CN104558014B - 具有3,4‑二氢异喹啉骨架的手性氮杂环卡宾前体盐、合成方法及用途 - Google Patents

具有3,4‑二氢异喹啉骨架的手性氮杂环卡宾前体盐、合成方法及用途 Download PDF

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CN104558014B
CN104558014B CN201510054189.7A CN201510054189A CN104558014B CN 104558014 B CN104558014 B CN 104558014B CN 201510054189 A CN201510054189 A CN 201510054189A CN 104558014 B CN104558014 B CN 104558014B
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游书力
李国泰
顾庆
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

本发明提供了一种具有3,4‑二氢异喹啉骨架的手性氮杂环卡宾前体盐、合成方法及用途。该类前体盐具有如下结构式：

Description

具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐、合成方 法及用途
技术领域
本发明涉及一类手性氮杂环卡宾前体盐、合成方法及用途，即一种具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐、合成方法及用途。
背景技术
近二十年来，氮杂环卡宾作为有机小分子催化剂得到了化学家们的广泛关注[(a)D.Enders and T.Balensiefer,Acc.Chem.Res.2004,37,534.(b)D.Enders,O.Niemeier,A.Henseler,Chem.Rev.2007,107,5606；(c)V.Nair,S.Vellalath,B.P.Babu,Chem.Soc.Rev.2008,37,2691；(d)A.T.Biju,N.Kuhl,F.Glorius,Acc.Chem.Res.2011,44,1182；(e)A.Grossmann,D.Enders,Angew.Chem.Int.Ed.2012,51,314；Angew.Chem.2012,124,320；(f)J.Izquierdo,G.E.Hutson,D.T.Cohen,K.A.Scheidt,Angew.Chem.Int.Ed.2012,51,11686；Angew.Chem.2012,124,11854；(g)S.J.Ryan,L.Candish,D.W.Lupton,Chem.Soc.Rev.2013,42,4906；(h)J.Mahatthananchai,J.W.Bode,Acc.Chem.Res.2014,47,696；(i)M.N.Hopkinson,C.Richter,M.Schedler,F.Glorius,Nature2014,510,485.]。
随着有机化学家们对氮杂环卡宾催化剂研究的日趋成熟，氮杂环卡宾催化的底物范围和反应类型丰富扩大，在有机合成中显示出了重要的作用。这其中陆续出现的一些优秀的氮杂环卡宾催化剂，在这一领域的发展中起到了举足轻重的作用。其中，具有并环结构的三氮唑卡宾催化剂在手性控制上具有显著的优势，在不对称合成中具有重要的应用。[(a)D.Enders,O.Niemeier,T.Balensiefer,Angew.Chem.,Int.Ed.2006,45,1463.(b)M.He,J.R.Struble,J.W.Bode,J.Am.Chem.Soc.2006,128,8418.(c)Q.Liu,S.Perreault,and T.Rovis,J.Am.Chem.Soc.2008,130,14066.(d)D.A.DiRocco,K.M.Oberg,D.M.Dalton,T.Rovis,J.Am.Chem.Soc.2009,131,10872.(e)L.Baragwanath,C.A.Rose,K.Zeitler,S.J.Connon,J.Org.Chem.2009,74,9214；(f)S.De Sarkar,A.Studer,Angew.Chem.2010,122,9452；Angew.Chem.Int.Ed.2010,49,9266；(g)S.J.Ryan,L.Candish,D.W.Lupton,J.Am.Chem.Soc.2011,133,4694；(h)M.-Q Jia,S.-L.You,Chem.Commun.2012,48,6363；()A.Grossmann,D.Enders,Angew.Chem.2012,124,320；Angew.Chem.Int.Ed.2012,51,314(i)H.Lv,W.-Q.Jia,L.-H.Sun,S.Ye,Angew.Chem.2013,125,8769；Angew.Chem.Int.Ed.2013,52,8607.(j)X.-Y.Chen,Z.-H.Gao,C.-Y.Song,C.-L.Zhang,Z-X.Wang,S.Ye,Angew.Chem.2014,126,11795,Angew.Chem.Int.Ed.2014,53,11611.]。但总体而言，目前氮杂环卡宾催化剂的骨架结构仍然有限，导致现在仍有大量反应在已有的氮杂环卡宾催化剂作用下无法取得理想的手性控制，比如萘并吡喃酮类化合物的催化不对称合成用现有的催化剂无法得到理想的对映选择性控制。(J.Kaeobamrung,J.Mahatthananchai,P.Zheng.J.W.Bode,J.Am.Chem.Soc.2010,132,8810；c)J.Mahatthananchai,J.Kaeobamrung,J.W.Bode,ACS Catal.2012,2,494；d)S.R.Yetra,A.Bhunia,A.Patra,M.V.Mane,K.Vanka,A.T.Biju,Adv.Synth.Catal.2013,355,1089.)。
寻找新型骨架的手性氮杂环卡宾催化剂并且使之适用于一些反应或者更多反应并能具有好的催化活性及对映选择性一直是化学工作者研究的热点之一。
为了解决这些问题，我们从商业可得的手性苯丙氨酸甲酯盐酸盐出发合成了具有3,4-二氢异喹啉骨架的手性氮杂环卡宾催化剂，该催化剂合成步骤简单，并容易通过重结晶提纯，在诸多氮杂环卡宾催化的反应中都具有非常好的效果。因此该催化剂对于氮杂环卡宾催化剂骨架的丰富和反应条件的优化都具有重要的意义。
发明内容
本发明的目的之一是提供一种具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐。
本发明的目的之二是提供该种手性氮杂环卡宾前体盐的合成方法。
本发明的目的之三是提供该种手性氮杂环卡宾前体盐的用途。
本发明提供一种具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐，其结构式为
进一步说可以为或
其中R1及R2任意选自C1～C16的烷基、芳基及取代的芳基；上述的芳基为苯基、1-萘基、2-萘基，9-蒽基、9-菲基；R3为H、芳基及C1～C16的烷基取代的硅基；X任意选自Cl、Br、I、OTf、BF4或ClO4；所述取代芳基上的取代基任意选自F、Cl、Br、I、C1～C16的烃氧基、C1～C16的烷基或C1～C16的氟代烷基、硝基或氨基。
本发明提供的氮杂环卡宾的前体盐的合成方法是从苯丙氨酸甲酯盐酸盐出发合成制得。根据具体结构，可分别用以下两个方程式表示：
方程式1：
方程式2：
反应方程式2中solvent指有机溶剂。
脱除保护基R3用的酸根据X的不同可为盐酸、氢溴酸、氢碘酸、四氟硼酸、三氟甲磺酸或高氯酸等。
其中R1及R2任意选自C1～C16的烷基、芳基及取代的芳基；R3为H、芳基及C1～C16的烷基取代的硅基；上述的芳基为苯基、1-萘基、2-萘基，9-蒽基、9-菲基；所述取代芳基上的取代基任意选自F、Cl、Br、I、C1～C16的烃氧基、C1～C16的烷基或C1～C16的氟代烷基、硝基或氨基；X任意选自Cl、Br、I、OTf、BF4或ClO4。
所述的3,4-二氢异喹啉酮、分子式H2NNHR2的肼、梅尔外因试剂、原甲酸三烷酯的摩尔比依次为1：1～2：1～2：5～10。反应在温度为-78℃至120℃，反应快慢跟温度有关，不同反应部分，反应的温度不同，具体温度及反应时间参考实例。
本发明方法中，所述有机溶剂可以是极性或非极性溶剂。如苯、四氯化碳、四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、三氯甲烷、甲苯、二甲苯、环己烷、正己烷、正庚烷、二氧六环或乙腈等，推荐有机溶剂为二氯甲烷和氯苯。
反应产生的副产物通常可以用柱层析或重结晶的方法顺利分开。反应产物即本发明的一种具有3,4-二氢异喹啉手性氮杂环卡宾前体盐。采用本发明方法所得产物－氮杂环卡宾前体盐以经过重结晶，薄层层析，柱层析等方法加以分离。如用重结晶的方法，推荐有机溶剂为极性有机溶剂与非极性有机溶剂的混合溶剂。推荐有机溶剂可为甲醇－丙酮、甲醇－乙酸乙酯、二氯甲烷―正己烷、异丙醇―石油醚、乙酸乙酯―石油醚、乙酸乙酯―正己烷或异丙醇―乙酸乙酯―石油醚等混合溶剂。用薄层层析和柱层析方法，所用的展开剂为极性有机溶剂与非极性有机溶剂的混合溶剂。推荐有机溶剂可为异丙醇―石油醚、乙酸乙酯―石油醚、乙酸乙酯―正己烷或异丙醇―乙酸乙酯―石油醚等混合溶剂，其体积比可以分别是：极性溶剂：非极性溶剂＝1：0.1～500。例如：乙酸乙酯：石油醚＝1：0.1～50，异丙醇：石油醚＝1：0.1～500。
本发明的具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐可以应用在氮杂环卡宾催化的反应中，并有效地制备手性的萘并吡喃酮类化合物。
本发明提供了一种全新的氮杂环卡宾催化剂前体盐，该化合物的合成方法简便、条件温和、起始原料便宜易得，适于工业化。该催化剂可用于氮杂环卡宾催化的多种反应，与现有的氮杂环卡宾催化剂前体盐相比，催化反应速率、产率、对映选择性都有很大的改进和提高，具有较高的实际应用价值，且适于大量生产。
具体实施方式
通过下述实施例将有助于理解本发明，但并不限制本发明的内容。
实施例1：手性3,4-二氢异喹啉酮的合成
0℃下，苯丙氨酸甲酯盐酸盐(1当量)加入二氯甲烷(3mL/mmol)搅拌，加入饱和碳酸氢钠溶液(3mL/mmol)，剧烈搅拌约15分钟至不再有气体放出。加入三光气(1当量)，剧烈搅拌15分钟。停止搅拌，分液，水相用二氯甲烷萃取两次，合并有机相，无水硫酸钠干燥，减压旋出溶剂，油泵抽干，直接用于下步反应。冰浴下，上步反应产物溶于二氯甲烷(3mL/mmol),缓慢加入无水三氯化铝并剧烈搅拌，加完后恢复至室温，并开始回流反应。TLC检测原料彻底反应完后，冰浴下缓慢加水淬灭，并继续搅拌30分钟。分液，水相用二氯甲烷提取三次，有机相合并，无水硫酸钠干燥，减压旋出溶剂，柱层析提纯(乙酸乙酯/石油醚＝1/10-1/4)。
在氩气保护下，将1溶于四氢呋喃(1mL/mmol)，冷至-70℃，缓慢滴加芳基格氏试剂(5当量,3M的四氢呋喃F溶液)，加完后在该温度下继续反应10分钟，将温度升至0℃继续反应2小时，TLC监测原料完全反应完。缓慢加入5％的盐酸淬灭反应，此时会有大量的白色沉淀产生，将白色沉淀过滤而出，并用石油醚和少量的乙酸乙酯清洗。母液分液，有机相分离出，水相用乙酸乙酯提取两次，合并有机相，饱和食盐水清洗，无水硫酸钠干燥，过滤，减压旋出溶剂。固体用石油醚和少量乙酸乙酯清洗。两次得到的固体合并，油泵抽干残留的溶剂，直接用于下步反应。
在氩气保护下，上步得到的固体溶于二氯甲烷(1mL/mmol)中，加入三乙胺(4当量)，冷至0℃下，缓慢滴加三氟甲磺酸三甲基硅酯(4当量)，加完后体系变成澄清的溶液，0℃下反应继续0.5h，TLC监测原料彻底反应完。0℃下滴加蒸馏水淬灭反应。分液，水相用二氯甲烷提取两次，合并有机相，饱和食盐水清洗，无水硫酸钠干燥，过滤，减压选出溶剂，柱层析提纯(乙酸乙酯：石油醚＝1:4)。
4.04g,83％产率yield(12.14mmol)(乙酸乙酯EA/石油醚PE＝1/4)；[α]D 20＝-94.9(c＝0.5,CHCl3)；m.p.＝142-143℃；1H NMR(300MHz,CDCl3)δ7.98(d,J＝7.5Hz,1H),7.44-7.24(m,12H),7.07(d,J＝7.5Hz,1H),6.06(s,1H),4.78(dd,J＝11.4,4.8Hz,1H),2.88(dd,J＝15.9,11.4Hz,1H),2.77(dd,J＝15.9,4.8Hz,1H),-0.07(s,9H)；HRMS(ESI)计算值calcdfor C25H28NO2Si[M+H]+:402.1884；实测值Found:402.1883.
