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• 不对称Friedel-Crafts (F-C)反应是芳香族化合物与醛、酮、活化烯烃及亚胺等反应构建C—C键最有效的方法之一, 提供了合成手性芳基衍生物的直接途径^[1].不对称aza-Friedel-Crafts反应更是有机合成领域中制备手性芳胺的重要反应^[2].大多数研究中, F-C反应的供体为反应活性高的富电子化合物, 例如吲哚^[3]、吡咯^[4]及具强给电子基的苯类等^[5].萘酚在F-C反应中表现出良好的反应活性, 可与含氮亲电体反应, 得到的手性氨基萘酚化合物是许多生物活性的天然产物和合成药物的重要骨架结构以及不对称反应的手性配体^[6].但是, 关于萘酚的不对称F-C研究还很少. 2011年, Wang和Chimni等^[7]分别报道了金鸡纳碱衍生物有机催化α-萘酚与亚胺的不对称F-C反应, 得到了好的产率和对映选择性. 2015年, Bajaj等^[8]报道了金属催化的不对称F-C反应, 将Cu-手性氨醇席夫碱配合物用于催化的α-萘酚与N-Ts亚胺的反应, 得到了78%~99% ee的对映选择性.最近, 我们^[9]报道了金鸡纳碱-硅醚衍生物有机催化的α-萘酚与N-Ts亚胺的不对称F-C反应, 得到了最高达85% ee的立体选择性.目前, 未见脲衍生物催化α-萘酚与亚胺的不对称F-C反应的报道.本工作将6种脲及硫脲类衍生物1a~1f(图 1)作为有机催化剂用于α-萘酚和N-Ts芳香醛亚胺的不对称aza-Friedel-Crafts反应.

  图 1

  

  图 1.  脲及硫脲催化剂1a~1f的结构

  Figure 1.  Structures of catalysts 1a~1f

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  1.   结果与讨论

  1.1   催化剂1a~1f催化不对称aza-Friedel-Crafts反应

  将催化剂1a~1f用于α-萘酚和苯甲醛亚胺的不对称aza-Friedel-Crafts反应, 以二氯甲烷为溶剂, 催化剂用量为10 mol%, 室温反应, 结果见表 1.

  表 1

  

  表 1  α-萘酚与苯甲醛亚胺的不对称aza-F-C反应^a

  Table 1.  Asymmetric aza-F-C reaction of α-nahthol with benzaldimine

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  Entry	Catalyst	Yieldb/%	eec/%	Conf.d
  1	1a	82	56	S
  2	1b	83	62	S
  3	1c	80	55	R
  4	1d	82	55	R
  5	1e	76	37	S
  6	1f	73	51	S
  a Reaction condition: 0.5 mmol of α-naphthol, 0.1 mmol of benzaldimine in 0.5 mL of CH2Cl2. b Isolated yield. c Determined by HPLC analysis (Chiralpak AS-H). d The configuration was established by comparison with the optical rotation from the literature[7].

  由表 1反应结果可以得出以下结论: 6种(硫)脲类催化剂在二氯甲烷中均能顺利催化α-萘酚和苯甲醛亚胺的不对称Friedel-Crafts反应, 得到73%~83%的产率.其中脲催化剂1b催化该反应得到了最好的对映选择性(62% ee, Entry 2), 产品的构型, 通过测定旋光值, 对比文献报道^[7]的旋光值确定主要产物的构型为S型.而由催化剂1d催化该反应得到了R构型的主要产物(55% ee, Entry 4).反应的过渡态如图 2所示, 脲催化剂与反应底物形成多重氢键, 稳定过渡态, 有利于手性诱导作用.

  图 2

  

  图 2.  1b催化反应的过渡态

  Figure 2.  Proposed transition state catalyzed by 1b

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  1.2   反应条件优化

  将上述最好的催化剂1b用于α-萘酚与苯甲醛亚胺的反应中, 考察溶剂、温度、催化剂用量等因素对反应立体选择性的影响, 以期获得更好的催化剂体系, 结果见表 2.

