一种环芳烷类面手性化合物的拆分方法转让专利
申请号 : CN201910895177.5
文献号 : CN112538033B
文献日 : 2022-02-11
发明人 : 周永贵 , 赵洋 , 孙蕾
申请人 : 中国科学院大连化学物理研究所
摘要 :
本发明提供一种环芳烷类面手性化合物的拆分方法，其用到的催化剂是钯的手性膦氮配合物。通过该方法可以得到环芳烷亚胺类面手性化合物(对映体过量可达99.9％)，以及环芳烷胺类面手性化合物(对映体过量可达99.4％，非对映体比例可达>20:1)，拆分系数可达到s＝368。本发明可以实现催化拆分，操作简单易行，催化剂商业可得，条件温和，能耗低，环境友好且拆分系数高，产率好。
权利要求 :
1.一种环芳烷类面手性化合物的拆分方法，其特征在于，所述拆分方法的催化剂是钯的手性膦氮配合物，具体反应式如下：式中：
R为苯基、萘基或含有取代基的苯环，所述的取代基为卤素，烷氧基或C1‑C20的烷基中的至少一种；
Ar为含有取代基的亚苯基或C6H3，所述的取代基为C1‑C20的烷基中的至少一种；
Ts为对甲苯磺酰基；
所述催化剂的制备方法为：在氮气气氛保护下，将钯的金属前体、手性膦氮配体和丙酮混合，室温搅拌1h，除去丙酮，得到所述催化剂；
所述钯的金属前体为三氟醋酸钯；
所述手性膦氮配体为下述中的一种：
2.根据权利要求1所述的拆分方法，其特征在于，所述拆分方法的具体反应步骤为：(1)在氮气保护下将催化剂、环芳烷亚胺、硼酸类化合物和有机溶剂混合，于40‑80℃搅拌反应15h后，旋干溶剂，柱层析分离得到面手性环芳烷亚胺和产物前体；
(2)将产物前体用N,N‑二甲基甲酰胺溶解，0℃下加入氢化钠，随后加入烯丙基溴，于室温搅拌2h后柱层析分离得到烯丙基保护的手性胺；
所述催化剂、环芳烷亚胺、硼酸类化合物和有机溶剂的用量比为0.05mmol:1mmol:1～
1.5mmol:20ml；所述产物前体、氢化钠、烯丙基溴和N,N‑二甲基甲酰胺的用量比为1mmol:
3mmol:6mmol:10ml。
3.根据权利要求1所述的拆分方法，其特征在于，所述钯的金属前体和手性膦氮配体的比例为1:1。
4.根据权利要求2所述的拆分方法，其特征在于，所述有机溶剂为三氟乙醇、六氟异丙醇中的一种或两种混合。
5.根据权利要求2所述的拆分方法，其特征在于，所述方法的反应温度为60℃，反应时间为15h。
6.根据权利要求2所述的拆分方法，其特征在于：R为苯基，Ar为C6H3，所述的催化剂为钯的手性二茂铁骨架膦噁唑啉配体的配合物，有机溶剂为三氟乙醇，温度为60℃，反应时间
15h，拆分后得到的面手性环芳烷亚胺对映体过量94.0％，烯丙基保护的手性胺对映体过量
97.8％，拆分系数s值为115。
说明书 :
一种环芳烷类面手性化合物的拆分方法
技术领域
[0001] 本发明属于不对称催化合成领域，就提涉及一种通过钯均相体系催化的加成反应实现环芳烷类面手性化合物拆分的方法。
技术背景
技术背景
[0002] 面手性[2.2]环芳烷化合物广泛应用于各种手性材料中，同时也可以作为配体或辅基在不对称合成中起着不可或缺的作用。(参考文献一：(a)Morisaki,Y.；Inoshita,K.；
Chujo,Y.Chem.Eur.J.2014,20,8386.(b)Gibson,S.E.；Knight,J.D.Org.Biomol.Chem.
2003,1,1256.(c)Fringuelli,F.；Piermatti,O.；Pizzo,F.；Ruzziconi,
R.Chem.Lett.2000, 38.)。目前，获得面手性[2.2]环芳烷化合物的方法主要有传统的化学
拆分，手性色谱分离等方法。(参考文献二：(a)Braddock,D.C.；MacGilp,I.D.；Perry,
B.G.J.Org.Chem. 2002,67,8679.(b)Wang,Y.；Yuan,H.；Lu,H.；Zheng,W.‑
H.Org.Lett.2018,20,2555.)。近年来，通过催化动力学拆分制备面手性环芳烷引起了人们
的注意，相比其他方法，它的优势在于可以显著降低手性试剂的用量。但目前发展的方法底
物范围受限。(参考文献三：(a)Dorizon,P.；Martin,C.；Daran,J.‑C.；Fiauda,J.‑C.；
Kagana,H.B.Tetrahedron: Asymmetry 2001,12,2625.(b)Akagawa,K.；Nishi,N.；
Yoshikawa,I.；Kudo,K.Eur.J.Org. Chem.2015,5055.)。
Chujo,Y.Chem.Eur.J.2014,20,8386.(b)Gibson,S.E.；Knight,J.D.Org.Biomol.Chem.
