WO2023142725A1 - 环丙烷骨架单膦配体及其钯配合物以及制备方法和应用 - Google Patents

环丙烷骨架单膦配体及其钯配合物以及制备方法和应用 Download PDF

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WO2023142725A1
WO2023142725A1 PCT/CN2022/138338 CN2022138338W WO2023142725A1 WO 2023142725 A1 WO2023142725 A1 WO 2023142725A1 CN 2022138338 W CN2022138338 W CN 2022138338W WO 2023142725 A1 WO2023142725 A1 WO 2023142725A1
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reaction
cyclopropane skeleton
palladium
monophosphine ligand
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French (fr)
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朱守非
刘华伟
孙伟
李文涛
党玲
黄明耀
张新羽
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南开大学
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Definitions

  • the invention relates to a cyclopropane skeleton monophosphine ligand and its palladium complex as well as a preparation method and application. Specifically, starting from trans-1,2-diarylethene, a trans-diaryl-substituted cyclopropane skeleton monophosphine ligand is synthesized through cyclopropanation reaction, debromination reaction, substitution reaction and other steps.
  • the palladium complex prepared after the coordination of the cyclopropane skeleton monophosphine ligand and the palladium salt exhibits high activity in catalyzing C-N bond coupling reactions and has a good application prospect.
  • the Buchwald-Hartwig reaction refers to the palladium-catalyzed C-N cross-coupling reaction of aryl electrophiles and amines, and is widely used in the synthesis of medicine, natural products and functional materials [(1) Ruiz-Castillo, P.; Buchwald, S.L.Chem.Rev.2016,116,12564. (2) Surry, D.S.; Buchwald, S.L.Chem.Sci.2011,2,27.].
  • the ligand can affect the activity and selectivity of the catalyst by adjusting the electrical and steric hindrance of the palladium center, so the design and synthesis of the ligand is the core research content of the Buchwald-Hartwig reaction.
  • the object of the present invention is to provide a cyclopropane skeleton monophosphine ligand and a preparation method thereof, so as to overcome the deficiencies of the prior art.
  • Another object of the present invention is to provide the adduct of the cyclopropane skeleton monophosphine ligand and borane and its preparation method.
  • Another object of the present invention is to provide the complex of the cyclopropane skeleton monophosphine ligand and palladium and its preparation method.
  • Another object of the present invention is to provide the complex of the cyclopropane skeleton monophosphine ligand and palladium as a catalyst in promoting the Buchwald-Hartwig reaction.
  • a class of cyclopropane skeleton monophosphine ligands which have the following structural formula of I or enantiomers and racemates of the following structural formula of I:
  • R 1 and R 2 are phenyl or substituted phenyl
  • R 3 and R 4 are phenyl, substituted phenyl or C 1 -C 8 alkyl
  • R 5 is a hydrogen atom, phenyl, substituted phenyl or C 1 -C 8 alkyl
  • R 1 , R 2 , R 3 , R 4 , R 5 are the same or different;
  • the substituents are C 1 -C 8 alkyl, C 1 -C 8 alkoxy, C 2 -C 8 acyloxy, hydroxyl, halogen, amino, (C 1 -C 8 acyl ) amino group, di(C 1 -C 8 alkyl) amino group, C 1 -C 8 acyl group, C 2 -C 8 ester group or one or more of haloalkanes; when R 1 and R 2 are substituted phenyl groups , the number of substituents is 0-2; when R 3 and R 4 are substituted phenyl groups, the number of substituents is 0-5.
  • the C 1 -C 8 alkyl group or the C 1 -C 8 alkoxy group in the alkyl group is methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, sec-pentyl, tert-pentyl, n-hexyl , isohexyl, neohexyl, sec-hexyl, tert-hexyl, n-heptyl, isoheptyl, neoheptyl, sec-heptyl, tert-heptyl, n-octyl, isooctyl, neooct
  • the C 1 -C 8 acyl group is formyl, acetyl, propionyl, n-butyryl, isobutyryl, n-valeryl, isovaleryl, sec-valeryl, pivaloyl, n-hexanoyl, isohexanoyl, neo Hexanoyl, sec-hexanoyl, n-heptanoyl, isoheptanoyl, neoheptanoyl, sec-heptanoyl, n-octanoyl, isooctanoyl, neooctanoyl, sec-octanoyl, 1-cyclopropylformyl, 1-cycloyl Butylformyl, 1-cyclopentylformyl, 1-cyclohexylformyl or 1-cycloheptylformyl;
  • the C 2 -C 8 acyloxy group is acetyloxy, propionyloxy, n-butyryloxy, isobutyryloxy, n-valeryloxy, isovaleryloxy, sec-valeryloxy , pivaloyloxy, n-hexanoyloxy, isohexanoyloxy, neohexanoyloxy, sec-hexanoyloxy, n-heptanoyloxy, isoheptanoyloxy, neoheptanoyloxy, sec-heptanoyl Oxygen, n-octanoyloxy, isooctanoyloxy, neooctanoyloxy, sec-octanoyloxy, 1-cyclopropylformyloxy, 1-cyclobutylformyloxy, 1-cyclopentyl Formyloxy, 1-cyclohexylformyloxy or 1-cycloh
  • the C 2 -C 8 ester group is methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, n-pentyloxycarbonyl, isopentyloxycarbonyl, neopentyloxy Carbonyl, sec-pentyloxycarbonyl, tert-pentyloxycarbonyl, cyclopentyloxycarbonyl, n-hexyloxycarbonyl, isohexyloxycarbonyl, neohexyloxycarbonyl, sec-hexyloxycarbonyl, tert-hexyloxycarbonyl, cyclohexyloxycarbonyl, n-heptyloxycarbonyl, Isoheptyloxycarbonyl, neoheptyloxycarbonyl, sec-heptyloxycarbonyl, tert-heptyloxycarbony
  • the haloalkyl group is a haloalkyl group containing fluorine, chlorine, bromine or iodine.
  • the cyclopropane skeleton monophosphine ligand is the following structural formula of I-a, I-b, I-c, I-d, I-e, I-f or I-g:
  • the preparation method of the cyclopropane skeleton monophosphine ligand is prepared through the following two routes:
  • R 5 H
  • its synthetic route is: in the presence of NaOH and phase transfer catalyst benzyltriethylammonium chloride, trans-1,2-diarylethene and bromoform undergo cyclopropanation reaction to prepare Obtain gem dibromocyclopropane intermediate III;
  • Gem dibromocyclopropane intermediate III carries out bromine lithium exchange with n-butyl lithium, then protonation, prepares monobromocyclopropane intermediate IV;
  • the reaction formula is:
  • R 1 -R 4 are as defined above;
  • the molar ratio of the trans-1,2-diarylethene, benzyltriethylammonium chloride, and NaOH is 1:(0.1-1):(50-100), cyclopropane
  • the reaction temperature is 0°C to room temperature
  • the molar ratio of gem-dibromocyclopropane intermediate III to n-butyllithium is 1:(1-2)
  • bromine lithium exchange and protonation are carried out at -120 to -60°C
  • the molar ratio of monobromocyclopropane intermediate IV, n-butyl lithium, R 3 R 4 PCl is 1:(1-2):(1-4), monobromocyclopropane intermediate IV and n-butyl lithium in- After bromine-lithium exchange at 120 ⁇ -60°C, substitution reaction with R 3 R 4 PCl occurs at -100°C ⁇ room temperature.
  • the synthetic route is as follows: after bromide-lithium exchange between gem-dibromocyclopropane intermediate III and n-butyllithium, add iodohydrocarbon R 5 I to prepare intermediate V; intermediate V and magnesium After the Grignard reagent is prepared in situ, the cyclopropane skeleton monophosphine ligand I is prepared by continuing the reaction with diphenylphosphine chloride under the catalysis of copper.
  • the reaction formula is:
  • R 1 -R 5 are as defined above.
  • the molar ratio of the gem-dibromocyclopropane intermediate III, n-butyllithium and iodohydrocarbon R 5 I is 1:(1-2):(1-5)
  • the bromine-lithium exchange The temperature is -120°C to room temperature
  • the molar ratio of the intermediate V to the copper in the magnesium and copper catalysts and diphenylphosphine chloride is 1:(1-10):(1-2):(1-5 )
  • the intermediate V reacts with magnesium at 40-90°C to prepare the Grignard reagent in situ, and at 40-90°C, it continues to react with diphenylphosphine chloride under the catalysis of copper to prepare the cyclopropane skeleton single Phosphine ligands.
  • the adduct of the cyclopropane skeleton monophosphine ligand and borane has the following structural formula II or an enantiomer or racemate of the following structural formula II:
  • R 1 -R 5 are as defined above.
  • the structure of the adduct is as follows II-a, II-b, II-c, II-d, II-e, II-f or II-g structural formula:
  • the preparation method of the adduct is as follows: the tetrahydrofuran solution of the cyclopropane skeleton monophosphine ligand and borane reacts to generate the corresponding adduct, and its reaction formula is:
  • R 1 -R 5 are as defined above.
  • the cyclopropane skeleton monophosphine ligand and borane tetrahydrofuran solution are reacted at 0° C. to room temperature, and the reaction solvent is toluene, trifluorotoluene, benzene, tetrahydrofuran or ether.
