CN108863855B - 一种合成(1r,2s)-1,2-二氢化萘-1,2-二胺衍生物的方法 - Google Patents
一种合成(1r,2s)-1,2-二氢化萘-1,2-二胺衍生物的方法 Download PDFInfo
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- 238000000034 method Methods 0.000 title abstract description 16
- 230000002194 synthesizing effect Effects 0.000 title description 3
- JWHXHGNOIRNWHR-VHSXEESVSA-N (1R,2S)-1,2-dihydronaphthalene-1,2-diamine Chemical class C1=CC=C2[C@H]([C@H](C=CC2=C1)N)N JWHXHGNOIRNWHR-VHSXEESVSA-N 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- JWHXHGNOIRNWHR-UHFFFAOYSA-N 1,2-dihydronaphthalene-1,2-diamine Chemical class C1=CC=C2C(N)C(N)C=CC2=C1 JWHXHGNOIRNWHR-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000007142 ring opening reaction Methods 0.000 claims abstract description 11
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 239000012298 atmosphere Substances 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 4
- 238000003786 synthesis reaction Methods 0.000 claims description 15
- 229910001494 silver tetrafluoroborate Inorganic materials 0.000 claims description 11
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 239000003446 ligand Substances 0.000 claims description 9
- 229910052723 transition metal Inorganic materials 0.000 claims description 8
- 150000003624 transition metals Chemical class 0.000 claims description 8
- 239000000654 additive Substances 0.000 claims description 7
- 230000000996 additive effect Effects 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 239000002841 Lewis acid Substances 0.000 claims description 5
- 150000007517 lewis acids Chemical class 0.000 claims description 5
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical group CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- 150000004703 alkoxides Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 239000012038 nucleophile Substances 0.000 claims description 2
- -1 amide compound Chemical class 0.000 abstract description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 10
- OCATYNXRPMXHFO-UHFFFAOYSA-N 9-oxatricyclo[6.2.1.02,7]undeca-2,4,6-triene Chemical compound C12=CC=CC=C2C2OCC1C2 OCATYNXRPMXHFO-UHFFFAOYSA-N 0.000 abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 5
- 239000012434 nucleophilic reagent Substances 0.000 abstract description 4
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- 238000003756 stirring Methods 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 13
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000012300 argon atmosphere Substances 0.000 description 6
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 6
- 238000012544 monitoring process Methods 0.000 description 6
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- 229910052751 metal Inorganic materials 0.000 description 5
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- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
