法，将卤代烃和金属镁加入乙醚或者四氢呋喃中进行制备。
化合物4/4’的在醚类溶剂的溶液中，室温下滴加草酰氯，然后低温下将格氏试剂溶液加入，反应混合物在搅拌的同时，温度缓慢升至室温。根据使用的格氏试剂中烃基种类的不同，得到化合物RP-5a到RP-5f。
以RP-2’-甲氧基-2-联苯基苄基薄荷基膦硼烷络合物(RP-5b)制备方法为例，合成步骤如下：
在N2保护下，室温下向RP-4/SP-4’(0.63g,1.7mmol,)在无水四氢呋喃(10mL)的溶液中，加入草酰氯(0.17mL,2.04mmol)反应5分钟，转移至-80℃搅拌半个小时，滴加苄基氯化镁(8.5mL,0.8mol/L)溶液，然后缓慢从-80℃恢复至室温，继续反应8小时，加入硼烷四氢呋喃溶液(8.5mL,1.0mol/L)，2小时后，在冰水浴条件下，滴加稀盐酸(10mL,7％HCl)终止反应。混合物用乙醚(3x 20mL)萃取，合并的萃取液用水洗涤一次，无水硫酸镁干燥。减压除去溶剂后，残留物用柱层析纯化，得到白色固体RP-5b.
本实施例按照上述方案制备得到的化合物RP-5a～5f化合物结构及结构确证信息如下：
(Rp)-薄荷基甲基(2’-甲氧基-1,1-联苯-2-基)膦硼烷络合物(5a)
Figure BDA0002263732120000091
CDCl3)δ＝20.5(broad m)；1H NMR(400MHz,CDCl3)δ＝8.07(dd,J＝13.7,7.9,1H),7.44(ddd,J＝15.5,13.4,7.8,3H),7.17(d,J＝7.4,1H),7.06–6.91(m,3H),3.73(s,3H),1.92–1.76(m,1H),1.67(d,J＝8.3,2H),1.31(d,J＝10.3,0.9H),1.25(s,1H),1.17(d,J＝10.3,2.1H),1.10–0.43(m,14H),0.39(dd,J＝6.8,4.5,4H)；13C{1H}NMR(101MHz,CDCl3)δ＝156.9(s),142.0(s),141.7(s),135.8(dd,J＝36.7,17.1),132.3–131.91(m),131.7(d,J＝6.3),130.6(s),130.4–129.9(m),129.8(s),129.3(s),127.2(dd,J＝12.6,9.6),119.7(d,J＝13.6),110.6(d,J＝4.8),55.5(s),55.1(s),44.0(d,J＝10.7),37.9(s),37.6(s),36.9(s),36.4(s),36.1(s),35.8(s),34.3(d,J＝4.4),33.5–33.2(m),28.4(dd,J＝6.9,2.4),24.9(dd,J＝11.5,9.1),22.4(d,J＝15.5),21.3(d,J＝13.8),15.3–14.8(m),12.2(s),11.8(s)；HRMS(ESI+)Calcd.forC24H34OP[M-BH3+H+]:369.2347,Found:369.2345.
(RP)-薄荷基苄基(2’-甲氧基-1,1-联苯-2-基)膦硼烷络合物(5b)
Figure BDA0002263732120000092
CDCl3)δ＝7.73(dd,J＝13.1,7.8,1H),7.67–7.62(m,1H),7.48(dd,J＝12.8,5.3,1H),7.45–7.38(m,1H),7.30(t,J＝7.6,1H),7.20(ddd,J＝13.4,6.4,5.2,1H),7.12–7.04(m,3H),7.03–6.92(m,2H),6.88(d,J＝7.2,1H),6.81(d,J＝7.2,1H),3.69(d,J＝9.2,3H),3.59(s,1H),3.43(dd,J＝15.6,14.1,1H),3.31(s,1H),2.93(dd,J＝13.6,6.9,1H),2.23(dd,J＝9.2,4.1,1H),2.14–2.08(m,1H),1.80–1.61(m,4H),1.53(d,J＝10.0,1H),1.46–1.42(m,1H),1.24(s,1H),1.18–1.09(m,1H),0.91(d,J＝6.7,2H),0.88(d,J＝6.9,1H),0.78(d,J＝6.4,2H),0.72(d,J＝6.3,1H),0.55(dd,J＝6.8,3.7,3H),0.44–0.10(m,1H)；13C{1H}NMR(126MHz,CDCl3)δ＝156.98(s),156.46(s),142.48(s),141.71(s),136.98(d,J＝15.9),136.60(d,J＝14.8),133.78(d,J＝4.1),132.67(d,J＝6.5),132.35(d,J＝6.8),131.17(s),130.81(s),130.64–129.65(m),127.57(dd,J＝17.8,2.3),127.43–126.73(m),126.64–126.19(m),119.96(s),119.69(s),111.23(s),110.63(s),55.45(s),54.84(s),44.13(d,J＝5.8),37.16(s),36.55(s),36.52–35.99(m),35.78(d,J＝34.1),35.43(s),34.30(s),34.19(d,J＝20.1),33.27–32.82(m),32.59(s),32.37(s),28.82(s),28.47(d,J＝1.6),24.94(dd,J＝11.3,5.7),22.38(d,J＝13.9),21.35(d,J＝15.7),15.43(s),15.24(s).
(RP)-薄荷基对甲基苄基(2’-甲氧基-1,1-联苯-2-基)膦硼烷络合物(5c)
＝7.75(dd,J＝13.2,7.8,1H),7.67(dd,J＝13.5,8.0,1H),7.48(t,J＝7.5,1H),7.42(ddd,J＝8.3,4.7,1.8,1H),7.31(dd,J＝10.8,4.5,1H),7.23–7.18(m,1H),7.06–6.95(m,2H),6.92–6.86(m,3H),6.83–6.78(m,1H),6.70(dd,J＝8.0,1.9,1H),3.68(d,J＝10.9,3H),3.54(d,J＝14.5,1H),3.42–3.35(m,1H),3.25(dd,J＝14.0,6.7,1H),2.88(dd,J＝13.7,6.9,1H),2.24(d,J＝5.5,3H),1.83–1.61(m,4H),1.48–1.39(m,1H),1.24(d,J＝3.4,1H),1.12(dd,J＝12.5,5.2,1H),0.91(d,J＝6.7,3H),0.89–0.80(m,2H),0.78(d,J＝6.5,2H),0.72(d,J＝6.2,1H),0.54(d,J＝6.9,3H)；13C{1H}NMR(126MHz,CDCl3)δ＝156.98(s),156.46(s),142.38(s),141.71(s),137.07(d,J＝15.8),136.75(d,J＝14.9),135.79(d,J＝3.4),132.63(d,J＝6.5),132.32(d,J＝6.7),131.16(s),130.88(s),130.58(d,J＝4.3),130.51–129.64(m),128.32(dd,J＝15.1,2.2),127.74(s),127.36(s),126.99(dd,J＝26.5,12.1),119.92(s),119.67(s),111.17(s),110.63(s),55.43(s),54.84(s),44.12(d,J＝9.4),37.18(s),36.48(s),36.27(s),36.08(s),35.86(s),34.96(s),34.28(s),34.11(s),33.01(dd,J＝11.7,8.2),32.00(s),31.77(s),28.80(s),28.45(s),24.94(dd,J＝11.5,5.5),22.39(d,J＝14.1),21.34(d,J＝16.4),21.04(d,J＝6.2),15.42(s),15.23(s).