  • the palladium complex of the cyclopropane skeleton monophosphine ligand has the following structural formula of VI or an enantiomer or racemate of VI:
  • R 1 -R 5 are as defined above;
  • X and Y are halogen, acid radical, 1,3-dicarbonyl ligand, allyl or aryl;
  • X and Y are the same or different.
  • the cyclopropane skeleton monophosphine ligand described in method (2), or the adduct of the cyclopropane skeleton monophosphine ligand and borane is complexed with palladium salt and X-Y in a solvent to prepare the palladium complex thing;
  • reaction formula of described method (1) or method (2) is:
  • R 1 -R 5 are as defined in claim 1; the palladium salt is (COD)Pd(CH 2 TMS) 2 , Pd 2 (dba) 3 .CHCl 3 , Pd 2 (dba) 4 , Pd(OAc ) 2 , one or more of Pd(TFA) 2 or [(allyl)PdCl] 2 , wherein COD is 1,5-cyclooctadiene, TMS is trimethylsilyl, and dba is dibenzylideneacetone , OAc is acetate, TFA is trifluoroacetate, allyl is allyl, preferably, the solvent is n-hexane, tetrahydrofuran, acetonitrile, dichloromethane, benzene, toluene, xylene or trifluoromethylbenzene one or more of them.
  • the palladium salt is (COD)Pd(CH 2 TMS) 2 , P
  • the mol ratio of the cyclopropane skeleton monophosphine ligand or the adduct of the cyclopropane skeleton monophosphine ligand and borane to palladium salt and aryl halogen is 1:1:( 1-5), the reaction temperature is 10-50°C.
  • the palladium complex is used as a catalyst to promote the Buchwald-Hartwig reaction.
  • the mixture of the palladium complex, the palladium complex and the cyclopropane skeleton monophosphine ligand or the palladium complex with the cyclopropane skeleton monophosphine ligand and borane acts as a catalyst to promote the Buchwald-Hartwig reaction, and the reaction formula is as follows:
  • Ar is phenyl, substituted phenyl, heteroaryl or alkenyl
  • X is bromine, chlorine, iodine, triflate, nitro or p-toluenesulfonate
  • R 6 -R 7 are phenyl , substituted phenyl, heteroaryl, alkenyl, alkyl or functional group substituted alkyl
  • R 6 and R 7 are the same or different;
  • the base is one or more of alkali metal salts or NaH;
  • the solvent is One or more of C 1 -C 8 ethers, toluene, alkanes or the substrate itself (excluding solvents).
  • the alkali metal salt is lithium salt, sodium salt or potassium salt of alkali metal.
  • the mol ratio of ArX, R 6 R 7 NH, palladium complex, cyclopropane skeleton monophosphine ligand, and alkali is 1: (1-2):(0.001-1%):(0.001-1%):(1-3);
  • the catalyst is the mixture of the palladium complex and cyclopropane skeleton monophosphine ligand and borane adduct
  • ArX, R 6 R 7 NH palladium complex, cyclopropane skeleton monophosphine ligand and borane
  • the molar ratio of the adduct to the base is 1:(1-2):(0.001-1%):(0.001-1%):(1-3).
  • the temperature of the Buchwald-Hartwig reaction is 50-200°C.
  • Fig. 1 is the single crystal structure of the adduct II-c of cyclopropane skeleton monophosphine ligand I and borane;
  • Fig. 2 is the single crystal structure of palladium complex VI-h of cyclopropane skeleton monophosphine ligand I.
  • Me is methyl, Et is ethyl, tBu is t-butyl, nBu is n-butyl, Ph is phenyl, THF is tetrahydrofuran, Et2O is diethyl ether, CHBr3 is bromoform, TEBAC is benzyltriethyl ammonium chloride, PE is petroleum ether, EA is ethyl acetate, Ar is argon, CDCl 3 is deuterated chloroform, COD is 1,5-cyclooctadiene, TMS is trimethylsilane substituent; dba is Dibenzylideneacetone, OAc is acetate, TFA is trifluoroacetate, allyl is allyl.
  • the solvents used were purified and dried by standard operations before use; the reagents used were all commercially available or synthesized according to existing literature methods, and were purified before use.
  • trans-1,2-di-p-tolylethylene (8.3g, 40mmol)
  • TEBAC benzyltriethylammonium chloride, 1.83g , 8mmol
  • add 80mL bromoform Take NaOH (88g, 222mmol) and add 80mL of water to form a saturated NaOH solution.
  • III-b The synthesis method of the following compounds (III-c–III-d) is the same as III-b.
  • Cyclopropane skeleton monophosphine ligands I-a ⁇ I-f are easily oxidized, and their borane adducts II-a ⁇ II-f are stable forms.
  • Cyclopropane-skeleton monophosphine ligands I-f are stable forms.
  • the cyclopropane skeleton monophosphine ligand I-g is easily oxidized, and its borane adduct II-g is a stable form, and 2,3-diphenyl-1-methylcyclopropane diphenylphosphine borane adduct II- Preparation of g:
  • Embodiment 6 Preparation of 2,3-diphenylcyclopropyl di-tert-butylphosphine I-a
  • Embodiment 7 the preparation of palladium complex VI-a
  • Embodiment 8 the preparation of palladium complex VI-h