- CTYPJIUQROQJBG-JWQCQUIFSA-N [(2r,4r)-4-diphenylphosphanylpentan-2-yl]-diphenylphosphane Chemical compound C=1C=CC=CC=1P([C@H](C)C[C@@H](C)P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 CTYPJIUQROQJBG-JWQCQUIFSA-N 0.000 description 2
- HGMLTMOEYCQDDR-UHFFFAOYSA-N [4-(5-diphenylphosphanyl-2,2-difluoro-1,3-benzodioxol-4-yl)-2,2-difluoro-1,3-benzodioxol-5-yl]-diphenylphosphane Chemical compound C=12OC(F)(F)OC2=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C1=C2OC(F)(F)OC2=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 HGMLTMOEYCQDDR-UHFFFAOYSA-N 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 2
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 2
- GYZZZILPVUYAFJ-UHFFFAOYSA-N phanephos Chemical compound C1CC(C(=C2)P(C=3C=CC=CC=3)C=3C=CC=CC=3)=CC=C2CCC2=CC=C1C=C2P(C=1C=CC=CC=1)C1=CC=CC=C1 GYZZZILPVUYAFJ-UHFFFAOYSA-N 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- SSJXIUAHEKJCMH-OLQVQODUSA-N (1s,2r)-cyclohexane-1,2-diamine Chemical compound N[C@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-OLQVQODUSA-N 0.000 description 1
- VLSRPVYKKHYHON-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalene-1,2-diamine Chemical compound C1=CC=C2C(N)C(N)CCC2=C1 VLSRPVYKKHYHON-UHFFFAOYSA-N 0.000 description 1
- YCMLQMDWSXFTIF-UHFFFAOYSA-N 2-methylbenzenesulfonimidic acid Chemical compound CC1=CC=CC=C1S(N)(=O)=O YCMLQMDWSXFTIF-UHFFFAOYSA-N 0.000 description 1
- 238000004679 31P NMR spectroscopy Methods 0.000 description 1
- MSFQEZBRFPAFEX-UHFFFAOYSA-N 4-methoxybenzenesulfonamide Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1 MSFQEZBRFPAFEX-UHFFFAOYSA-N 0.000 description 1
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
- JWHXHGNOIRNWHR-NXEZZACHSA-N N[C@H]1[C@@H](C=CC2=CC=CC=C12)N Chemical compound N[C@H]1[C@@H](C=CC2=CC=CC=C12)N JWHXHGNOIRNWHR-NXEZZACHSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
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- 238000004440 column chromatography Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- YTCLURCISMZCOA-UHFFFAOYSA-N n-diaminophosphoryl-n-phenylaniline Chemical compound C=1C=CC=CC=1N(P(N)(=O)N)C1=CC=CC=C1 YTCLURCISMZCOA-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/36—Amides thereof
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- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
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Abstract
Description
技术领域
本发明属于化学技术领域,进一步属于化学合成技术领域,具体涉及一种高效合成(1R,2S)-1,2-二氢化萘-1,2-二胺衍生物的方法。
背景技术
顺式1,2-环己二胺为众多天然产物和生物活性分子中的骨架部分,也是能源、化工、制药等领域中应用广泛的合成中间体。目前已有一些文献报道了有关1,2-二氢化萘-1,2-二胺衍生物的合成方法。其中2006年Mark Lautens课题组报道了在铑催化下脂肪胺和芳香胺对氮杂苯并降冰片烯的不对称开环反应(如下式所示),成功制备了反式的1, 2-二氢萘-1, 2-二胺(J. Am. Chem. Soc.2006, 128, 6837-6848),该方法虽然成功的制备了1,2-二氢萘-1, 2-二胺,但是所采用的金属铑和二茂铁配体价格昂贵,不易实现工业化生产。
