CN117903174A - 手性萘啶-氮氧配体及其制备方法与在不对称催化反应中的应用 - Google Patents
手性萘啶-氮氧配体及其制备方法与在不对称催化反应中的应用 Download PDFInfo
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- 239000003446 ligand Substances 0.000 title claims abstract description 120
- 238000002360 preparation method Methods 0.000 title claims description 12
- 238000006555 catalytic reaction Methods 0.000 title abstract description 19
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims abstract description 50
- -1 nitroxide groups Chemical group 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 8
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 38
- 229960004042 diazoxide Drugs 0.000 claims description 25
- 238000003547 Friedel-Crafts alkylation reaction Methods 0.000 claims description 22
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 19
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 238000006482 condensation reaction Methods 0.000 claims description 6
- 239000012467 final product Substances 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 238000007254 oxidation reaction Methods 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
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- 239000002184 metal Substances 0.000 abstract description 11
- 229910052751 metal Inorganic materials 0.000 abstract description 11
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical group N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 abstract description 8
- 238000007036 catalytic synthesis reaction Methods 0.000 abstract description 4
- 150000002739 metals Chemical class 0.000 abstract description 3
- 238000001308 synthesis method Methods 0.000 abstract description 3
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- 230000003197 catalytic effect Effects 0.000 description 10
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- 229910000144 sodium(I) superoxide Inorganic materials 0.000 description 7
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- 150000001875 compounds Chemical class 0.000 description 5
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- 238000001228 spectrum Methods 0.000 description 5
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- 238000004440 column chromatography Methods 0.000 description 4
- 229910001873 dinitrogen Inorganic materials 0.000 description 4
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- 238000011160 research Methods 0.000 description 4
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- 239000002841 Lewis acid Substances 0.000 description 2
- 239000000460 chlorine Chemical group 0.000 description 2