  • Embodiment 9 Situation of palladium catalyzed C-N bond coupling reaction in different solvents
  • Example 10 Palladium-catalyzed coupling reaction of bromobenzene and diphenylamine under the action of different bases
  • reaction liquid was filtered through a burette column, and the filtrate was concentrated by rotary evaporation, and n-tridecane was added as an internal standard.
  • the yield calculated by GC was 87%, and the conversion number was 8700.

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Abstract

本发明提供了环丙烷骨架单膦配体及其钯配合物以及制备方法和应用，具体的讲是从反式1,2-二芳基乙烯出发，经环丙烷化反应、脱溴反应、取代反应等步骤合成具有反式二芳基取代的环丙烷骨架单膦配体。上述环丙烷骨架单膦配体和钯盐配位后制备的钯配合物，在催化C-N键偶联反应中表现出很高的活性，具有很好的应用前景。

Description

环丙烷骨架单膦配体及其钯配合物以及制备方法和应用 技术领域
本发明涉及环丙烷骨架单膦配体及其钯配合物以及制备方法和应用。具体的讲是从反式1,2-二芳基乙烯出发，经环丙烷化反应、脱溴反应、取代反应等步骤合成具有反式二芳基取代的环丙烷骨架单膦配体。上述环丙烷骨架单膦配体和钯盐配位后制备的钯配合物，在催化C-N键偶联反应中表现出很高的活性，具有很好的应用前景。
背景技术
Buchwald-Hartwig反应是指钯催化芳基亲电试剂与胺的C-N交叉偶联反应，被广泛应用于医药、天然产物和功能材料等的合成中[(1)Ruiz-Castillo,P.；Buchwald,S.L.Chem.Rev.2016,116,12564.(2)Surry,D.S.；Buchwald,S.L.Chem.Sci.2011,2,27.]。在该反应中，配体可以通过调节钯中心的电性和位阻而影响催化剂的活性和选择性，因此配体的设计合成是Buchwald-Hartwig反应的核心研究内容。
在过去二十余年中，配体的设计合成极大地促进了C-N键偶联的发展，其中最具代表性的是Buchwald课题组设计的系列联芳基膦配体，实现了一级胺(Brettphos和Gphos)、二级胺(RuPhos)、含有大位阻取代基( tBuPhCPhos)以及杂环胺(EPhos)的高效偶联。虽然Buchwald-Hartwig反应得到了长足发展，但是绝大多数该类反应需要较高的钯催化剂用量(1mol％或更高)，转化数(产物的物质的量/钯催化剂的物质的量)不到100，这样一方面造成合成成本较高，同时还带来重金属残留的问题，影响该反应在制药领域的更为广泛的应用。以二芳胺与卤代芳烃的C-N键偶联为例，目前，仅有少数几例催化剂可以给出1000以上的转化数，包括P tBu 3和钯的配合物可给出最高3960的转化数[Yamamoto,T.；Nishiyama,M.；Koie,Y.Tetrahedron Lett.1998,39,2367.]，RuPhos和钯的配合物最高可给出1980的转化数[Fors,B.P.；Buchwald,S.L.J.Am.Chem.Soc.2010,132,15914.]，Cy-vBRIDP和钯的配合物最高可给出1980的转化数[Nkayama,Y.；Yokoyama,N.；Nara,H.；Kobayashi,T.；Fujiwhara,M.Adv.Synth.Catal.2015,357,2322.]。因此，通过设计合成新的膦配体，提高Buchwald-Hartwig反应的活性，降低钯催化剂用量，是本领域的研究重点之一，具有重要的理论和现实意义。
Figure PCTCN2022138338-appb-000001
发明内容
本发明的目的在于提供一种环丙烷骨架单膦配体及其制备方法，以克服已有技术的不足。
本发明的另一个目的是提供所述环丙烷骨架单膦配体和硼烷的加合物及其制备方法。
本发明的另一个目的是提供所述环丙烷骨架单膦配体与钯的络合物及其制备方法。
本发明的另一个目的是提供所述环丙烷骨架单膦配体与钯的络合物作为催化剂在促进Buchwald-Hartwig反应中的应用。
一类环丙烷骨架单膦配体，其具有如下I的结构式或如下I的结构式的对映体、消旋体：
Figure PCTCN2022138338-appb-000002
其中：
R 1、R 2为苯基或取代的苯基，R 3、R 4为苯基、取代的苯基或C 1-C 8烷基，R 5为氢原子、苯基、取代的苯基或C 1-C 8烷基，R 1、R 2、R 3、R 4、R 5相同或不同；
所述取代的苯基中，取代基为C 1-C 8烷基、C 1-C 8烷氧基、C 2-C 8酰氧基、羟基、卤素、氨基、(C 1-C 8酰基)氨基、二(C 1-C 8烷基)氨基、C 1-C 8酰基、C 2-C 8酯基或卤代烷中的一种或 几种；R 1、R 2为取代的苯基时，取代基数目为0-2；R 3、R 4为取代的苯基时，取代基数目为0-5。
在上述技术方案中，所述环丙烷骨架单膦配体中，所述的C 1-C 8烷基或者所述的C 1-C 8烷氧基中的烷基为甲基、乙基、正丙基、异丙基、环丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、仲戊基、叔戊基、正己基、异己基、新己基、仲己基、叔己基、正庚基、异庚基、新庚基、仲庚基、叔庚基、正辛基、异辛基、新辛基、仲辛基或叔辛基；
所述的C 1-C 8酰基为甲酰基、乙酰基、丙酰基、正丁酰基、异丁酰基、正戊酰基、异戊酰基、仲戊酰基、新戊酰基、正己酰基、异己酰基、新己酰基、仲己酰基、正庚酰基、异庚酰基、新庚酰基、仲庚酰基、正辛酰基、异辛酰基、新辛酰基、仲辛酰基、1-环丙基甲酰基、1-环丁基甲酰基、1-环戊基甲酰基、1-环己基甲酰基或1-环庚基甲酰基；
所述的C 2-C 8酰氧基为乙酰氧基、丙酰氧基、正丁酰氧基、异丁酰氧基、正戊酰氧基、异戊酰氧基、仲戊酰氧基、新戊酰氧基、正己酰氧基、异己酰氧基、新己酰氧基、仲己酰氧基、正庚酰氧基、异庚酰氧基、新庚酰氧基、仲庚酰氧基、正辛酰氧基、异辛酰氧基、新辛酰氧基、仲辛酰氧基、1-环丙基甲酰氧基、1-环丁基甲酰氧基、1-环戊基甲酰氧基、1-环己基甲酰氧基或1-环庚基甲酰氧基；
所述的C 2-C 8酯基为甲氧羰基、乙氧羰基、丙氧羰基、异丙氧羰基、丁氧羰基、异丁氧羰基、正戊氧羰基、异戊氧羰基、新戊氧羰基、仲戊氧羰基、叔戊氧羰基、环戊氧羰基、正己氧羰基、异己氧羰基、新己氧羰基、仲己氧羰基、叔己氧羰基、环己氧羰基、正庚氧羰基、异庚氧羰基、新庚氧羰基、仲庚氧羰基、叔庚氧羰基或环庚氧羰基；
所述的卤代烷基为含氟、氯、溴或碘的卤代烷基。
在上述技术方案中，所述环丙烷骨架单膦配体为如下I-a、I-b、I-c、I-d、I-e、I-f或I-g的结构式：
Figure PCTCN2022138338-appb-000003
本发明的另一方面，所述的环丙烷骨架单膦配体的制备方法，它们是经过如下两种路线制备：
当R 5＝H时，其合成路线为：在NaOH和相转移催化剂苄基三乙基氯化铵存在下，反式-1,2-二芳基乙烯与溴仿进行环丙烷化反应，制备得到偕二溴环丙烷中间体III；偕二溴环丙烷中间体III与正丁基锂进行溴锂交换，然后质子化，制备得到单溴环丙烷中间体IV；单溴环丙烷中间体IV与正丁基锂进行溴锂交换后，与R 3R 4PCl发生取代反应，制备得到环丙烷骨架单膦配体I，其反应式为：
Figure PCTCN2022138338-appb-000004
其中，R 1-R 4如上述定义；
在上述技术方案中，所述反式-1,2-二芳基乙烯、苄基三乙基氯化铵、NaOH的摩尔比为1:(0.1-1):(50-100)，环丙烷化反应温度为0℃～室温，偕二溴环丙烷中间体III与正丁基锂的摩尔比为1:(1-2)，于-120～-60℃下进行溴锂交换和质子化，单溴环丙烷中间体IV、正丁基锂、R 3R 4PCl的摩尔比为1:(1-2):(1-4)，单溴环丙烷中间体IV与正丁基锂于-120～-60℃下进行溴锂交换后，于-100℃～室温条件下与R 3R 4PCl发生取代反应。
当R 5≠H时，其合成路线为：偕二溴环丙烷中间体III与正丁基锂进行溴锂交换后， 加入碘代烃R 5I，制备得到中间体V；中间体V与镁反应原位制备得到格氏试剂后，在铜催化下与二苯基氯化膦继续反应制备环丙烷骨架单膦配体I，其反应式为：
Figure PCTCN2022138338-appb-000005
其中，R 1-R 5为上述定义。
在上述技术方案中，所述偕二溴环丙烷中间体III、正丁基锂和碘代烃R 5I的摩尔比为1:(1-2):(1-5)，溴锂交换的温度为-120℃～室温，所述中间体V与镁、铜催化剂中的铜、二苯基氯化膦的摩尔比为1:(1-10):(1-2):(1-5)，中间体V与镁在40～90℃下反应原位制备得到格氏试剂，于40～90℃下，在铜催化下与二苯基氯化膦继续反应制备所述的环丙烷骨架单膦配体。
本发明的另一方面，所述的环丙烷骨架单膦配体和硼烷的加合物，其具有如下II的结构式或如下II的结构式的对映体、消旋体：
Figure PCTCN2022138338-appb-000006
其中，R 1-R 5为上述定义。
在上述技术方案中，所述加合物的结构如下II-a、II-b、II-c、II-d、II-e、II-f或II-g的结构式：
Figure PCTCN2022138338-appb-000007
本发明的另一方面，所述加合物的制备方法如下：所述的环丙烷骨架单膦配体和硼烷的四氢呋喃溶液反应生成相应的加合物，其反应式为：
Figure PCTCN2022138338-appb-000008
其中，R 1-R 5为上述定义。
在上述技术方案中，所述环丙烷骨架单膦配体和硼烷的四氢呋喃溶液在0℃～室温条件下反应，反应溶剂为甲苯、三氟甲苯、苯、四氢呋喃或乙醚。
本发明的另一方面，所述的环丙烷骨架单膦配体的钯配合物，它具有如下VI的结构式或VI的对映体、消旋体：
Figure PCTCN2022138338-appb-000009
其中，R 1-R 5为上述定义；X和Y是卤素、酸根、1,3-二羰基配体、烯丙基或芳基；X和Y相同或不同。
本发明的另一方面，所述的钯配合物的合成方法，经过方法(1)或方法(2)制备：