2003,1,1256.(c)Fringuelli,F.；Piermatti,O.；Pizzo,F.；Ruzziconi,
R.Chem.Lett.2000, 38.)。目前，获得面手性[2.2]环芳烷化合物的方法主要有传统的化学
拆分，手性色谱分离等方法。(参考文献二：(a)Braddock,D.C.；MacGilp,I.D.；Perry,
B.G.J.Org.Chem. 2002,67,8679.(b)Wang,Y.；Yuan,H.；Lu,H.；Zheng,W.‑
H.Org.Lett.2018,20,2555.)。近年来，通过催化动力学拆分制备面手性环芳烷引起了人们
的注意，相比其他方法，它的优势在于可以显著降低手性试剂的用量。但目前发展的方法底
物范围受限。(参考文献三：(a)Dorizon,P.；Martin,C.；Daran,J.‑C.；Fiauda,J.‑C.；
Kagana,H.B.Tetrahedron: Asymmetry 2001,12,2625.(b)Akagawa,K.；Nishi,N.；
Yoshikawa,I.；Kudo,K.Eur.J.Org. Chem.2015,5055.)。
[0003] 金属催化芳基硼试剂对亚胺的加成反应是一种构建手性化合物的有效手段。近年来钯催化硼酸对亚胺的加成反应上取得了重要进展(参考文献四：(a)Yan,Z.；Wu,B.； Gao,
X.；Zhou.Y.‑G.Chem.Commun.2016,52,10882.(b)Quan,M.；Wu,L.；Yang,G.； Zhang,
W.Chem.Commun.2018,54,10394.(c)Zhao,Z.‑B.；Shi,L.；Meng,F.‑J.；Li,Y.； Zhou,Y.‑
G.Org.Chem.Front.2019,6,1572.)，我们设想能否通过钯催化环芳烷亚胺的不对称加成反
应实现该面手性化合物的动力学拆分，并且一次性获得含有中心手性和面手性的环芳烷衍
生物。
X.；Zhou.Y.‑G.Chem.Commun.2016,52,10882.(b)Quan,M.；Wu,L.；Yang,G.； Zhang,
W.Chem.Commun.2018,54,10394.(c)Zhao,Z.‑B.；Shi,L.；Meng,F.‑J.；Li,Y.； Zhou,Y.‑
G.Org.Chem.Front.2019,6,1572.)，我们设想能否通过钯催化环芳烷亚胺的不对称加成反
应实现该面手性化合物的动力学拆分，并且一次性获得含有中心手性和面手性的环芳烷衍
生物。
发明内容
[0004] 本发明的目的是提供一种通过对亚胺的硼酸加成反应实现环芳烷类外消旋面手性化合物拆分的方法。
[0005] 本发明操作简便实用，原料易得，拆分系数高，产率好，能耗低且反应具有环境友好等优点。
[0006] 为实现上述目的，本发明以钯的手性膦氮配合物为催化剂，以环芳烷亚胺和硼酸类化合物为底物，通过对亚胺的硼酸加成反应实现环芳烷类外消旋面手性化合物拆分。
[0007] 本发明的技术方案如下：
[0008] 本发明一方面提供一种拆分环芳烷亚胺的方法，所述方法以钯的手性膦氮配合物为催化剂，以环芳烷亚胺和硼酸类化合物为底物，通过对亚胺的硼酸反应实现环芳烷类外
消旋面手性化合物拆分，拆分得到面手性环芳烷亚胺1和手性胺3；手性胺3与烯丙基溴反应
得到烯丙基保护的手性胺2。所述方法的反应式如下：
消旋面手性化合物拆分，拆分得到面手性环芳烷亚胺1和手性胺3；手性胺3与烯丙基溴反应
得到烯丙基保护的手性胺2。所述方法的反应式如下：
[0009]
[0010] 式中：