  表 2

  

  表 2  1b催化不对称aza-F-C反应的条件筛选

  Table 2.  Screening of reaction conditions for the asymmetric aza-F-C reaction catalyzed by 1b

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  Entry	Solvent	Cat./mol%	Temp./℃	Yieldb/%	ee c/%
  1	CH2Cl2	10	r.t.	80	62
  2	THF	10	r.t.	79	65
  3	PhMe	10	r.t.	80	61
  4	CH3CN	10	r.t.	78	51
  5	EtOAc	10	r.t.	76	63
  6	Et2O	10	r.t.	83	69
  7	Et2O	5	r.t.	84	69
  8	Et2O	20	r.t.	85	69
  9d	Et2O	5	r.t.	80	65
  10	Et2O	5	0	83	78
  11	Et2O	10	0	84	75
  12	Et2O	5	－20	65	72
  a Reaction condition: 0.5 mmol of α-naphthol, 0.1 mmol of benzaldimine in 0.5 mL of solvent. b Isolated yield. c Determined by HPLC analysis (Chiralpak AS-H). d 1 mL of solvent.

  由表 2结果可以得出以下结论: (1)溶剂对反应的立体选择性有明显的影响, 其中乙醚为最适合溶剂(69% ee, Entry 6); (2)催化剂用量对反应的立体选择性影响不大, 5、10和20 mol%的用量得到相似的结果(Entries 6~8); (3)反应温度对立体选择性有明显的影响, 当温度由室温降至0 ℃, 产品的对映体过量值增加了9% ee (Entry 10 vs Entry 7).但是继续降温至－20 ℃, 产物的ee值没有提高, 而产率有所下降(Entry 12); (4)当反应溶剂量加倍, 即反应体系稀释条件下, 反应的产率和立体选择性都有所下降(Entry 9).综上所述, 筛选出最佳催化剂体系为: 5 mol%催化剂1b, 以乙醚为溶剂, 0 ℃反应.

  1.3   底物的扩展

  将筛选出的最优催化条件应用于不同取代苯甲醛亚胺与α-萘酚的不对称aza-Friedel-Crafts反应中, 考察催化剂体系的普适性, 结果见表 3.

  表 3

  

  表 3  α-萘酚与不同取代对甲苯磺酰亚胺的不对称aza-Friedel-Crafts反应^a

  Table 3.  Scope of the enantioselective aza-Friedel-Crafts reaction of α-naphthol with N-Ts aldimines

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  Entry	X	R	Product	Yieldb/%	ee c/%	[α]D22
  1	H	H	3a	83	78	－30.7
  2	H	2-Cl	3b	80	73	－56.9
  3	H	2-Me	3c	78	65	－32.0
  4	H	2-CF3	3d	85	70	－22.4
  5	H	3-F	3e	79	65	－14.2
  6	H	3-Cl	3f	72	63	－29.8
  7	H	3-Me	3g	70	73	－29.2
  8	H	4-Cl	3h	80	63	－18.2
  9	H	4-Me	3i	72	70	－16.6
  10	H	4-iPr	3j	75	67	－15.3
  11	H	4-tBu	3k	75	67	－14.5
  12	H	4-NO2	3l	86	70	－50.9
  13	H	4-OMe	3m	—	—	—
  14	Cl	H	3n	78	57	－13.0
  a Reaction condition: 0.5 mmol of α-naphthol, 0.1 mmol of N-Ts aldimines and 0.005 mmol of catalyst 1b in ether (0.5 mL) at 0 ℃. b Isolated yield. c Determined by HPLC analysis (Chiralpak AS-H, AD-H).