方法(1)所述的环丙烷骨架单膦配体、或者所述的环丙烷骨架单膦配体和硼烷的加合物与钯盐和X-Y在溶剂中反应后分离提纯得到所述的钯配合物；
方法(2)所述的环丙烷骨架单膦配体、或者所述环丙烷骨架单膦配体和硼烷的加合物与钯盐和X-Y在溶剂中现场络合制得所述的钯配合物；
所述方法(1)或方法(2)的反应式为：
Figure PCTCN2022138338-appb-000010
或者
Figure PCTCN2022138338-appb-000011
其中，R 1-R 5如权利要求1所定义；所述钯盐为(COD)Pd(CH 2TMS) 2、Pd 2(dba) 3.CHCl 3、Pd 2(dba) 4、Pd(OAc) 2、Pd(TFA) 2或[(allyl)PdCl] 2中的一种或几种，其中COD为1,5-环辛二烯，TMS为三甲基硅基，dba为二苄叉丙酮，OAc为乙酸根，TFA为三氟乙酸根，allyl为烯丙基，优选的，所述的溶剂为正己烷、四氢呋喃、乙腈、二氯甲烷、苯、甲苯、二甲苯或三氟甲基苯中的一种或几种。
在上述技术方案中，所述环丙烷骨架单膦配体、或者所述的环丙烷骨架单膦配体和硼烷的加合物与钯盐和芳基卤素的摩尔比为1:1:(1-5)，反应温度为10～50℃。
本发明的另一方面，所述的钯配合物作为催化剂促进Buchwald-Hartwig反应中的应用。
在上述技术方案中，所述的钯配合物、所述的钯配合物与所述环丙烷骨架单膦配体的混合物或者所述的钯配合物与环丙烷骨架单膦配体和硼烷的加合物的混合物，作为催化剂促进Buchwald-Hartwig反应，反应式如下：
Figure PCTCN2022138338-appb-000012
其中：Ar是苯基、取代苯基、杂芳基或烯基，X是溴、氯、碘、三氟甲磺酸酯、硝基或对甲苯磺酸酯，R 6-R 7是苯基、取代苯基、杂芳基、烯基、烷基或官能团取代的烷基，R 6、R 7相同或不同；优选的，碱为碱金属盐或NaH中的一种或几种；溶剂是C 1-C 8的醚类、甲苯、烷烃或底物本身(不包含溶剂)中的一种或几种。
在上述技术方案中，所述碱金属盐为碱金属的锂盐、钠盐或钾盐。
在上述技术方案中，在Buchwald-Hartwig反应中，先合成所述的钯配合物再投入反应系统，或者，将钯盐和所述环丙烷骨架单膦配体直接投入反应系统，在反应系统中合成所述的钯配合物。在上述技术方案中，当催化剂为所述钯配合物时，ArX、R 6R 7NH、钯配合物、碱的摩尔比为1:(1-2):(0.001-1％):(1-3)；
当催化剂为所述的钯配合物与所述环丙烷骨架单膦配体的混合物时，ArX、R 6R 7NH、钯配合物、环丙烷骨架单膦配体、碱的摩尔比为1:(1-2):(0.001-1％):(0.001-1％):(1-3)；
当催化剂为所述的钯配合物与环丙烷骨架单膦配体和硼烷的加合物的混合物时，ArX、R 6R 7NH、钯配合物、环丙烷骨架单膦配体和硼烷的加合物、碱的摩尔比为1:(1-2):(0.001-1％):(0.001-1％):(1-3)。
在上述技术方案中，所述Buchwald-Hartwig反应的温度为50～200℃。
附图说明
图1为环丙烷骨架单膦配体I和硼烷的加合物II-c的单晶结构；
图2为环丙烷骨架单膦配体I的钯配合物VI-h的单晶结构。
具体实施方式
通过下述实施实例将有助于进一步理解本发明，但不应将此理解为本发明上述主题的范围仅限于以下的实施例，凡基于本发明上述内容所实现的技术均属于本发明的范围。一般说明：
以下实例中使用了缩写，其含义如下：
Me是甲基，Et是乙基， tBu是叔丁基， nBu是正丁基，Ph是苯基，THF是四氢呋喃，Et 2O是乙醚，CHBr 3是溴仿，TEBAC是苄基三乙基氯化铵，PE是石油醚，EA是乙酸乙酯，Ar是氩气，CDCl 3是氘代氯仿，COD是1,5-环辛二烯，TMS是三甲基硅烷取代基；dba为二苄叉丙酮，OAc为乙酸根，TFA为三氟乙酸根，allyl为烯丙基。
eq.是当量，rt代表室温，TLC是薄层色谱，NMR是核磁共振，HRMS是高分辨质谱，GC是气相色谱，转化率＝转化的原料的物质的量/起始原料的物质的量，转化数＝目标产物的物质的量/钯催化剂的物质的量。
所用溶剂在使用前经标准操作提纯，干燥；所用试剂均为市售或按照已有文献方法合成得到，并在使用前提纯。
实施例1：1,2-二芳基-3,3-二溴环丙烷III-b–III-d的制备
1,2-二对甲苯基-3,3-二溴环丙烷III-b的合成：
Figure PCTCN2022138338-appb-000013
在空气下，向装有磁子搅拌、250mL的三口烧瓶中称入反式-1,2-二对甲苯基乙烯(8.3g，40mmol)，TEBAC(苄基三乙基氯化铵，1.83g，8mmol)，加入80mL溴仿。取NaOH(88g,222mmol)加入80mL水配置成饱和NaOH溶液，于0℃下向三口烧瓶中逐滴加入80mL饱和NaOH水溶液，在0℃下继续搅拌20分钟后恢复至室温搅拌，5小时后，加入水淬灭反应，分液，水相用二氯甲烷萃取(100mL×3)。水洗有机相，无水Na 2SO 4干燥。过滤，通过旋蒸浓缩滤液，所得粗产物以硅胶柱层析分离(洗脱剂为石油醚)得产物III-b(16.0g，95％yield)，为淡黄色固体，熔点55.1-56.2℃。
1H NMR (400MHz,CDCl 3)δ7.26–7.24(m,4H),7.20–7.18(m,4H),3.18(s,2H),2.36(s,6H).
13C NMR (101MHz,CDCl 3)δ137.67,133.15,129.26,128.88,39.86,37.67,21.37.
以下化合物(III-c–III-d)的合成方法与III-b相同。
1,2-二对叔丁基苯基-3,3-二溴环丙烷III-c：
Figure PCTCN2022138338-appb-000014
淡黄色固体，收率86％，熔点:119.1-120.5℃。
1H NMR (400MHz,CDCl 3)δ7.43–7.39(m,4H),7.31–7.28(m,4H),3.19(s,2H),1.34(s,18H).
13C NMR (101MHz,CDCl 3)δ150.87,133.17,128.68,125.47,39.98,37.60,34.76,31.48.
1,2-二(3,5-二叔丁基苯基)-3,3-二溴环丙烷III-d：
Figure PCTCN2022138338-appb-000015
淡黄色固体，收率61％，熔点:140.9-142.2℃。
1H NMR (400MHz,CDCl 3)δ7.43–7.39(m,2H),7.23–7.20(m,4H),3.26(s,2H),1.38(s,36H).
13C NMR (101MHz,CDCl 3)δ150.94,135.43,123.37,121.76,40.84,37.91,35.04,31.64.
实施例2：1,2-二芳基-3-溴环丙烷IV-a–IV-d的制备
1,2-二苯基-3-溴环丙烷IV-a的合成：
Figure PCTCN2022138338-appb-000016
在氩气保护下，向装有磁子搅拌的10mL干燥的Schlenk管中加入LiBr(96mg，1.1mmol)、1mL乙醚和1mL四氢呋喃，用冰水浴将体系冷却至0℃，缓慢滴加 nBuLi的正己烷溶液(440μL，2.5M，1.1mmol)。将体系移至液氮乙醇(-100℃)的体系中，使用注射泵滴加III-a(352mg,1mmol)的四氢呋喃(5mL)溶液，约1小时滴加完。保持低温搅拌1小时后用甲醇淬灭反应体系，加入水，使用石油醚萃取三次(10mL×3)，用无水MgSO 4干燥，过滤，通过旋蒸浓缩滤液，所得粗产物以硅胶柱层析分离(洗脱剂为石油醚)得产物IV-a为白色固体(197mg，72％yield)，熔点82.8-84.4℃。
1H NMR (400MHz,CDCl 3)δ7.42–7.26(m,8H),7.24–7.20(m,2H),3.55(dd,J＝7.9,4.4Hz,1H),2.78(dd,J＝7.0,4.4Hz,1H),2.71–2.67(m,1H).
13C NMR (101MHz,CDCl 3)δ139.63,136.64,129.29,128.85,128.27,127.22,126.96,126.44,32.48,32.14,30.63.
以下化合物的合成方法与IV-a相同：
1,2-二对甲苯基-3-溴环丙烷IV-b：
Figure PCTCN2022138338-appb-000017
白色固体，收率55％，熔点:74.1-75.2℃。
1H NMR(400MHz,CDCl 3)δ7.25–7.21(m,2H),7.19–7.13(m,4H),7.12–7.08(m,2H),
3.49(dd,J＝7.9,4.3Hz,1H),2.71(dd,J＝6.9,4.3Hz,1H),2.64–2.59(m,1H),2.36
(s,3H),2.34(s,3H).
13C NMR(101MHz,CDCl 3)δ139.71,136.75,136.65,136.51,135.29,133.65,129.45,129.10,
128.96,126.29,125.76,32.12,31.69,30.98,30.80,21.29,21.17.
1,2-二对叔丁基苯基-3-溴环丙烷IV-c：
Figure PCTCN2022138338-appb-000018
黄色油状化合物，收率57％。
1H NMR(400MHz,CDCl 3)δ7.37–7.33(m,4H),7.28–7.23(m,2H),7.14–7.09(m,2H),
3.48(dd,J＝7.9,4.4Hz,1H),2.71(dd,J＝6.9,4.4Hz,1H),2.63–2.56(m,1H),1.32
(s,9H),1.30(s,9H).
13C NMR(101MHz,CDCl 3)δ149.84,149.79,136.76,133.69,128.87,126.10,125.68,125.11,
34.60,34.58,32.33,31.64,31.52,31.49,31.40,30.91,27.05.
1,2-二(3,5-二叔丁基苯基)-3-溴环丙烷IV-d
Figure PCTCN2022138338-appb-000019
黄色油状化合物，收率70％。
1H NMR (400MHz,CDCl 3)δ7.36–7.33(m,2H),7.21–7.18(m,2H),7.08–7.05(m,2H),3.56(dd,J＝7.8,4.5Hz,1H),2.78–2.69(m,2H),1.36(s,18H),1.34(s,18H).
13C NMR (101MHz,CDCl 3)δ151.29,150.38,138.94,135.81,123.63,121.16,120.94,120.67,35.06,34.98,33.60,32.23,31.68,31.65,31.60,31.33.