[0011] R为苯基、萘基或含有取代基的苯环，所述的取代基为卤素，烷氧基或C1‑C20的烷基取代基中的至少一种；
[0012] Ar为含有取代基的芳环，所述的取代基为C1‑C20的烷基取代基中的至少一种；
[0013] Ts为对甲苯磺酰基。
[0014] 基于以上技术方案，优选的，所述方法使用的有机溶剂为三氟乙醇、六氟异丙醇中的一种或两种混合。
[0015] 基于以上技术方案，优选的，所述方法的反应温度为40‑80℃，反应时间为15h。
[0016] 催化剂的制备方法为：把钯的金属前体和手性膦氮配体在丙酮中室温搅拌1小时，然后真空浓缩除去丙酮。
[0017] 基于以上技术方案，优选的，所述钯的金属前体为三氟醋酸钯；所述手性膦氮配体为一系列膦噁唑啉配体。
[0018] 基于以上技术方案，优选的，所述方法的具体反应步骤为：
[0019] 在氮气保护下，在反应瓶中投入三氟醋酸钯(环芳烷亚胺用量的5mol％)和手性膦氮配体(环芳烷亚胺用量的5mol％)，氮气置换后加入1毫升丙酮，室温搅拌1h。然后真空浓
缩，氮气下加入有机溶剂，环芳烷亚胺和芳基硼酸，60℃反应15h。除去溶剂后直接柱层析分
离得到纯的面手性环芳烷亚胺和产物前体。在反应瓶中将产物前体用N,N‑二甲基甲酰胺溶
解，0℃下加入氢化钠，随后加入烯丙基溴，于室温搅拌2h 后柱层析分离得到产物。；所述催
化剂(mmol)、环芳烷亚胺(mmol)、硼酸类化合物(mmol) 和有机溶剂(ml)的用量比为0.05:
1:1～1.5:20；所述产物前体(mmol)、氢化钠(mmol)、烯丙基溴(mmol)和N,N‑二甲基甲酰胺
(ml)的用量比为1:3:6:10。
缩，氮气下加入有机溶剂，环芳烷亚胺和芳基硼酸，60℃反应15h。除去溶剂后直接柱层析分
离得到纯的面手性环芳烷亚胺和产物前体。在反应瓶中将产物前体用N,N‑二甲基甲酰胺溶
解，0℃下加入氢化钠，随后加入烯丙基溴，于室温搅拌2h 后柱层析分离得到产物。；所述催
化剂(mmol)、环芳烷亚胺(mmol)、硼酸类化合物(mmol) 和有机溶剂(ml)的用量比为0.05:
1:1～1.5:20；所述产物前体(mmol)、氢化钠(mmol)、烯丙基溴(mmol)和N,N‑二甲基甲酰胺
(ml)的用量比为1:3:6:10。
[0020] 基于以上技术方案，优选的，所述的反应为环芳烷亚胺与硼酸类化合物发生钯催化的加成反应实现环芳烷亚胺的拆分，R为苯基，Ar为C6H3，所述的催化剂为钯的手性二茂铁
骨架膦噁唑啉配体L2的配合物，有机溶剂为三氟乙醇，温度为60℃，反应时间为15h，拆分后
得到的面手性环芳烷亚胺1a对映体过量94.0％，烯丙基保护的手性胺2a对映体过量
97.8％，s值为115。
骨架膦噁唑啉配体L2的配合物，有机溶剂为三氟乙醇，温度为60℃，反应时间为15h，拆分后
得到的面手性环芳烷亚胺1a对映体过量94.0％，烯丙基保护的手性胺2a对映体过量
97.8％，s值为115。
[0021] 有益效果
[0022] 本发明具有以下优点
[0023] 1.反应活性和对映选择性高，且拆分系数高。
[0024] 2.能得到环芳烷亚胺面手性化合物以及环芳烷胺类面手性化合物。
[0025] 3.催化剂商业可得，反应操作简便。
[0026] 4.反应条件温和，能耗低。
具体实施方式
[0027] 下面通过实施例详述本发明，但本发明并不限于下述的实施例。
[0028] 本发明手性二茂铁骨架膦噁唑啉配体的合成参考文献(a)Richards,C.J.； Mulvaney,A.W.Tetrahedron:Asymmetry,1996,7,1419.