(RP)-薄荷基邻甲基苄基(2’-甲氧基-1,1-联苯-2-基)膦硼烷络合物(5d)
NMR(500MHz,CDCl3)δ＝7.80(d,J＝7.8,1H),7.37(d,J＝7.5,1H),7.32(dd,J＝8.4,4.4,1H),7.21(t,J＝7.5,1H),7.13(d,J＝6.7,1H),7.06–6.99(m,2H),6.97–6.87(m,3H),6.84(d,J＝8.3,1H),6.79(d,J＝7.5,1H),6.69(t,J＝7.5,1H),6.52(d,J＝7.5,1H),6.41(d,J＝7.4,1H),3.57(s,1H),3.44(s,2H),3.27(d,J＝16.2,1H),2.98(s,1H),2.82(s,1H),2.25(d,J＝3.3,1H),2.14(s,2H),2.09(d,J＝7.7,2H),1.75(d,J＝11.6,1H),1.62(t,J＝23.6,3H),1.44–1.36(m,1H),1.21(d,J＝9.4,1H),1.11–1.03(m,1H),0.95(s,1H),0.86(d,J＝6.6,2H),0.80(dd,J＝10.9,8.3,2H),0.70(d,J＝6.4,2H),0.66(d,J＝5.0,1H),0.59–0.43(m,3H)；13C{1H}NMR(126MHz,CDCl3)δ＝155.99(s),155.46(s),141.22(s),141.02(s),136.78(d,J＝42.9),136.56–135.80(m),135.53(s),135.33–134.83(m),134.67(d,J＝6.8),131.94–131.35(m),130.60(s),130.41(s),129.95(s),129.64(d,J＝22.2),129.46–128.56(m),128.34(d,J＝5.2),127.58(s),127.10(s),126.72(d,J＝2.4),126.41(s),126.04(t,J＝12.1),125.67(s),125.63–125.07(m),124.94(d,J＝11.4),124.47(dd,J＝31.7,18.2),124.28–123.79(m),118.77(d,J＝16.8),110.06(s),109.71(s),69.63(s),54.53(s),53.73(s),43.39(s),43.17(s),40.74(s),37.81(d,J＝28.8),36.16(s),35.67(s),35.45(s),35.14(d,J＝12.8),34.87(s),34.37(s),33.69(s),33.24(s),33.02(d,J＝9.3),31.96(t,J＝13.1),29.99(s),29.76(s),28.61(s),27.93(s),27.46(s),27.23(s),26.95(d,J＝14.4),25.87(s),25.33(d,J＝12.7),23.91(t,J＝11.1),21.91(s),21.66(s),21.40(d,J＝9.9),20.41(d,J＝12.5),20.14(s),19.77–19.40(m),19.38–18.93(m),18.75(s),18.17(s),17.81(t,J＝24.1),14.47(s),14.26(s),13.13(d,J＝5.3).
(RP)-薄荷基对叔丁基苄基(2’-甲氧基-1,1-联苯-2-基)膦硼烷络合物(5e)
Figure BDA0002263732120000112
CDCl3)δ＝7.77–7.70(m,1H),7.64(dd,J＝13.3,7.9,1H),7.48–7.41(m,1H),7.38(dd,J＝11.6,4.5,1H),7.34–7.28(m,2H),7.16(dd,J＝8.4,4.6,2H),7.08(d,J＝8.1,2H),7.01(dd,J＝11.4,5.3,1H),6.95–6.91(m,1H),6.86(dd,J＝8.3,1.7,1H),6.73(dd,J＝8.4,2.0,1H),3.74–3.63(m,3H),3.54–3.46(m,1H),3.38–3.30(m,1H),3.27–3.17(m,1H),2.98–2.90(m,1H),2.27–2.18(m,1H),1.80(dd,J＝17.8,7.2,1H),1.73–1.65(m,2H),1.31(d,J＝4.7,6H),1.28(d,J＝4.0,1H),1.24(d,J＝9.6,8H),0.90(d,J＝6.7,2H),0.87(t,J＝7.9,2H),0.78(d,J＝6.4,2H),0.72(d,J＝6.1,1H),0.58(d,J＝6.9,2H),0.54(d,J＝6.8,1H)；13C{1H}NMR(126MHz,CDCl3)δ＝157.01(s),156.63(s),149.14(s),142.87(s),134.39(s),132.27(d,J＝7.0),131.15(s),130.92(s),130.53(d,J＝5.9),130.42–130.40(m),129.94(ddd,J＝26.0,20.8,13.4),129.39(s),128.68(s),128.02(s),127.64(s),126.93(dd,J＝28.4,11.7),125.34(d,J＝8.7),125.12(d,J＝21.7),124.61(s),124.61–124.31(m),119.79(d,J＝10.0),111.23(s),110.53(s),55.46(s),54.88(s),45.23(s),44.12(s),37.21(s),36.96(s),36.75(s),36.33(s),34.43(d,J＝8.3),34.25(d,J＝23.3),33.07(dd,J＝15.5,11.7),32.64(s),32.42(s),31.38(t,J＝6.0),28.82(s),28.49(s),25.05(d,J＝10.9),22.42(d,J＝14.9),21.39(d,J＝15.3),15.48(s),15.32(s).