实施例3：2,3-二芳基环丙基膦硼烷加合物IIa-IIf的制备
环丙烷骨架单膦配体I-a～I-f易被氧化，其硼烷加合物II-a～II-f为稳定形态。
2,3-二苯基环丙基二叔丁基膦硼烷加合物II-a的合成：
Figure PCTCN2022138338-appb-000020
向装有磁子搅拌50mL Schlenk瓶中称入反应物IV-a(300mg，1mmol)，在氩气氛围下，用无水四氢呋喃溶解，在-100℃条件下滴加 nBuLi的正己烷溶液(0.5mL，2.5M，1.2mmol)，保持低温搅拌1小时。加入重蒸的P tBu 2Cl(361mg，2mmol)，反应体系自然升温至室温，搅拌4小时。TLC监测反应结束后，冰水浴控温(0℃)，向体系中加入硼烷四氢呋喃溶液(4mL，1.0M，4mmol)，体系恢复室温搅拌12小时。冰水浴控温，用水淬灭反应体系，水相用乙酸乙酯萃取(10mL×3)，合并有机相，用无水MgSO 4干燥，过滤，旋蒸浓缩滤液，所得粗产物以硅胶柱层析分离(洗脱剂：石油醚/乙酸乙酯＝100:1)，得到目标产物II-a为白色固体(229mg，65％yield)，熔点115-117℃。
1H NMR (400MHz,CDCl 3)7.45–7.40(m,2H),7.36–7.30(m,2H),7.29–7.19(m,6H),3.25–3.16(m,1H),2.85–2.77(m,1H),1.68–1.61(m,1H),1.19(d,J＝12.3Hz,9H),1.14(d,J＝12.7Hz,9H).
13C NMR (101MHz,CDCl 3)δ140.45,135.41,135.39,130.50,128.92,127.64,127.08,126.66,125.84,34.17,34.12,34.06,33.78,32.79,32.52,28.47,28.45,27.94,27.93,26.62,22.25,21.88.
31P NMR (162MHz,CDCl 3)δ47.68,47.16.
11B NMR (128MHz,CDCl 3)δ-42.81.
HRMS (ESI)calcd for[M+Na,C 23H 34BNaP] +:375.2389,found:375.2388.
以下化合物的合成方法与II-a相同：
2,3-二对甲基苯基环丙基二叔丁基膦硼烷加合物II-b
Figure PCTCN2022138338-appb-000021
白色固体，收率80％，熔点:174-176℃。
1H NMR (400MHz,CDCl 3)δ7.33–7.29(m,2H),7.17–7.12(m,4H),7.10–7.06(m,2H),3.20–3.11(m,1H),2.79–2.71(m,1H),2.34(s,3H),2.31(s,3H),1.61–1.56(m,1H),1.20(d,J＝12.3Hz,9H),1.15(d,J＝12.7Hz,9H).
13C NMR (101MHz,CDCl 3)δ137.43,136.47,136.10,132.36,132.33,130.30,129.54,128.29,125.69,33.99,33.70,32.74,32.46,28.51,28.41,27.97,27.87,26.37,26.17,21.25,21.14.
31P NMR (162MHz,CDCl 3)δ47.27,46.82.
11B NMR (128MHz,CDCl 3)δ-42.87.
HRMS(ESI)calcd for[M+Na,C 25H 38BNaP] +:403.2702,found:403.2701.
2,3-二对叔丁基苯基环丙基二叔丁基膦硼烷加合物II-c：
Figure PCTCN2022138338-appb-000022
白色固体，收率48％，熔点:200-202℃。
1H NMR (400MHz,CDCl 3)δ7.35–7.30(m,4H),7.27–7.25(m,2H),7.17–7.12(m,2H),3.21–3.11(m,1H),2.77–2.67(m,1H),1.64–1.57(m,1H),1.30(s,9H),1.28(s,9H),1.20(d,J＝12.2Hz,9H),1.11(d,J＝12.7Hz,9H).
13C NMR (101MHz,CDCl 3)δ149.81,149.36,137.39,132.54,132.51,130.01,125.67,125.49,124.44,34.52,34.50,33.98,33.78,33.73,33.69,32.70,32.42,31.48,31.46,28.41,28.39,27.99,27.97.
31P NMR (162MHz,CDCl 3)δ47.43,47.15.
11B NMR (128MHz,CDCl 3)δ-43.20.
HRMS(ESI)calcd for[M+Na,C 31H 50BNaP] +:487.3641,found:487.3640.
2,3-二(3,5-二叔丁基苯基)环丙基二叔丁基膦硼烷加合物II-d：
Figure PCTCN2022138338-appb-000023
白色固体，收率79％，熔点:195-197℃。
1H NMR (400MHz,CDCl 3)δ7.26–7.24(m,4H),7.10–7.07(m,2H),3.32–3.24(m,1H),2.93–2.83(m,1H),1.56–1.50(m,1H),1.33(s,36H),1.21(d,J＝12.1Hz,9H),1.09(d,J＝12.7Hz,9H).
13C NMR (101MHz,CDCl 3)δ151.06,149.67,139.35,134.46,134.43,124.97,120.74,120.51,120.49,35.01,34.94,34.01,33.72,33.55,33.50,32.83,32.56,31.66,31.66,31.60,28.55,28.53,28.00,27.99,26.99,22.05,21.68.
31P NMR (162MHz,CDCl 3)δ47.68.
11B NMR (128MHz,CDCl 3)δ-42.52.
HRMS(ESI)calcd for[M+Na,C 39H 66BNaP] +:599.4893,found:599.4895.
2,3-二苯基环丙基二环己基膦硼烷加合物II-e：
Figure PCTCN2022138338-appb-000024
白色固体，收率80％，熔点:82-84℃。
1H NMR (400MHz,CDCl 3)δ7.42–7.36(m,2H),7.36–7.27(m,4H),7.25–7.20(m,4H),3.27–3.16(m,1H),2.91–2.81(m,1H),1.92–1.61(m,11H),1.53–1.44(m,1H),1.39–1.06(m,11H).
13C NMR (101MHz,CDCl 3)δ140.31,135.60,129.84,128.65,127.87,127.05,126.49,126.11,99.96,34.62,34.28,33.05,32.73,32.09,29.68,27.29,27.19,27.07,27.00,26.91,26.81,26.77,26.24,25.95,21.96,21.53.
31P NMR (162MHz,CDCl 3)δ29.52,29.12.
11B NMR (128MHz,CDCl 3)δ-43.40.
HRMS(ESI)calcd for[M+Na,C 27H 38BNaP] +:427.2702,found:427.2698.
实施例4：2,3-二苯基环丙基二苯基膦I-f的制备
环丙烷骨架单膦配体I-f为稳定形态。
2,3-二苯基环丙基二叔丁基膦I-f的合成：
Figure PCTCN2022138338-appb-000025
向装有磁子搅拌的50mL Schlenk瓶中称入反应物IV-a(273mg，1mmol)，在氩气氛围下，用无水四氢呋喃溶解，在-100℃条件下滴加 nBuLi的正己烷溶液(0.5mL，2.5M， 2.5mmol)，保持低温搅拌1小时。加入重蒸的PPh 2Cl(441mg，2mmol)，反应体系自然升温至室温，搅拌4小时结束后，冰水浴控温，滴入水淬灭反应体系，水相用乙酸乙酯萃取(10mL×3)，合并有机相，用无水MgSO 4干燥，过滤，旋蒸浓缩滤液，所得粗产物以硅胶柱层析分离(洗脱剂：石油醚/乙酸乙酯＝100:1)。得到目标产物I-f为白色固体(303mg，80％yield)，熔点:82-84℃。
1H NMR (400MHz,CDCl 3)δ7.41–7.35(m,2H),7.33–7.14(m,18H),2.97–2.82(m,2H),2.12–2.03(m,1H).
13C NMR (101MHz,CDCl 3)δ141.29,139.47,139.37,139.14,139.04,138.25,138.19,133.09,132.90,132.71,132.53,129.22,129.19,128.67,128.57,128.50,128.44,128.36,128.29,128.06,126.65,126.59,126.37,32.41,32.35,29.92,29.84,29.48,29.35.
31P NMR (162MHz,CDCl 3)δ-16.18.
HRMS(ESI)calcd for[M+H,C 41H 35P 2] +:379.1616,found:379.1615.
实施例5：1,2-二苯基-3-溴偕甲基环丙烷V-a的制备
Figure PCTCN2022138338-appb-000026
于100mL Schlenk瓶中称入IV-a(2.1g,6mmol)，将体系置换为氩气氛围，加入无水THF(30mL),将体系置于-78℃下搅拌，逐滴加入 nBuLi(2.4mL,2.5M,6mmol)，-78℃下搅拌10min，向体系中逐滴加入MeI(3.4g,24mmol)，-78℃下继续搅拌30分钟后恢复至室温下反应8小时。待反应完毕后加饱和NH 4Cl水溶液淬灭反应，水相用正己烷萃取(10mL×3)，合并的有机相用无水Na 2SO 4干燥、过滤，旋蒸浓缩滤液，所得粗产物以硅胶柱层析分离(洗脱剂：石油醚/乙酸乙酯＝100:1)。得目标产物V-a(1.3g,74％yield)，无色油状液体。
1H NMR (400MHz,CDCl 3)δ7.41–7.28(m,10H),3.15(d,J＝7.7Hz,1H),2.49(d,J＝7.7Hz,1H),1.68(s,3H).