2016年,H. Xu 课题组在金属铁和高碘试剂的催化下成功的合成了具有氢化萘结构的1, 2-二胺的磺酸盐(Angew. Chem. Int. Ed.2016, 55, 534-538.)。该方法虽然能够高效的合成1, 2, 3, 4-四氢萘-1,2 –二胺(如下式所示),但是该方法使用了比较危险的叠氮化合物并且还会生成含有两个叠氮基的中间体,反应操作具有很大的危险性,同时也不易大规模的生产。
因此,开发一种能解决上述技术问题的方法是非常必要的。
发明内容
本发明的目的在于提供一种高效合成(1R,2S)-1,2-二氢化萘-1,2-二胺衍生物的方法。
本发明的目的是这样实现的,是在有机溶剂体系中,在惰性氛围下以酰胺类化合物作为亲核试剂对氮/氧杂苯并降冰片烯进行不对称顺式开环,得到目标物(1R,2S)-1,2-二氢化萘-1,2二胺衍生物,其反应通式如下:
本发明的目的是提供一种制备(1R,2S)-1,2-二氢化萘-1,2-二胺衍生物的高效方法。
本发明中的(1R,2S)-1,2-二氢化萘-1,2-二胺衍生物的制备方法如下:
式中,R1=R2=-Me, -OMe, -Br; R3= aryl, alkyl; R4= aryl, alkyl, alkoxide;R5=R6= aryl, alkyl。该方法包括在二氯乙烷、四氢呋喃、二氧六环和甲苯等溶剂中,以酰胺类作为亲核试剂对氮杂杂苯并降冰片烯进行不对称顺式开环化反应制备(1R, 2S)-1, 2-二氢萘-1, 2-二胺。
金属催化剂为醋酸钯,用量在0.1%-10%之间,其中5%为最佳用量。
添加剂为AgBF4、Zn(OTf)2、Al(OTf)3、Fe(OTf)2、Cu(OTf)2、AgOTf、ZnI、CuBr等路易斯酸,优选AgBF4。
配体为(R)-Binap、(R)-Seghos、(R,R)-BDPP、(R)-Phanephos、(R)-Synphos、(R)-Difluorphos等手性膦配体,优选(R)-Binap。
该方法反应在0ºC-90ºC进行,其中60ºC为最适温度,配体的用量在0.12%-12%之间,其中添6%为最佳用量,添加剂用量在0%-100%之间,其中10%的添加剂反应结果最优。反应过程采用TLC检测跟踪,反应完成后, 浓缩之后用柱层析得产物。
所合成的顺式手性1,2-二胺,其代表化合物如下:
本发明从易得的原料酰胺和氮杂苯并降冰片烯出发,通过简单快捷的方法合成一系列(1R, 2S)-1, 2-二氢萘-1, 2-二胺。整个合成过程中,采用金属钯催化剂,商业上较为便宜的双膦配体为手型控制源,便宜的金属盐为添加剂以提高反应活性,实现酰胺对氮杂苯并降冰片烯的不对称顺式开环得到(1R, 2S)-1, 2-二氢萘-1, 2-二胺。具有成本低、效率高、反应时间短等优点,适合生产各类(1R,2S)-1,2-二氢化萘-1,2-二胺衍生物。
本发明人也报道了大量的有关胺类与氮杂苯并降冰片烯为原料制备取代的1, 2-二氢萘-1, 2-二胺衍生物的方法,我们课题组主要采用过渡金属有钯和铱,使用苯胺类化合物为亲核试剂对氮杂苯并降冰片烯进行不对称开环(Adv. Synth. Catal. 2015, 357,3121-3125; Org. Biomol. Chem.2015, 13, 8425-8428.),虽然能够高立体选择性地得到1, 2-二氢萘-1, 2-二胺衍生物(如下式所示),但是芳香胺类化合物不易脱除保护基,这将使得产物的衍生化受到一定的限制。
本发明应用钯/银共催化体系使得酰胺能够与氮杂苯并降冰片烯发生不对称顺式开环,弥补了之前胺类化合物对氮杂苯并降冰片烯只能发生不对称反式开环的不足,并且酰胺保护基更易脱除进而可实现产物的衍生化。
本发明以过渡金属钯为催化剂,市售较为便宜的手性膦配体为手性源,路易斯酸作为添加剂,简单、高效的合成(1R,2S)-1,2-二氢化萘-1,2-二胺衍生物。
本发明首次高立体选择性实现了胺类化合物对氮杂苯并降冰片烯类化合物的不对称顺式开环反应,高效地得到(1R,2S)-1,2-二氢化萘-1,2-二胺衍生物。
具体实施方式
下面结合实施例对本发明作进一步的说明,但不以任何方式对本发明加以限制,基于本发明教导所作的任何变换或替换,均属于本发明的保护范围。
本发明所述的高效合成(1R,2S)-1,2-二氢化萘-1,2-二胺衍生物的方法,是在有机溶剂体系中,在惰性氛围下以酰胺类化合物作为亲核试剂对氮/氧杂苯并降冰片烯进行不对称顺式开环,得到目标物(1R,2S)-1,2-二氢化萘-1,2二胺衍生物,其反应通式如下:
所述的惰性气体为氩气。
所述的有机溶剂为1,2-二氯乙烷、四氢呋喃、二氧六环或甲苯。
所述的过渡金属为醋酸钯。
所述的过渡金属用量为氮/氧杂苯并降冰片烯摩尔百分比0.1~10%。
所述的过渡金属用量为氮/氧杂苯并降冰片烯摩尔百分比5%。
所述的配体为(R)-Binap、(R)-Seghos、(R,R)-BDPP、(R)-Phanephos、(R)-Synphos或(R)-Difluorphos。
所述的配体为(R)-Binap。
添加剂为路易斯酸。
所述的路易斯酸为AgBF4、Zn(OTf)2、Al(OTf)3、Fe(OTf)2、Cu(OTf)2、Ag(OTf)、ZnI或CuBr。
所述的路易斯酸为AgBF4。
反应的温度为0~90℃。
下面以具体实施案例对本发明做进一步说明:
实施例1
Tert-butyl ((1R,2S)-2-acetamido-1,2-dihydronaphthalen-1-yl)carbamate的合成:在氩气氛围下的无水无氧手套箱中,将2.3mg Pd(AcO)2 和7.5mg (R)-Binap在1mL1,2-二氯乙烷中搅拌30min,紧接着加入3.9mg AgBF4搅拌10min,然后加入48.6mg 由Boc保护的氮杂苯并降冰片烯和1ml 1,2-二氯乙烷搅拌10min,再加入35.5mg 乙酰胺,之后塞好塞子将反应拿出手套箱,将反应置于90℃的油浴锅中搅拌,TLC监测反应完成后,浓缩后用硅胶过柱得白色固体,产率为89%,ee值为91%。
1H NMR (400 MHz, CDCl3): δ 7.33-7.26 (m, 3H), 7.12 (d, J=6.8 Hz ,1H),6.56 (d, J=9.6 Hz , 2H), 6.08 (d, J=6.8 Hz,3H), 5.95 (d, J=6.4 Hz,1H), 5.08(d, J=8.4 Hz, 1H), 4.93-4.88 (m, 2H), 1.99 (s, 3H), 1.48 (s, 9H). 13C NMR(100MHz, CDCl3): δ 170.6, 156.2, 133.9, 132.2, 129.0, 128.4, 128.3, 128.1, 127.1,126.9, 80.1, 51.5, 48.2, 28.3, 23.5 .