  由表 3可以看出, 催化剂1b能够催化大多数不同取代苯甲醛亚胺为底物的F-C反应, 以70%~86%的产率得到相应的产品.但是, 4-甲氧基苯甲醛亚胺为底物的反应没能进行, 可见强供电子基团对反应不利(Entry 13).其中, 苯甲醛亚胺为底物的反应得到了最高的ee值(78% ee, Entry 1), 4-氯取代萘酚与苯甲醛亚胺的反应仅得到了57% ee (Entry 14).芳环上取代基的种类和位置对反应的立体选择性有一定的影响.

  2.   结论

  将(硫)脲类衍生物催化剂用于有机催化的芳香醛亚胺和α-萘酚的不对称aza-Friedel-Crafts反应.筛选出最佳的催化条件, 催化剂用量仅为5 mol%, 应用于14种不同取代的苯甲醛亚胺的反应, 以苯甲醛亚胺为底物的反应获得了最好的立体选择性.催化剂体系对底物普适性的提高还有待于进一步研究.

  3.   实验部分

  3.1   仪器与试剂

  Bruker Avance-500型核磁共振谱仪(以CDCl₃为溶剂, TMS为基准物质, 德国Bruker公司); Bruker Apex Ⅳ FTMS型质谱仪(德国Bruker公司); RUDOLPH AUTOPOL Ⅵ型旋光仪(美国鲁道夫公司); VERTEX70型傅立叶变换红外光谱仪(德国Bruker公司); YRT-3型熔点测定仪(天津天光光学仪器有限公司); LC-20A高效液相色谱仪(日本岛津公司), Daicel Chiralpak AS-H, AD-H手性色谱柱(日本大赛璐公司).脲及硫脲衍生物为上海大赛璐药物手性技术(上海)有限公司产品, 其他试剂均为市售分析纯产品.芳香醛亚胺根据文献方法合成^[10].

  3.2   不对称aza-Friedel-Crafts反应

  将α-萘酚(0.5 mmol)、芳香醛亚胺(0.1 mmol)、催化剂(0.005 mmol)溶于0.5 mL乙醚, 0 ℃反应24 h, 薄层色谱(TLC)监测反应.反应结束后, 经硅胶柱层析分离, 正己烷/乙酸乙酯(V:V＝12:1)洗脱, 得到产品3, 为无色或淡黄色油状物.其中产品3a~3i为已知化合物, 产品3j、3k和3n为未知化合物.

  N-((1-羟基萘基-2-)(苯基)甲基)-4-甲基苯磺酰胺(3a):白色固体, 产率83%. m.p. 120~122 ℃; [α]_D²⁵－30.7 (c 1.0, CH₂Cl₂)[文献值^[7a] [α]_D²²－38.8 (c 1.0, CH₂Cl₂)]; ¹H NMR (500 MHz, CDCl₃) δ: 8.08~8.06 (m, 1H), 7.76~7.74 (m, 1H), 7.56 (d, J＝8.0 Hz, 2H), 7.51~7.48 (m, 2H), 7.31~7.25 (m, 4H), 7.23~7.20 (m, 2H), 6.99 (d, J＝8.0 Hz, 2H), 6.92 (d, J＝8.5 Hz, 1H), 6.75 (s, 1H), 5.93 (d, J＝7.5 Hz, 1H), 5.37 (d, J＝7.0 Hz, 1H), 2.21 (s, 3H); ATR-FTIR ν: 3433, 1640, 1569, 1413, 1160, 1019, 811, 644, 562 cm^－1; HPLC (Daicel Chiralpak AD-H, V_hexane:V_i-PrOH＝80:20, 1.0 mL/min, 235 nm), t_R: 10.8 min (major), 12.3 min (minor); ee 78%.