- GDLBFKVLRPITMI-UHFFFAOYSA-N diazoxide Chemical group ClC1=CC=C2NC(C)=NS(=O)(=O)C2=C1 GDLBFKVLRPITMI-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Chemical group 0.000 description 2
- 229910052739 hydrogen Chemical group 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000001555 benzenes Chemical group 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000002221 olecranon process Anatomy 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- 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
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1825—Ligands comprising condensed ring systems, e.g. acridine, carbazole
- B01J31/183—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline
- B01J31/1835—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline comprising aliphatic or saturated rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- 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
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/847—Nickel
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- C07—ORGANIC CHEMISTRY
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Abstract
本发明公开了一种手性萘啶‑氮氧配体，此类手性萘啶‑氮氧配体包括以两种不同的合成路线获得的手性萘啶‑双氮氧配体Nap‑2NO；以及手性萘啶‑单氮氧配体Nap‑NO。该类配体包含萘啶基团和氮氧基团，可以和路易斯金属形成六元环配位，从而生成手性配体金属复合物，发明人还发现此类配体在不对称催化反应中作为手性配体应用。因此，在不对称催化合成领域具有重要的应用价值，且其合成方法非常经济简便。也具有较好的空气稳定性，适用性广，对于各种取代基都有很好的兼容性。
Description
技术领域
本发明涉及手性化学技术领域和不对称催化合成领域，尤其是一种手性萘啶-氮氧配体(Nap-2NO和Nap-NO)及其制备方法与在不对称催化吲哚参与的Friedel-Crafts烷基化反应中的应用。
背景技术
手性制药是医药行业的前沿领域，2001年和2021年诺贝尔化学奖就授予手性催化的主要贡献者。目前世界上使用的药物总数约为2000种，手性药物占50％以上，在临床常用的250种药物中，手性药物多达200种。
手性药物的关键制备技术入选IUPAC提出的“十大改变世界的化学技术发明”。不对称催化技术是获得手性分子最高效最绿色的途径,其核心科学问题之一是优势手性配体和催化剂的创制。原创性优势手性配体的设计和合成在不对称催化反应的发展中起着关键作用，是不对称催化中最具吸引力和挑战性的目标，可以为手性药物、候选药物的高效绿色合成提供了核心技术。此外，经济可行的合成路线对于优势手性配体也至关重要，因此它们才能得到广泛应用。特别地，胺的N-氧化物是高极性物质，通过吡啶类化合物或叔胺的N-氧化反应很容易制备胺的N-氧化物。N-氧化物中生成的氧原子属于富电子配位位点。因此，N-氧化物的电子对的独特性质提供了与多种金属形成络合物的机会。一些研究集中于开发用于金属催化反应的新型手性胺N-氧化物配体。
在叔胺衍生的N-氧化物中，如果母体叔胺包含三个不同的基团，则相应的N-氧基团上的氮中心将产生稳定手性中心。在这个背景下，因此，我们设计并开发了一个新类型的手性叔胺衍生的萘啶-双氮氧配体Nap-2NO，并测试了它们在吲哚不对称Friedel-Crafts烷基化反应中的应用。基于新类型手性萘啶-双氮氧配体金属复合物的设计合成，我们的设计思路参照"老鹰抓小鸡"仿生模型的多齿配体螯合催化机理：双氮氧基团类比喻两个鹰爪，金属类比喻小鸡，两个苯基类比喻老鹰的翅膀，萘啶的氮基团类比喻鹰嘴(如图1和图2所示)。
发明内容
本发明的目的是：提供一种手性萘啶-氮氧配体(Nap-2NO和Nap-NO)及其制备方法与应用，它是一类重要的手性萘啶-氮氧配体，该类配体包含萘啶基团和氮氧基团(萘啶的氮基团和氮氧基团的氧原子属于富电子配位位点)，可以和路易斯金属形成六元环配位，从而生成手性配体金属复合物，在不对称催化反应中作为手性配体应用。因此，在不对称催化合成领域具有重要的应用价值，且其合成方法非常经济简便。也具有较好的空气稳定性，适用性广，对于各种取代基都有很好的兼容性。
本发明是这样实现的：一种手性萘啶-氮氧配体(Nap-2NO和Nap-NO)，手性萘啶-双氮氧配体Nap-2NO具有如通式(Ⅰ)所示的结构，手性萘啶-单氮氧配体Nap-NO具有如通式(Ⅱ)所示的结构；
式中，R为羟基或氢；Ar为氟、氯、溴、乙基、甲基或氢取代的苯环。