2.8g,79％yield(7.8mmol),(EA/PE＝1/7),[α]D 20＝-103.6(c＝0.5,CHCl3),m.p.＝93-94℃.1H NMR(400MHz,CDCl3)δ7.98(d,J＝7.6Hz,1H),7.36(td,J＝7.6,1.2Hz,1H),7.25(t,J＝7.6Hz,1H),7.07(d,J＝7.6Hz,1H),7.00(s,2H),6.95(s,2H),6.88(s,2H),6.04(s,1H),4.72(dd,J＝11.6,4.8Hz,1H),2.92(dd,J＝16.0,11.6Hz,1H),2.73(dd,J＝16.0,4.4Hz,1H),2.28(s,12H),-0.06(s,9H)；HRMS(ESI)calcd for C29H36NO2Si[M+H]+:458.2510；Found:458.2515.
0.47g,41％yield(EA/PE＝1/4),[α]D 20＝-63.4.(c＝0.5,CHCl3),m.p.＝74-75℃.1H NMR(400MHz,CDCl3)δ8.08(d,J＝7.6Hz,1H),7.44(t,J＝7.6Hz,1H),7.34(t,J＝7.6Hz,1H),7.20(d,J＝7.6Hz,1H),6.25(s,1H),3.60(dd,J＝10.4,6.4Hz,1H),2.88–2.77(m,2H),1.35(s,3H),1.27(s,3H),0.16(s,9H)；HRMS(ESI)calcd for C15H24NO2Si[M+H]+:278.1571；Found:278.1575.
3.6g,91％yield(8.4mmol),EA/PE＝1/4,[α]D 20＝-108.3(c＝0.5,CHCl3),m.p.＝65-67℃.1H NMR(400MHz,CDCl3)δ7.96(d,J＝7.6Hz,1H),7.36(t,J＝7.6Hz,1H),7.34–7.22(m,5H),7.14–7.06(m,5H),6.07(s,1H),4.73(dd,J＝10.8,5.6Hz,1H),2.88–2.75(m,2H),2.33(s,6H),-0.09(s,9H)；HRMS(ESI)calcd for C27H32NO2Si[M+H]+:430.2197；Found:430.2198.
3.9g,93％yield(8.38mmol),EA/PE＝1/4,[α]D 20＝-153.3(c＝0.5,CHCl3),m.p.＝113-114℃.1H NMR(400MHz,CDCl3)δ8.03-8.98(m,3H),7.89–7.74(m,6H),7.57-7.45(m,5H),7.38-7.32(m,2H),7.27–7.23(m,1H),7.05(d,J＝7.6Hz,1H),6.28(s,1H),5.04(dd,J＝12.0,4.4Hz,1H),3.05(dd,J＝16.0,12.0Hz,1H),2.79(dd,J＝16.0,4.0Hz,1H),-0.00(d,J＝3.3Hz,9H)；HRMS(ESI)calcd for C33H32NO2Si[M+H]+:502.2197；Found:502.2197.
MS(ESI):[M+H]+501.2124
在氩气保护下，将由格氏试剂加成得到的固体溶于二氯甲烷(1mL/mmol)中，加入2,6-二甲基吡啶(4当量)，冷至0℃下，缓慢滴加三氟甲磺酸叔丁基二甲基硅酯(TBSOTf)(4当量)，加完后升至室温，继续反应24h。0℃下补加4当量的2,6-二甲基吡啶和TBSOTf，室温下继续反应12h，TLC监测原料彻底反应完。0℃下缓慢滴加蒸馏水淬灭，分液，有机相分离出，水相用二氯甲烷提取两次，合并有机相，饱和食盐水清洗，无水硫酸钠干燥，减压选出溶剂，柱层析提纯(EA：PE＝1:4)。
5.76g,86％yield(15.17mmol)(EA/PE＝1/4),[α]D 20＝-118.8(c＝0.5,CHCl3),m.p.＝155–156℃.1H NMR(300MHz,CDCl3)δ7.95(d,J＝7.5Hz,1H),7.44–7.22(m,12H),7.07(d,J＝7.5Hz,1H),6.11(s,1H),4.78(dd,J＝9.9,5.7Hz,1H),2.96–2.80(m,2H),1.00(s,9H),-0.31(s,3H),-0.36(s,3H)；HRMS(ESI)calcd for C28H34NO2Si[M+H]+:444.2353；Found:444.2357.
实施例2：羟基保护的手性3,4-二氢异喹啉骨架的氮杂环卡宾前体盐的合成
实施例1中的3,4-二氢异喹啉酮(1当量)溶于二氯甲烷(10mL/mmol)，三甲基氧四氟硼酸盐(Meerwein试剂，1.4当量)快速加入，20℃下反应12h。肼R2NHNH2(1.4当量)室温下继续反应48h。减压除去溶剂,原甲酸三乙酯(10mL/mmol)加入，80℃下继续反应。核磁监测原料彻底反应完,减压除去溶剂。柱层析初步提纯，并用乙酸乙酯和石油醚重结晶。
1.05g,59％yield(3mmol),(EA/PE＝1/4-1/1)[α]D 20＝-29.8(c＝0.5,CHCl3),m.p.＝197-198℃.1H NMR(300MHz,CDCl3)δ10.12(s,1H),7.98(d,J＝7.8Hz,2H),7.69-7.59(m,5H),7.53-7.48(m,4H),7.32(t,J＝7.5Hz,1H),7.10(t,J＝7.5Hz,1H),7.01(d,J＝7.8Hz,1H),6.99–6.94(m,1H),6.84(s,4H),6.40(d,J＝8.7Hz,1H),3.92(dd,J＝18.0,8.7Hz,1H),3.40(d,J＝18.3Hz,1H),-0.22(s,9H)；19F NMR(400MHz,CDCl3)δ-151.58；HRMS(ESI)calcd for C32H32N3OSi[M–BF4]+:502.2309；Found:502.2323.
0.70g,38％yield(3mmol),(EA/PE＝1/4-1/1),[α]D 20＝-47.6(c＝0.5,CHCl3),m.p.＝150-151℃.1H NMR(300MHz,CDCl3)δ9.99(s,1H),7.88(d,J＝9.0Hz,2H),7.62-7.58(m,2H),7.51-7.46(m,4H),7.31(t,J＝7.5Hz,1H),7.14–7.06(m,3H),7.02–6.94(m,2H),6.86–6.79(m,4H),6.37(d,J＝9.0Hz,1H),3.96–3.85(m,4H),3.39(d,J＝18.3Hz,1H),-0.22(s,9H)；19F NMR(376MHz,CDCl3)δ-151.59；HRMS(ESI)calcd for C33H34N3O2Si[M–BF4]+:532.2415；Found:532.2432.
0.8g,42％yield(3.0mmol),(EA/PE＝1/4-1/1)[α]D 20＝-15.0(c＝0.5,CHCl3),m.p.＝215–216℃.1H NMR(300MHz,CDCl3)δ9.54(s,1H),7.65(bs,2H),7.50-7.47(m,3H),7.39(d,J＝7.8Hz,1H),7.32(t,J＝7.5Hz,1H),7.09–6.92(m,7H),6.81(t,J＝7.2Hz,2H),6.50(d,J＝9.3Hz,1H),4.04(dd,J＝18.3,9.0Hz,1H),3.41(d,J＝18.3Hz,1H),2.40(s,3H),2.26(s,6H),-0.23(s,9H)；HRMS(ESI)calcd for C35H38N3OSi[M–BF4]+:544.2779；Found:544.2788.
2.3g,27％yield(12.5mmol),(EA/PE＝1/3-1/1),[α]D 20＝-27.8(c＝0.5,CHCl3),m.p.＝247-248℃.1H NMR(300MHz,CDCl3)δ10.11(s,1H),7.61-7.58(m,2H),7.51–7.48(m,3H),7.38–7.34(m,2H),7.10(t,J＝7.5Hz,1H),7.04(d,J＝8.1Hz,1H),6.98(t,J＝6.9Hz,1H),6.88-6.78(m,4H),6.27(d,J＝9.0Hz,1H),3.96(dd,J＝18.3,9.3Hz,1H),3.43(d,J＝18.0Hz,1H),-0.20(s,9H)；19F NMR(282MHz,CDCl3)δ-144.8(m),-145.9(m),-152.4,-158.4(m)；HRMS(ESI)calcd for C32H27F5N3OSi[M–BF4]+:592.1838；Found:592.1853.
1.1g,61％yield(2.5mmol),(EA/PE＝1/4-1/1),[α]D 20＝-26.4(c＝0.5,CHCl3),m.p.＝184-185℃.1H NMR(400MHz,CDCl3)δ10.33(s,1H),8.51(s,2H),8.11(s,1H),7.59-7.57(m,3H),7.52-7.50(m,3H),7.38(t,J＝7.6Hz,1H),7.15(t,J＝7.6Hz,1H),7.05(d,J＝7.6Hz,1H),7.03-6.98(m,1H),6.85(d,J＝4.4Hz,4H),6.39(d,J＝9.2Hz,1H),3.95(dd,J＝18.0,9.2Hz,1H),3.44(d,J＝18.0Hz,1H),-0.19(s,9H)；HRMS(ESI)calcd forC34H30F6N3OSi[M–BF4]+:638.2057；Found:638.2064.
MS(ESI):570[M-BF4]+.
MS(ESI):536[M-BF4]+.
MS(ESI):570[M-BF4]+.
MS(ESI):586[M-BF4]+.
MS(ESI):516[M-BF4]+.
MS(ESI):530[M-BF4]+.
MS(ESI):547[M-BF4]+.
MS(ESI):602[M-BF4]+.
MS(ESI):602[M-BF4]+.
MS(ESI):552[M-BF4]+.
MS(ESI):552[M-BF4]+.
MS(ESI):516[M-BF4]+.