[0029] 本发明的底物环芳烷亚胺分两个步骤合成：步骤(1)氮气保护下，向反应瓶中加入环芳烷、二氯甲烷，0℃下向该体系中加入1,1‑二氯甲醚、四氯化钛，搅拌3小时，可以得到环
芳烷醛；步骤(2)氮气保护下，将步骤(1)得到的环芳烷醛投入反应瓶中，随后加入对甲苯磺
酰胺、原硅酸四乙酯，升温至160℃，搅拌10小时，可以得到环芳烷亚胺。
芳烷醛；步骤(2)氮气保护下，将步骤(1)得到的环芳烷醛投入反应瓶中，随后加入对甲苯磺
酰胺、原硅酸四乙酯，升温至160℃，搅拌10小时，可以得到环芳烷亚胺。
[0030] 本发明实施例18‑19进行底物拓展使用的环芳烷亚胺为rac‑1b是由4‑甲基环芳烷为原料合成的，环芳烷亚胺rac‑1b具体合成步骤参照上文。4‑甲基环芳烷的合成参考文献
(a)Gready,J.E.；Hambley,T.W.；Kakiuchi,K.；Kobiro,K.；Sternhell,S.；Tansey,C. W.；
Tobe,Y.J.Am.Chem.Soc.1990,112,7537.其余原料均商业可得。
(a)Gready,J.E.；Hambley,T.W.；Kakiuchi,K.；Kobiro,K.；Sternhell,S.；Tansey,C. W.；
Tobe,Y.J.Am.Chem.Soc.1990,112,7537.其余原料均商业可得。
[0031]
[0032] 本发明得到的产物面手性环芳烷亚胺可以作为手性碳氮配体应用于不对称合成中。产物烯丙基保护的手性胺可以进行一系列的转化合成带有面手性的胺基化合物，可以
作为手性辅基应用于手性合成中。
作为手性辅基应用于手性合成中。
[0033] 实施例1‑7
[0034] 条件的优化
[0035] 改变手性膦氮配体、有机溶剂的种类以及硼酸类化合物的量。
[0036] 在反应瓶中投入三氟醋酸钯(1a用量的5mol％)和手性膦氮配体(1a用量的5 mol％)，氮气置换后加入1毫升丙酮，室温搅拌1h。然后真空浓缩，氮气下加入2 毫升有机溶
剂，环芳烷亚胺1a(0.1毫摩尔)和苯硼酸(实施例1‑6中为1a用量的150 mol％，实施例7中为
1a用量的100mol％)。60℃反应15h。除去溶剂后直接柱层析分离得到纯的面手性环芳烷亚
胺1a和产物前体3a。在反应瓶中将产物前体3a用1ml N,N‑二甲基甲酰胺溶解，0℃下加入
6mg氢化钠(质量分数为60％)，随后加入26μl 烯丙基溴，于室温搅拌2h后柱层析分离得到
产物2a。回收环芳烷亚胺1a的转化率用核磁测定，回收环芳烷亚胺1a和产物2a的对映体过
量用手性液相色谱测定，产物2a 的非对映体比例用核磁测定，拆分系数s值用这一算式算
得s＝ln[(1‑C)(1‑ee of 1a)]/ln[(1‑C)(1+ee of 1a)]，改变配体、有机溶剂的种类以及
硼酸的量，具体结果如表1； dr为非对映体比例。
剂，环芳烷亚胺1a(0.1毫摩尔)和苯硼酸(实施例1‑6中为1a用量的150 mol％，实施例7中为
1a用量的100mol％)。60℃反应15h。除去溶剂后直接柱层析分离得到纯的面手性环芳烷亚
胺1a和产物前体3a。在反应瓶中将产物前体3a用1ml N,N‑二甲基甲酰胺溶解，0℃下加入
6mg氢化钠(质量分数为60％)，随后加入26μl 烯丙基溴，于室温搅拌2h后柱层析分离得到
产物2a。回收环芳烷亚胺1a的转化率用核磁测定，回收环芳烷亚胺1a和产物2a的对映体过
量用手性液相色谱测定，产物2a 的非对映体比例用核磁测定，拆分系数s值用这一算式算
得s＝ln[(1‑C)(1‑ee of 1a)]/ln[(1‑C)(1+ee of 1a)]，改变配体、有机溶剂的种类以及
硼酸的量，具体结果如表1； dr为非对映体比例。
[0037]
[0038] 表1.环芳烷亚胺类面手性化合物动力学拆分条件的优化
[0039]
[0040] 实施例8‑19
[0041] 用一系列硼酸拆分环芳烷亚胺化合物。
[0042] 在反应瓶中投入三氟醋酸钯(1用量的5mol％)和手性膦氮配体L2(1用量的5 mol％)，氮气置换后加入1毫升丙酮，室温搅拌1h。然后真空浓缩，氮气下加入4 毫升三氟乙
醇，环芳烷亚胺1(0.2毫摩尔，实施例8‑17中所用环芳烷亚胺为rac‑1a，实施例18‑19中所用
环芳烷亚胺为rac‑1b)和芳基硼酸(1用量的100mol％)，60℃反应15h。除去溶剂后直接柱层
析分离得到纯的面手性环芳烷亚胺1和产物前体3。在反应瓶中将产物前体3用2ml N,N‑二
甲基甲酰胺溶解，0℃下加入12mg氢化钠(质量分数为60％)，随后加入52μl烯丙基溴，于室
温搅拌2h后柱层析分离得到产物2。回收环芳烷亚胺1的转化率用核磁测定，回收环芳烷亚
胺1和产物2的对映体过量用手性液相色谱测定，产物2的非对映体比例用核磁测定，s值用
这一算式算得s＝ ln[(1‑C)(1‑ee of 1)]/ln[(1‑C)(1+ee of 1)]，改变反应中环芳烷亚
胺和硼酸的种类得到12 个不同的实施例，改变的种类具体见表2。
醇，环芳烷亚胺1(0.2毫摩尔，实施例8‑17中所用环芳烷亚胺为rac‑1a，实施例18‑19中所用
环芳烷亚胺为rac‑1b)和芳基硼酸(1用量的100mol％)，60℃反应15h。除去溶剂后直接柱层
析分离得到纯的面手性环芳烷亚胺1和产物前体3。在反应瓶中将产物前体3用2ml N,N‑二