手性萘啶-双氮氧配体Nap-2NO的制备方法，由相应的脯氨酰胺或羟脯氨酰胺1与萘啶-二甲醛2先发生缩合反应，生成中间体3，然后中间体3中的氮原子在氧化剂间氯过氧苯甲酸的作用下发生氮氧化反应，生成最终产物手性萘啶-双氮氧配体Nap-2NO。
合成路线如下：
手性萘啶-单氮氧配体Nap-NO的制备方法，由相应的脯氨酰胺或羟脯氨酰胺1与萘啶-单甲醛2先发生缩合反应，生成中间体3，然后中间体3中的氮原子在氧化剂间氯过氧苯甲酸的作用下发生氮氧化反应，生成最终产物手性萘啶-单氮氧配体Nap-NO。
合成路线如下：
本发明还发现手性萘啶-双氮氧配体Nap-2NO作为配体在不对称催化吲哚参与的Friedel-Crafts烷基化反应中的应用。
本发明还发现手性萘啶-单氮氧配体Nap-NO在不对称催化吲哚参与的Friedel-Crafts烷基化反应中的应用。
我们的设计思路是：
通过采用上述技术方案，由相应的脯氨酰胺或羟脯氨酰胺1与萘啶-二甲醛2先发生缩合反应，生成中间体3，然后中间体3中的氮原子在氧化剂间氯过氧苯甲酸的作用下发生氮氧化反应，生成最终产物手性萘啶-双氮氧配体Nap-2NO；由相应的脯氨酰胺或羟脯氨酰胺1与萘啶-单甲醛2先发生缩合反应，生成中间体3，然后中间体3中的氮原子在氧化剂间氯过氧苯甲酸的作用下发生氮氧化反应，生成最终产物手性萘啶-单氮氧配体Nap-NO。该类配体包含萘啶基团和氮氧基团(萘啶的氮基团和氮氧基团的氧原子属于富电子配位位点)，可以和路易斯金属形成六元环配位，从而生成手性配体金属复合物，在不对称催化反应中作为手性配体应用。因此，在不对称催化合成领域具有重要的应用价值，且其合成方法非常经济简便。也具有较好的空气稳定性，适用性广，对于各种取代基都有很好的兼容性。
附图说明
图1和图2为本发明所合成的手性萘啶-双氮氧配体复合物的设计思路及其创造性图；
图2中，双氮氧基团类比喻两个鹰爪，金属类比喻小鸡，两个苯基类比喻老鹰的翅膀，萘啶的氮基团类比喻鹰嘴；
图3和图4为本发明实施例的手性萘啶-双氮氧配体Nap-1-2NO谱图数据；
图5和图6为本发明实施例的手性萘啶-双氮氧配体Nap-2-2NO谱图数据；
图7和图8为本发明实施例的手性萘啶-单氮氧配体Nap-1-NO谱图数据；
图9和图10为本发明实施例的手性萘啶-单氮氧配体Nap-2-NO谱图数据；
图11为本发明的实施例的化合物6a的消旋体和手性液相谱图数据；
图12和图13为本发明实施例的化合物6a核磁谱图数据。
具体实施方式
(一)手性萘啶-双氮氧配体Nap-2NO的制备
手性萘啶-双氮氧配体Nap-1-2NO:将原料脯氨酰胺1a(2.5eq)与萘啶-二甲醛(1eq,0.78mmol)2溶于适量无水乙醇中，回流10h,反应液处理后，通过柱层析纯化，得到白色固体中间体3。将第二步反应的中间体3(100mg,1eq)与间氯过氧苯甲酸(2.5eq),溶于适量二氯甲烷中，在常温下反应20min,反应液处理后，通过柱层析纯化，得到白色固体Nap-1-2NO；熔点：247.1-247.9℃；总产率51％,>20:1dr。核磁共振和高分辨质谱测试结果如下：1HNMR(CD3OD,400MHz)δ:2.20-2.27(m,2H),2.44-2.58(m,6H),3.92-3.96(m,2H),4.13-4.20(m,2H),4.80-4.82(m,2H),7.02(s,2H),7.14-7.18(m,2H),7.26-7.30(m,4H),7.47-7.50(m,4H),7.95(d,J＝8.4Hz,2H),8.54(d,J＝8.4Hz,2H)；13C NMR(CD3OD,100MHz)δ:22.3,24.1,70.8,76.8,87.3,122.4,124.1,125.6,126.6,129.0,135.6,138.5,154.4,156.0,168.8；HRMS(ESI-TOF)m/z:Calcd.for C32H30N6NaO4[M+Na]+:585.2221；Found:585.2228。
通过实施例制备的手性萘啶-双氮氧配体Nap-2-2NO～Nap-13-2NO的制备方法同手性萘啶-双氮氧配体Nap-1-2NO，投料比与配体Nap-1-2NO相同，可得到配体Nap-2-2NO～Nap-13-2NO，反应产率见表1，但需强调的是实施例旨在阐述而不是限制本发明的范围。本发明的化合物不限于表1所表示的内容。
表1为制备手性萘啶-双氮氧配体Nap-2NO的化学结构
本实施例制备手性萘啶-双氮氧配体Nap-2-2NO:白色固体,熔点：247.1-247.9℃；总产率45％,>20:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.57-2.63(m,2H),2.83-2.90(m,2H),3.95(d,J＝12.4Hz,2H),4.41-4.45(m,2H),4.66(s,2H),5.02-5.05(m,2H),7.02(s,2H),7.14-7.17(m,2H),7.26-7.30(m,4H),7.46-7.48(m,4H),7.94(d,J＝8.4Hz,2H),8.52(d,J＝8.4Hz,2H)；13C NMR(CD3OD,100MHz)δ:35.1,69.8,76.5,76.8,87.9,122.6,124.2,125.7,126.7,129.0,135.4,138.5,154.3,155.6,168.0；HRMS(ESI-TOF)m/z:Calcd.for C32H30N6NaO6[M+Na]+:617.2119；Found:617.2118。