(RP)-薄荷基(间甲氧基苄基(2’-甲氧基-1,1-联苯-2-基)膦硼烷络合物(5f)
Figure BDA0002263732120000121
MHz,CDCl3)δ＝7.76(dd,J＝13.0,7.8,1H),7.71(d,J＝8.2,1H),7.43(ddt,J＝15.7,10.7,7.5,2H),7.33–7.27(m,1H),7.22–7.17(m,1H),7.00(ddd,J＝13.5,11.5,5.9,2H),6.89(d,J＝7.3,1H),6.72(d,J＝12.1,1H),6.65(s,1H),6.54(d,J＝9.9,1H),6.48(d,J＝7.5,1H),6.35(s,1H),3.70(d,J＝4.5,1H),3.68(s,2H),3.60(s,1H),3.52(s,2H),3.40(t,J＝14.8,1H),2.95–2.91(m,1H),2.25–2.19(m,1H),1.71(ddd,J＝24.2,19.8,11.8,3H),1.51–1.40(m,1H),1.25(d,J＝11.9,1H),0.91(d,J＝6.7,2H),0.88(d,J＝6.8,1H),0.79(d,J＝6.4,2H),0.72(d,J＝6.0,1H),0.55(d,J＝6.9,3H)；13C{1H}NMR(126MHz,CDCl3)δ＝158.87(t,J＝7.5),157.00(s),156.47(s),142.54(s),141.79(s),137.01(d,J＝15.9),136.65(d,J＝14.8),135.06(dd,J＝19.7,4.6),132.70(d,J＝6.5),132.43(d,J＝6.8),131.21(s),130.80(s),130.38(d,J＝1.7),130.19(s),129.91(dd,J＝23.3,7.2),129.30(d,J＝4.1),128.54(d,J＝1.7),128.33(d,J＝2.2),127.78(s),127.40(s),127.00(dd,J＝25.7,12.0),123.05(d,J＝5.0),122.73(d,J＝5.2),120.82(d,J＝6.9),119.98(s),119.70(s),114.98(dd,J＝13.6,4.5),114.19(s),112.96(dd,J＝13.7,2.8),111.27(d,J＝8.7),110.67(s),55.45(s),55.22–54.75(m),44.10(d,J＝10.0),37.82(s),37.17(s),36.64(s),36.43(s),36.24(d,J＝4.9),36.00(s),35.63(s),35.41(s),34.28(s),34.10(s),33.00(dd,J＝11.8,7.2),32.76(s),32.54(s),29.69(s),28.83(s),28.49(s),24.95(dd,J＝11.5,4.6),22.38(d,J＝13.1),21.36(d,J＝14.7),15.45(s),15.24(s).
步骤1-5：二氢9-薄荷基-9-磷杂菲的硼烷络合物RP-6的制备
RP-5的醚类溶剂的溶液中，低温下滴加丁基锂，RP-5a可以直接形成环化产物RP-6a，RP-5b～5f需要在反应体系中加入碘化亚铜，低温下淬灭反应后，得到一系列的RP-6。以RP-5a制备RP-6的步骤为例，具体操作如下：
在氮气保护下，RP-5a(80mg，0.21mmol)在无水THF(1mL)的溶液冷却到-30℃，将LDA(0.31mmol,2M)逐滴加入反应溶液中，反应混合液在室温下继续搅拌2小时，然后冷却到0℃，加入碘化亚铜(4mg,0.02mmol)，搅拌10小时同时升至室温，然后冷却到-80℃，加入乙酸：THF(1:4，2mL)终止反应。减压除去部分溶剂，混合物用二氯甲烷(30mL)萃取，萃取液用水洗涤，无水硫酸镁干燥。减压除去溶剂后，残留物用薄层层析纯化，得到纯的化合物。
本实施例中合成的RP-6a～6f络合物结构及结构确证信息如下：
(SP,RA)-5-薄荷基-5,6-二氢膦杂菲硼烷络合物(6a)
Figure BDA0002263732120000131
＝6.21(broad,m)；1H NMR(400MHz,CDCl3)δ＝7.90(dd,J＝10.2,7.9,1H),7.83–7.73(t,J＝7.5,2H),7.58(t,J＝7.6,1H),7.42(t,J＝7.4,2H),7.33(t,J＝7.3,1H),7.27(d,J＝7.7,1H),3.35(dd,J＝16.2,10.6,1H),3.20(dd,J＝16.2,4.7,1H),2.40–2.18(m,1H),1.68–1.50(m,4H),1.00(d,J＝6.7,4H),0.97–0.75(m,6H),0.71(d,J＝6.9,3H),0.65(d,J＝5.6,4H)；13C{1H}NMR(101MHz,CDCl3)δ＝138.51(s),134.91(s),134.85–134.30(m),131.89(d,J＝2.2),130.86(d,J＝5.3),130.37(d,J＝9.8),128.41(d,J＝17.9),127.70(d,J＝11.3),126.57(s),125.92(d,J＝6.0),125.36(s),124.81(s),43.85(d,J＝3.5),36.98(s),34.10(s),32.96(d,J＝11.2),30.35(d,J＝13.5),30.05(d,J＝7.2),29.41(d,J＝3.7),24.51(d,J＝11.8),22.24(s),21.27(s),15.92(s)；HRMS(ESI+)Calcd.for C23H30P[M-BH3+K+]:375.1644,Found:375.1845.
(SC,RP,RA)-5-薄荷基-6-苯基-5,6-二氢膦杂菲硼烷络合物(6b)
Figure BDA0002263732120000141
J＝7.9,1.7,1H),7.69(dd,J＝10.6,7.7,1H),7.58(t,J＝7.7,1H),7.49(dd,J＝11.1,4.1,1H),7.40–7.27(m,3H),7.14–6.96(m,3H),6.93–6.82(m,2H),4.60(d,J＝8.6,1H),2.67–2.52(m,1H),1.81–1.64(m,3H),1.56(s,2H),1.10(dd,J＝12.3,6.8,3H),0.91(ddd,J＝18.2,16.1,6.0,3H),0.86–0.75(m,5H),0.69–0.55(m,3H),0.48(dd,J＝24.1,5.8,1H)；13C{1H}NMR(126MHz,CDCl3)δ＝138.94(s),135.81(d,J＝12.8),135.65–135.31(m),133.92(d,J＝7.4),132.43–131.89(m),129.03(t,J＝5.5),128.26(d,J＝11.0),127.83(d,J＝2.1),127.10–126.66(m),125.35(d,J＝5.8),44.98(s),44.76(s),43.86(d,J＝3.6),37.37(s),34.08(s),33.12(d,J＝10.3),32.78(s),32.57(s),29.69(d,J＝3.5),24.68(d,J＝11.7),22.31(s),21.31(s),16.01(s).
(SC,RP,RA)-5-薄荷基-6-对甲基苯基-5,6-二氢膦杂菲硼烷络合物(6c)
Figure BDA0002263732120000142
7.82(m,1H),7.69(dd,J＝10.5,7.8,1H),7.58(t,J＝7.6,1H),7.48(dd,J＝11.7,4.3,1H),7.34(q,J＝8.5,2H),7.28(d,J＝7.6,1H),6.89–6.83(m,2H),6.74(dd,J＝8.1,1.7,2H),4.56(d,J＝8.4,1H),2.63–2.54(m,1H),2.17(s,3H),1.76–1.72(m,1H),1.69–1.62(m,3H),1.56(d,J＝8.8,1H),1.10(dd,J＝14.2,6.6,3H),0.93–0.86(m,2H),0.84–0.76(m,5H),0.62(d,J＝6.0,3H)；13C{1H}NMR(126MHz,CDCl3)δ＝138.97(s),136.51(d,J＝2.9),135.82(d,J＝12.8),135.46(d,J＝6.7),134.15(d,J＝7.4),132.40(s),132.11(dd,J＝16.3,3.7),128.91(dd,J＝20.3,9.9),128.61(d,J＝2.5),128.22(d,J＝11.1),126.72(s),125.34(d,J＝5.7),76.77(s),44.63(s),44.41(s),43.85(d,J＝3.5),37.39(s),34.08(s),33.11(d,J＝10.3),32.78(s),32.58(s),29.68(d,J＝3.3),24.68(d,J＝11.8),22.31(s),21.31(s),20.95(s),16.01(s).