实施例2
Tert-butyl((1R,2S)-2-((diphenylphosphoryl)amino)-1,2-dihydronaphthalen-1-yl)carbamate的合成:在氩气氛围下的无水无氧手套箱中,将2.3mgPd(AcO)2 和7.5mg (R)-Binap在1mL 1,2-二氯乙烷中搅拌30min,紧接着加入3.9mg AgBF4搅拌10min,然后加入48.6mg 由Boc保护的氮杂苯并降冰片烯和1ml 1,2-二氯乙烷搅拌10min,再加入130.3mg 二苯基磷酰胺,之后塞好塞子将反应拿出手套箱,将反应置于90℃的油浴锅中搅拌,TLC监测反应完成后,浓缩后用硅胶过柱得白色固体,产率为66%,ee值为99%。
1H NMR (400 MHz, CDCl3): δ 7.98-7.88 (m, 4H), 7.54-7.36 (m,7H), 7.28-7.20 (m, 2H), 7.08 (t, J=8.8 Hz, 1H), 6.67 (d, J=9.6 Hz, 1H), 6.17 (dd, J=5.6Hz, J=9.6 Hz, 1H), 4.97 (dd, J=5.2 Hz, J=9.6 Hz, 1H), 3.76-3.69 (m, 1H), 3.03(dd, J=6.8Hz, J=11.2 Hz, 1H), 1.52 (s, 9H). 13C NMR (100 MHz, CDCl3): δ156.4,134.4, 132.5, 132.4, 132.3, 132.2, 129.1, 128.9, 128.8, 128.7, 128.6, 128.5,127.8, 126.7, 126.5, 79.5, 52.7, 49.9, 28.6. 31P NMR(161 MHz, CDCl3 ) δ 23.5.
实施例3
Tert-butyl((1R,2S)-2-((2-methylphenyl)sulfonamido)-1,2-dihydronaphthalen-1-yl)carbamate的合成:在氩气氛围下的无水无氧手套箱中,将2.3mgPd(AcO)2 和7.5mg (R)-Binap在1mL 1,2-二氯乙烷中搅拌30min,紧接着加入3.9mg AgBF4搅拌10min,然后加入48.6mg 由Boc保护的氮杂苯并降冰片烯和1ml 1,2-二氯乙烷搅拌10min,再加入103.0mg 邻甲基苯磺酰胺,之后塞好塞子将反应拿出手套箱,将反应置于60℃的油浴锅中搅拌,TLC监测反应完成后,浓缩后用硅胶过柱得白色固体,产率为82%,ee值为96%。
1H NMR (400 MHz, CDCl3): δ 8.02-8.00 (m, 1H), 7.52-7.48 (m,1H), 7.36-7.33 (m, 2H), 7.31-7.25 (m,3H), 7.10-7.08 (m,1H), 6.47 (d, J=9.6 Hz, 1H),5.67 (dd, J=4.8 Hz, J=9.6 Hz,1H), 5.15 (d, J=9.6 Hz ,1H), 4.87 (dd, J=5.2Hz, J=9.6 Hz, 1H), 3.95-3.91 (m,1H), 2.59 (s, 3H), 1.49 (s, 9H). 13C NMR(100 MHz,CDCl3): δ 156.1, 137.9, 136.9, 133.5, 133.2, 132.7, 131.9, 129.8, 129.7,128.8, 128.3, 127.1, 126.6, 126.4, 126.2, 80.2, 51.4, 51.1, 28.4, 20.3 .
实施例4
Tert-butyl (1R,2S)-2-(phenylsulfonamido)-1,2-dihydronaphthalen-1-yl)carbamate的合成:在氩气氛围下的无水无氧手套箱中,将2.3mg Pd(AcO)2 和7.5mg (R)-Binap在1mL 1,2-二氯乙烷中搅拌30min,紧接着加入3.9mg AgBF4搅拌10min,然后加入48.6mg 由Boc保护的氮杂苯并降冰片烯和1ml 1,2-二氯乙烷搅拌10min,再加入93.4mg 苯磺酰胺,之后塞好塞子将反应拿出手套箱,将反应置于60℃的油浴锅中搅拌,TLC监测反应完成后,浓缩后用硅胶过柱得白色固体,产率为94%,ee值为98%。
1H NMR (400 MHz, CDCl3): δ 7.88 (d, J=7.6 Hz, 2H), 7.65-7.53 (m,3H),7.29-7.25 (m, 3H), 7.08 (t, J=4.4 Hz, 1H), 6.45 (d, J=5.6 Hz, 1H), 5.65 (dd, J=4.8 Hz, J=9.6 Hz,1H), 5.20 (d, J=9.6 Hz ,1H), 4.97-4.89 (m,2H), 4.04-3.99(m,1H) , 1.51 (s, 9H). 13C NMR(100 MHz, CDCl3): δ 156.1, 140.4, 133.5, 132.9,131.9, 129.9, 129.3, 128.8, 128.2, 127.1, 126.4, 125.9, 80.2, 51.3, 51.0,28.4 .