  N-((1-羟基萘基-2-)(2-氯苯基)甲基)-4-甲基苯磺酰胺(3b):白色固体, 产率80%. m.p. 158~160 ℃; [α]_D²⁵－56.9 (c 1.0, CH₂Cl₂)[文献值^[7a] [α]_D²²－63.0 (c 1.0, CH₂Cl₂)]; ¹H NMR (500 MHz, CDCl₃) δ: 8.23~8.21 (m, 1H), 7.74~7.71 (m, 1H), 7.59 (d, J＝8.0 Hz, 2H), 7.50~7.48 (m, 2H), 7.32~7.28 (m, 2H), 7.24 (d, J＝8.5 Hz, 1H), 7.21~7.16 (m, 2H), 7.04 (d, J＝8.0 Hz, 2H), 6.74 (d, J＝8.5 Hz, 1H), 6.21 (d, J＝8.5 Hz, 1H), 5.41 (d, J＝7.0 Hz, 1H), 2.27 (s, 3H); ATR-FTIR ν: 3434, 1640, 1562, 1415, 1021, 809, 643, 530 cm^－1; HPLC (Daicel Chiralpak AS-H, V_hexane:V_i-PrOH＝60:40, 0.6 mL/min, 254 nm), t_R: 37.9 min (major), 51.7 min (minor); ee 73%.

  N-((1-羟基萘基-2-)(2-甲基苯基)甲基)-4-甲基苯磺酰胺(3c):黄色固体, 产率78%. m.p. 129~131 ℃; [α]_D²⁵－32.0 (c 1.0, CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃) δ: 8.23~8.20 (m, 1H), 7.72~7.70 (m, 1H), 7.56 (d, J＝8.5 Hz, 2H), 7.50~7.47 (m, 2H), 7.23~7.20 (m, 4H), 7.17~6.99 (m, 2H), 6.74 (d, J＝8.5 Hz, 2H), 6.10 (d, J＝7.5 Hz, 1H), 5.17 (d, J＝7.5 Hz, 1H), 2.23 (s, 3H), 2.13 (s, 3H); ATR-FTIR ν: 3256, 1640, 1571, 1415, 1321, 1271, 1143, 942, 810, 745, 664, 564 cm^－1; HPLC (Daicel Chiralpak AS-H, V_hexane:V_i-PrOH＝60:40, 0.6 mL/min, 254 nm), t_R: 31.0 min (major), 50.4 min (minor); ee 65%.

  N-((1-羟基萘基-2-)(2-三氟甲基苯基)甲基)-4-甲基苯磺酰胺(3d):白色固体, 产率85%. m.p. 156~158 ℃; [α]_D²⁵－22.4 (c 1.0, CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃) δ: 8.23~8.21 (m, 1H), 7.72~7.70 (m, 1H), 7.65 (d, J＝7.5 Hz, 1H), 7.60 (d, J＝9.0 Hz, 1H), 7.62~7.57 (m, 3H), 7.52~7.46 (m, 3H), 7.37 (t, J＝8.0 Hz, 1H), 7.23~7.20 (m, 2H), 7.05 (d, J＝8.0 Hz, 2H), 6.65 (d, J＝8.5 Hz, 1H), 6.35 (d, J＝6.5 Hz, 1H), 5.25 (d, J＝6.5 Hz, 1H), 2.29 (s, 3H); ATR-FTIR ν: 3433, 1640, 1562, 1415, 1313, 1164, 1107, 1021, 806, 644, 565 cm^－1; HPLC (Daicel Chiralpak AS-H, V_hexane:V_i-PrOH＝60:40, 0.6 mL/min, 254 nm), t_R: 19.8 min (major), 54.3 min (minor); ee 70%.