(SC,RP,RA)-5-薄荷基-6-邻甲基苯基-5,6-二氢膦杂菲硼烷络合物(6d)
Figure BDA0002263732120000151
2H),7.79(dd,J＝10.9,7.6,1H),7.63(t,J＝7.6,1H),7.45(t,J＝7.6,1H),7.38(d,J＝7.4,1H),7.31(t,J＝7.4,1H),7.22(d,J＝7.6,1H),7.13(d,J＝7.5,1H),6.95(d,J＝7.4,1H),6.66(d,J＝7.6,1H),6.26(d,J＝7.9,1H),4.85(d,J＝8.8,1H),2.68–2.63(m,3H),1.75–1.64(m,3H),1.57(s,2H),1.08(d,J＝6.6,3H),0.96–0.75(m,10H),0.63(d,J＝6.3,3H)；13C{1H}NMR(126MHz,CDCl3)δ＝139.33(s),136.28(s),135.95(d,J＝12.5),135.62(d,J＝7.2),135.40(s),134.95(s),132.53–132.11(m),130.58(s),129.04(s),128.79(s),128.17(dd,J＝22.1,7.4),126.69(s),125.79(s),125.50(d,J＝5.7),122.22(s),121.81(s),44.08(d,J＝3.6),40.25(s),40.03(s),37.39(s),34.06(s),33.62–33.44(m),33.27(dd,J＝18.0,15.0),29.71(s),29.52(d,J＝3.7),24.70(d,J＝11.4),22.32(s),21.22(d,J＝17.9),15.86(s).
(SC,RP,RA)-5-薄荷基-6-对叔丁基苯基-5,6-二氢膦杂菲硼烷络合物(6e)
Figure BDA0002263732120000152
1H),7.47(t,J＝7.3,1H),7.34(t,J＝7.4,2H),7.28(d,J＝7.4,1H),7.06(d,J＝8.2,2H),6.78(d,J＝7.0,2H),4.58(t,J＝12.8,1H),2.66–2.56(m,1H),1.69(ddd,J＝22.9,19.6,11.0,4H),1.56(d,J＝8.6,1H),1.17(d,J＝6.8,8H),1.08(t,J＝7.3,3H),0.95–0.87(m,2H),0.81(dd,J＝13.0,7.4,6H),0.63(d,J＝5.9,3H)；13C{1H}NMR(126MHz,CDCl3)δ＝149.55(d,J＝2.9),139.00(s),135.84(d,J＝12.7),135.37(d,J＝7.0),134.22(d,J＝7.3),132.48(s),132.15(dd,J＝8.3,3.6),128.96(d,J＝15.8),128.57(d,J＝4.2),128.21(d,J＝11.0),126.75(s),125.31(d,J＝6.2),125.12(s),124.82(d,J＝2.4),122.41(s),122.00(s),44.53(s),44.30(s),43.89(d,J＝3.5),37.38(s),34.31(s),34.19(d,J＝23.0),33.11(d,J＝10.4),32.74(s),32.53(s),31.25(d,J＝7.8),29.65(d,J＝3.2),24.69(d,J＝11.5),22.36(d,J＝11.8),21.31(s),16.10(d,J＝19.4).
(SC,RP,RA)-5-薄荷基-6-间甲氧基苯基-5,6-二氢膦杂菲硼烷络合物(6f)
Figure BDA0002263732120000161
(dd,J＝7.8,1.4,1H),7.71(dd,J＝10.8,7.8,1H),7.57(t,J＝7.7,1H),7.48(t,J＝7.2,1H),7.35(dd,J＝13.2,6.2,2H),7.29(d,J＝7.2,1H),6.98(t,J＝8.0,1H),6.60(d,J＝8.2,1H),6.51(d,J＝7.7,1H),6.39(d,J＝1.7,1H),4.57(d,J＝8.6,1H),3.53(d,J＝6.8,3H),2.57(s,1H),1.76–1.68(m,2H),1.67(dd,J＝7.9,3.7,1H),1.57(d,J＝6.4,2H),1.08(d,J＝6.6,3H),0.97–0.86(m,3H),0.85–0.73(m,7H),0.63(d,J＝6.0,3H)；13C{1H}NMR(126MHz,CDCl3)δ＝158.98(d,J＝2.4),139.01(s),136.98(s),135.80(d,J＝12.9),135.45(d,J＝7.2),133.90(d,J＝7.4),132.33–131.95(m),129.08(d,J＝3.5),128.69(d,J＝2.5),128.27(d,J＝11.1),126.81(s),125.34(d,J＝6.1),122.41(s),122.00(s),121.59(d,J＝4.2),114.63(d,J＝3.8),112.64(d,J＝2.7),55.00(s),44.98(s),44.76(s),43.84(d,J＝3.5),37.35(s),34.07(s),33.12(d,J＝10.6),32.79(s),32.58(s),29.69(d,J＝3.4),24.68(d,J＝11.8),22.31(s),21.32(s),16.02(s).
步骤2-1：双(二氢9-薄荷基-9-磷杂-10-菲)的双硼烷络合物7的制备
本实施例中通过RP-6a的脱氢偶联反应制备双硼烷络合物RP-7：向RP-6a的醚类溶剂的溶液中，低温下条件下滴加丁基锂，然后加入无水氯化铜，低温淬灭后，得到双膦配体RP-7。
具体说明如下：在氮气保护及-30℃温度下，向6a(50mg 0.15mmol)在四氢呋喃(1mL)的溶液中，滴加正丁基锂(0.45mmol/1.6M)，恢复室温后继续搅拌2小时，然后冷却到-80℃，加入CuCl2(20mg,0.15mmol)，室温搅拌10小时，加入氨水(25％，0.5mL)淬灭，除去溶剂，混合物用二氯甲烷(30mL)萃取，水洗涤，无水硫酸镁干燥，产物用TLC纯化，得到纯的化合物7。
上述制备方法获得的(RP,RP',RC,RC',RA,RA')-5,5'-双薄荷基-5,5',6,6'-四氢双膦杂菲-5,5'-双硼烷络合物，结构及结构确证信息如下：
(t,J＝7.4,2H),7.13(d,J＝7.6,2H),6.97(t,J＝7.4,2H),6.87(d,J＝7.8,2H),6.71(d,J＝7.5,2H),6.47(t,J＝7.3,2H),4.27(d,J＝6.9,2H),2.51–2.37(m,2H),1.73–1.58(m,4H),1.56(s,1H),1.49(s,2H),1.44–1.30(m,3H),1.05(d,J＝6.5,9H),0.77(d,J＝6.7,15H),0.63(s,2H),0.56(d,J＝2.1,6H)；13C{1H}NMR(101MHz,CDCl3)δ＝139.50(s),134.77(dd,J＝16.2,9.4),133.33–132.84(m),131.61(s),130.09–129.72(m),127.59(s),127.56–127.04(m),126.70(s),125.41(s),124.56–124.17(m),122.74(s),43.61(s),36.65(d,J＝16.5),36.23(s),34.06(s),33.04–32.72(m),31.90(s),31.62(s),29.31(s),24.63(d,J＝12.0),22.18(s),21.15(s),15.78(s)；HRMS(ESI+)Calcd.for C46H57P2[M-BH3+H+]:671.3935,Found:671.3940.