环丙烷骨架单膦配体I-g易被氧化，其硼烷加合物II-g为稳定形态，2,3-二苯基-1-甲基环丙烷二苯基膦硼烷加合物II-g的制备：
Figure PCTCN2022138338-appb-000027
于50mL三口圆底烧瓶中称入Mg屑(900mg,37.4mmol)，连接回流冷凝管和恒压滴液漏斗，将体系置换为氩气氛围后抽真空，加热枪对体系加热干燥30分钟后充入氩气，恢复至室温后加入一小粒碘。加入无水THF(10mL),预先用无水THF(5mL)溶解底物V-a(2.15g,7.5mmol)并转移至滴液漏斗并向反应体系中逐滴加入5-10滴，后使用吹风机对体系加热至微沸引发格氏反应，待碘的颜色褪去后继续滴加剩余底物溶液，保持体系微沸状态。滴加完毕后50℃下继续搅拌30分钟。于另一只100mL Schlenk瓶中称入CuI(1.71g,9mmol),加入无水THF(20mL),将制备好的格氏试剂转移至Schlenk瓶中，加入PPh 2Cl(4.95g,22.5mmol)后于50℃下加热24小时。随后在0℃下逐滴加入硼烷四氢呋喃溶液(30mmol,1M in THF)，完毕后恢复至室温继续反应8小时。反应结束后冰水浴控温，滴入水淬灭反应，水相用乙酸乙酯萃取(20mL×3)，合并有机相，用无水MgSO 4干燥，过滤，旋蒸浓缩滤液，所得粗产物以硅胶柱层析分离(洗脱剂：石油醚/乙酸乙酯＝100:1)，得到目标产物II-g为白色固体(1.98g，65％yield)，熔点:139-141℃。
1H NMR (400MHz,CDCl 3)δ7.57–7.47(m,4H),7.46–7.35(m,6H),7.34–7.25(m,5H),7.11–6.95(m,5H),3.47(dd,J＝14.4,7.6Hz,1H),2.92(t,J＝7.1Hz,1H),1.25(d,J＝11.6Hz,3H).
13C NMR (101MHz,CDCl 3)δ136.3,135.0,133.6,133.5,133.4,130.8,130.6,129.7,129.4,128.5,128.4,128.3,127.8,127.1,126.5,36.3,31.0,19.3,19.2.
31P NMR (162MHz,CDCl 3)δ30.04.
11B NMR (128MHz,CDCl 3)δ-38.29.
HRMS(ESI)calcd for[M+Na,C 28H 28BNaP] +:429.1914,found:429.1916.
实施例6：2,3-二苯基环丙基二叔丁基膦I-a的制备
Figure PCTCN2022138338-appb-000028
于25mL Schlenk烧瓶中称入II-a(0.071g,0.2mmol)和DABCO(0.067g,0,6mmol)，将体系置换为氩气氛围，加入无水THF(4mL),将体系置于50℃下搅拌8小时。无水无氧条件下过硅胶柱分离纯化，得目标产物I-a为无色油状化合物(0.064g,94％yield)。
1H NMR (400MHz,CDCl 3)δ7.33–7.24(m,6H),7.23–7.14(m,4H),2.63–2.55(m,1H),2.55–2.47(m,1H),1.79–1.71(m,1H),1.16(d,J＝10.9Hz,9H),0.95(d,J＝10.8Hz,9H).
13C NMR (101MHz,CDCl 3)δ141.93,139.73,139.70,128.64,127.68,126.06,125.87,125.71,33.84,33.81,32.30,32.28,32.11,32.09,31.97,31.87,31.79,30.45,30.33,30.22,30.00,29.92,29.87,29.79,26.88,26.80,26.63,26.53.
31P NMR (162MHz,CDCl 3)δ12.88.
以下化合物的合成方法与I-a相同：
2,3-二对甲苯基环丙基二叔丁基膦I-b：
Figure PCTCN2022138338-appb-000029
无色油状液体，收率95％。
1H NMR (400MHz,CDCl 3)δ7.13–7.08(m,2H),7.04–6.95(m,6H),2.45(dt,J＝9.1,6.3Hz,1H),2.38–2.32(m,1H),2.22(s,3H),2.20(s,3H),1.64–1.57(m,1H),1.07(d,J＝10.8Hz,9H),0.88(d,J＝10.8Hz,9H).
13C NMR (101MHz,CDCl 3)δ138.97,136.68,136.65,135.43,135.18,129.44,129.38,129.31,129.26,128.46,128.35,125.60,33.38,33.32,32.29,32.27,32.11,32.09,31.40,31.30,31.20,30.51,30.35,30.20,30.07,29.94,29.81,26.49,26.26,26.02,21.13.
31P NMR (162MHz,CDCl 3)δ13.01.
2,3-二对叔丁基苯基环丙基二叔丁基膦I-c：
Figure PCTCN2022138338-appb-000030
无色油状化合物，收率96％。
1H NMR (400MHz,CDCl 3)δ7.24–7.18(m,4H),7.16–7.12(m,2H),7.06–7.01(m,2H),2.53–2.44(m,1H),2.38–2.32(m,1H),1.69–1.61(m,1H),1.22(s,9H),1.20(s,9H),1.10(d,J＝10.8Hz,9H),0.88(d,J＝10.8Hz,9H).
13C NMR (101MHz,CDCl 3)δ148.72,148.51,138.91,136.72,136.69,128.22,125.58,125.38,124.67,124.42,34.49,34.46,33.35,32.30,32.28,32.11,31.61,31.42,31.26,30.57,30.42,30.27,30.03,29.91,29.79,27.13,26.01,22.79,14.32,14.24.
31P NMR (162MHz,CDCl 3)δ13.01.
2,3-二(3,5-二叔丁基苯基)环丙基二叔丁基膦I-d：
Figure PCTCN2022138338-appb-000031
无色油状化合物，收率91％。
1H NMR (400MHz,CDCl 3)δ7.19–7.06(m,4H),7.05–6.94(m,2H),2.58–2.44(m,1H),2.44–2.29(m,1H),1.75–1.61(m,1H),1.35–1.21(m,36H),1.16–1.07(m,9H),0.88–0.74(m,9H).
13C NMR (101MHz,CDCl 3)δ150.69,149.51,141.08,139.23,123.50,123.32,120.66,120.61,120.51,119.87,119.86,119.40,119.23,35.03,34.93,34.02,33.04,32.28,32.07,31.82,31.63,30.64,30.48,30.34,30.11,29.99,29.87,25.05.
31P NMR (162MHz,CDCl 3)δ14.58.
2,3-二对苯基环丙基二环己基基膦I-e：
Figure PCTCN2022138338-appb-000032
无色油状化合物，收率90％。
1H NMR (400MHz,CDCl 3)δ7.25–7.17(m,6H),7.13–7.05(m,4H),2.53–2.43(m,2H),1.73–1.35(m,13H),1.22–0.97(m,10H).
13C NMR (101MHz,CDCl 3)δ142.05,139.33,128.63,127.69,126.00,33.99,32.30,31.01,30.75,30.17,29.28,27.45,26.59,26.43,22.78,14.30,14.21.
31P NMR (162MHz,CDCl 3)δ-11.30.
2,3-二对苯基-1-偕甲基环丙基二苯基膦I-g：
Figure PCTCN2022138338-appb-000033
无色油状化合物，收率96％。
1H NMR (400MHz,CDCl 3)δ7.55–7.49(m,2H),7.45–7.41(m,2H),7.36–7.18(m,10H),7.17–7.07(m,6H),3.28(dd,J＝15.1,6.7Hz,1H),2.77(dd,J＝6.8,3.7Hz,1H),0.98(d,J＝2.8Hz,3H).
13C NMR (101MHz,CDCl 3)δ138.44,138.37,137.40,137.37,137.29,137.16,136.60,136.46,133.92,133.75,133.57,133.33,129.42,129.34,129.25,128.43,128.23,128.03,127.96,127.93,127.86,126.56,126.51,126.45,36.12,36.04,35.94,35.87,34.20,34.03,33.86,29.34,29.22,17.12,16.98.
31P NMR (162MHz,CDCl 3)δ7.44.
实施例7：钯配合物VI-a的制备
Figure PCTCN2022138338-appb-000034
于25mL Schlenk烧瓶中称入I-a(0.067g,0.2mmol)、(COD)Pd(CH 2TMS) 2(0.078g,0,2mmol)和4-溴苯甲酸-2-(三甲基硅基)乙酯(0.12g,0.4mmol)，将体系置换为氩气氛围，加入无水正己烷(4mL),将体系置于常温下搅拌12小时。反应结束后利用正己烷抽滤洗涤得目标产物VI-a为黄色固体(0.075g,50％yield)，熔点:108.1-110.2℃。
1H NMR (400MHz,CDCl 3)δ8.24(s,2H),7.76–7.27(m,7H),7.18(s,5H),4.36–4.26(m,2H),2.79(s,1H),1.75–1.40(m,11H),1.11–1.02(m,2H),0.77(s,9H),0.05(s,9H).
31P NMR (162MHz,CDCl 3)δ44.27,40.59.