0.32g,44％yield(1.44mmol),(EA/PE＝1/4-1/1),[α]D 20＝73.5(c＝0.5,CHCl3),m.p.＝87-89℃.1H NMR(400MHz,CDCl3)δ9.67(s,1H),7.99(d,J＝7.6Hz,1H),7.57(t,J＝7.2Hz,1H),7.42(d,J＝8.0Hz,1H),7.38(d,J＝7.2Hz,1H),7.07(s,2H),5.21(d,J＝7.6Hz,1H),3.82(dd,J＝17.6,7.6Hz,1H),3.37(d,J＝17.6Hz,1H),2.39(s,3H),2.16(s,6H),1.43(s,3H),1.20(s,3H),-0.14(s,9H)；HRMS(ESI)calcd for C25H34N3OSi[M–BF4]+:420.2466；Found:420.2482；
0.35g,13％yield,(3.5mmol),m.p.＝202-203℃,[α]D 20＝-219.1(c＝0.2,CHCl3).1H NMR(300MHz,CDCl3)δ9.42(s,1H),8.27(d,J＝7.5Hz,1H),8.06(d,J＝8.4Hz,1H),7.82(t,J＝8.4Hz,2H),7.57(d,J＝8.7Hz,1H),7.45(d,J＝7.5Hz,1H),7.38(d,J＝8.1Hz,1H),7.24–7.16(m,3H),7.13(s,2H),6.97(t,J＝7.2Hz,1H),6.87(d,J＝8.7Hz,1H),6.82–6.66(m,4H),6.55(t,J＝7.8Hz,1H),6.06(d,J＝8.1Hz,1H),4.15(dd,J＝17.7,8.4Hz,1H),3.70(d,J＝17.7Hz,1H),2.43–2.32(m,9H),-0.28(s,9H)；HRMS(ESI)calcd forC43H42N3OSi[M–BF4]+:644.3092；Found:644.3093.
0.93g,26％yield,[α]D 20＝-137.5(c＝0.5,CHCl3),m.p.＝189-190℃.1H NMR(400MHz,CDCl3)δ9.65(s,1H),8.23(bs,1H),7.97(d,J＝8.4Hz,1H),7.92(d,J＝8.0Hz,2H),7.83–7.71(m,1H),7.65–7.53(m,3H),7.50(s,1H),7.46–7.36(m,3H),7.28–7.24(m,1H),7.14(t,J＝7.6Hz,1H),7.10(s,2H),7.04(d,J＝8.0Hz,1H),7.00–6.97(m,2H),6.72(d,J＝8.8Hz,1H),6.68(d,J＝7.6Hz,1H),4.11(dd,J＝18.4,9.2Hz,1H),3.54(d,J＝18.0Hz,1H),2.40(s,3H),2.31(s,6H),-0.22(s,9H)；HRMS(ESI)calcd for C43H42N3OSi[M-BF4]+:644.3092；Found:644.3094.
0.34g,10.3％yield(5mmol),白色固体white solid,m.p.＝202-203℃,[α]D 20＝-43.7(c＝0.2,CHCl3).1H NMR(400MHz,CDCl3)δ9.52(s,1H),7.52(bs,2H),7.37–7.25(m,4H),7.10–7.06(m,3H),6.99(d,J＝7.6Hz,1H),6.76(d,J＝8.0Hz,2H),6.57(d,J＝7.6Hz,2H),6.40(d,J＝8.8Hz,1H),3.98(dd,J＝18.0,9.2Hz,1H),3.37(d,J＝18.4Hz,1H),2.42(s,3H),2.40(s,3H),2.26(s,6H),2.10(s,3H),-0.24(s,9H)；HRMS(ESI)calcd forC37H42N3OSi[M–BF4]+:572.3092；Found:572.3103.
1.2g,40％yield(5mmol),m.p.＝230-232℃,[α]D 20＝-52.3(c＝0.2,CHCl3).1HNMR(400MHz,CDCl3)δ9.47(s,1H),7.45(d,J＝7.6Hz,1H),7.34(t,J＝7.6Hz,1H),7.24–7.17(m,1H),7.09–7.07(m,3H),7.04(t,J＝7.6Hz,2H),6.57–6.55(m,3H),6.41(d,J＝8.8Hz,1H),4.00(dd,J＝18.0,9.2Hz,1H),3.42(d,J＝18.2Hz,1H),2.40(s,3H),2.36(s,6H),2.26(s,6H),1.96(s,6H),-0.25(s,9H)；HRMS(ESI)calcd for C39H46N3OSi[M-BF]+:600.3405；Found:600.3406.
0.67g,47％yield(2.25mmol),(EA/PE＝1/3-1/1),[α]D 20＝-23.6(c＝0.5,CHCl3),m.p.＝193-195℃.1H NMR(300MHz,CDCl3)δ9.99(s,1H),7.95(d,J＝7.5Hz,2H),7.66–7.57(m,3H),7.55–7.52(m,2H),7.44–7.39(m,4H),7.29(d,J＝7.5Hz,1H),7.07–6.94(m,5H),6.86(t,J＝7.5Hz,2H),6.44(d,J＝9.0Hz,1H),3.91(dd,J＝18.3,8.7Hz,1H),3.39(d,J＝18.3Hz,1H),0.83(s,9H),-0.42(s,3H),-0.58(s,3H)；HRMS(ESI)calcd forC35H38N3OSi[M–BF4]+:544.2779；Found:544.2788.
0.8g,40％yield(3mmol),(EA/PE＝1/3-1/1),[α]D 20＝-35.4(c＝0.5,CHCl3),m.p.＝188-189℃.1H NMR(300MHz,CDCl3)δ9.90(s,1H),7.88(d,J＝9.0Hz,2H),7.54(bs,2H),7.41(bs,4H),7.31-7.28(m,1H),7.11(d,J＝9.0Hz,2H),7.08–6.97(m,5H),6.91-6.86(m,2H),6.43(d,J＝8.7Hz,1H),3.97–3.87(m,4H),3.41(d,J＝18.0Hz,1H),0.85(s,9H),-0.40(s,3H),-0.56(s,3H)；HRMS(ESI)calcd for C36H40N2OSi[M–BF4]+:574.2884；Found:574.2887.
0.39g,23％yield(2.25mmol),(EA/PE＝1/3-1/1),[α]D 20＝-22.6(c＝0.5,CHCl3),m.p.＝232-234℃.1H NMR(300MHz,CDCl3)δ10.26(s,1H),8.52(s,2H),8.12(s,1H),7.60–7.57(m,2H),7.51–7.46(m,4H),7.35(t,J＝7.5Hz,1H),7.11(t,J＝7.5Hz,1H),7.05–7.00(m,2H),6.95(d,J＝7.2Hz,2H),6.86(t,J＝7.2Hz,2H),6.45(d,J＝8.7Hz,1H),3.96(dd,J＝18.3,9.0Hz,1H),3.42(d,J＝18.3Hz,1H),0.92(s,9H),-0.38(s,3H),-0.57(s,3H)；HRMS(ESI)calcd for C37H36F6N3OSi[M–BF4]+:680.2526；Found:680.2536.
0.51g,31％yield(2.25mmol),(EA/PE＝1/3-1/1),[α]D 20＝-2.0(c＝0.5,CHCl3),m.p.＝133-134℃.1H NMR(300MHz,CDCl3)δ9.94(s,1H),7.43–7.32(m,7H),7.14–7.07(m,4H),7.05–6.96(m,3H),6.39(d,J＝8.7Hz,1H),3.96(dd,J＝18.0,8.7Hz,1H),3.59(d,J＝18.3Hz,1H),0.87(s,9H),-0.35(s,3H),-0.45(s,3H)；HRMS(ESI)calcd for C35H33N3OSi[M–BF4]+:634.2308；Found:634.2317.
0.59g,29％yield(3mmol),(EA/PE＝1/3-1/1),[α]D 20＝-6.8(c＝0.5,CHCl3),m.p.＝211-213℃.1H NMR(300MHz,Acetone)δ10.01(bs,1H),7.54(bs,2H),7.47-7.41(m,5H),7.29(d,J＝7.5Hz,3H),7.22-7.14(m,4H),7.09-7.06(m,2H),6.59(d,J＝8.7Hz,1H),4.02(dd,J＝18.3,8.7Hz,1H),3.77(d,J＝18.0Hz,1H),2.40(s,3H),2.23(s,6H),0.85(s,9H),-0.24(s,3H),-0.44(s,3H)；19F NMR(300MHz,Acetone)δ-151.9；HRMS(ESI)calcd forC38H44N3OSi[M–BF4]+:586.3247；Found:586.3252.
实施例3：含氯负离子的手性氮杂环卡宾前体盐的合成
实施例1中的3,4-二氢异喹啉酮(1当量)溶于CH2Cl2(10mL/mmol)，三甲基氧四氟硼酸盐(Meerwein试剂，1.4当量)快速加入，20℃下反应12h。加入饱和的碳酸氢钠水溶液淬灭反应，分液，有机相分离而出，水相用二氯甲烷提取两次，有机相合并，饱和食盐水清洗，无水硫酸钠干燥，柱层析提纯。
上步产物溶于二氯甲烷中，加入肼的盐酸盐(R2NHNH2)(1.4当量)，室温下继续反应48h。减压除去溶剂,原甲酸三乙酯(10mL/mmol)加入，80℃下继续反应。核磁监测原料彻底反应完,减压除去溶剂。柱层析初步提纯，并用乙酸乙酯和石油醚重结晶，得到氯负离子的氮杂环卡宾催化剂。
1H NMR(300MHz,CDCl3)δ10.12(s,1H),7.98(d,J＝7.8Hz,2H),7.69-7.59(m,5H),7.53-7.48(m,4H),7.32(t,J＝7.5Hz,1H),7.10(t,J＝7.5Hz,1H),7.01(d,J＝7.8Hz,1H),6.99–6.94(m,1H),6.84(s,4H),6.40(d,J＝8.7Hz,1H),3.92(dd,J＝18.0,8.7Hz,1H),3.40(d,J＝18.3Hz,1H),-0.22(s,9H)；HRMS(ESI)calcd for C32H32N3OSi[M–Cl]+:502.2309；Found:502.2323.
1H NMR(300MHz,CDCl3)δ9.99(s,1H),7.88(d,J＝9.0Hz,2H),7.62-7.58(m,2H),7.51-7.46(m,4H),7.31(t,J＝7.5Hz,1H),7.14–7.06(m,3H),7.02–6.94(m,2H),6.86–6.79(m,4H),6.37(d,J＝9.0Hz,1H),3.96–3.85(m,4H),3.39(d,J＝18.3Hz,1H),-0.22(s,9H)；HRMS(ESI)calcd for C33H34N3O2Si[M–Cl]+:532.2415；Found:532.2432.
1H NMR(300MHz,CDCl3)δ9.54(s,1H),7.65(bs,2H),7.50-7.47(m,3H),7.39(d,J＝7.8Hz,1H),7.32(t,J＝7.5Hz,1H),7.09–6.92(m,7H),6.81(t,J＝7.2Hz,2H),6.50(d,J＝9.3Hz,1H),4.04(dd,J＝18.3,9.0Hz,1H),3.41(d,J＝18.3Hz,1H),2.40(s,3H),2.26(s,6H),-0.23(s,9H)；HRMS(ESI)calcd for C35H38N3OSi[M–Cl]+:544.2779；Found:544.2788.