步骤3-1：二氢9-薄荷基-9-磷杂菲-9氧化物RP-9的制备
RP-8以及SP-8a’的制备见参考文献(J.Org.Chem.2019,84,8423-8439，DOI:10.1021/acs.joc.9b00346)。
向化合物RP-8以及SP-8a’的醚类溶剂的溶液中，低温下滴加丁基锂，RP-8a以及SP-8a’，直接形成分子内取代的环化产物RP-9a，其他的烃基衍生物，需要在反应体系中加入碘化亚铜，低温下淬灭反应后，得到一系列的RP-9
以RP-9a的制备为例，具体操作步骤如下：
在氮气保护及-30℃温度下，向RP-8a(0.1g,0.26mmol)的四氢呋喃(1mL)溶液滴加二异丙基氨基锂(0.78mmol/2M)，反应混合物在室温下搅拌2小时，在0℃下加入碘化亚铜(5.0mg,0.026mmol)，室温搅拌10小时后，-80℃下用氨水(25％，0.5mL)淬灭，减压除去溶剂，混合物用二氯甲烷(30mL)萃取，用水洗涤，无水硫酸镁干燥。产物用薄层色谱纯化，得到纯的化合物RP-9a。
上述方法制备得到9a～9e以及9a’化合物结构及结构确证信息如下：
(Rp,SA)-5-(-)-薄荷基-5,6-二氢膦杂菲-5-氧化物(9a)
Figure BDA0002263732120000171
7.6,1H),7.70(d,J＝7.7,1H),7.65(dd,J＝7.4,4.9,1H),7.59(t,J＝7.5,1H),7.43(dt,J＝20.6,7.5,2H),7.31(t,J＝7.5,1H),7.24(d,J＝7.4,1H),3.45–3.23(m,2H),2.29–2.09(m,1H),1.79–1.49(m,5H),1.21(ddd,J＝24.5,12.2,6.6,1H),1.04(s,1H),0.84(d,J＝6.8,4H),0.82(d,J＝6.4,4H),0.13(d,J＝6.8,3H)；13C{1H}NMR(101MHz,CDCl3)δ＝139.65(d,J＝7.7),135.18(d,J＝8.7),132.34–131.93(m),131.35–130.82(m),130.56(d,J＝9.2),130.17(d,J＝5.5),128.95(s),128.50(d,J＝1.8),127.90(d,J＝10.4),126.26(d,J＝2.5),125.93(d,J＝8.7),42.44(d,J＝3.2),37.59(s),36.90(s),34.78(d,J＝2.9),34.12(s),33.11–32.73(m),32.38(s),28.69(d,J＝3.0),24.27(d,J＝12.4),22.51(s),21.40(s),14.61(s)；HRMS(ESI+)Calcd.for C23H30OP[M-BH3+H+]:353.2034,Found:353.2027.
(Sp,RA)-5-(-)-薄荷基-5,6-二氢膦杂菲-5-氧化物(9a’)
Figure BDA0002263732120000181
1H),7.71(t,J＝7.3,2H),7.60(t,J＝7.6,1H),7.47(t,J＝7.4,1H),7.40(t,J＝7.5,1H),7.30(dd,J＝9.8,4.8,1H),7.23(d,J＝7.4,1H),3.69–3.19(m,2H),2.58–2.44(m,1H),1.81(s,1H),1.70(s,1H),1.62–1.47(m,2H),1.04(d,J＝6.7,6H),0.82(d,J＝7.0,5H),0.65(d,J＝6.0,3H)；13C{1H}NMR(101MHz,CDCl3)δ＝138.98(d,J＝7.4),134.62(d,J＝9.0),132.25(d,J＝2.2),131.27(dd,J＝23.6,7.1),130.15(d,J＝5.1),129.87(s),128.89(d,J＝14.0),128.48(d,J＝1.6),127.93(d,J＝10.2),126.43(d,J＝2.3),125.88(d,J＝8.8),42.97(d,J＝3.0),36.51–36.05(m),35.65(s),35.20(s),34.52(s),34.04(s),32.80(d,J＝13.7),29.46(d,J＝3.0),24.26(d,J＝12.2),22.30(s),21.76(s),16.16(s)；HRMS(ESI+)Calcd.for C23H30OP[M-BH3+H+]:353.2034,Found:353.2026.
(SC,Sp,SA)-5-(-)-薄荷基-6-苯基-5,6-二氢膦杂菲-5-氧化物(9b)
7.51(dd,J＝17.1,7.9,2H),7.36(t,J＝7.4,1H),7.29(t,J＝7.3,2H),7.06(d,J＝7.1,3H),6.93(d,J＝7.3,2H),4.61(d,J＝17.7,1H),2.28–2.14(m,1H),1.81(d,J＝12.0,2H),1.71–1.54(m,3H),1.39(ddd,J＝24.3,12.3,6.8,1H),1.04(s,1H),0.86(d,J＝6.4,4H),0.82(d,J＝6.8,4H),0.11(d,J＝6.8,3H)；13C{1H}NMR(101MHz,CDCl3)δ＝139.71(d,J＝7.9),136.02(d,J＝9.7),133.78(d,J＝6.6),133.27(d,J＝2.6),132.33(dd,J＝19.6,3.9),131.94(d,J＝9.7),129.41(d,J＝12.1),129.01(d,J＝4.0),128.01(dd,J＝19.8,6.3),126.47(dd,J＝7.0,2.1),125.49(d,J＝8.8),46.00(s),45.42(s),43.12(d,J＝3.5),39.05(s),38.38(s),34.83(d,J＝3.3),34.08(s),33.03(d,J＝13.1),28.54(d,J＝2.8),24.40(d,J＝12.3),22.62(s),21.36(s),14.66(s)；HRMS(ESI+)Calcd.for C29H34OP[M-BH3+H+]:429.2347,Found:429.2343.