  N-((1-羟基萘基-2-)(3-氟苯基)甲基)-4-甲基苯磺酰胺(3e):白色固体, 产率79%. m.p. 148~150 ℃; [α]_D²⁵－14.2 (c 1.0, CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃) δ: 8.10~8.07 (m, 1H), 8.05 (s, 1H), 7.97~7.94 (m, 1H), 7.80~7.77 (m, 1H), 7.62 (d, J＝8.0 Hz, 1H), 7.58 (d, J＝ 8.5 Hz, 2H), 7.55~7.51 (m, 2H), 7.48~7.42 (m, 1H), 7.33 (d, J＝8.5 Hz, 1H), 7.00 (d, J＝8.0 Hz, 2H), 6.90 (d, J＝8.5 Hz, 1H), 6.28 (s, 1H), 6.03 (d, J＝8.5 Hz, 1H), 5.65 (d, J＝8.5 Hz, 1H), 2.20 (s, 3H); ATR-FTIR ν: 3434, 1640, 1562, 1414, 1021, 812, 644, 522 cm^－1; HPLC (Daicel Chiralpak AS-H, V_hexane:V_i-PrOH＝60:40, 0.6 mL/min, 254 nm), t_R: 27.0 min (minor), 30.1 min (major); ee 65%.

  N-((1-羟基萘基-2-)(3-氯苯基)甲基)-4-甲基苯磺酰胺(3f):白色固体, 产率72%. m.p. 159~161 ℃; [α]_D²⁵－29.8 (c 1.0, CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃) δ: 7.94 (d, J＝3.5 Hz, 1H), 7.93 (d, J＝6.0 Hz, 1H), 7.47~7.35 (m, 4H), 7.18 (d, J＝8.0 Hz, 1H), 7.13~7.02 (m, 4H), 6.85 (d, J＝8.0 Hz, 2H), 6.78 (d, J＝8.5 Hz, 1H), 6.59 (s, 1H), 5.81 (d, J＝8.0 Hz, 1H), 5.60 (d, J＝8.5 Hz, 1H), 2.09 (s, 3H); ATR-FTIR ν: 3434, 1640, 1561, 1413, 1020, 811, 643, 525 cm^－1; HPLC (Daicel Chiralpak AS-H, V_hexane:V_i-PrOH＝80:20, 0.6 mL/min, 254 nm), t_R: 50.6 min (minor), 55.7 min (major); ee 63%.

  N-((1-羟基萘基-2-)(3-甲基苯基)甲基)-4-甲基苯磺酰胺(3g):白色固体, 产率70%. m.p. 133~135 ℃; [α]_D²⁵－29.2 (c 1.0, CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃) δ: 8.23~8.21 (m, 1H), 7.72~7.70 (m, 1H), 7.65 (d, J＝7.5 Hz, 1H), 7.60 (d, J＝9.0 Hz, 1H), 7.62~7.57 (m, 3H), 7.52~7.46 (m, 3H), 7.37 (t, J＝8.0 Hz, 1H), 7.23~7.20 (m, 2H), 7.05 (d, J＝8.0 Hz, 2H), 6.65 (d, J＝8.5 Hz, 1H), 6.35 (d, J＝6.5 Hz, 1H), 5.25 (d, J＝6.5 Hz, 1H), 2.29 (s, 3H), 2.18 (s, 3H); ATR-FTIR ν: 3434, 1640, 1561, 1414, 1021, 808, 644, 524 cm^－1; HPLC (Daicel Chiralpak AD-H, V_hexane:V_i-PrOH＝80:20, 0.6 mL/min, 254 nm), t_R: 15.4 min (major), 19.2 min (minor); ee 73%.

  N-((1-羟基萘基-2-)(4-氯苯基)甲基)-4-甲基苯磺酰胺(3h):白色固体, 产率80%. m.p. 137~139 ℃; [α]_D²⁵－18.2 (c 1.0, CH₂Cl₂)[文献值^[7b] [α]_D²⁵－25.6 (c 1.0, CH₂Cl₂)]; ¹H NMR (500 MHz, CDCl₃) δ: 8.01~7.82 (m, 1H), 7.72~7.70 (m, 1H), 7.49~7.46 (m, 4H), 7.26 (d, J＝8.5 Hz, 1H), 7.17~7.08 (m, 4H), 6.88 (d, J＝8.5 Hz, 2H), 6.85 (d, J＝8.5 Hz, 1H), 6.70 (s, 1H), 5.88 (d, J＝8.5 Hz, 1H), 5.80~5.78 (m, 1H), 2.17 (s, 3H); ATR-FTIR ν: 3434, 1640, 1562, 1414, 1021, 803, 643, 530 cm^－1; HPLC (Daicel Chiralpak AS-H, V_hexane:V_i-PrOH＝80:20, 0.6 mL/ min, 254 nm), t_R: 24.9 min (minor), 29.8 min (major); ee 63%.