1H NMR(300MHz,CDCl3)δ10.11(s,1H),7.61-7.58(m,2H),7.51–7.48(m,3H),7.38–7.34(m,2H),7.10(t,J＝7.5Hz,1H),7.04(d,J＝8.1Hz,1H),6.98(t,J＝6.9Hz,1H),6.88-6.78(m,4H),6.27(d,J＝9.0Hz,1H),3.96(dd,J＝18.3,9.3Hz,1H),3.43(d,J＝18.0Hz,1H),-0.20(s,9H)；19F NMR(282MHz,CDCl3)δ-144.8(m),-145.9(m),-152.4,-158.4(m)；HRMS(ESI)calcd for C32H27F5N3OSi[M–Cl]+:592.1838；Found:592.1853.
1H NMR(400MHz,CDCl3)δ10.33(s,1H),8.51(s,2H),8.11(s,1H),7.59-7.57(m,3H),7.52-7.50(m,3H),7.38(t,J＝7.6Hz,1H),7.15(t,J＝7.6Hz,1H),7.05(d,J＝7.6Hz,1H),7.03-6.98(m,1H),6.85(d,J＝4.4Hz,4H),6.39(d,J＝9.2Hz,1H),3.95(dd,J＝18.0,9.2Hz,1H),3.44(d,J＝18.0Hz,1H),-0.19(s,9H)；HRMS(ESI)calcd for C34H30F6N3OSi[M–Cl]+:638.2057；Found:638.2064.
MS(ESI):570[M-Cl]+.
MS(ESI):536[M-Cl]+.
MS(ESI):570[M-Cl]+.
MS(ESI):586[M-Cl]+.
MS(ESI):516[M-Cl]+.
MS(ESI):530[M-Cl]+.
MS(ESI):547[M-Cl]+.
MS(ESI):602[M-Cl]+.
MS(ESI):602[M-Cl]+.
MS(ESI):552[M-Cl]+.
MS(ESI):552[M-Cl]+.
MS(ESI):516[M-Cl]+.
1H NMR(400MHz,CDCl3)δ9.67(s,1H),7.99(d,J＝7.6Hz,1H),7.57(t,J＝7.2Hz,1H),7.42(d,J＝8.0Hz,1H),7.38(d,J＝7.2Hz,1H),7.07(s,2H),5.21(d,J＝7.6Hz,1H),3.82(dd,J＝17.6,7.6Hz,1H),3.37(d,J＝17.6Hz,1H),2.39(s,3H),2.16(s,6H),1.43(s,3H),1.20(s,3H),-0.14(s,9H)；HRMS(ESI)calcd for C25H34N3OSi[M–Cl]+:420.2466；Found:420.2482；
1H NMR(300MHz,CDCl3)δ9.42(s,1H),8.27(d,J＝7.5Hz,1H),8.06(d,J＝8.4Hz,1H),7.82(t,J＝8.4Hz,2H),7.57(d,J＝8.7Hz,1H),7.45(d,J＝7.5Hz,1H),7.38(d,J＝8.1Hz,1H),7.24–7.16(m,3H),7.13(s,2H),6.97(t,J＝7.2Hz,1H),6.87(d,J＝8.7Hz,1H),6.82–6.66(m,4H),6.55(t,J＝7.8Hz,1H),6.06(d,J＝8.1Hz,1H),4.15(dd,J＝17.7,8.4Hz,1H),3.70(d,J＝17.7Hz,1H),2.43–2.32(m,9H),-0.28(s,9H)；HRMS(ESI)calcd forC43H42N3OSi[M–Cl]+:644.3092；Found:644.3093.
1H NMR(400MHz,CDCl3)δ9.65(s,1H),8.23(bs,1H),7.97(d,J＝8.4Hz,1H),7.92(d,J＝8.0Hz,2H),7.83–7.71(m,1H),7.65–7.53(m,3H),7.50(s,1H),7.46–7.36(m,3H),7.28–7.24(m,1H),7.14(t,J＝7.6Hz,1H),7.10(s,2H),7.04(d,J＝8.0Hz,1H),7.00–6.97(m,2H),6.72(d,J＝8.8Hz,1H),6.68(d,J＝7.6Hz,1H),4.11(dd,J＝18.4,9.2Hz,1H),3.54(d,J＝18.0Hz,1H),2.40(s,3H),2.31(s,6H),-0.22(s,9H)；HRMS(ESI)calcd forC43H42N3OSi[M-Cl]+:644.3092；Found:644.3094.
1H NMR(400MHz,CDCl3)δ9.52(s,1H),7.52(bs,2H),7.37–7.25(m,4H),7.10–7.06(m,3H),6.99(d,J＝7.6Hz,1H),6.76(d,J＝8.0Hz,2H),6.57(d,J＝7.6Hz,2H),6.40(d,J＝8.8Hz,1H),3.98(dd,J＝18.0,9.2Hz,1H),3.37(d,J＝18.4Hz,1H),2.42(s,3H),2.40(s,3H),2.26(s,6H),2.10(s,3H),-0.24(s,9H)；HRMS(ESI)calcd for C37H42N3OSi[M–Cl]+:572.3092；Found:572.3103.
1.2g,40％yield(5mmol),m.p.＝230-232℃,[α]D 20＝-52.3(c＝0.2,CHCl3).1HNMR(400MHz,CDCl3)δ9.47(s,1H),7.45(d,J＝7.6Hz,1H),7.34(t,J＝7.6 Hz,1H),7.24–7.17(m,1H),7.09–7.07(m,3H),7.04(t,J＝7.6Hz,2H),6.57–6.55(m,3H),6.41(d,J＝8.8Hz,1H),4.00(dd,J＝18.0,9.2Hz,1H),3.42(d,J＝18.2Hz,1H),2.40(s,3H),2.36(s,6H),2.26(s,6H),1.96(s,6H),-0.25(s,9H)；HRMS(ESI)calcd for C39H46N3OSi[M-Cl]+:600.3405；Found:600.3406.
1H NMR(300MHz,CDCl3)δ9.99(s,1H),7.95(d,J＝7.5Hz,2H),7.66–7.57(m,3H),7.55–7.52(m,2H),7.44–7.39(m,4H),7.29(d,J＝7.5Hz,1H),7.07–6.94(m,5H),6.86(t,J＝7.5Hz,2H),6.44(d,J＝9.0Hz,1H),3.91(dd,J＝18.3,8.7Hz,1H),3.39(d,J＝18.3Hz,1H),0.83(s,9H),-0.42(s,3H),-0.58(s,3H)；HRMS(ESI)calcd for C35H38N3OSi[M–Cl]+:544.2779；Found:544.2788.
1H NMR(300MHz,CDCl3)δ9.90(s,1H),7.88(d,J＝9.0Hz,2H),7.54(bs,2H),7.41(bs,4H),7.31-7.28(m,1H),7.11(d,J＝9.0Hz,2H),7.08–6.97(m,5H),6.91-6.86(m,2H),6.43(d,J＝8.7Hz,1H),3.97–3.87(m,4H),3.41(d,J＝18.0Hz,1H),0.85(s,9H),-0.40(s,3H),-0.56(s,3H)；HRMS(ESI)calcd for C36H40N2OSi[M–Cl]+:574.2884；Found:574.2887.
1H NMR(300MHz,CDCl3)δ10.26(s,1H),8.52(s,2H),8.12(s,1H),7.60–7.57(m,2H),7.51–7.46(m,4H),7.35(t,J＝7.5Hz,1H),7.11(t,J＝7.5Hz,1H),7.05–7.00(m,2H),6.95(d,J＝7.2Hz,2H),6.86(t,J＝7.2Hz,2H),6.45(d,J＝8.7Hz,1H),3.96(dd,J＝18.3,9.0Hz,1H),3.42(d,J＝18.3Hz,1H),0.92(s,9H),-0.38(s,3H),-0.57(s,3H)；HRMS(ESI)calcd for C37H36F6N3OSi[M–Cl]+:680.2526；Found:680.2536.
1H NMR(300MHz,CDCl3)δ9.94(s,1H),7.43–7.32(m,7H),7.14–7.07(m,4H),7.05–6.96(m,3H),6.39(d,J＝8.7Hz,1H),3.96(dd,J＝18.0,8.7Hz,1H),3.59(d,J＝18.3Hz,1H),0.87(s,9H),-0.35(s,3H),-0.45(s,3H)；HRMS(ESI)calcd for C35H33N3OSi[M–Cl]+:634.2308；Found:634.2317.
1H NMR(300MHz,Acetone)δ10.01(bs,1H),7.54(bs,2H),7.47-7.41(m,5H),7.29(d,J＝7.5Hz,3H),7.22-7.14(m,4H),7.09-7.06(m,2H),6.59(d,J＝8.7Hz,1H),4.02(dd,J＝18.3,8.7Hz,1H),3.77(d,J＝18.0Hz,1H),2.40(s,3H),2.23(s,6H),0.85(s,9H),-0.24(s,3H),-0.44(s,3H)；1HRMS(ESI)calcd for C38H44N3OSi[M–Cl]+:586.3247；Found:586.3252.
实施例5：其他负离子的手性氮杂环卡宾前体盐的合成
将含有氯负离子的手性氮杂环卡宾前体盐溶于甲苯中，不同阴离子的的银盐加入，室温反应24h,直到有比较明显的沉淀析出。过滤，减压旋出溶剂，柱层析提纯，乙酸乙酯-石油醚重结晶。
1H NMR(300MHz,CDCl3)δ10.12(s,1H),7.98(d,J＝7.8Hz,2H),7.69-7.59(m,5H),7.53-7.48(m,4H),7.32(t,J＝7.5Hz,1H),7.10(t,J＝7.5Hz,1H),7.01(d,J＝7.8Hz,1H),6.99–6.94(m,1H),6.84(s,4H),6.40(d,J＝8.7Hz,1H),3.92(dd,J＝18.0,8.7Hz,1H),3.40(d,J＝18.3Hz,1H),-0.22(s,9H)；HRMS(ESI)calcd for C32H32N3OSi[M–OTf]+:502.2309；Found:502.2323.
1H NMR(300MHz,CDCl3)δ9.99(s,1H),7.88(d,J＝9.0Hz,2H),7.62-7.58(m,2H),7.51-7.46(m,4H),7.31(t,J＝7.5Hz,1H),7.14–7.06(m,3H),7.02–6.94(m,2H),6.86–6.79(m,4H),6.37(d,J＝9.0Hz,1H),3.96–3.85(m,4H),3.39(d,J＝18.3Hz,1H),-0.22(s,9H)；HRMS(ESI)calcd for C33H34N3O2Si[M–OTf]+:532.2415；Found:532.2432.
1H NMR(300MHz,CDCl3)δ9.54(s,1H),7.65(bs,2H),7.50-7.47(m,3H),7.39(d,J＝7.8Hz,1H),7.32(t,J＝7.5Hz,1H),7.09–6.92(m,7H),6.81(t,J＝7.2Hz,2H),6.50(d,J＝9.3Hz,1H),4.04(dd,J＝18.3,9.0Hz,1H),3.41(d,J＝18.3Hz,1H),2.40(s,3H),2.26(s,6H),-0.23(s,9H)；HRMS(ESI)calcd for C35H38N3OSi[M–OTf]+:544.2779；Found:544.2788.