本实施例制备手性萘啶-双氮氧配体Nap-3-2NO:白色固体,熔点：231.3-232.2℃；总产率46％,19:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:1.08-1.12(m,6H),2.22-2.27(m,2H),2.45-2.59(m,10H),3.93-3.97(m,2H),4.13-4.20(m,2H),4.80-4.83(m,2H),6.99(s,2H),7.11(d,J＝8.8Hz,4H),7.39(d,J＝8.4Hz,4H),7.94(d,J＝8.4Hz,2H),8.53(d,J＝8.0Hz,2H)；13C NMR(CD3OD,100MHz)δ:14.6,22.3,24.1,27.9,70.8,76.9,87.6,122.7,124.1,125.6,128.3,133.1,138.4,143.2,154.4,156.0,168.7；HRMS(ESI-TOF)m/z:Calcd.for C36H38N6NaO4[M+Na]+:641.2834；Found:641.2826。
本实施例制备手性萘啶-双氮氧配体Nap-4-2NO:白色固体,熔点：246.7-247.1℃；总产率41％,>20:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.30-2.34(m,2H),2.46-2.64(m,6H),4.01-4.05(m,2H),4.25-4.34(m,2H),4.82-4.84(m,2H),6.85(s,2H),7.06-7.10(m,2H),7.22-7.27(m,2H),7.32-7.40(m,4H),7.90(d,J＝8.4Hz,2H),8.52(d,J＝8.4Hz,2H)；13C NMR(CD3OD,100MHz)δ:22.4,24.1,71.1,76.2,87.7,116.3(d,JCF＝19.4Hz),121.9(d,JCF＝12.1Hz),124.2,124.8(d,JCF＝3.3Hz),125.8,129.5,130.5(d,JCF＝8.2Hz),138.3,154.2,155.7,157.8(d,JCF＝248.4Hz),169.4；HRMS(ESI-TOF)m/z:Calcd.for C32H28F2N6NaO4[M+Na]+:621.2032；Found:621.2037。
本实施例制备手性萘啶-双氮氧配体Nap-5-2NO:白色固体,熔点：247.3-248.3℃；总产率51％,18:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.22-2.27(m,2H),2.46-2.58(m,6H),3.93-3.97(m,2H),4.14-4.21(m,2H),4.75-4.78(m,2H),7.05(s,2H),7.41-7.47(m,8H),7.97(d,J＝8.0Hz,2H),8.56(d,J＝8.4Hz,2H)；13C NMR(CD3OD,100MHz)δ:26.2,28.1,74.8,80.6,90.9,123.4,127.9,128.1,129.7,135.9,138.7,142.5,158.3,159.6,172.6；HRMS(ESI-TOF)m/z:Calcd.for C32H28Br2N6NaO4[M+Na]+:741.0417；Found:741.0405。
本实施例制备手性萘啶-双氮氧配体Nap-6-2NO:白色固体,熔点：260.4-260.9℃；总产率52％,17:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.23-2.28(m,2H),2.45-2.59(m,6H),3.93-3.97(m,2H),4.14-4.21(m,2H),4.75-4.78(m,2H),7.05(s,2H),7.27-7.30(m,4H),7.49-7.53(m,4H),7.97(d,J＝8.4Hz,2H),8.57(d,J＝8.4Hz,2H)；13C NMR(CD3OD,100MHz)δ:22.3,24.1,70.8,76.7,87.0,123.8,124.2,125.7,128.9,131.8,134.3,138.6,154.4,155.7,168.7；HRMS(ESI-TOF)m/z:Calcd.forC32H28Cl2N6NaO4[M+Na]+:653.1434；Found:653.1428。
本实施例制备手性萘啶-双氮氧配体Nap-7-2NO:白色固体,熔点：241.6-242.3℃；总产率45％,17:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:1.07-1.10(m,6H),2.47-2.53(m,4H),2.57-2.63(m,2H),2.83-2.89(m,2H),3.96(d,J＝12.4Hz,2H),4.41-4.45(m,2H),4.66(s,2H),5.03-5.06(m,2H),6.99(s,2H),7.10(d,J＝8.8Hz,4H),7.37(d,J＝8.4Hz,4H),7.93(d,J＝8.4Hz,2H),8.50(d,J＝8.4Hz,2H)；13C NMR(CD3OD,100MHz)δ:14.6,27.9,35.1,69.9,76.4,76.8,88.1,122.8,124.2,125.7,128.3,132.9,138.5,143.3,154.3,155.6,168.0；HRMS(ESI-TOF)m/z:Calcd.for C36H38N6NaO6[M+Na]+:673.2745；Found:673.2745。
本实施例制备手性萘啶-双氮氧配体Nap-8-2NO:白色固体,熔点：223.2-224.0℃；总产率41％,15:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.30-2.36(m,4H),2.51(s,6H),2.56-2.62(m,4H),3.99-4.04(m,2H),4.28-4.35(m,2H),4.82-4.86(m,2H),6.92(s,2H),7.08-7.12(m,2H),7.17-7.26(m,6H),7.84(d,J＝8.4Hz,2H),8.46(d,J＝8.4Hz,2H)；13C NMR(CD3OD,100MHz)δ:17.8,22.5,23.8,70.9,76.7,88.7,124.2,125.8,126.5,126.8,128.7,131.4,133.0,136.6,138.1,153.9,155.7,168.6；HRMS(ESI-TOF)m/z:Calcd.for C34H34N6NaO4[M+Na]+:613.2517；Found:613.2509。