甲基甲酰胺溶解，0℃下加入12mg氢化钠(质量分数为60％)，随后加入52μl烯丙基溴，于室
温搅拌2h后柱层析分离得到产物2。回收环芳烷亚胺1的转化率用核磁测定，回收环芳烷亚
胺1和产物2的对映体过量用手性液相色谱测定，产物2的非对映体比例用核磁测定，s值用
这一算式算得s＝ ln[(1‑C)(1‑ee of 1)]/ln[(1‑C)(1+ee of 1)]，改变反应中环芳烷亚
胺和硼酸的种类得到12 个不同的实施例，改变的种类具体见表2。
[0043]
[0044] 表2.用一系列硼酸拆分环芳烷亚胺
[0045]
[0046]
[0047] (+)‑N‑Allyl‑N‑{[2.2]paracyclophan‑4‑yl(phenyl)methyl}‑4‑methylbenzenesulfonamide(2a):48.9 mg,48％yield,12:1 dr,white solid,mp＝144‑
146℃ ,new compound ,Rf＝0 .50(hexanes/ethyl acetate
13
3H). C
NMR(100 MHz,CDCl3)δ143.5,140.9,140.0,139.5,139.2,138.9,138.6,136.9,136.0,
134.0, 133.7,132.6,132.3,132.2,131.4,130.5,129.7,129.4,128.4,128.2,128.0,
117.2,64.6,48.5,35.5,35.4, 34.6,34.5,21.7.HPLC:Chiracel AD‑H column,254nm,30
℃,n‑Hexane/i‑PrOH＝90/10,flow＝1.0 mL/min,retention time 6.9min(major)and
+
7.5min.HRMS:Calculated for C33H33KNO2S[M+K] 546.1864,found:546.1861.
146℃ ,new compound ,Rf＝0 .50(hexanes/ethyl acetate
13
3H). C
NMR(100 MHz,CDCl3)δ143.5,140.9,140.0,139.5,139.2,138.9,138.6,136.9,136.0,
134.0, 133.7,132.6,132.3,132.2,131.4,130.5,129.7,129.4,128.4,128.2,128.0,
117.2,64.6,48.5,35.5,35.4, 34.6,34.5,21.7.HPLC:Chiracel AD‑H column,254nm,30
℃,n‑Hexane/i‑PrOH＝90/10,flow＝1.0 mL/min,retention time 6.9min(major)and
+
7.5min.HRMS:Calculated for C33H33KNO2S[M+K] 546.1864,found:546.1861.
[0048] (‑)‑N‑Tosyl[2.2]paracyclophane‑4‑methanimine(1a):Kinetic resolution from the addition of [2.2]paracyclophane aldimine 1a with phenylboronic acid,
20
30.7mg,39％yield,93.7％ee,[α] D＝ ‑356.96(c 0.63,CHCl3).HPLC:Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow ＝0.8mL/min,retention time
16.6min and 18.9min(major).
20
30.7mg,39％yield,93.7％ee,[α] D＝ ‑356.96(c 0.63,CHCl3).HPLC:Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow ＝0.8mL/min,retention time
16.6min and 18.9min(major).
[0049] (+)‑N‑Allyl‑N‑{[2.2]paracyclophan‑4‑yl(o‑tolyl)methyl}‑4‑methylbenzenesulfonamide(2b):51.9 mg,50％yield,7:1 dr,white solid,mp＝58‑60
℃ ,new c om po und ,R f＝ 0 .60 (he xa nes /e th yl ac et at e
143.6,
140.0,139.7,139.4,139.3,138.5,138.2,137.7,137.1,136.0,133.6,133.4,132.6,
132.1,132.0, 131.1,130.9,130.4,130.3,129.4,128.6,127.9,125.6,115.7,61.1,47.4,
35.5,35.4,34.8,34.1,21.6,20.0. HPLC:Chiracel AD‑H column,254nm,30℃,n‑Hexane/
i‑PrOH＝90/10,flow＝1.0mL/min,retention time 5.3min(major)and 7.0min.HRMS:
+
Calculated for C34H35NaNO2S[M+Na]544.2281,found: 544.2282.