1H NMR(300MHz,CDCl3)δ10.11(s,1H),7.61-7.58(m,2H),7.51–7.48(m,3H),7.38–7.34(m,2H),7.10(t,J＝7.5Hz,1H),7.04(d,J＝8.1Hz,1H),6.98(t,J＝6.9Hz,1H),6.88-6.78(m,4H),6.27(d,J＝9.0Hz,1H),3.96(dd,J＝18.3,9.3Hz,1H),3.43(d,J＝18.0Hz,1H),-0.20(s,9H)；19F NMR(282MHz,CDCl3)δ-144.8(m),-145.9(m),-152.4,-158.4(m)；HRMS(ESI)calcd for C32H27F5N3OSi[M–OTf]+:592.1838；Found:592.1853.
1H NMR(400MHz,CDCl3)δ10.33(s,1H),8.51(s,2H),8.11(s,1H),7.59-7.57(m,3H),7.52-7.50(m,3H),7.38(t,J＝7.6Hz,1H),7.15(t,J＝7.6Hz,1H),7.05(d,J＝7.6Hz,1H),7.03-6.98(m,1H),6.85(d,J＝4.4Hz,4H),6.39(d,J＝9.2Hz,1H),3.95(dd,J＝18.0,9.2Hz,1H),3.44(d,J＝18.0Hz,1H),-0.19(s,9H)；HRMS(ESI)calcd for C34H30F6N3OSi[M–OTf]+:638.2057；Found:638.2064.
MS(ESI):570[M-OTf]+.
MS(ESI):536[M-OTf]+.
MS(ESI):570[M-OTf]+.
1H NMR(300MHz,CDCl3)δ10.12(s,1H),7.98(d,J＝7.8Hz,2H),7.69-7.59(m,5H),7.53-7.48(m,4H),7.32(t,J＝7.5Hz,1H),7.10(t,J＝7.5Hz,1H),7.01(d,J＝7.8Hz,1H),6.99–6.94(m,1H),6.84(s,4H),6.40(d,J＝8.7Hz,1H),3.92(dd,J＝18.0,8.7Hz,1H),3.40(d,J＝18.3Hz,1H),-0.22(s,9H)；HRMS(ESI)calcd for C32H32N3OSi[M–ClO4]+:502.2309；Found:502.2323.
1H NMR(300MHz,CDCl3)δ9.54(s,1H),7.65(bs,2H),7.50-7.47(m,3H),7.39(d,J＝7.8Hz,1H),7.32(t,J＝7.5Hz,1H),7.09–6.92(m,7H),6.81(t,J＝7.2Hz,2H),6.50(d,J＝9.3Hz,1H),4.04(dd,J＝18.3,9.0Hz,1H),3.41(d,J＝18.3Hz,1H),2.40(s,3H),2.26(s,6H),-0.23(s,9H)；HRMS(ESI)calcd for C35H38N3OSi[M–ClO4]+:544.2779；Found:544.2788.
0.67g,47％yield(2.25mmol),(EA/PE＝1/3-1/1),[α]D 20＝-23.6(c＝0.5,CHCl3),m.p.＝193-195℃.1H NMR(300MHz,CDCl3)δ9.99(s,1H),7.95(d,J＝7.5Hz,2H),7.66–7.57(m,3H),7.55–7.52(m,2H),7.44–7.39(m,4H),7.29(d,J＝7.5Hz,1H),7.07–6.94(m,5H),6.86(t,J＝7.5Hz,2H),6.44(d,J＝9.0Hz,1H),3.91(dd,J＝18.3,8.7Hz,1H),3.39(d,J＝18.3Hz,1H),0.83(s,9H),-0.42(s,3H),-0.58(s,3H)；HRMS(ESI)calcd forC35H38N3OSi[M–ClO4]+:544.2779；Found:544.2788.
实施例6：含羟基的手性氮杂环卡宾前体盐的合成
将实施例2中具有硅基保护的氮杂环卡宾前体盐溶于四氢呋喃溶液中，加入HX溶液(X视前体盐的负离子而定，回流条件下反应24h，核磁监控反应完全，冷至室温，减压除去溶剂，柱层析提纯，乙酸乙酯-石油醚重结晶。
1H NMR(400MHz,CDCl3)δ9.75(s,1H),7.83(d,J＝6.8Hz,2H),7.77(d,J＝7.6Hz,1H),7.64–7.55(m,3H),7.47(d,J＝7.2Hz,2H),7.43–7.34(m,4H),7.26–7.23(m,2H),7.12–7.07(m,4H),7.06–67.02(m,2H),6.35(d,J＝8.4Hz,1H),3.98(dd,J＝17.6,8.4Hz,1H),3.55(d,J＝18.0Hz,1H),3.47(s,1H)；HRMS(ESI)calcd for C29H24N3O[M–Cl]+:430.1914；Found:430.1927.
1H NMR(400MHz,CDCl3)δ9.55(s,1H),7.75(d,J＝8.4Hz,1H),7.72(d,J＝9.2Hz,2H),7.46(d,J＝7.6Hz,2H),7.41-7.32(m,4H),7.27–7.21(m,1H),7.14–7.03(m,8H),6.29(d,J＝8.4Hz,1H),3.95(dd,J＝18.4,8.4Hz,1H),3.87(s,3H),3.52(d,J＝18.0Hz,1H),3.32(s,1H)；HRMS(ESI)calcd for C30H26N3O2[M–Cl]+:460.2020；Found:460.2032.
1H NMR(400MHz,CDCl3)δ9.24(s,1H),7.68(d,J＝7.6Hz,1H),7.54(d,J＝7.6Hz,2H),7.42–7.29(m,4H),7.26–7.17(m,3H),7.12–7.02(m,6H),6.46(d,J＝8.4Hz,1H),4.05(dd,J＝18.0,8.8Hz,1H),3.55(d,J＝18.0Hz,1H),3.28(s,1H),2.36(s,3H),2.12(s,6H)；HRMS(ESI)calcd for C32H30N3O[M–Cl]+:472.22383；Found:472.2397.
MS(ESI):520[M-Cl]+.
MS(ESI):566[M-Cl]+.
1H NMR(400MHz,CDCl3)δ9.75(s,1H),7.83(d,J＝6.8Hz,2H),7.77(d,J＝7.6Hz,1H),7.64–7.55(m,3H),7.47(d,J＝7.2Hz,2H),7.43–7.34(m,4H),7.26–7.23(m,2H),7.12–7.07(m,4H),7.06–67.02(m,2H),6.35(d,J＝8.4Hz,1H),3.98(dd,J＝17.6,8.4Hz,1H),3.55(d,J＝18.0Hz,1H),3.47(s,1H)；HRMS(ESI)calcd for C29H24N3O[M–BF4]+:430.1914；Found:430.1927.
1H NMR(400MHz,CDCl3)δ9.55(s,1H),7.75(d,J＝8.4Hz,1H),7.72(d,J＝9.2Hz,2H),7.46(d,J＝7.6Hz,2H),7.41-7.32(m,4H),7.27–7.21(m,1H),7.14–7.03(m,8H),6.29(d,J＝8.4Hz,1H),3.95(dd,J＝18.4,8.4Hz,1H),3.87(s,3H),3.52(d,J＝18.0Hz,1H),3.32(s,1H)；HRMS(ESI)calcd for C30H26N3O2[M–BF4]+:460.2020；Found:460.2032.
1H NMR(400MHz,CDCl3)δ9.24(s,1H),7.68(d,J＝7.6Hz,1H),7.54(d,J＝7.6Hz,2H),7.42–7.29(m,4H),7.26–7.17(m,3H),7.12–7.02(m,6H),6.46(d,J＝8.4Hz,1H),4.05(dd,J＝18.0,8.8Hz,1H),3.55(d,J＝18.0Hz,1H),3.28(s,1H),2.36(s,3H),2.12(s,6H)；HRMS(ESI)calcd for C32H30N3O[M–BF4]+:472.22383；Found:472.2397.
应用实施例7：不对称分子内Stetter反应
催化剂前体盐(0.01mmol)溶于二甲苯中，加入碱二异丙基乙胺(0.01mmol)，室温搅拌0.5小时。加入底物0.1mmol，室温反应。TLC跟踪反应完全后，0℃加入蒸馏水淬灭，乙酸乙酯萃取，合并有机相，无水硫酸钠干燥，减压除去溶剂，柱层析提纯(石油醚:乙酸乙酯)得产品。
II-1，51％yield 87％ee，无色油状。1H NMR(300MHz,CDCl3)δ7.89(dd,J＝1.8,7.8Hz,1H),7.51-7.45(m,1H),7.05-6.96(m,2H),4.60(dd,J＝5.4,11.1Hz,1H),4.30(t,J＝11.7Hz,1H),4.19(q,J＝7.2Hz,2H),3.39-3.29(m,1H),2.94(dd,J＝4.8,17.1Hz,1H),2.42(dd,J＝8.1,17.1Hz,1H),1.28(t,J＝7.2Hz,3H).
应用实施例8：不对称分子内Stetter反应
催化剂前体盐溶(0.02mmol)于乙醚(1mL)中，加入醋酸钾(10mmol％)，室温搅拌0.5小时。加入底物0.2mmol，再加入1mL乙醚，室温反应。TLC跟踪反应完全后，加入蒸馏水淬灭，乙酸乙酯萃取，合并有机相，无水硫酸钠干燥，减压除去溶剂，柱层析提纯(石油醚:乙酸乙酯)得产品。
II-2，92％yield,64％ee；1H NMR(400MHz,CDCl3)δ10.79(s,1H),7.86(d,J＝6.4Hz,1H),7.52-7.42(m,2H),7.35(d,J＝7.2Hz,1H),6.98(d,J＝10.0Hz,2H),6.49(d,J＝10.0Hz,2H),3.43(s,3H)；MS(EI,m/z,rel.intensity)228([M]+,3),168(100)；HRMS(EI)calcd for C14H12O3[M]+:228.0786.Found:228.0788.
应用实施例9：不对称[2+3]反应
氩气保护下，加入靛红(0.2mmol),不饱和醛底物(0.2mmol)，催化剂前体(10mol％)和1mL的四氢呋喃，用微量注射器加入3.4μL的DBU(1,8-二氮杂二环十一碳-7-烯)，再加入1mL的四氢呋喃，室温搅拌。TLC跟踪反应完全后，加入蒸馏水淬灭，乙酸乙酯萃取，合并有机相，无水硫酸钠干燥，减压除去溶剂，柱层析提纯(石油醚:乙酸乙酯)得产品。
95％yield,dr＝1:1.9,86％ee.
1H NMR(300MHz,CDCl3)δ7.54(d,J＝7.2Hz,1H),7.39(t,J＝7.2Hz,1H),7.24-7.15(m,4H),6.93(d,J＝6.6Hz,2H),6.67(d,J＝7.8Hz,1H),4.07(dd,J＝15.1,8.1Hz,1H),3.83(dd,J＝16.8,15.1Hz,1H),2.92(dd,J＝16.8,8.4Hz,1H),2.82(s,3H).
93％ee,dr＝5.28:1,38％yield,MS(EI):259M+。
90％ee,dr＝3.43:1,34％yield
1H NMR(300MHz,CDCl3)δ7.37-7.25(m,7H),7.12-7.07(m,1H),6.75(d,J＝7.8Hz,1H),5.01(d,J＝15.6Hz,1H),4.73(d,J＝15.6Hz,1H),3.09-2.94(m,1H),2.89-2.72(m,2H),1.51-1.42(m,1H),1.29-1.17(m,2H),1.13-1.04(m,1H),0.78(t,J＝14.0Hz,3H).HRMS(EI)m/z:M+Cal.for C21H21NO3,335.1521,Found 335.1525.