钯配合物VI-b：
Figure PCTCN2022138338-appb-000035
黄色固体，收率65％，熔点:131.0-133.3℃。
1H NMR (400MHz,CDCl 3)δ8.01(s,2H),7.59–7.32(m,5H),7.17–6.81(m,5H),4.32(t,J＝8.5Hz,2H),2.69(s,1H),2.45(s,3H),2.32(s,3H),1.87–1.35(m,10H),1.28(s,1H),1.08(t,J＝8.5Hz,2H),0.81(s,9H),0.06(s,9H).
31P NMR (162MHz,CDCl 3)δ46.01,41.24.
钯配合物VI-c：
Figure PCTCN2022138338-appb-000036
黄色固体，收率76％，熔点:158.1-160.0℃。
1H NMR (400MHz,CDCl 3)δ8.64–7.86(m,2H),7.81–7.36(m,5H),7.24(s,5H),4.33(t,J＝8.4Hz,2H),2.93–2.60(m,1H),1.71–1.49(m,9H),1.45–1.26(m,20H),1.13–1.05(m,2H),0.77(s,9H),0.06(s,9H).
31P NMR (162MHz,CDCl 3)δ43.65,40.42,39.03.
钯配合物VI-d：
Figure PCTCN2022138338-appb-000037
黄色固体，收率80％，熔点:158.2-160.5℃。
1H NMR (400MHz,CDCl 3)δ7.89–7.28(m,7H),7.21(s,1H),7.03–6.79(m,2H),4.34(t,J＝8.5Hz,2H),1.62–1.40(m,27H),1.38–1.20(m,28H),1.11(t,J＝8.5Hz,4H),0.09(s,9H).
31P NMR (162MHz,CDCl 3)δ56.36,40.28.
钯配合物VI-e：
Figure PCTCN2022138338-appb-000038
淡黄色固体，收率47％，熔点:140.1-142.5℃。
1H NMR (400MHz,CDCl 3)δ8.21–7.86(m,2H),7.85–6.82(m,12H),4.37–4.23(m,2H),3.12–2.77(m,1H),2.24–1.59(m,10H),1.32–0.84(m,16H),0.07(s,9H).
31P NMR (162MHz,CDCl 3)δ29.21,27.84,22.23,19.88.
钯配合物VI-f：
Figure PCTCN2022138338-appb-000039
淡黄色固体，收率76％，熔点:126.2-128.4℃。
1H NMR (400MHz,CDCl 3)δ7.49–7.07(m,20H),7.03–6.83(m,4H),4.34(s,2H),2.93(s,1H),1.33–1.29(m,1H),1.14–1.05(m,2H),0.92(t,J＝6.8Hz,1H),0.09(s,9H).
31P NMR (162MHz,CDCl 3)δ23.00.
钯配合物VI-g：
Figure PCTCN2022138338-appb-000040
黄色固体，收率75％，熔点:145.0-147.5℃。
1H NMR (400MHz,CDCl 3)δ8.17–7.90(m,4H),7.78–7.29(m,10H),7.22–7.11(m,2H),7.04–6.70(m,8H),4.28(t,J＝8.3Hz,2H),2.98(t,J＝7.6Hz,1H),1.30(s,3H),1.05(t,J＝8.2Hz,2H),0.93(s,1H),0.07(s,9H).
31P NMR (162MHz,CDCl 3)δ30.82,29.89.
实施例8：钯配合物VI-h的制备
Figure PCTCN2022138338-appb-000041
于25mL Schlenk烧瓶中称入I-a(0.067g,0.2mmol)、(COD)Pd(CH 2TMS) 2(0.078g,0,2mmol)和溴苯(0.12g,0.4mmol)，将体系置换为氩气氛围，加入无水正己烷(4mL),将体系置于常温下搅拌12小时。反应结束后利用正己烷抽滤洗涤得目标产物VI-h为黄色固体(0.101g,83％yield)，熔点:161.1-162.5℃。
1H NMR (400MHz,CDCl 3)δ8.17(s,2H),7.69–7.60(m,2H),7.40–7.34(m,1H),7.17(s,7H),6.82–6.66(m,3H),2.75(dt,J＝10.7,5.8Hz,1H),1.64–1.41(m,10H),1.26(s,1H),0.93–0.69(m,9H).
31P NMR (162MHz,CDCl 3)δ40.96,37.30.
表1：II-c的单晶测试参数
Figure PCTCN2022138338-appb-000042
表2：钯配合物VI-h的单晶测试参数
Figure PCTCN2022138338-appb-000043
Figure PCTCN2022138338-appb-000044
实施例9：不同溶剂中钯催化C-N键偶联反应情况
Figure PCTCN2022138338-appb-000045
在充满氩气的手套箱中，向25mL Schlenk管中加入二苯胺(169mg,1mmol),溴苯(173mg,1.1mmol)，叔丁醇钠(125mg,1.3mmol)，溶剂(2mL)，随后向其中加入0.0183g的[(allyl)PdCl] 2甲苯溶液(1mg/g)和0.0704g的配体II-a甲苯溶液(1mg/g)，用橡胶塞塞好后搅拌24小时。反应结束后，将反应液通过滴管柱过滤，滤液通过旋蒸浓缩后加入正十三烷作为内标，利用GC计算收率和转化率。
表3：不同溶剂中钯催化溴苯与二苯胺偶联反应实验结果
Figure PCTCN2022138338-appb-000046
Figure PCTCN2022138338-appb-000047
a转化率，收率由GC测定。
实施例10：不同碱作用下钯催化溴苯与二苯胺偶联反应
Figure PCTCN2022138338-appb-000048
在充满氩气的手套箱中，向25mL Schlenk管中加入二苯胺(169mg,1mmol),溴苯(173mg,1.1mmol)，碱(1.3mmol)，甲苯(2mL)，随后向其中加入0.0183g的[(allyl)PdCl] 2甲苯溶液(1mg/g)和0.0704g的配体II-a甲苯溶液(1mg/g)，用橡胶塞塞好后在110℃搅拌24小时。反应结束后，将反应液通过滴管柱过滤，滤液通过旋蒸浓缩后加入正十三烷作为内标，利用GC计算收率和转化率。
表4：不同碱作用下钯催化溴苯与二苯胺偶联反应实验结果
Figure PCTCN2022138338-appb-000049
a转化率，收率由GC测定。
实施例11：不同钯催化剂下环丙烷骨架单膦配体硼烷加合物调控C-N键偶联反应
Figure PCTCN2022138338-appb-000050
在充满氩气的手套箱中，向25mL Schlenk管中加入二苯胺(169mg,1mmol),溴苯(173mg,1.1mmol)，叔丁醇钠(125mg,1.3mmol)，甲苯(2mL)，随后向其中加入配制好的Pd的 甲苯溶液(1mg/g)和配体II的甲苯溶液(1mg/g)，用橡胶塞塞好后在110℃搅拌24小时。反应结束后，将反应液通过滴管柱过滤，滤液旋蒸浓缩后加入正十三烷作为内标，利用GC计算收率和转化率。
表5：不同钯催化剂下环丙烷骨架单膦配体硼烷加合物调控溴苯与二苯胺偶联实验结果
Figure PCTCN2022138338-appb-000051
a转化率，收率由GC测定。 bII(2x mol％)，125℃。 cII(1x mol％)。
实施例12：钯催化C-N键偶联反应底物评价
Figure PCTCN2022138338-appb-000052
在充满氩气的手套箱中，向25mL Schlenk管中加入二级胺(1mmol),溴代芳烃化合物(1.1mmol)，叔丁醇钠(125mg,1.3mmol)，甲苯(2mL)，随后向其中加入[(allyl)PdCl] 2的甲苯溶液(1mg/mL)和配体II-a的甲苯溶液(1mg/mL)，用橡胶塞塞好后在110℃搅拌24小时。反应结束后，通过柱色谱法分离计算分离收率。
表6：钯催化C-N键偶联反应底物范围
Figure PCTCN2022138338-appb-000053
Figure PCTCN2022138338-appb-000054
a分离收率； b[(allyl)PdCl] 2作为催化剂 ； c VI-a作为催化剂； d125℃； e150℃,12h,邻二甲苯(2mL)； f180℃,12h,邻二甲苯(2mL)。参考文献：[1]Hajipour,A.R.；Dordahan,F.；Rafiee,F.Appl.Organometal.Chem.2013,27,704.[2]Xue,Y.-Y.；Guo,P.-P.；Yip,H.；Li,Y.；Cao,Y.J.Mater.Chem.A.2017,5,3780.[3]Steiner,A.；Williams,J.D.；Rincon,J.A.；Frutos,O.D.；Mateos,C.Eur.J.Org.Chem.2019,5807.[4]Yamamoto,T.；Nishiyama,M.；Koie,Y.Tetrahedron Lett.1998,39,2367.[5]Silberg,J.；Schareina,T.；Kempe,R.；Wurst,K.；Buchmeiser,M.R.J.Organomet.Chem.2001,622,6.[6]Heshmatpour,F.；Abazari,R.RSC Adv.2014,4,55815.[7]Prashad,M.；Mak,X.Y.；Liu,Y.-G.；Repic,O.J.Org.Chem.2003,68,1163.[8]Mao,J.-Y.；Zhang,J.-D.；Zhang,S.-G.；Walsh,P.J.Dalton Trans.2018,47,8690.[9]Basolo,L.；Bernasconi,A.；Broggini,G.；Beccalli,E.M.ChemSusChem 2011,4,1637.[10]Shao,Q.-L.；Jiang,Z.-J.；Su,W.-K.Tetrahedron Lett.2018,59,2277.