℃ ,new c om po und ,R f＝ 0 .60 (he xa nes /e th yl ac et at e
143.6,
140.0,139.7,139.4,139.3,138.5,138.2,137.7,137.1,136.0,133.6,133.4,132.6,
132.1,132.0, 131.1,130.9,130.4,130.3,129.4,128.6,127.9,125.6,115.7,61.1,47.4,
35.5,35.4,34.8,34.1,21.6,20.0. HPLC:Chiracel AD‑H column,254nm,30℃,n‑Hexane/
i‑PrOH＝90/10,flow＝1.0mL/min,retention time 5.3min(major)and 7.0min.HRMS:
+
Calculated for C34H35NaNO2S[M+Na]544.2281,found: 544.2282.
[0050] (‑)‑N‑Tosyl[2.2]paracyclophane‑4‑methanimine(1a):Kinetic resolution from the addition of [2.2]paracyclophane aldimine 1a with 2‑
methylphenylboronic acid,29.6mg,38％yield,80.1％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.7min and 18.9min(major).
methylphenylboronic acid,29.6mg,38％yield,80.1％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.7min and 18.9min(major).
[0051] (+)‑N‑Allyl‑N‑{[2.2]paracyclophan‑4‑yl(m‑tolyl)methyl}‑4‑methylbenzenesulfonamide(2c):50.7 mg,49％yield,12:1 dr,white solid,mp＝63‑65
℃ ,new c om po und ,R f＝ 0 .60 (he xa nes /e th yl ac et at e
2H),
13
2.12(s,3H). C NMR(100MHz,CDCl3)δ143.4,140.7,140.0,139.6,139.2,139.0,138.7,
137.9, 137.0,136.0,134.3,133.8,132.7,132.3,132.2,131.5,130.5,130.2,129.7,
128.7,128.3,128.2,126.3, 117.3,64.6,48.6,35.5,35.4,34.6,34.6,21.7,21.4.HPLC:
Chiracel IC column,254nm,30℃, n‑Hexane/i‑PrOH＝90/10,flow＝1.0mL/min,
retention time 15.8min and 21.7min(major).HRMS: Calculated for C34H35NaNO2S[M+
+
Na]544.2281,found:544.2282.
℃ ,new c om po und ,R f＝ 0 .60 (he xa nes /e th yl ac et at e
2H),
13
2.12(s,3H). C NMR(100MHz,CDCl3)δ143.4,140.7,140.0,139.6,139.2,139.0,138.7,
137.9, 137.0,136.0,134.3,133.8,132.7,132.3,132.2,131.5,130.5,130.2,129.7,
128.7,128.3,128.2,126.3, 117.3,64.6,48.6,35.5,35.4,34.6,34.6,21.7,21.4.HPLC:
Chiracel IC column,254nm,30℃, n‑Hexane/i‑PrOH＝90/10,flow＝1.0mL/min,
retention time 15.8min and 21.7min(major).HRMS: Calculated for C34H35NaNO2S[M+
+
Na]544.2281,found:544.2282.
[0052] (‑)‑N‑Tosyl[2.2]paracyclophane‑4‑methanimine(1a):Kinetic resolution from the addition of [2.2]paracyclophane aldimine 1a with 3‑
methylphenylboronic acid,21.7mg,28％yield,91.2％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.6min and 18.9min(major).
methylphenylboronic acid,21.7mg,28％yield,91.2％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.6min and 18.9min(major).
[0053] (+)‑N‑Allyl‑N‑{[2.2]paracyclophan‑4‑yl(p‑tolyl)methyl}‑4‑methylbenzenesulfonamide(2d):55.2 mg,53％yield,13:1 dr,white solid,mp＝56‑58
℃ ,new c om po und ,R f＝ 0 .55 (he xa nes /e th yl ac et at e
3H)2.28
13
(s,3H). C NMR(100MHz,CDCl3)δ143.4,140.0,139.5,139.3,139.0,138.7,137.9,137.7,
137.2,136.0,134.2,133.7,132.6,132.3,132.2,131.5,130.5,129.7,129.3,129.0,
128.2,117.2,64.4,48.5, 35.5,35.4,34.6,34.6,21.7,21.2.HPLC:Chiracel AD‑H
column,254nm,30℃,n‑Hexane/i‑PrOH＝ 90/10,flow＝1.0mL/min,retention time
+
7.1min and 8.5min(major).HRMS:Calculated for C34H35NaNO2S[M+Na]544.2281,found:
544.2284.