应用实施例10：2-萘酚和烯醛的不对称环化反应
氩气保护下，在干燥的反应管中加入三唑盐(12.6mg,0.02mmol,10mol％),K3PO4(8.5mg,0.04mmol,20mol％)，烯醛(0.2～0.4mmol,1.0～2.0equiv),2-萘酚(0.2mmol,1当量)，3,3',5,5'-四叔丁基-4,4'-联苯醌做氧化剂(0.2～0.4mmol,1.0～2.0当量)，THF(2mL),0℃下反应，TLC监测原料完全反应完，加水(2mL)淬灭，乙酸乙酯提取，有机相合并，无水硫酸钠干燥，过滤，旋干。柱层析提纯的到产物。
白色固体45.8mg,73％yield,87％ee[手性柱Daicel Chiralpak AD-H(25cm),正己烷n-hexanes/异丙醇2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(major)＝9.92min,t(minor)＝11.60min].m.p.＝91-92℃；[α]D 20＝+32.2(c＝1,CHCl3)；1H NMR(300MHz,CDCl3)δ7.80-7.73(m,2H),7.70(s,1H),7.42-7.39(m,2H),7.04(d,J＝8.4Hz,2H),6.79(d,J＝8.4Hz,2H),4.90(t,J＝4.2Hz,1H),3.72(s,3H),3.13(d,J＝4.8Hz,2H),2.54(s,3H)；13C NMR(75MHz,CDCl3)δ167.7,159.1,149.3,132.7,131.1,130.0,129.6,128.2,128.1,126.9,126.6,125.4,123.1,118.1,114.8,55.5,37.8,37.1,17.1；IR(thinfilm):νmax(cm-1)＝3675,2988,2901,1754,1610,1511,1394,1304,1251,1175,1137,1066,1057,949,879,828,809,785,742,711,697,680,645,612；HRMS(ESI)calcd for C21H22NO3[M+NH4]+:336.1594；Found:336.1602.
蜡状固体,27.9mg,46％yield,88％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝90/10,v＝0.9mL/min,λ＝254nm,t(major)＝17.07min,t(minor)＝18.28min].[α]D 20＝+19.5(c＝0.5,CHCl3)；1H NMR(300MHz,CDCl3)δ7.90-7.84(m,2H),7.82-7.77(m,1H),7.51-7.41(m,2H),7.35(d,J＝9.0Hz,1H),7.04(d,J＝8.7Hz,2H),6.75(d,J＝8.7Hz,2H),4.92(dd,J＝6.3,2.4Hz,1H),3.73(s,3H),3.20(dd,J＝15.6,6.3Hz,1H),3.13(dd,J＝15.6,2.4Hz,1H)；13C NMR(75MHz,CDCl3)δ167.6,159.1,149.9,132.7,131.3,131.2,130.1,129.0,128.3,127.7,125.5,123.3,118.2,117.8,114.8,55.5,37.9,37.1；IR(thin film):νmax(cm-1)＝3063,2921,2851,1760,1625,1609,1582,1509,1462,1437,1395,1354,1304,1282,1245,1208,1174,1157,1130,1083,1029,965,886,863,814,785,747,733,681,658,633,610；HRMS(ESI)calcd for C20H20NO3[M+NH4]+:322.1438；Found:322.1447.
白色固体,50.2mg,75％yield,88％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(minor)＝24.64min,t(major)＝28.69min].[α]D 20＝+95.3(c＝0.5,CHCl3)；m.p.＝126-127℃；1H NMR(300MHz,CDCl3)δ7.78-7.69(m,2H),7.44-7.31(m,2H),7.22(s,1H),7.06(d,J＝8.7Hz,2H),6.78(d,J＝8.7Hz,2H),4.91(dd,J＝5.7,2.4Hz,1H),4.05(s,3H),3.73(s,3H),3.23-3.08(m,2H)；13CNMR(75MHz,CDCl3)δ166.7,159.1,147.7,141.9,132.4,131.5,128.3,127.6,126.0,125.9,125.3,123.2,119.8,114.8,107.3,56.2,55.5,37.6,37.3；IR(thin film):νmax(cm-1)＝2923,2851,1777,1608,1510,1465,1330,1294,1243,1176,1113,1089,1016,975,899,869,831,783,748,727,690,622；HRMS(ESI)calcd for C21H22NO4[M+NH4]+:352.1543；Found:352.1557.
白色固体，64.5mg,79％yield,90％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(major)＝29.91min,t(minor)＝42.03min]；[α]D 20＝+64.1(c＝0.5,CHCl3),m.p.＝169-170℃；1H NMR(300MHz,CDCl3)δ＝7.72(d,J＝8.1Hz,2H),7.56(d,J＝7.2Hz,2H),7.45-7.31(m,5H),7.29(s,1H),7.06(d,J＝8.7Hz,2H),6.79(d,J＝8.7Hz,2H),5.31(s,2H),4.91(dd,J＝5.7,2.1Hz,1H),3.73(s,3H),3.22-3.09(m,2H)；13C NMR(75MHz,CDCl3)δ166.9,159.1,146.7,142.2,136.5,132.4,131.4,128.9,128.4,128.3,127.7,127.6,126.1,126.0,125.4,123.2,120.0,114.8,109.3,71.0,55.5,37.7,37.4；IR(thin film):νmax(cm-1)＝2916,1767,1626,1610,1584,1509,1470,1457,1414,1388,1329,1296,1275,1241,1180,1154,1130,1111,1089,1033,1017,978,957,927,906,870,846,827,812,784,764,742,695,642,626；HRMS(ESI)calcdfor C27H26NO4[M+NH4]+:428.1856；Found:428.1867.
白色固体55.0mg,76％yield,88％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(major)＝18.42min,t(minor)＝20.37min]；[α]D 20＝+27.5(c＝0.5,CHCl3)；m.p.＝109-110℃；1H NMR(400MHz,CDCl3)δ＝7.74-7.69(m,2H),7.42-7.37(m,1H),7.36-7.31(m,1H),7.23(s,1H),7.05(d,J＝8.8Hz,2H),6.78(d,J＝8.8Hz,2H),6.18(ddd,J＝17.2,10.8,5.2Hz,1H),5.55(dd,J＝17.2,1.2Hz,1H),5.37(dd,J＝10.8,1.2Hz,1H),4.90(dd,J＝6.0,2.0Hz,1H),4.77(d,J＝5.2Hz,2H),3.73(s,3H),3.20-3.09(m,2H)；13C NMR(75MHz,CDCl3)δ166.8,159.1,146.6,142.1,132.8,132.4,131.5,128.3,127.6,126.0,125.3,123.2,119.9,118.6,114.8,108.78,103.0,69.9,55.5,37.7,37.4；IR(thin film):νmax(cm-1)＝3379,2922,2853,1774,1610,1507,1458,1414,1329,1292,1239,1176,1125,1029,932,894,868,825,785,742,694,624；HRMS(ESI)calcd for C23H24NO4[M+NH4]+:378.1700；Found:378.1711.
白色固体,70.8mg,90％yield,84％ee[Phenomenex Lux 5u Cellulose-2(0.46cm×25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(major)＝17.22min,t(minor)＝40.68min]；[α]D 20＝+30.1(c＝0.18,CHCl3)；m.p.＝148-149℃；1H NMR(300MHz,CDCl3)δ7.73(d,J＝7.5Hz,2H),7.58(s,1H),7.40-7.29(m,7H),7.02(d,J＝8.7Hz,2H),6.77(d,J＝8.4Hz,2H),4.88(t,J＝4.2Hz,1H),4.29(AB,J＝15.6Hz,1H),4.20(AB,J＝15.6Hz,1H),3.70(s,3H),3.08(d,J＝3.9Hz,2H)；13C NMR(75MHz,CDCl3)δ167.4,159.1,148.7,139.8,132.7,131.1,130.2,129.6,129.5,128.9,128.6,128.3,127.0,126.6,125.5,123.1,118.5,114.8,55.5,37.7,37.2,36.5；IR(thin film):νmax(cm-1)＝2918,2851,1760,1606,1508,1439,1352,1301,1241,1213,1175,1137,1104,1027,993,953,882,848,818,784,746,728,701,666,618；HRMS(ESI)calcd for C27H26NO3[M+NH4]+:412.1907；Found:412.1919.
白色固体,72.4mg,87％yield,88％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝95/5,v＝1.0mL/min,λ＝254nm,t(major)＝14.69min,t(minor)＝20.06min].[α]D 20＝+125.6(c＝0.5,CHCl3)；m.p.＝150-151℃；1H NMR(400MHz,CDCl3)δ7.91-7.88(m,2H),7.84(d,J＝8.0Hz,1H),7.70(d,J＝8.8Hz,2H),7.53-7.45(m,2H),7.35(d,J＝8.4Hz,2H),7.09(d,J＝8.4Hz,2H),6.81(d,J＝8.4Hz,2H),5.00(d,J＝3.6Hz,1H),3.74(s,3H),3.24-3.14(m,2H)；13C NMR(100MHz,CDCl3)δ166.8,159.0,148.9,147.0,135.4,132.1,131.3,130.78,130.5,130.4,129.3,128.8,128.0,127.6,125.8,123.0,121.8,120.8,119.1,114.6,55.2,37.4,37.1；IR(thin film):νmax(cm-1)＝2925,1762,1608,1508,1440,1413,1249,1210,1179,1135,1036,970,917,877,836,809,737,658,619；19F NMR(376MHz,CDCl3)δ-57.66；HRMS(ESI)calcd for C27H23F3NO4[M+NH4]+:482.1574；Found:482.1590.
黄色固体，64.3mg,84％yield,95％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(major)＝14.23min,t(minor)＝15.56min].[α]D 20＝+145.7(c＝0.5,CHCl3)；m.p.＝96-97℃；1H NMR(300MHz,CDCl3)δ7.90(s,1H),7.88-7.80(m,2H),7.67(d,J＝7.2Hz,2H),7.52-7.38(m,5H),7.09(d,J＝8.7Hz,2H),6.80(d,J＝8.7Hz,2H),4.98(dd,J＝6.0,2.4Hz,1H),3.73(s,3H),3.25-3.09(m,2H)；13C NMR(75MHz,CDCl3)δ167.2,159.1,147.5,136.9,132.5,131.1,131.1,130.6,130.6,130.1,129.0,128.6,128.3,128.0,127.6,125.8,123.2,119.1,114.8,55.5,37.7,37.4；IR(thin film):νmax(cm-1)＝2923,2853,1768,1607,1507,1450,1423,1300,1244,1179,1127,1030,970,894,876,853,828,788,747,697,665,632；HRMS(ESI)calcd for C26H24NO3[M+NH4]+:398.1751；Found:398.1753.