实施例13：钯催化氯苯与二苯胺C-N键偶联反应
Figure PCTCN2022138338-appb-000055
在充满氩气的手套箱中，向25mL Schlenk管中加入二苯胺(203mg,1.2mmol),氯苯(113mg,1mmol)，叔丁醇钠(125mg,1.3mmol)，邻二甲苯(2mL)，随后向其中加入0.0183g的[(allyl)PdCl] 2邻二甲苯溶液(1mg/mL)和0.0704g的配体II-a邻二甲苯溶液(1mg/mL)，用橡胶塞塞好后在150℃搅拌12小时。反应结束后，将反应液通过滴管柱过滤，滤液通过旋蒸浓缩后加入正十三烷作为内标，利用GC计算收率为87％，转化数为8700。
以上所述的仅是本发明的优选实施方式，应当指出，对于本领域的普通技术人员来说，在不脱离发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。

Claims (10)

  1. 一类环丙烷骨架单膦配体，其特征在于，其具有如下I的结构式或如下I的结构式的对映体、消旋体：
    Figure PCTCN2022138338-appb-100001
    其中：
    R 1、R 2为苯基或取代的苯基，R 3、R 4为苯基、取代的苯基或C 1-C 8烷基，R 5为氢原子、苯基、取代的苯基或C 1-C 8烷基，R 1、R 2、R 3、R 4、R 5相同或不同；
    所述取代的苯基中，取代基为C 1-C 8烷基、C 1-C 8烷氧基、C 2-C 8酰氧基、羟基、卤素、氨基、(C 1-C 8酰基)氨基、二(C 1-C 8烷基)氨基、C 1-C 8酰基、C 2-C 8酯基或卤代烷基中的一种或几种；R 1、R 2为取代的苯基时，取代基数目为0-2；R 3、R 4为取代的苯基时，取代基数目为0-5。
  2. 如权利要求1所述的环丙烷骨架单膦配体，其特征在于，
    所述的C 1-C 8烷基或者所述的C 1-C 8烷氧基中的烷基为甲基、乙基、正丙基、异丙基、环丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、仲戊基、叔戊基、正己基、异己基、新己基、仲己基、叔己基、正庚基、异庚基、新庚基、仲庚基、叔庚基、正辛基、异辛基、新辛基、仲辛基或叔辛基；
    所述的C 1-C 8酰基为甲酰基、乙酰基、丙酰基、正丁酰基、异丁酰基、正戊酰基、异戊酰基、仲戊酰基、新戊酰基、正己酰基、异己酰基、新己酰基、仲己酰基、正庚酰基、异庚酰基、新庚酰基、仲庚酰基、正辛酰基、异辛酰基、新辛酰基、仲辛酰基、1-环丙基甲酰基、1-环丁基甲酰基、1-环戊基甲酰基、1-环己基甲酰基或1-环庚基甲酰基；
    所述的C 2-C 8酰氧基为乙酰氧基、丙酰氧基、正丁酰氧基、异丁酰氧基、正戊酰氧基、异戊酰氧基、仲戊酰氧基、新戊酰氧基、正己酰氧基、异己酰氧基、新己酰氧基、仲己酰氧基、正庚酰氧基、异庚酰氧基、新庚酰氧基、仲庚酰氧基、正辛酰氧基、异辛酰氧基、新辛酰氧基、仲辛酰氧基、1-环丙基甲酰氧基、1-环丁基甲酰氧基、1-环戊基甲酰氧基、1-环己基甲酰氧基或1-环庚基甲酰氧基；
    所述的C 2-C 8酯基为甲氧羰基、乙氧羰基、丙氧羰基、异丙氧羰基、丁氧羰基、异丁氧羰基、正戊氧羰基、异戊氧羰基、新戊氧羰基、仲戊氧羰基、叔戊氧羰基、环戊氧羰基、 正己氧羰基、异己氧羰基、新己氧羰基、仲己氧羰基、叔己氧羰基、环己氧羰基、正庚氧羰基、异庚氧羰基、新庚氧羰基、仲庚氧羰基、叔庚氧羰基或环庚氧羰基；
    所述的卤代烷基为含氟、氯、溴或碘的卤代烷基。
  3. 如权利要求2所述的环丙烷骨架单膦配体，其特征在于，其为如下I-a、I-b、I-c、I-d、I-e、I-f或I-g的结构式：
    Figure PCTCN2022138338-appb-100002
  4. 如权利要求1-3中任一项所述的环丙烷骨架单膦配体的制备方法，其特征在于，它们是经过如下两种路线制备：
    当R 5＝H时，其合成路线为：在NaOH和相转移催化剂苄基三乙基氯化铵存在下，反式-1,2-二芳基乙烯与溴仿进行环丙烷化反应，制备得到偕二溴环丙烷中间体III；偕二溴环丙烷中间体III与正丁基锂进行溴锂交换，然后质子化，制备得到单溴环丙烷中间体IV；单溴环丙烷中间体IV与正丁基锂进行溴锂交换后，与R 3R 4PCl发生取代反应，制备得到环丙烷骨架单膦配体I，其反应式为：
    Figure PCTCN2022138338-appb-100003
    其中，R 1-R 4如权利要求1所定义；
    当R 5≠H时，其合成路线为：偕二溴环丙烷中间体III与正丁基锂进行溴锂交换后，加入碘代烃R 5I，制备得到中间体V；中间体V与镁反应原位制备得到格氏试剂后，在铜催化下与二苯基氯化膦继续反应制备环丙烷骨架单膦配体I，其反应式为：
    Figure PCTCN2022138338-appb-100004
    其中，R 1-R 5如权利要求1所定义。
  5. 如权利要求1-3中任一项所述的环丙烷骨架单膦配体和硼烷的加合物，其特征在于，其具有如下II的结构式或如下II的结构式的对映体、消旋体：
    Figure PCTCN2022138338-appb-100005
    其中，R 1-R 5如权利要求1所定义。
  6. 如权利要求5所述的加合物的制备方法，其特征在于，经过如下步骤制备：所述的环丙烷骨架单膦配体和硼烷的四氢呋喃溶液反应生成相应的加合物，其反应式为：
    Figure PCTCN2022138338-appb-100006
    其中，R 1-R 5如权利要求1所定义。
  7. 如权利要求1-3中任一项所述的环丙烷骨架单膦配体的钯配合物，其特征在于，它具有如下VI的结构式或VI的对映体、消旋体：
    Figure PCTCN2022138338-appb-100007
    其中，R 1-R 5如权利要求1所定义；X和Y是卤素、酸根、1,3-二羰基配体、烯丙基或芳基；X和Y相同或不同。
  8. 如权利要求7所述的钯配合物的合成方法，其特征在于，经过方法(1)或方法(2)制 备：
    方法(1)所述的环丙烷骨架单膦配体、或者所述的环丙烷骨架单膦配体和硼烷的加合物与钯盐和X-Y在溶剂中反应后分离提纯得到所述的钯配合物；
    方法(2)所述的环丙烷骨架单膦配体、或者所述环丙烷骨架单膦配体和硼烷的加合物与钯盐和X-Y在溶剂中现场络合制得所述的钯配合物；
    所述方法(1)或方法(2)的反应式为：
    Figure PCTCN2022138338-appb-100008
    或者
    Figure PCTCN2022138338-appb-100009
    其中，R 1-R 5如权利要求1所定义；所述钯盐为(COD)Pd(CH 2TMS) 2、Pd 2(dba) 3.CHCl 3、Pd 2(dba) 4、Pd(OAc) 2、Pd(TFA) 2或[(allyl)PdCl] 2中的一种或几种，COD为1,5-环辛二烯，TMS为三甲基硅基，dba为二苄叉丙酮，OAc为乙酸根，TFA为三氟乙酸根，allyl为烯丙基；优选的，所述的溶剂为正己烷、四氢呋喃、乙腈、二氯甲烷、苯、甲苯、二甲苯或三氟甲基苯中的一种或几种。
  9. 如权利要求7所述的钯配合物作为催化剂促进Buchwald-Hartwig反应中的应用。
  10. 如权利要求9所述的应用，其特征在于，所述的钯配合物、所述的钯配合物与所述环丙烷骨架单膦配体的混合物、或者所述的钯配合物与环丙烷骨架单膦配体和硼烷的加合物的混合物，作为催化剂促进Buchwald-Hartwig反应：
    Figure PCTCN2022138338-appb-100010
    其中：Ar是苯基、取代苯基、杂芳基或烯基，X是溴、氯、碘、三氟甲磺酸酯、硝基或对甲苯磺酸酯，R 6-R 7是苯基、取代苯基、杂芳基、烯基、烷基或官能团取代的烷基，R 6、R 7相同或不同；优选的，碱为碱金属盐或NaH中的一种或几种；溶剂是C 1-C 8的醚类、甲苯、烷烃或底物本身中的一种或几种；
    优选的，在Buchwald-Hartwig反应中，先合成所述的钯配合物再投入反应系统，或者，将钯盐和所述环丙烷骨架单膦配体直接投入反应系统，在反应系统中合成所述的钯配合物。
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