℃ ,new c om po und ,R f＝ 0 .55 (he xa nes /e th yl ac et at e
3H)2.28
13
(s,3H). C NMR(100MHz,CDCl3)δ143.4,140.0,139.5,139.3,139.0,138.7,137.9,137.7,
137.2,136.0,134.2,133.7,132.6,132.3,132.2,131.5,130.5,129.7,129.3,129.0,
128.2,117.2,64.4,48.5, 35.5,35.4,34.6,34.6,21.7,21.2.HPLC:Chiracel AD‑H
column,254nm,30℃,n‑Hexane/i‑PrOH＝ 90/10,flow＝1.0mL/min,retention time
+
7.1min and 8.5min(major).HRMS:Calculated for C34H35NaNO2S[M+Na]544.2281,found:
544.2284.
[0054] (‑)‑N‑Tosyl[2.2]paracyclophane‑4‑methanimine(1a):Kinetic resolution from the addition of [2.2]paracyclophane aldimine 1a with 4‑
methylphenylboronic acid,27.8mg,36％yield,88.0％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.5min and 18.8min(major).
methylphenylboronic acid,27.8mg,36％yield,88.0％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.5min and 18.8min(major).
[0055] (+)‑N‑Allyl‑N‑{[2.2]paracyclophan‑4‑yl(4‑fluorophenyl)methyl}‑4‑methylbenzenesulfonamide (2e):51.9mg,49％yield,16:1 dr,white solid,mp＝164‑
166℃,new compound,Rf＝0.45
(100MHz,CDCl3)δ162.4(d,JC‑F＝247.7Hz),143.7,140.2,139.6,139.2,138.9,138.5,
137.0(d,JC‑F＝ 3.3Hz),136.8,136.1,133.9,133.7,132.7,132.5,132.3,131.4,131.1(d,
JC‑F＝8.1Hz),130.4,129.8, 128.1,117.4,115.3(d,JC‑F＝21.3Hz),63.8,48.5,35.5,
19
35.4,34.6,34.5,21.7. F NMR(376MHz, CDCl3)δ‑113.8.HPLC:Chiracel IB column,
254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝1.0 mL/min,retention time 5.1min
+
(major)and 5.5min.HRMS:Calculated for C33H32FNaNO2S[M+Na] 548.2030,found:
548.2026.
166℃,new compound,Rf＝0.45
(100MHz,CDCl3)δ162.4(d,JC‑F＝247.7Hz),143.7,140.2,139.6,139.2,138.9,138.5,
137.0(d,JC‑F＝ 3.3Hz),136.8,136.1,133.9,133.7,132.7,132.5,132.3,131.4,131.1(d,
JC‑F＝8.1Hz),130.4,129.8, 128.1,117.4,115.3(d,JC‑F＝21.3Hz),63.8,48.5,35.5,
19
35.4,34.6,34.5,21.7. F NMR(376MHz, CDCl3)δ‑113.8.HPLC:Chiracel IB column,
254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝1.0 mL/min,retention time 5.1min
+
(major)and 5.5min.HRMS:Calculated for C33H32FNaNO2S[M+Na] 548.2030,found:
548.2026.
[0056] (‑)‑N‑Tosyl[2.2]paracyclophane‑4‑methanimine(1a):Kinetic resolution from the addition of [2.2]paracyclophane aldimine 1a with 4‑
fluorophenylboronic acid,33.8mg,43％yield,99.2％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.4min and 18.6min(major).
fluorophenylboronic acid,33.8mg,43％yield,99.2％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.4min and 18.6min(major).
[0057] (+)‑N‑Allyl‑N‑{[2.2]paracyclophan‑4‑yl(4‑(trifluoromethyl)phenyl)methyl}‑4‑methylbenzenesulfo namide(2f):58.2mg,51％yield,>20:1 dr,white
solid,mp＝108‑110℃,new compound,Rf＝0.43
(100MHz,CDCl3)δ145.1,143.8,140.3,139.6,139.1,138.7,138.3,136.2,135.9,133.6,
133.5,132.7, 132.7,132.4,131.4,130.4,130.2(q,JC‑F＝32.4Hz),129.8,129.8,128.1,
125.3(q,JC‑F＝3.7Hz),124.0 (q,JC‑F＝272.2Hz),117.5,64.0,48.6,35.4,35.4,34.6,
19
34.5,21.7. F NMR(376MHz,CDCl3)δ‑62.5. HPLC:Chiracel IB column,254nm,30℃,n‑
Hexane/i‑PrOH＝90/10,flow＝1.0mL/min,retention time 5.9min(major)and
+
6.6min.HRMS:Calculated for C34H36F3N2O2S[M+NH4]593.2444,found: 593.2462.