白色固体,56.1mg,73％yield,82％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(minor)＝13.67min,t(major)＝17.78min].[α]D 20＝+87.3(c＝0.2,CHCl3),m.p.＝145-146℃；1H NMR(400MHz,CDCl3)δ＝8.15(s,1H),7.80-7.74(m,2H),7.50-7.43(m,2H),7.02(d,J＝8.4Hz,2H),6.79(d,J＝8.4Hz,2H),4.93(t,J＝4.0Hz,1H),3.73(s,3H),3.21-3.12(m,2H)；13C NMR(100MHz,CDCl3)δ166.0,160.0,146.1,132.5,131.7,131.4,130.0,127.9,127.8,127.7,126.1,123.1,120.1,114.6,110.9,55.2,37.3,29.7；IR(thin film):νmax(cm-1)＝3074,2922,2845,1764,1610,1582,1507,1428,1306,1283,1248,1228,1177,1124,1092,1023,970,931,905,869,838,811,782,747,694,671,636,614；HRMS(ESI)calcd for C20H29BrNO3[M+NH4]+:400.0543；Found:400.0552.
黄色固体,57.7mg,73％yield,76％ee[Daicel Chiralpak AD-H(15cm),n-hexanes/2-propanol＝70/30,v＝0.5mL/min,λ＝254nm,t(major)＝18.01min,t(minor)＝35.81min].[α]D 20＝+115.8(c＝0.5,CHCl3),m.p.＝102-103℃；1H NMR(400MHz,CDCl3)δ9.67(s,1H),8.88(s,1H),7.98(d,J＝8.0Hz,1H),7.82-7.45(m,3H),7.59-7.54(m,1H),7.52-7.47(m,1H),7.40-7.25(m,2H),7.18-7.14(m,1H),7.06(d,J＝8.8Hz,2H),6.82(d,J＝8.8Hz,2H),5.00(t,J＝4.2Hz,1H),3.73(s,3H),3.23(d,J＝4.2Hz,2H)；13C NMR(100MHz,CDCl3)δ165.2,161.8,159.1,146.6,138.0,134.4,132.5,131.5,130.3,129.5,129.1,128.0,126.2,124.7,122.9,121.5,120.6,119.2,114.7,55.3,36.9,36.8；IR(thin film):νmax(cm-1)＝2930,2164,1777,1653,1599,1540,1507,1439,1317,1245,1200,1178,1121,1029,980,897,865,830,792,749,692,632；HRMS(ESI)calcd for C27H22NO4[M+H]+:424.1543；Found:424.1552.
黄色油状固体,62.5mg,86％yield,83％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝80/20,v＝1.0mL/min,λ＝254nm,t(major)＝19.41min,t(minor)＝28.13min].[α]D 20＝-33.7；1H NMR(400MHz,CDCl3)δ8.60(d,J＝1.6Hz,1H),8.05(dd,J＝8.8,1.6Hz,1H),7.97(d,J＝8.8Hz,1H),7.83(d,J＝8.8Hz,1H),7.40(d,J＝9.2Hz,1H),7.02(d,J＝8.8Hz,2H),6.79(d,J＝8.8Hz,2H),4.93(dd,J＝6.4,1.8Hz,1H),3.96(s,3H),3.73(s,3H),3.24-3.13(m,2H)；13C NMR(75MHz,CDCl3)δ166.7,158.9,151.3,133.3,132.0,131.5,131.2,130.1,127.9,126.8,126.7,123.3,118.4,118.1,114.6,55.2,52.3,37.4,36.8；IR(thin film):νmax(cm-1)＝2922,2852,2360,1772,1713,1626,1510,1467,1390,1276,1248,1184,1127,1083,1030,964,878,810,787,752；HRMS(ESI)calcd for C27H22NO4[M+Na]+:385.1046；Found:385.1043.
黄色固体,41.5mg,62％yield,91％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(minor)＝15.15min,t(major)＝23.61min].m.p.＝124-125℃；[α]D 20＝-54.6(c＝1.0,CHCl3)；1H NMR(400MHz,CDCl3)δ7.76(t,J＝8.0Hz,2H),7.19(d,J＝9.2Hz,1H),7.11-7.03(m,4H),6.79(d,J＝8.8Hz,2H),4.80(dd,J＝6.4,1.2Hz,1H),3.80(s,3H),3.74(s,3H),3.19(dd,J＝15.6,6.8Hz,1H),3.11(dd,J＝15.6,2.0Hz,1H)；13C NMR(100MHz,CDCl3)δ167.3,158.9,158.8,150.2,132.5,132.4,130.3,129.4,128.0,126.4,117.2,116.9,115.0,114.6,102.26,55.2,55.2,37.7,37.1；HRMS(ESI)calcd for C21H22NO4[M+NH4]+:352.1543；Found:352.1542.
黄色固体,33.1mg,60％yield,85％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝95/5,v＝0.8mL/min,λ＝254nm,t(major)＝10.91min,t(minor)＝11.70min].[α]D 20＝+44.8(c＝0.5,CHCl3)；1H NMR(400MHz,CDCl3)δ7.89-7.85(m,2H),7.79(d,J＝8.0Hz,1H),7.50-7.41(m,2H),7.35(d,J＝8.8Hz,1H),7.29-7.19(m,4H),7.13(d,J＝7.2Hz,2H),4.96(dd,J＝6.8,2.0Hz,1H),3.23(dd,J＝15.6,6.4Hz,1H),3.16(dd,J＝15.6,2.0Hz,1H).
白色固体，37.4mg,65％yield,79％ee[Phenomenex Lux 5u Cellulose-2(0.46cm×25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(major)＝12.30min,t(minor)＝16.55min].[α]D 20＝+153.4(c＝0.5,CHCl3),m.p.＝106-107℃；1HNMR(300MHz,CDCl3)δ7.80-7.73(m,2H),7.70(s,1H),7.42-7.38(m,2H),7.29-7.17(m,4H),7.12(d,J＝6.9Hz,2H),4.95(dd,J＝5.4,3.3Hz,1H),3.24-3.12(m,2H),2.55(s,3H)；13C NMR(75MHz,CDCl3)δ167.5,149.4,140.7,131.1,130.0,129.8,129.4,128.2,127.8,127.2,127.0,126.7,125.5,123.09,117.7,37.9,37.6,17.1；IR(thin film):νmax(cm-1)＝3064,2924,2851,1759,1603,1507,1492,1450,1416,1351,1232,1207,1173,1152,1128,1103,1076,1055,1031,975,954,883,862,791,774,752,736,713,697,676,650,628；HRMS(ESI)calcdfor C20H20NO2[M+NH4]+:306.1489；Found:306.1493.
白色固体,57.2mg,82％yield,91％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝95/5,v＝1.0mL/min,λ＝254nm,t(major)＝13.15min,t(minor)＝15.18min].[α]D 20＝+142.1(c＝0.5,CHCl3)；m.p.＝139-140℃；1H NMR(400MHz,CDCl3)δ7.92(s,1H),7.91-7.88(m,1H),7.84-7.81(m,1H),7.68(d,J＝7.6Hz,2H),7.7.53-7.42(m,5H),7.30-7.22(m,3H),7.19(d,J＝7.2Hz,2H),5.04(dd,J＝6.4,1.6Hz,1H),3.24(dd,J＝6.8,15.6Hz,1H),3.18(dd,J＝2.0,15.6Hz,1H)；13C NMR(100MHz,CDCl3)δ166.7,147.4,140.3,136.6,130.9,130.8,130.5,130.4,129.8,129.2,128.8,128.3,127.8,127.6,127.4,127.0,125.6,122.9,118.4,37.9,37.2；IR(thin film):νmax(cm-1)＝3522,2922,2853,1768,1599,1493,1452,1418,1336,1240,1177,1148,1124,1028,965,875,852,793,769,750,727,694；HRMS(ESI)calcd for C25H22NO2[M+NH4]+:368.1645；Found:368.1649.
白色固体，65.3mg,89％yield,96％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(major)＝8.24min,t(minor)＝10.96min].[α]D 20＝+237.6(c＝0.5,CHCl3)；m.p.＝96-97℃；1H NMR(400MHz,CDCl3)δ7.95(s,1H),7.92-7.88(m,1H),7.73(d,J＝7.6Hz,2H),7.65-7.62(m,1H),7.56-7.51(m,2H),7.47-7.43(m,3H),7.30(d,J＝7.6Hz,1H),7.18-7.13(m,1H),7.02-6.98(m,1H),6.79(d,J＝7.6Hz,1H),5.23(d,J＝7.6Hz,1H),3.20(dd,J＝15.6,7.2Hz,1H),3.05(d,J＝15.2Hz,1H),2.67(s,3H)；13C NMR(100MHz,CDCl3)δ166.7,147.9,138.0,136.7,134.4,131.2,130.9,130.7,130.5,130.3,129.9,128.8,128.4,127.8,127.7,127.4,127.0,126.6,125.6,122.8,118.7,35.6,34.7,19.5；IR(thin film):νmax(cm-1)＝3059,1769,1600,1498,1452,1425,1246,1189,1134,1087,10301,969,894,874,851,791,765,740,697,665,636；HRMS(ESI)calcd for C26H24NO2[M+NH4]+:382.1802；Found:382.1816.
白色固体,64.4mg,85％yield,92％ee[Daicel Chiralpak IC(25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(minor)＝12.20min,t(major)＝14.26min].m.p.＝150-151℃；[α]D 20＝+165.9(c＝0.5,CHCl3)；1H NMR(300MHz,CDCl3)δ7.92(s,1H),7.91-7.87(m,1H),7.78-7.74(m,1H),7.72-7.69(m,2H),7.52-7.43(m,5H),7.25-7.19(m,1H),6.96(d,J＝8.1Hz,1H),6.75-6.71(m,2H),5.42(dd,J＝6.9,1.5Hz,1H),4.00(s,3H),3.24(dd,J＝15.9,1.8Hz,1H),3.13(dd,J＝15.9,7.2Hz,1H)；13C NMR(75MHz,CDCl3)δ167.5,156.3,147.9,136.8,130.8,130.7,130.4,130.3,129.8,128.8,128.6,128.3,127.9,127.9,127.7,127.2,125.5,123.1,120.9,118.4,110.5,55.4,35.2,31.9；IR(thin film):νmax(cm-1)＝2929,1770,1580,1486,1456,1425,1337,1285,1239,1188,1149,1130,1104,1082,1020,972,933,913,895,842,797,765,746,700；HRMS(ESI)calcd forC26H24NO3[M+NH4]+:398.1751；Found:398.1766.
白色固体,67.3mg,92％yield,92％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝97/3,v＝1.0mL/min,λ＝254nm,t(major)＝16.35min,t(minor)＝18.93min].[α]D 20＝+161.4(c＝0.5,CHCl3)；m.p.＝78-79℃；1H NMR(400MHz,CDCl3)δ7.93(s,1H),7.90(d,J＝8.0Hz,1H),7.85(d,J＝7.6Hz,1H),7.71(d,J＝7.6Hz,2H),7.55-7.42(m,5H),7.10(s,4H),5.00(d,J＝3.6Hz,1H),3.23-3.14(m,2H),2.30(s,3H)；13C NMR(100MHz,CDCl3)δ166.9,147.3,137.4,137.3,136.7,130.9,130.8,130.4,130.4,129.9,129.9,128.8,128.4,127.8,127.4,126.9,125.6,123.0,118.8,37.6,37.3,21.0；IR(thinfilm):νmax(cm-1)＝3371,2963,1770,1506,1449,1424,1372,1244,1181,1125,1092,1027,970,909,874,851,813,789,746,697,665,631；HRMS(ESI)calcd for C26H24NO2[M+NH4]+:382.1802；Found:382.1817.