本实施例制备手性萘啶-双氮氧配体Nap-9-2NO:白色固体,熔点：236.0-237.1℃；总产率40％,>20:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.33(s,6H),2.36-2.42(m,2H),2.48(s,6H),2.52-2.59(m,4H),2.63-2.70(m,2H),3.91-3.96(m,2H),4.30-4.37(m,2H),4.96-5.00(m,2H),6.80(s,2H),6.94-6.97(m,2H),7.04-7.10(m,4H),7.88(d,J＝8.4Hz,2H),8.36(d,J＝8.4Hz,2H)；13C NMR(CD3OD,100MHz)δ:18.4,18.7,22.8,24.0,70.6,77.2,88.2,123.9,125.7,128.8,129.0,129.5,131.0,135.4,137.6,138.0,153.0,155.0,168.1；HRMS(ESI-TOF)m/z:Calcd.for C36H38N6NaO4[M+Na]+:641.2845；Found:641.2836。
本实施例制备手性萘啶-双氮氧配体Nap-10-2NO:白色固体,熔点：239.0-239.9℃；总产率51％,18:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.21(s,6H),2.24-2.28(m,2H),2.45-2.58(m,6H),3.92-3.96(m,2H),4.13-4.20(m,2H),4.79-4.82(m,2H),6.97(s,2H),7.08(d,J＝8.4Hz,4H),7.35(d,J＝8.8Hz,4H),7.93(d,J＝8.4Hz,2H),8.53(d,J＝8.4Hz,2H)；13C NMR(CD3OD,100MHz)δ:19.6,22.3,24.1,70.8,76.9,87.6,122.6,124.0,125.6,129.4,132.9,136.8,138.4,154.4,156.0,168.7；HRMS(ESI-TOF)m/z:Calcd.for C34H34N6NaO4[M+Na]+:613.2534；Found:613.2529。
本实施例制备手性萘啶-双氮氧配体Nap-11-2NO:白色固体,熔点：245.7-246.6℃；总产率48％,17:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.26-2.29(m,2H),2.46-2.60(m,6H),3.95-3.99(m,2H),4.18-4.25(m,2H),4.78-4.81(m,2H),7.01-7.07(m,6H),7.50-7.53(m,4H),7.95(d,J＝8.4Hz,2H),8.55(d,J＝8.4Hz,2H)；13C NMR(CD3OD,100MHz)δ:22.3,24.1,70.8,76.7,87.6,115.6(d,JCF＝23.1Hz),124.2,125.3(d,JCF＝8.3Hz),125.8,131.5,138.5,154.4,155.8,160.8(d,JCF＝241.1Hz),168.9；HRMS(ESI-TOF)m/z:Calcd.for C32H28F2N6NaO4[M+Na]+:621.2032；Found:621.2036。
本实施例制备手性萘啶-双氮氧配体Nap-13-2NO:白色固体,熔点：232.9-233.2℃；总产率44％,12:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.56-2.62(m,2H),2.83-2.89(m,2H),3.96(d,J＝12.4Hz,2H),4.41-4.45(m,2H),4.65(s,2H),4.95-4.98(m,2H),7.09(s,2H),7.14-7.18(m,2H),7.28-7.30(m,2H),7.36-7.39(m,2H),7.87-7.88(m,2H),7.98(d,J＝8.4Hz,2H),8.55(d,J＝8.0Hz,2H)；13C NMR(CD3OD,100MHz)δ:35.2,69.9,76.4,76.6,87.3,120.7,122.1,124.3,125.5,125.9,129.4,130.4,136.8,138.6,154.2,155.1,168.1；HRMS(ESI-TOF)m/z:Calcd.for C32H28Br2N6NaO6[M+Na]+:773.0308；Found:773.0299。
(二)手性萘啶-单氮氧配体Nap-NO的制备
手性萘啶-单氮氧配体Nap-1-NO:将原料脯氨酰胺1a(1.5eq)与萘啶-单甲醛(1eq,0.78mmol)2溶于适量无水乙醇中，回流10h,反应液处理后，通过柱层析纯化，得到白色固体中间体3。将第二步反应的中间体3(100mg,1eq)与间氯过氧苯甲酸(1.5eq),溶于适量二氯甲烷中，在常温下反应20min,反应液处理后，通过柱层析纯化，得到白色固体Nap-1-NO,熔点：215.5-216.9℃；总产51％,12:1dr。核磁共振和高分辨质谱测试结果如下：1H NMR(CD3OD,400MHz)δ:2.25-2.32(m,1H),2.48-2.62(m,3H),3.96-4.01(m,1H),4.20-4.27(m,1H),4.85-4.88(m,1H),7.06(s,1H),7.13-7.17(m,1H),7.26-7.30(m,2H),7.53-7.55(m,2H),7.63-7.66(m,1H),7.93(d,J＝8.4Hz,1H),8.44-8.47(m,1H),8.49(d,J＝8.0Hz,1H),9.05-9.07(m,1H)；13C NMR(CD3OD,100MHz)δ:22.3,24.1,70.8,76.9,87.5,122.9,123.3,123.7,125.1,126.7,128.9,135.5,138.3,138.5,153.9,154.5,155.1,168.7；HRMS(ESI-TOF)m/z:Calcd.for C20H18N4NaO2[M+Na]+:369.1322；Found:369.1316。