(SC,Sp,SA)-5-(-)-薄荷基-6-对甲基苯基-5,6-二氢膦杂菲-5-氧化物(9c)
＝7.82(d,J＝7.8,1H),7.75(dd,J＝11.2,7.5,1H),7.67(dd,J＝7.7,4.8,1H),7.50(dt,J＝15.0,7.5,2H),7.35(t,J＝7.3,1H),7.29(dd,J＝13.1,7.2,2H),6.87(d,J＝8.0,2H),6.81(d,J＝7.6,2H),4.57(d,J＝17.6,1H),2.20(d,J＝6.7,1H),2.15(s,3H),1.79(t,J＝11.3,2H),1.69–1.54(m,3H),1.39(ddd,J＝24.7,12.1,7.1,1H),1.04(s,1H),0.86(d,J＝6.2,4H),0.82(d,J＝6.8,4H),0.10(t,J＝9.0,3H)；13C{1H}NMR(101MHz,CDCl3)δ＝139.75(d,J＝7.9),136.02(dd,J＝12.4,6.2),133.51(d,J＝2.5),132.50(d,J＝5.4),132.18(d,J＝2.3),131.91(d,J＝9.8),130.61(d,J＝6.6),129.55–128.98(m),128.78(dd,J＝10.1,3.1),128.32(s),128.07(d,J＝10.2),126.40(d,J＝1.8),125.47(d,J＝8.8),45.67(s),45.09(s),43.10(d,J＝3.5),39.02(s),38.35(s),34.83(d,J＝3.4),34.08(s),33.04(d,J＝13.0),28.53(d,J＝2.8),24.40(d,J＝12.2),22.64(s),21.38(s),20.88(s),14.67(s)；HRMS(ESI+)Calcd.for C30H36OP[M-BH3+H+]:443.2504,Found:443.2502.
(SC,Sp,SA)-5-(-)-薄荷基-6-对叔丁基苯基-5,6-二氢膦杂菲-5-氧化物(9d)
(dd,J＝7.6,4.9,1H),7.54(t,J＝7.6,1H),7.48(t,J＝7.6,1H),7.40–7.28(m,2H),7.26(d,J＝4.4,1H),7.08(d,J＝8.3,2H),6.84(d,J＝6.7,2H),4.57(d,J＝17.7,1H),2.24(dd,J＝6.7,4.4,1H),1.79(d,J＝2.6,2H),1.63(dd,J＝16.2,8.0,3H),1.42–1.29(m,1H),1.17(s,9H),1.04(s,1H),0.85(d,J＝6.9,4H),0.83(d,J＝6.9,4H),0.13(d,J＝6.8,3H)；13C{1H}NMR(101MHz,CDCl3)δ＝149.07(d,J＝2.8),139.78(d,J＝7.9),135.92(d,J＝9.6),133.56(d,J＝2.4),132.60(d,J＝5.4),132.10(dd,J＝26.0,6.1),130.61(d,J＝6.7),129.51–128.95(m),128.60(d,J＝4.0),128.30–127.91(m),126.39(d,J＝1.8),125.41(d,J＝8.8),125.04(d,J＝2.3),45.64(s),45.06(s),43.15(d,J＝3.5),39.20(s),38.53(s),34.88(d,J＝3.4),34.14(d,J＝16.3),33.05(d,J＝13.0),31.21(s),28.55(d,J＝2.8),24.44(d,J＝12.1),22.62(s),21.36(s),14.71(s)；HRMS(ESI+)Calcd.for C33H42OP[M-BH3+H+]:485.2973,Found:485.2974.
(SC,Sp,SA)-5-(-)-薄荷基-6-对氯苯基-5,6-二氢膦杂菲-5-氧化物，9e
Figure BDA0002263732120000201
＝7.83(d,J＝7.8,1H),7.74(dd,J＝11.1,7.6,1H),7.67(dd,J＝7.4,5.0,1H),7.53(dd,J＝15.9,8.0,2H),7.38(t,J＝7.5,1H),7.32(t,J＝7.5,1H),7.27(d,J＝6.3,1H),7.03(d,J＝8.2,2H),6.86(d,J＝7.9,2H),4.55(d,J＝17.7,1H),2.24–2.10(m,1H),1.80(d,J＝7.6,2H),1.62(d,J＝12.2,3H),1.38(ddd,J＝24.4,12.1,7.1,1H),1.04(s,1H),0.86(d,J＝6.1,4H),0.82(d,J＝6.7,4H),0.10(d,J＝6.7,3H)；13C{1H}NMR(101MHz,CDCl3)δ＝139.47(d,J＝8.0),135.89(d,J＝9.5),132.50(ddd,J＝12.0,9.4,5.9),131.87(d,J＝9.6),130.26(d,J＝3.9),129.62(s),128.17(dd,J＝21.9,6.3),126.58(d,J＝1.4),125.56(d,J＝8.8),45.37(s),44.80(s),43.11(d,J＝3.4),38.94(s),38.27(s),34.77(d,J＝3.5),34.04(s),33.01(d,J＝13.1),28.60(s),24.36(d,J＝12.3),22.61(s),21.36(s),14.62(s)；HRMS(ESI+)Calcd.for C29H33ClOP[M-BH3+H+]:463.1958,Found:463.1955.
步骤4-1：双(二氢9-薄荷基-9-磷杂-9-氧-10-菲)RP-10的制备
RP-9a的脱氢偶联反应制备RP-10：RP-9a的醚类溶剂的溶液中，低温下滴加丁基锂，然后加入无水氯化铜，低温淬灭后，得到双膦氧化物RP-10。
操作步骤：
在氮气保护-30℃温度下，向9a(0.14mmol)的无水四氢呋喃(1mL)的溶液中，滴加二异丙基氨基锂(0.42mmol/2M)，恢复室温后继续搅拌2小时，冷却至-80℃，加入氯化铜(0.14mmol)，室温搅拌10小时，加入氨水(25％，0.5mL)淬灭，除去溶剂，混合物用二氯甲烷(30mL)萃取，用水洗涤，无水硫酸镁干燥。产物用TLC纯化，得到纯化合物10。
(SP,SP',RC,RC',SA,SA')-5,5'-双薄荷基-5,5',6,6'-四氢双膦杂菲-5,5'-双氧化物(10)
J＝7.4,1H),7.08(d,J＝7.7,1H),6.95(t,J＝7.4,1H),6.83(d,J＝6.6,1H),6.72(d,J＝7.4,1H),6.55(t,J＝7.3,1H),4.33(s,1H),2.43–2.31(m,1H),1.59(dd,J＝22.7,10.4,3H),1.53–1.41(m,2H),0.89(d,J＝6.5,4H),0.84–0.75(m,1H),0.73–0.63(m,2H),0.61(d,J＝6.0,3H),0.30(d,J＝6.4,3H)；13C{1H}NMR(126MHz,CDCl3)δ＝140.58(t,J＝3.6),135.29(t,J＝4.3),134.02(t,J＝4.8),132.10(s),131.76(s),129.85(s),127.96(s),127.59(s),127.44(t,J＝13.1),125.28(s),124.46(t,J＝3.8),43.06(s),40.21(s),39.67(s),34.64(s),34.07(s),32.98(t,J＝6.7),28.74(s),24.64(t,J＝6.1),22.27(s),21.35(s),15.15(s)；HRMS(ESI+)Calcd.for C46H57O2P2[M+H+]:703.3834,Found:703.3836.