白色固体,71.6mg,91％yield,92％ee[Daicel Chiralpak IC(25cm),n-hexanes/2-propanol＝90/10,v＝0.8mL/min,λ＝254nm,t(major)＝27.44min,t(minor)＝30.65min].[α]D 20＝+62.1(c＝0.5,CHCl3)；m.p.＝96-97℃；1H NMR(400MHz,CDCl3)δ7.87-7.86(m,3H),7.66(d,J＝7.2Hz,2H),7.51-7.45(m,5H),7.05(d,J＝8.4Hz,2H),6.62(d,J＝8.4Hz,2H),4.95(dd,J＝2.4,5.6Hz,1H),3.23-3.11(m,2H),2.88(s,6H)；13C NMR(100MHz,CDCl3)δ167.3,149.9,147.2,136.9,130.9,130.8,130.5,130.2,129.9,128.7,128.3,127.9,127.7,127.7,127.3,125.5,123.2,119.4,113.1,40.5,37.5,37.0；IR(thin film):νmax(cm-1)＝2918,2162,1766,1611,1518,1447,1422,1348,1242,1182,1124,1027,969,946,874,801,763,745,698,664；HRMS(ESI)calcd for C27H24NO2[M+H]+:394.1802；Found:394.1816.
蜡状固体,69.2mg,94％yield,86％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝95/5,v＝1.0mL/min,λ＝254nm,t(major)＝13.38min,t(minor)＝16.07min].[α]D 20＝+146.0(c＝0.5,CHCl3)；1H NMR(400MHz,CDCl3)δ7.95(s,1H),7.91(d,J＝8.4Hz,1H),7.80(d,J＝7.2Hz,1H),7.69(d,J＝7.6Hz,2H),7.54-7.42(m,5H),7.26-7.15(m,2H),6.98(t,J＝8.4Hz,2H),5.03(d,J＝6.4Hz,1H),3.25-3.12(m,2H)；19F NMR(282MHz,CDCl3)δ-113.5；13C NMR(100MHz,CDCl3)δ166.6,162.1(d,J＝245.0Hz),147.3,136.5,136.0(d,J＝3.1Hz),130.9,130.9,130.7,130.5,129.8,128.9,128.7(d,J＝8.1Hz)128.4,127.9,127.5,125.7,122.8,118.3,116.1(d,J＝21.4Hz),37.3,37.2；IR(thin film):νmax(cm-1)＝2918,1770,1732,1601,1504,1450,1424,1371,1228,1181,1126,1039,970,895,875,831,789,747,697,665,632；HRMS(ESI)calcd for C25H21FNO2[M+NH4]+:386.1551；Found:386.1563.
白色固体,73.3mg,95％yield,85％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(major)＝9.67min,t(minor)＝11.27min].[α]D 20＝+143.0(c＝0.5,CHCl3)；m.p.＝88-89℃；1H NMR(300MHz,CDCl3)δ7.92(s,1H),7.91-7.87(m,1H),7.78-7.72(m,1H),7.68-7.64(m,2H),7.52-7.39(m,5H),7.27-7.23(m,2H),7.11(d,J＝8.4Hz,2H),5.00(d,J＝5.7Hz,1H),3.22(dd,J＝15.9,6.9Hz,1H),3.13(dd,J＝15.3,0.9Hz,1H)；13C NMR(75MHz,CDCl3)δ166.6,147.6,139.0,136.7,133.8,131.1,131.1,131.0,130.5,130.1,129.7,129.1,128.7,128.6,128.1,127.8,126.0,122.9,118.2,37.6,37.3；IR(thin film):νmax(cm-1)＝2962,2231,1768,1490,1425,1245,1180,1126,1089,1013,969,894,874,822,793,746,697,664；HRMS(ESI)calcd forC25H21ClNO2[M+NH4]+:402.1255；Found:402.1270.
82.7mg,96％yield,85％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(major)＝10.77min,t(minor)＝12.62min].[α]D 20＝+155.7(c＝0.5,CHCl3)；m.p.＝99-100℃；1H NMR(300MHz,CDCl3)δ7.94(s,1H),7.93-7.89(m,1H),7.79-7.75(m,1H),7.68(d,J＝7.2Hz,2H),7.54-7.47(m,4H),7.41(d,J＝8.7Hz,2H),7.07(d,J＝8.7Hz,2H),4.99(dd,J＝6.3,1.2Hz,1H),3.23(dd,J＝15.7,6.6Hz,1H),3.13(dd,J＝15.6,1.8Hz,1H)；13C NMR(75MHz,CDCl3)δ166.6,147.6,139.6,136.7,132.6,131.1,131.1,131.0,130.5,130.0,129.1,129.1,128.6,128.1,127.8,126.0,122.9,121.9,118.1,37.6,37.2；IR(thin film):νmax(cm-1)＝3057,1768,1487,1425,1245,1182,1129,1032,1009,970,894,875,853,821,791,747,698,653；HRMS(ESI)calcd for C25H21BrNO2[M+NH4]+:446.0750；Found:446.0768.
白色固体,56.9mg,82％yield,71％ee[Daicel Chiralpak IC(25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(major)＝40.44min,t(minor)＝46.24min].[α]D 20＝+31.6(c＝0.5,CHCl3)；m.p.＝131-136℃；1H NMR(300MHz,CDCl3)δ＝7.94(d,J＝8.1Hz,2H),7.81-7.79(m,1H),7.73(s,1H),7.73-7.67(m,1H),7.43-7.39(m,2H),7.20(d,J＝8.1Hz,2H),5.00(d,J＝5.1Hz,1H),3.87(s,3H),3.28-3.10(m,2H),2.55(s,3H)；13C NMR(75MHz,CDCl3)δ167.0,166.8,149.5,145.9,131.2,130.8,130.2,129.8,129.7,128.3,127.4,127.0,126.9,125.6,122.8,116.8,52.4,37.9,37.2,17.1；IR(thinfilm):νmax(cm-1)＝2926,1761,1710,1608,1507,1431,1321,1280,1235,1201,1175,1135,1104,1018,987,975,945,883,849,830,795,770,757,743,716,685,637；HRMS(ESI)calcdfor C22H22NO4[M+NH4]+:364.1543；Found:364.1551.
白色固体59.9mg,91％yield,85％ee[Daicel Chiralpak IC(25cm),n-hexanes/2-propanol＝90/10,v＝1.0mL/min,λ＝254nm,t(major)＝15.05min,t(minor)＝17.60min].[α]D 20＝+40.7(c＝0.5,CHCl3)；m.p.＝124-125℃；1H NMR(400MHz,CDCl3)δ7.99(d,J＝8.4Hz,1H),7.89-7.85(m,2H),7.62-7.58(m,2H),7.56(d,J＝7.6Hz,1H),7.51-7.44(m,3H),7.41-7.37(m,1H),7.32(s,1H),6.21(dd,J＝2.8,2.0Hz,1H),5.96(d,J＝3.2Hz,1H),5.07(d,J＝6.0Hz,1H),3.37(dd,J＝15.6,1.2Hz,1H),3.08(dd,J＝16.0,6.8Hz,1H)；13C NMR(100MHz,CDCl3)δ166.7,152.8,147.1,142.6,136.5,130.9,130.8,130.6,130.2,129.8,128.8,128.3,127.8,127.4,125.6,122.8,116.7,110.4,106.9,33.7,31.6；IR(thinfilm):νmax(cm-1)＝2919,1772,1500,1452,1422,1343,1240,1187,1125,1090,1008,974,926,896,874,853,808,786,746,696；HRMS(ESI)calcd for C23H20NO3[M+NH4]+:358.1438；Found:358.1452.
白色固体,37.8mg,65％yield,75％ee[Daicel Chiralpak AD-H(25cm),n-hexanes/2-propanol＝98/2,v＝1.0mL/min,λ＝254nm,t(major)＝13.85min,t(minor)＝16.11min].[α]D 20＝+5.1(c＝0.5,CHCl3)；m.p.＝154-156℃；1H NMR(400MHz,CDCl3)δ7.96(d,J＝8.4Hz,1H),7.89(d,J＝8.0Hz,1H),7.82(s,1H),7.63-7.58(m,3H),7.52-7.46(m,3H),7.43-7.39(m,1H),3.95-3.88(m,1H),2.96(dd,J＝15.6,5.6Hz,1H),2.89(d,J＝15.2Hz,1H),1.43(d,J＝7.2Hz,3H)；13C NMR(75MHz,CDCl3)δ168.1,146.3,137.0,131.1,131.1,130.0,129.9,129.8,129.1,128.5,127.9,127.4,125.7,122.5,121.8,36.2,27.1,20.1；IR(thin film):νmax(cm-1)＝2960,2928,1766,1598,1497,1446,1427,1375,1357,1262,1235,1191,1149,1112,1079,1031,1000,978,944,895,877,840,799,784,769,750,725,703,659,609；HRMS(ESI)calcd for C20H20NO2[M+NH4]+:306.1489；Found:306.1498。

Claims (8)

1.一种具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐，其结构通式为：
*表示手性中心；
其中R1及R2任意选自C1～C16的烷基、芳基及取代的芳基；
R3为H、芳基及C1～C16的烷基取代的硅基；
上述的芳基为苯基、1-萘基、2-萘基，9-蒽基、9-菲基；所述取代芳基上的取代基任意选自F、Cl、Br、I、C1～C16的烃氧基、C1～C16的烷基或C1～C16的氟代烷基、硝基或氨基；
X任意选自Cl、Br、I、OTf、BF4或ClO4。
2.如权利要求1所述的一种具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐，其结构分子通式为：
其中R1、R2、R3和X如权利要求1所述。
3.一种如权利要求1或2所述具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐的合成方法，其特征是在有机溶剂中，在0℃至150℃温度下，3,4-二氢异喹啉酮、分子式为H2NNHR2的肼、Meerwein试剂和原甲酸三烷酯反应10分钟～5天，所述的3,4-二氢异喹啉酮、分子式H2NNHR2的肼、Meerwein试剂和原甲酸三烷酯的摩尔比依次为1：0.8～5：1～5：1～20；
所述的Meerwein试剂的结构式为：Me3O+BF4 -或者Et3O+BF4 -；
所述的原甲酸三烷基酯为CH(OEt)3；
所述的3,4-二氢异喹啉酮具有如下的结构式:
其中R1、R3和*如权利要求1所述。
4.如权利要求3所述一种具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐的合成方法，其特征是所述的3,4-二氢异喹啉酮：分子式H2NNHR2的肼：Meerwein试剂：原甲酸三烷酯的摩尔比依次为1：1～2：1～2：5～10。
5.如权利要求3所述一种具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐的合成方法，其特征是所述的有机溶剂是氯苯、苯、四氯化碳、石油醚、四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、三氯甲烷、甲苯、二甲苯、环己烷、正己烷、正庚烷、二氧六环或乙腈。
6.如权利要求3所述一种具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐的合成方法，其特征是所得产物经过重结晶或柱层析的方法提纯。
7.一种如权利要求1所述的具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐的用途，其特征是用在氮杂环卡宾催化的反应。
8.如权利要求7所述的具有3,4-二氢异喹啉骨架的手性氮杂环卡宾前体盐的用途，其特征是手性氮杂环卡宾前体盐与碱反应现场生成卡宾催化剂用于催化酚和α，β-不饱和醛的环化反应，合成萘并吡喃酮类化合物。
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