通过实施例制备的手性萘啶-单氮氧配体Nap-2-NO～Nap-12-NO的制备方法同手性萘啶-单氮氧配体Bpy-1-NO，投料比与配体Nap-1-NO相同，可得到配体Nap-2-NO～Nap-12-NO，反应产率见表2，但需强调的是实施例旨在阐述而不是限制本发明的范围。本发明的化合物不限于表2所表示的内容。
表2为制备手性萘啶-单氮氧配体Nap-NO的化学结构
本实施例制备手性萘啶-单氮氧配体Nap-2-NO:白色固体,熔点：203.4-204.7℃；总产率47％,13:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.62-2.69(m,1H),2.87-2.93(m,1H),3.99(d,J＝8.4Hz,1H),4.48-4.53(m,1H),4.69-4.72(m,1H),5.08-5.11(m,1H),7.07(s,1H),7.13-7.17(m,1H),7.26-7.30(m,2H),7.50-7.53(m,2H),7.64-7.67(m,1H),7.91(d,J＝8.0Hz,1H),8.44-8.49(m,2H),9.06-9.08(m,1H)；13CNMR(CD3OD,100MHz)δ:35.1,69.9,76.4,76.8,88.0,123.0,123.3,123.7,125.1,126.8,128.9,135.3,138.3,138.5,154.0,154.4,154.7,168.1；HRMS(ESI-TOF)m/z:Calcd.forC20H18N4NaO3[M+Na]+:385.1271；Found:385.1267。
本实施例制备手性萘啶-单氮氧配体Nap-3-NO:白色固体,熔点：206.3-207.2℃；总产率46％,14:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:1.05-1.09(m,3H),2.27-2.30(m,1H),2.46-2.59(m,5H),3.96-4.01(m,1H),4.20-4.27(m,1H),4.85-4.88(m,1H),7.03(s,1H),7.11(d,J＝8.8Hz,2H),7.43(d,J＝8.8Hz,2H),7.62-7.65(m,1H),7.91(d,J＝8.4Hz,1H),8.43-8.45(m,1H),8.47(d,J＝8.4Hz,1H),9.04-9.06(m,1H)；13C NMR(CD3OD,100MHz)δ:14.5,22.3,24.1,27.8,70.8,76.9,87.7,123.2,123.3,123.7,125.1,128.3,133.0,138.3,138.4,143.4,153.9,154.4,155.2,168.7；HRMS(ESI-TOF)m/z:Calcd.for C22H22N4NaO2[M+Na]+:397.1635；Found:397.1632。
本实施例制备手性萘啶-单氮氧配体Nap-4-NO:白色固体,熔点：207.3-208.3℃；总产率49％,19:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.15(s,3H),2.34-2.37(m,1H),2.50(s,3H),2.54-2.69(m,3H),3.94-4.00(m,1H),4.36-4.41(m,1H),5.30-5.33(m,1H),6.78(s,1H),6.88-6.90(m,1H),7.05-7.07(m,2H),7.66-7.69(m,1H),7.79(d,J＝8.0Hz,1H),8.40(d,J＝8.4Hz,1H),8.44-8.46(m,1H),9.11-9.12(m,1H)；13C NMR(CD3OD,100MHz)δ:18.4,18.5,22.7,24.0,70.8,77.1,87.9,123.3,123.6,124.8,128.9,129.0,129.4,131.0,135.7,137.9,138.2,138.3,154.1,154.2,154.8,168.4；HRMS(ESI-TOF)m/z:Calcd.for C20H17ClN4NaO2[M+Na]+:403.0932；Found:403.0927。
本实施例制备手性萘啶-单氮氧配体Nap-6-NO:白色固体,熔点：208.0-208.7℃；总产率42％,20:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.31-2.36(m,1H),2.38(s,3H),2.48-2.64(m,3H),4.01-4.05(m,1H),4.30-4.37(m,1H),5.02-5.05(m,1H),6.86(s,1H),7.03-7.07(m,1H),7.15-7.23(m,3H),7.68-7.71(m,1H),7.80(d,J＝8.4Hz,1H),8.46-8.50(m,2H),9.12-9.14(m,1H)；13C NMR(CD3OD,100MHz)δ:17.4,22.5,24.0,71.0,76.8,88.5,123.3,123.7,125.1,126.6,128.8,131.3,133.0,136.5,138.4,138.5,154.1,154.4,155.3,169.0；HRMS(ESI-TOF)m/z:Calcd.forC21H20N4NaO2[M+Na]+:383.1478；Found:383.1481。