  N-((1-羟基萘基-2-)(4-甲基苯基)甲基)-4-甲基苯磺酰胺(3i):白色固体, 产率72%. m.p. 124~126 ℃; [α]_D²⁵－16.6 (c 1.0, CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃) δ: 8.06~8.04 (m, 1H), 7.74~7.72 (m, 1H), 7.54 (d, J＝8.0 Hz, 2H), 7.50~7.46 (m, 2H), 7.27 (d, J＝8.5 Hz, 1H), 7.10~7.05 (m, 4H), 6.98 (d, J＝8.0 Hz, 1H), 6.92 (d, J＝8.5 Hz, 1H), 6.74 (s, 1H), 5.87 (d, J＝7.0 Hz, 1H), 5.28 (d, J＝7.0 Hz, 1H), 2.30 (s, 3H), 2.20 (s, 3H); ATR-FTIR ν: 3434, 1640, 1562, 1414, 1159, 1021, 808, 643, 539 cm^－1; HPLC (Daicel Chiralpak AS-H, V_hexane:V_i-PrOH＝80:20, 0.6 mL/min, 254 nm), t_R: 30.1 min (minor), 37.0 min (major); ee 70%.

  N-((1-羟基萘基-2-)(4-异丙基苯基)甲基)-4-甲基苯磺酰胺(3j):白色固体, 产率75%. m.p. 128~130 ℃; [α]_D²⁵－15.3 (c 1.0, CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃) δ: 8.09~8.07 (m, 1H), 7.74~7.72 (m, 1H), 7.52 (d, J＝8.0 Hz, 2H), 7.49~7.46 (m, 2H), 7.28 (d, J＝3.5 Hz, 1H), 7.13~7.08 (m, 4H), 6.94 (d, J＝8.5 Hz, 3H), 6.86 (s, 1H), 5.90 (d, J＝7.5 Hz, 1H), 5.56 (d, J＝7.5 Hz, 1H), 2.86 (hept, J＝2.0 Hz, 1H), 2.18 (s, 3H), 1.22 (d, J＝6.5 Hz, 6H); ¹³C NMR (125 MHz, CDCl₃) δ: 149.5, 148.6, 143.5, 136.1, 136.0, 134.1, 129.1 (×2), 127.5, 127.2 (×2), 127.1 (×2), 126.8 (×2), 126.4, 126.2, 125.4, 125.2, 121.4, 120.4, 119.3, 58.8, 33.7, 23.9 (×2), 21.2; ATR-FTIR ν: 3436, 2961, 1640, 1572, 1416, 1320, 1160, 1091, 1021, 807, 673, 561 cm^－1; HRMS (ESI) calcd for C₂₇H₂₆NO₃S [M－H]^－ 444.1639, found 444.1635; HPLC (Daicel Chiralpak AS-H, V_hexane:V_i-PrOH＝70:30, 0.6 mL/ min, 254 nm), t_R: 24.5 min (minor), 34.4 min (major); ee 67%.