实施例2化合物6的应用
如上所述，化合物6a可立体选择性地转化为7。
另外，对化合物6b在不对称氢化反应中的应用，进行了初步和开发：
在氮气条件下，化合物6b(119毫克,0.28毫摩尔)溶于无水甲苯中，加入三亚乙基二胺DABCO(49毫克，0.43毫摩尔)，70℃下搅拌5小时，冷却后，通过短硅胶柱过滤纯化。另将双(1,5-环辛二烯)-氯化铑(25毫克，0.1毫摩尔)和无水乙腈(1毫升)的混合物冷却至-20℃，激烈搅拌下，将上述脱DABCO的滤液滴加入其中，同时升至室温并继续搅拌30分钟，减压浓缩至2毫升，加入10毫升无水乙醚，过滤出所形成的固体，并用无水乙醚洗涤三次，得到棕红色固体，重120毫克，产率78％。
氮气条件下，上述得到的6b和氯化铑的络合物(2.8毫克，约0.005毫摩尔)加入异丙醇(10毫升)，室温搅拌30分钟后，加入氢氧化钾(280毫克，5毫摩尔)，再次搅拌30分钟后，加入苯乙酮(585微升，5毫摩尔)。反应混合物在45℃搅拌12小时，通过GC-MS检测苯乙醇产率91％。以稀盐酸(2N)调反应pH值至中性，减压移除溶剂，水相用乙醚萃取三次，无水硫酸镁干燥，移除溶剂后，产物用HPLC分析(CHIRALCEL OZ-H柱)ee值13％。
实施例3化合物7的应用
在氮气条件下，化合物7(100毫克,0.14毫摩尔)溶解在无水甲苯中，加入三亚乙基二胺DABCO(49毫克，0.43毫摩尔)，反应混合物在70℃下搅拌5小时，冷却后，通过短硅胶柱进行过滤纯化。另将双(1,5-环辛二烯)-三氟甲磺酸铑(47毫克，0.1毫摩尔)和无水四氢呋喃(1毫升)的混合物冷却至-20℃，激烈搅拌下，将上述脱DABCO的滤液滴加入其中，升至室温并继续搅拌30分钟，混合物减压浓缩至2毫升，加入10毫升无水乙醚，过滤出所形成的固体，并用无水乙醚洗涤三次，得到棕红色固体，重6590毫克，产率70％。
氮气条件下，上述7和三氟甲磺酸铑的络合物(4.6毫克，0.005毫摩尔)加入异丙醇(10毫升)，室温搅拌30分钟后，加入氢氧化钾(280毫克，5毫摩尔)，再次搅拌30分钟后，加入苯乙酮(585微升，5毫摩尔)，45℃搅拌12小时，通过GC-MS检测苯乙醇产率95％。以稀盐酸(2N)调pH值至中性，减压移除溶剂，水相用乙醚萃取三次，无水硫酸镁干燥，移除溶剂后，产物用HPLC分析(CHIRALCEL OZ—H柱)ee值56％。
实施例4化合物9的应用
氮气保护下，化合物9a(70毫克，0.2毫摩尔)溶于甲苯(2毫升)，室温下滴加草酰氯(0.025毫升，0.3毫摩尔)。反应混合物在室温下搅拌30分钟后，冷却至-65℃，加入硼氢化钠-氯化锌在四氢呋喃中的溶液(0.2毫升，含有0.4毫摩尔的硼氢化钠)，缓慢升至室温，继续搅拌12小时，加入稀盐酸(0.2N，5毫升)，水层用乙醚萃取三次，每次20毫升，合并的有机相用无水硫酸镁干燥，减压移除溶剂后，残留物薄层层析纯化，得到纯的化合物6a，为白色固体，重53毫克，产率76％，dr值大于99:1，其波谱表征数据，同前述所得化合物相同。
实施例5化合物10的应用
氮气保护下，化合物10(141毫克，0.2毫摩尔)溶于甲苯(2毫升)，室温下滴加草酰氯(0.025毫升，0.3毫摩尔)。反应混合物在室温下搅拌30分钟后，冷却至-65℃，加入硼氢化钠-氯化锌在四氢呋喃中的溶液(0.2毫升，含有0.4毫摩尔的硼氢化钠)，缓慢升至室温，继续搅拌12小时，加入稀盐酸(0.2N，5毫升)，水层用乙醚萃取三次，每次20毫升，合并的有机相用无水硫酸镁干燥，减压移除溶剂后，残留物薄层层析纯化，得到纯的化合物7，为白色固体，重113毫克，产率81％，dr值大于99:1，其波谱表征数据，同前述所得化合物相同。
以上所述仅为本公开的优选实施例而已，并不用于限制本公开，对于本领域的技术人员来说，本公开可以有各种更改和变化。凡在本公开的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本公开的保护范围之内。

Claims (10)

1.一种化合物，或所述化合物的异构体或溶剂化物，其特征在于，所述化合物具有下式1或式2所示的结构：
Figure FDA0002263732110000011
其中，所述R1＝H，Ph，p-MeC6H4,o-MeC6H4，p-tBuC6H4或m-MeO6H4；
优选的，所述异构体包括通过(+)薄荷基，形成的和式1、式2所述化合物结构相同但每个手性位点构型相反的化合物。
2.所述式1化合物的制备方法，其特征在于，所述制备方法工艺流程如下：
Figure FDA0002263732110000012
3.如权利要求2所述式1化合物的制备方法，其特征在于，R1＝H，Ph，p-MeC6H4,o-MeC6H4，p-tBuC6H4或m-MeO6H4时，所述制备方法包括以下步骤：
(1)将薄荷基卤化镁或薄荷基锂加入化合物1的醚溶剂的溶液中，加热得到化合物2/2’的RP和SP构型的混合物；
(2)向步骤(1)得到的混合物中加入盐酸得到化合物3/3’的RP和SP构型的混合物；
(3)将化合物3/3’碱性醇溶液中，加入碘甲烷，室温搅拌，得到化合物4/4’的RP和SP构型的混合物；
(4)将化合物4/4’加入醚类溶剂中，室温下滴加草酰氯，然后低温下加入格式试剂，搅拌的同时，温度缓慢升至室温，得到式1所述化合物。
4.如式2所示化合物的制备方法，所述制备方法如下：将式1化合物加入醚类溶剂的溶液中，低温下滴加丁基锂，然后加入无水氯化铜，低温淬灭后得到所述式2化合物，所述式1化合物的R1＝H。
5.一种化合物，或所述化合物的异构体、溶剂化物或可药用盐，其特征在于，所述化合物具有下式3或式4所示的结构：
Figure FDA0002263732110000021
所述R2＝H，Ph，p-MeC6H4,o-MeC6H4，p-tBuC6H4或ClC6H4；
优选的，所述异构体包括通过(+)薄荷基，获得和式3或式4所述化合物结构相同但每个手性位点构型相反的化合物。
6.所述式3化合物的制备方法，其特征在于，所述制备方法流程如下：
Figure FDA0002263732110000022
7.如权利要求6所述式3化合物的制备方法，其特征在于，R2＝H时，所述制备方法包括以下步骤：向RP-8所示化合物的醚类溶剂的溶液中，低温下滴加丁基锂，低温下淬灭得到所述式3化合物。
8.如权利要求6所述式3化合物的制备方法，其特征在于，当R＝Ph，p-MeC6H4,o-MeC6H4，p-tBuC6H4或ClC6H4时，向RP-8所示化合物的醚类溶剂的溶液中，低温下滴加丁基锂，加入碘化亚铜，低温下淬灭得到所述式3化合物。
9.所述式4化合物的制备方法，其特征在于，所述制备方法如下：
向所述RP-9a的醚类溶剂的溶液中，低温下滴加丁基锂，然后加入无水氯化铜，低温淬灭后，得到所述式4化合物。
10.式1、式2、式3和/或式4所述化合物作为催化剂的应用。
CN201911080219.6A 2019-11-07 2019-11-07 一种磷杂菲类叔膦衍生物、其合成方法及应用 Active CN110669073B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201911080219.6A CN110669073B (zh) 2019-11-07 2019-11-07 一种磷杂菲类叔膦衍生物、其合成方法及应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201911080219.6A CN110669073B (zh) 2019-11-07 2019-11-07 一种磷杂菲类叔膦衍生物、其合成方法及应用

Publications (2)

Publication Number Publication Date
CN110669073A true CN110669073A (zh) 2020-01-10
CN110669073B CN110669073B (zh) 2022-10-11

Family

ID=69086265

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201911080219.6A Active CN110669073B (zh) 2019-11-07 2019-11-07 一种磷杂菲类叔膦衍生物、其合成方法及应用

Country Status (1)

Country Link