本实施例制备手性萘啶-单氮氧配体Nap-7-NO:白色固体,熔点：209.3-209.9℃；总产率40％,19:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:1.05-1.10(m,3H),2.48-2.51(m,2H),2.62-2.68(m,1H),2.86-2.93(m,1H),4.01(d,J＝12.4Hz,1H),4.48-4.53(m,1H),4.71(s,1H),5.09(d,J＝8.8Hz,1H),7.02(s,1H),7.09-7.12(m,2H),7.39-7.41(m,2H),7.63-7.68(m,1H),7.89(d,J＝8.0Hz,1H),8.45-8.47(m,2H),9.06-9.08(m,1H)；13C NMR(CD3OD,100MHz)δ:14.5,27.8,35.1,69.9,76.4,76.8,88.2,123.3,123.4,123.7,125.1,128.3,132.8,138.3,138.4,143.4,154.0,154.4,154.7,168.1；HRMS(ESI-TOF)m/z:Calcd.for C22H22N4NaO3[M+Na]+:413.1584；Found:413.1586。
本实施例制备手性萘啶-单氮氧配体Nap-8-NO:白色固体,熔点：205.3-205.7℃；总产率50％,>20:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.23(s,3H),2.25-2.30(m,1H),2.48-2.61(m,3H),3.96-4.00(m,1H),4.19-4.26(m,1H),4.84-4.86(m,1H),6.98(d,J＝7.6Hz,1H),7.04(s,1H),7.13-7.17(m,1H),7.28(d,J＝8.0Hz,1H),7.41(s,1H),7.65-7.68(m,1H),7.91(d,J＝8.4Hz,1H),8.47-8.51(m,2H),9.06-9.08(m,1H)；13C NMR(CD3OD,100MHz)δ:19.9,22.3,24.1,70.8,76.9,87.6,120.0,123.3,123.6,123.7,125.1,127.4,128.7,135.3,138.3,138.4,139.2,153.9,154.4,155.2,168.7；HRMS(ESI-TOF)m/z:Calcd.for C21H20N4NaO2[M+Na]+:383.1478；Found:383.1477。
本实施例制备手性萘啶-单氮氧配体Nap-9-NO:白色固体,熔点：204.4-205.2℃；总产率52％,15:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.19(s,3H),2.25-2.30(m,1H),2.47-2.62(m,3H),3.96-4.00(m,1H),4.20-4.27(m,1H),4.84-4.88(m,1H),7.01(s,1H),7.08(d,J＝8.4Hz,2H),7.39(d,J＝8.8Hz,2H),7.64-7.67(m,1H),7.90(d,J＝8.4Hz,1H),8.45-8.48(m,1H),8.49(d,J＝8.4Hz,1H),9.06-9.07(m,1H)；13C NMR(CD3OD,100MHz)δ:19.5,22.3,24.1,70.8,76.9,87.7,123.1,123.3,123.7,125.1,129.4,132.8,137.0,138.3,138.4,153.9,154.4,155.2,168.7；HRMS(ESI-TOF)m/z:Calcd.for C21H20N4NaO2[M+Na]+:383.1478；Found:383.1475。
本实施例制备手性萘啶-单氮氧配体Nap-10-NO:白色固体,熔点：203.4-204.2℃；总产率47％,17:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.63-2.69(m,1H),2.88-2.94(m,1H),4.01(d,J＝12.4Hz,1H),4.46-4.51(m,1H),4.69-4.72(m,1H),5.06-5.10(m,1H),6.87-6.92(m,1H),7.13(s,1H),7.23-7.31(m,2H),7.53-7.56(m,1H),7.67-7.70(m,1H),7.97(d,J＝8.4Hz,1H),8.49-8.51(m,1H),8.53(d,J＝8.4Hz,1H),9.07-9.09(m,1H)；13CNMR(CD3OD,100MHz)δ:35.1,69.9,76.5,76.7,87.4,109.7(d,JCF＝26.1Hz),113.1(d,JCF＝21.2Hz),117.6(d,JCF＝3.3Hz),123.4,123.8,125.2,130.3(d,JCF＝9.1Hz),136.9(d,JCF＝10.0Hz),138.5(d,JCF＝26.1Hz),154.1,154.4(d,JCF＝4.4Hz),162.4(d,JCF＝244.2Hz),168.0；HRMS(ESI-TOF)m/z:Calcd.for C20H17FN4NaO3[M+Na]+:403.1177；Found:403.1181。