  N-((1-羟基萘基-2-)(4-叔丁基苯基)甲基)-4-甲基苯磺酰胺(3k):白色固体, 产率75%. m.p. 132~134 ℃; [α]_D²⁵－14.5 (c 1.0, CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃) δ: 8.07~8.05 (m, 1H), 7.72~7.70 (m, 1H), 7.51~7.48 (m, 2H), 7.46~7.44 (m, 2H), 7.25~7.22 (m, 3H), 7.10 (d, J＝8.5 Hz, 2H), 6.93~6.90 (m, 3H), 5.88 (d, J＝7.5 Hz, 1H), 5.55 (d, J＝7.0 Hz, 1H), 2.16 (s, 3H), 1.26 (s, 9H); ¹³C NMR (125 MHz, CDCl₃) δ: 150.9, 149.5, 143.4, 136.1, 135.7, 134.1, 129.1 (×2), 127.5, 127.2 (×2), 126.8 (×2), 126.4, 126.2, 125.6 (×2), 125.4, 125.2, 121.4, 120.4, 119.3, 58.7, 34.4, 31.2 (×3), 21.2; HRMS (ESI, m/z) calcd for C₂₈H₂₈NO₃S [M－H]^－ 458.1795, found 458.1790; ATR-FTIR ν: 3435, 1640, 1562, 1414, 1158, 1021, 808, 643, 528 cm^－1; HPLC (Daicel Chiralpak AS-H, V_hexane:V_i-PrOH＝70:30, 0.6 mL/min, 254 nm), t_R: 23.5 min (minor), 30.1 min (major); ee 67%.

  N-((1-羟基萘基-2-)(4-硝基苯基)甲基)-4-甲基苯磺酰胺(3l):白色固体, 产率86%. m.p. 160~162 ℃; [α]_D²⁵－50.9 (c 1.0, CH₂Cl₂)[文献值^[7a] [α]_D²²－73.4 (c 1.0, CH₂Cl₂)]; ¹H NMR (500 MHz, CDCl₃) δ: 8.10 (d, J＝9.0 Hz, 2H), 7.95~7.92 (m, 1H), 7.80~7.77 (m, 1H), 7.57 (d, J＝8.0 Hz, 2H), 7.55~7.51 (m, 2H), 7.44 (d, J＝8.5 Hz, 2H), 7.32 (d, J＝8.5 Hz, 1H), 6.99 (d, J＝8.0 Hz, 2H), 6.88 (d, J＝8.5 Hz, 1H), 6.21 (s, 1H), 6.01 (d, J＝8.5 Hz, 1H), 5.65 (d, J＝8.5 Hz, 1H), 2.20 (s, 3H); ATR-FTIR ν: 3432, 1640, 1562, 1414, 1346, 1156, 1020, 804, 644, 528 cm^－1; HPLC (Daicel Chiralpak AS-H, V_hexane:V_i-PrOH＝70:30, 0.6 mL/min, 254 nm), t_R: 33.4 min (minor), 36.7 min (major); ee 70%.

  N-((1-羟基-4-氯萘基-2-)(苯基)甲基)-4-甲基苯磺酰胺(3n):白色固体, 产率78%. m.p. 169~171 ℃; [α]_D²⁵－13.0 (c 1.0, CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃) δ: 8.14 (t, J＝10.0 Hz, 2H), 7.61 (t, J＝7.5 Hz, 1H), 7.56 (d, J＝7.0 Hz, 1H), 7.53 (d, J＝8.0 Hz, 2H), 7.27~7.26 (m, 3H), 7.22~7.20 (m, 2H), 7.04 (br, 1H), 6.96~6.94 (m, 3H), 5.89 (d, J＝7.0 Hz, 1H), 5.71 (d, J＝7.5 Hz, 1H), 2.20 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 148.6, 143.8, 138.3, 135.8, 130.9, 129.2 (×2), 128.8 (×2), 128.0, 127.6, 127.1, 127.0 (×2), 126.4 (×2), 126.3, 125.9, 124.2, 123.5, 122.0, 119.9, 58.1, 21.3; HRMS (ESI) calcd for C₂₄H₁₉ClNO₃S [M－H]^－ 436.0779, found 436.0774; ATR-FTIR 3432, 1640, 1561, 1416, 1161, 1020, 808, 643, 550 cm^－1; HPLC (Daicel Chiralpak AS-H, V_hexane: V_i-PrOH＝70:30, 0.6 mL/min, 254 nm), t_R: 28.0 min (minor), 36.7 min (major); ee 57%.