CN (1) CN110669073B (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113816880A (zh) * 2020-06-19 2021-12-21 万华化学集团股份有限公司 一种高效合成n-甲基牛磺酸及n-甲基牛磺酸钠的方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103665038A (zh) * 2013-12-26 2014-03-26 聊城大学 一种碳磷手性二烃基氧膦及其合成方法
CN108164561A (zh) * 2018-02-02 2018-06-15 聊城大学 一种手性薄荷基苯基膦酰胺类化合物及制备方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103665038A (zh) * 2013-12-26 2014-03-26 聊城大学 一种碳磷手性二烃基氧膦及其合成方法
CN108164561A (zh) * 2018-02-02 2018-06-15 聊城大学 一种手性薄荷基苯基膦酰胺类化合物及制备方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BARBARA MOHAR等: "P‑Stereogenic Phospholanes or Phosphorinanes from o‑Biarylylphosphines: Two Bridges Not Too Far", 《J. ORG. CHEM.》 *
YU ZHANG等: "Functional Phosphine Derivatives Having Stationary and Flexible Chiralities: Their Preparation and Chirality Controlling", 《J. ORG. CHEM.》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113816880A (zh) * 2020-06-19 2021-12-21 万华化学集团股份有限公司 一种高效合成n-甲基牛磺酸及n-甲基牛磺酸钠的方法
CN113816880B (zh) * 2020-06-19 2023-08-11 万华化学集团股份有限公司 一种高效合成n-甲基牛磺酸及n-甲基牛磺酸钠的方法

Also Published As

Publication number Publication date
CN110669073B (zh) 2022-10-11

Similar Documents

Publication Publication Date Title
Mash et al. Homochiral ketals in organic synthesis. Diastereoselective cyclopropanation
CN110117260B (zh) 一种3-烷基喹喔啉-2(1h)-酮类化合物的制备方法
Brunner et al. Enantioselective catalysis. Part 143: Astonishingly high enantioselectivity in the transfer hydrogenation of acetophenone with 2-propanol using Ru complexes of the Schiff base derived from (S)-2-amino-2′-hydroxy-1, 1′-binaphthyl (NOBIN) and 2-pyridinecarbaldehyde
CN109942364B (zh) 一种以水为氢源的烯烃合成方法
Xu et al. Rhodium-Catalyzed Regio-and Enantioselective Allylic Amination of Racemic 1, 2-Disubstituted Allylic Phosphates
CN111574450B (zh) 一种新型手性联苯类季铵盐相转移催化剂及其制备方法和应用
Kumar et al. Enantioselective cross dehydrogenative coupling reaction catalyzed by Rose Bengal incorporated-Cu (I)-dimeric chiral complexes
US5760266A (en) Method for the cyclotrimerization of alkynes in aqueous solutions
CN110128341B (zh) 一种手性2,2’-联吡啶配体及其制备方法和在制备手性环丙烷衍生物中的应用
Wang et al. The synthesis of a new generation of MAP ligands containing two types of chiral elements for asymmetric catalysis
CN110669073B (zh) 一种磷杂菲类叔膦衍生物、其合成方法及应用
Bauer et al. Enantioselective addition of diethylzinc to aldehydes catalyzed by d-glucosamine derivatives: Highly pronounced effect of trifluoromethylsulfonamide
Tucker et al. Resolution and coupling of 1-(2′-hydroxy-1′-naphthyl) isoquinolines
Malfait et al. Enantioselective synthesis and use in catalytic asymmetric addition of diethylzinc to benzaldehyde of new chiral cyclic hydroxyamino ferrocene and chromium complexes: influence of the complexation on the enantioselectivity
CN111848480A (zh) 一种由芳基硼酸合成芳基二氟甲硒基醚的方法及其应用
Kong et al. Synthesis of spiro dienones from internal acetylene and cyclic 3-iodo enones in the presence of nickel bromide and zinc powder
CN109575060A (zh) 螺环双硼催化剂的合成及其在氢化反应中的应用
DE10044793A1 (de) Diphosphine
Yuan et al. Making CN and CP bonds on the quinone derivatives through the assistance of silver-mediated CH functionalization processes
CN108191736B (zh) 一种2,3-二取代吲哚类衍生物及其制备方法
Chelucci et al. Chiral 2-(2-phenylthiophenyl)-5, 6, 7, 8-tetrahydroquinolines: new N–S ligands for asymmetric catalysis: Palladium-catalyzed allylic alkylation and copper-catalyzed cyclopropanation reactions
CN111205184A (zh) 一种合成(9z,12e)-十四碳-9,12-二烯-1-醇乙酸酯的方法
Chelucci et al. Chiral 8-substituted 2-(2-methoxyphenyl) and 2-(2-hydroxyphenyl)-5, 6, 7, 8-tetrahydro-6, 6-dimethyl-5, 7-methanoquinolines as ligands for enantioselective catalysis: palladium catalyzed allylic substitution and addition of diethylzinc to benzaldehyde
CN109678862A (zh) 一种多取代二苯乙烯基吲哚衍生物的制备方法
CN115650824B (zh) 手性二醇及其制备方法、制得的催化剂及制备方法和应用

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