实施例5
Tert-butyl methyl ((1R,2S)-1,2-dihydronaphthalene-1,2-diyl)dicarbamate的合成:在氩气氛围下的无水无氧手套箱中,将2.3mg Pd(AcO)2 和7.5mg (R)-Binap在1mL 1,2-二氯乙烷中搅拌30min,紧接着加入3.9mg AgBF4搅拌10min,然后加入48.6mg 由Boc保护的氮杂苯并降冰片烯和1ml 1,2-二氯乙烷搅拌10min,再加入45mg 氨基甲酸甲酯,之后塞好塞子将反应拿出手套箱,将反应置于60℃的油浴锅中搅拌,TLC监测反应完成后,浓缩后用硅胶过柱得白色固体,产率为94%,ee值为90%。
1H NMR (400 MHz, CDCl3): δ 7.33-7.24 (m, 3H), 7.12 (d, J=8.4 Hz,1H),6.55 (d, J=9.6 Hz, 1H), 5.98 (dd, J=7.6Hz, J=9.2 Hz, 1H), 5.08-4.62 (m, 4H),3.68 (s, 3H), 1.48 (s,9H). 13C NMR(100 MHz, CDCl3): δ 156.9,155.9, 134.0,132.1, 129.2, 128.4, 128.3, 127.8, 126.9, 126.8, 80.0, 52.3, 51.4, 49.2,28.4.
实施例6
Tert-butyl((1R,2S)-2-((4-methoxyphenyl)sulfonamido)-1,2-dihydronaphthalen-1-yl)carbamate的合成:在氩气氛围下的无水无氧手套箱中,将2.3mgPd(AcO)2 和7.5mg ( R)-Binap在1mL 1,2-二氯乙烷中搅拌30min,紧接着加入3.9mg AgBF4搅拌10min,然后加入48.6mg 由Boc保护的氮杂苯并降冰片烯和1ml 1,2-二氯乙烷搅拌10min,再加入112.3mg对甲氧基苯磺酰胺,之后塞好塞子将反应拿出手套箱,将反应置于60℃的油浴锅中搅拌,TLC监测反应完成后,浓缩后用硅胶过柱得白色固体,产率为93%,ee值为98%。
1H NMR (400 MHz, CDCl3): δ 7.82-7.78 (m, 3H), 7.31-7.24 (m, 3H), 7.08-6.97 (m, 3H), 6.44 (d, J=9.6Hz, 1H), 5.67 (dd, J=5.6Hz, J=9.6 Hz ,1 H), 5.20(d, J=9.6 Hz, 1H), 4.90 (dd, J=4.8Hz, J=9.6 Hz, 1H), 3.75 (d, J=9.2 Hz, 1H ),3.97-3.92 (m, 1H), 3.89 (s, 3H), 1.49 (s,9H). 13C NMR(100 MHz, CDCl3): δ163.0, 156.1, 133.6, 131.9, 129.9, 129.3, 128.8, 128.2, 127.0, 126.6, 125.9,114.4, 80.1, 55.7, 51.3, 50.9, 28.4。
Claims (3)
2.根据权利要求1所述的合成(1R,2S)-1,2-二氢化萘-1,2-二胺衍生物的方法,其特征在于所述的过渡金属用量为氮杂苯并降冰片烯摩尔百分比0.1~10%。
3.根据权利要求2所述的合成(1R,2S)-1,2-二氢化萘-1,2-二胺衍生物的方法,其特征在于所述的过渡金属用量为氮杂苯并降冰片烯摩尔百分比5%。
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Rhodium-Catalyzed Asymmetric Alcoholysis and Aminolysis of Oxabenzonorbornadiene: A New Enantioselective Carbon-Heteroatom Bond Forming Process;Mark Lautens et al.;《Journal of the American Society》;20000524;第122卷;第5650-5651页 * |
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