  辅助材料(Supporting Information) 催化剂的¹H NMR, 新化合物¹H NMR、¹³C NMR、IR、HRMS图谱及化合物3对映体过量值测定的HPLC图谱.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

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• 

  图 1  脲及硫脲催化剂1a~1f的结构

  Figure 1  Structures of catalysts 1a~1f

  下载: 全尺寸图片 幻灯片
  

  图 2  1b催化反应的过渡态

  Figure 2  Proposed transition state catalyzed by 1b

  下载: 全尺寸图片 幻灯片

  表 1  α-萘酚与苯甲醛亚胺的不对称aza-F-C反应^a

  Table 1.  Asymmetric aza-F-C reaction of α-nahthol with benzaldimine

  Entry	Catalyst	Yieldb/%	eec/%	Conf.d
  1	1a	82	56	S
  2	1b	83	62	S
  3	1c	80	55	R
  4	1d	82	55	R
  5	1e	76	37	S
  6	1f	73	51	S
  a Reaction condition: 0.5 mmol of α-naphthol, 0.1 mmol of benzaldimine in 0.5 mL of CH2Cl2. b Isolated yield. c Determined by HPLC analysis (Chiralpak AS-H). d The configuration was established by comparison with the optical rotation from the literature[7].

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  表 2  1b催化不对称aza-F-C反应的条件筛选

  Table 2.  Screening of reaction conditions for the asymmetric aza-F-C reaction catalyzed by 1b

  Entry	Solvent	Cat./mol%	Temp./℃	Yieldb/%	ee c/%
  1	CH2Cl2	10	r.t.	80	62
  2	THF	10	r.t.	79	65
  3	PhMe	10	r.t.	80	61
  4	CH3CN	10	r.t.	78	51
  5	EtOAc	10	r.t.	76	63
  6	Et2O	10	r.t.	83	69
  7	Et2O	5	r.t.	84	69
  8	Et2O	20	r.t.	85	69
  9d	Et2O	5	r.t.	80	65
  10	Et2O	5	0	83	78
  11	Et2O	10	0	84	75
  12	Et2O	5	－20	65	72
  a Reaction condition: 0.5 mmol of α-naphthol, 0.1 mmol of benzaldimine in 0.5 mL of solvent. b Isolated yield. c Determined by HPLC analysis (Chiralpak AS-H). d 1 mL of solvent.

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  表 3  α-萘酚与不同取代对甲苯磺酰亚胺的不对称aza-Friedel-Crafts反应^a

  Table 3.  Scope of the enantioselective aza-Friedel-Crafts reaction of α-naphthol with N-Ts aldimines

  Entry	X	R	Product	Yieldb/%	ee c/%	[α]D22
  1	H	H	3a	83	78	－30.7
  2	H	2-Cl	3b	80	73	－56.9
  3	H	2-Me	3c	78	65	－32.0
  4	H	2-CF3	3d	85	70	－22.4
  5	H	3-F	3e	79	65	－14.2
  6	H	3-Cl	3f	72	63	－29.8
  7	H	3-Me	3g	70	73	－29.2
  8	H	4-Cl	3h	80	63	－18.2
  9	H	4-Me	3i	72	70	－16.6
  10	H	4-iPr	3j	75	67	－15.3
  11	H	4-tBu	3k	75	67	－14.5
  12	H	4-NO2	3l	86	70	－50.9
  13	H	4-OMe	3m	—	—	—
  14	Cl	H	3n	78	57	－13.0
  a Reaction condition: 0.5 mmol of α-naphthol, 0.1 mmol of N-Ts aldimines and 0.005 mmol of catalyst 1b in ether (0.5 mL) at 0 ℃. b Isolated yield. c Determined by HPLC analysis (Chiralpak AS-H, AD-H).

  下载: 导出CSV
•