本实施例制备手性萘啶-单氮氧配体Nap-12-NO:白色固体,熔点：188.0-188.9℃；总产率50％,19:1dr；核磁共振和高分辨质谱测试等结果如下：1H NMR(CD3OD,400MHz)δ:2.28-2.32(m,1H),2.47-2.63(m,3H),3.97-4.01(m,1H),4.23-4.30(m,1H),4.82-4.89(m,1H),7.02-7.07(m,3H),7.55-7.58(m,2H),7.68-7.71(m,1H),7.91(d,J＝8.0Hz,1H),8.49-8.54(m,2H),9.08-9.10(m,1H)；13C NMR(CD3OD,100MHz)δ:22.3,24.0,70.8,76.7,87.7,115.6(d,JCF＝21.3Hz),123.3,123.7,125.2,125.7(d,JCF＝8.3Hz),138.4(d,JCF＝17.4Hz),154.0,154.4,154.9,161.3(d,JCF＝244.3Hz),168.8；HRMS(ESI-TOF)m/z:Calcd.for C20H17FN4NaO2[M+Na]+:387.1228；Found:387.1233。
(三)手性萘啶-氮氧配体(Nap-2NO和Nap-NO)在不对称催化吲哚Friedel-Crafts烷基化反应中的应用
本发明的式(1)手性萘啶-氮氧配体(Nap-2NO和Nap-NO)，该类配体包含萘啶基团和氮氧基团(萘啶的氮原子和氮氧基团的氧原子属于富电子配位位点)，从而可以和路易斯金属形成六元环配位，生成手性配体金属复合物，在不对称催化吲哚参与的Friedel-Crafts烷基化反应中作为优势手性配体应用。但需强调的是本发明的手性萘啶-氮氧配体不限于只在不对称催化吲哚Friedel-Crafts烷基化反应中作为手性配体应用。
实施例1：各种取代基的手性配体Nap-2NO在吲哚4a与硝基苯乙烯5a的不对称催化Friedel-Crafts烷基化反应中的应用
为了证明所开发的手性配体Nap-2NO在不对称催化体系中的应用价值，我们选择吲哚4a和硝基苯乙烯5a的参与Friedel-Crafts烷基化反应作为模板反应，选择化合物Nap-1-2NO～Nap-13-2NO作为手性萘啶-双氮氧配体与路易斯酸Ni(OTf)2原位生成手性复合物，验证手性配体Nap-2NO的不对称催化效果(表3)。
表3为各种取代基的手性配体Nap-2NO在不对称催化反应中的应用
实验结论：选择不对称催化吲哚4a和硝基苯乙烯5a的Friedel-Crafts烷基化模板反应作为评价指标。实验结果表明此类式(1)所示的各种取代基的手性配体Nap-1-2NO～Nap-13-2NO对吲哚4a和硝基苯乙烯5a参与的Friedel-Crafts烷基化反应中都显示了不对称催化效果，能够发展成新的优势手性萘啶-双氮氧配体Nap-2NO，值得继续深入研究下去。
实施例2：手性配体Nap-1-2NO在各种取代基的吲哚4与各种取代基的硝基苯乙烯5的不对称催化Friedel-Crafts烷基化反应中的应用
为了证明所开发的手性配体Nap-1-2NO在不对称催化体系中的应用价值，我们选择各种取代基的吲哚4与各种取代基的硝基苯乙烯5的Friedel-Crafts烷基化反应作为模板反应，验证手性配体Nap-1-2NO的催化效果(表4)。
表4为手性配体Nap-1-2NO在不对称催化各种取代基的吲哚4与各种取代基的硝基苯乙烯5的Friedel-Crafts烷基化反应中的应用
实验结论：选择不对称催化各种取代基的吲哚4与各种取代基的硝基苯乙烯5的Friedel-Crafts烷基化模板反应作为评价指标。实验结果表明此类式(1)所示的手性配体Nap-1-2NO与Ni(OTf)2原位生成手性复合物对各种取代基的吲哚4与各种取代基的硝基苯乙烯5的Friedel-Crafts烷基化反应中都显示了不对称催化效果，能够发展成新的优势手性萘啶-双氮氧配体，值得继续深入研究下去。
实施例3：各种取代基的手性配体Nap-NO在催化吲哚4a和硝基苯乙烯5a的不对称Friedel-Crafts烷基化反应中的应用
为了证明所开发的手性配体Nap-NO在不对称催化体系中的应用价值，我们选择吲哚4a和硝基苯乙烯5a参与的Friedel-Crafts烷基化反应作为模板反应，选择化合物Nap-1-NO～Nap-12-NO作为手性萘啶-单氮氧配体与路易斯酸Ni(OTf)2原位生成手性复合物，验证手性配体Nap-NO的不对称催化效果(表5)。
表5为各种取代基的手性配体Nap-NO在不对称催化反应中的应用
实验结论：选择不对称催化吲哚4a和烯酮酯6a的Friedel-Crafts烷基化模板反应作为评价指标。实验结果表明此类式(1)所示的各种取代基的手性配体Nap-1-NO～Nap-12-NO对吲哚4a和烯酮酯6a参与的Friedel-Crafts烷基化反应中都显示了不对称催化效果，能够发展成新的手性萘啶-单氮氧配体Nap-NO，值得继续深入研究下去。
Claims (5)
1.一种手性萘啶-氮氧配体，其特征在于：手性萘啶-氮氧配体包括萘啶-双氮氧配体Nap-2NO和萘啶-单氮氧配体Nap-NO，手性萘啶-双氮氧配体Nap-2NO具有如通式(Ⅰ)所示的结构，手性萘啶-单氮氧配体Nap-NO具有如通式(Ⅱ)所示的结构；
其中，手性萘啶-双氮氧配体Nap-2NO具体为如下结构式之一:
手性萘啶-单氮氧配体Nap-NO具体为如下结构式之一:
2.一种如权利要求1所述的手性萘啶-双氮氧配体Nap-2NO的制备方法，其特征在于：由相应的脯氨酰胺或羟脯氨酰胺1与萘啶-二甲醛2先发生缩合反应，生成中间体3，然后中间体3中的氮原子在氧化剂间氯过氧苯甲酸的作用下发生氮氧化反应，生成最终产物手性萘啶-双氮氧配体Nap-2NO；
合成路线如下：
3.一种如权利要求1所述的手性萘啶-单氮氧配体Nap-NO的制备方法，其特征在于：由相应的脯氨酰胺或羟脯氨酰胺1与萘啶-单甲醛2先发生缩合反应，生成中间体3，然后中间体3中的氮原子在氧化剂间氯过氧苯甲酸的作用下发生氮氧化反应，生成最终产物手性联吡啶-单氮氧配体Nap-NO；
合成路线如下：
4.一种如权利要求1所述的手性萘啶-双氮氧配体Nap-2NO作为配体在不对称催化吲哚参与的Friedel-Crafts烷基化反应中的应用。
5.一种如权利要求1所述的手性萘啶-单氮氧配体Nap-NO在不对称催化吲哚参与的Friedel-Crafts烷基化反应中的应用。
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