solid,mp＝108‑110℃,new compound,Rf＝0.43
(100MHz,CDCl3)δ145.1,143.8,140.3,139.6,139.1,138.7,138.3,136.2,135.9,133.6,
133.5,132.7, 132.7,132.4,131.4,130.4,130.2(q,JC‑F＝32.4Hz),129.8,129.8,128.1,
125.3(q,JC‑F＝3.7Hz),124.0 (q,JC‑F＝272.2Hz),117.5,64.0,48.6,35.4,35.4,34.6,
19
34.5,21.7. F NMR(376MHz,CDCl3)δ‑62.5. HPLC:Chiracel IB column,254nm,30℃,n‑
Hexane/i‑PrOH＝90/10,flow＝1.0mL/min,retention time 5.9min(major)and
+
6.6min.HRMS:Calculated for C34H36F3N2O2S[M+NH4]593.2444,found: 593.2462.
[0058] (‑)‑N‑Tosyl[2.2]paracyclophane‑4‑methanimine(1a):Kinetic resolution from the addition of [2.2]paracyclophane aldimine 1a with 4‑
trifluoromethylphenylboronic acid,28.8mg,37％yield,98.5％ ee.HPLC:Chiralcel
AD‑3 column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min, retention time
16.1min and 18.3min(major).
trifluoromethylphenylboronic acid,28.8mg,37％yield,98.5％ ee.HPLC:Chiralcel
AD‑3 column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min, retention time
16.1min and 18.3min(major).
[0059] (+)‑N‑Allyl‑N‑{[2.2]paracyclophan‑4‑yl(4‑chlorophenyl)methyl}‑4‑methylbenzenesulfonamide (2g):54.1mg,50％yield,>20:1 dr,white solid,mp＝139‑
141℃,new compound,Rf＝0.43
2.50(s,
13
3H),2.44‑2.33(m,1H). C NMR(100MHz,CDCl3)δ143.7,140.2,139.6,139.5,139.1,138.8,
138.4,136.4,136.1,133.9,133.8,133.6,132.7,132.6,132.3,131.4,130.7,130.4,
129.8,128.6,128.1, 117.5,63.8,48.5,35.4,35.4,34.6,34.5,21.7.HPLC:Chiracel IB
column,254nm,30℃, n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
+
6.4min(major)and 7.0min.HRMS: Calculated for C33H36ClN2O2S[M+NH4] 559.2181,
35 37
found:559.2175( Cl),561.2160( Cl).
141℃,new compound,Rf＝0.43
2.50(s,
13
3H),2.44‑2.33(m,1H). C NMR(100MHz,CDCl3)δ143.7,140.2,139.6,139.5,139.1,138.8,
138.4,136.4,136.1,133.9,133.8,133.6,132.7,132.6,132.3,131.4,130.7,130.4,
129.8,128.6,128.1, 117.5,63.8,48.5,35.4,35.4,34.6,34.5,21.7.HPLC:Chiracel IB
column,254nm,30℃, n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
+
6.4min(major)and 7.0min.HRMS: Calculated for C33H36ClN2O2S[M+NH4] 559.2181,
35 37
found:559.2175( Cl),561.2160( Cl).
[0060] (‑)‑N‑Tosyl[2.2]paracyclophane‑4‑methanimine(1a):Kinetic resolution from the addition of [2.2]paracyclophane aldimine 1a with 4‑
chlorophenylboronic acid,31.2mg,40％yield,99.6％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.4min and 18.6min(major).
chlorophenylboronic acid,31.2mg,40％yield,99.6％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.4min and 18.6min(major).
[0061] (+)‑N‑Allyl‑N‑{[2.2]paracyclophan‑4‑yl(3‑fluorophenyl)methyl}‑4‑methylbenzenesulfonamide (2h):52.2mg,50％yield,>20:1 dr,white solid,mp＝134‑
136℃,new compound,Rf＝0.43
(m,2H),
13
3.06‑2.89(m,4H),2.57‑2.46(m,1H),2.51(s,3H),2.46‑2.37(m,1H). C NMR(100MHz,
CDCl3)δ162.7(d,JC‑F＝246.7Hz),143.8,143.5(d,JC‑F＝6.6Hz),140.2,139.6,139.2,
138.7,138.5, 136.2,136.1,133.8,133.7,132.7,132.6,132.3,131.4,130.4,129.8(d,
JC‑F＝8.0Hz),129.8,128.1,125.1 (d,JC‑F＝2.8Hz),117.4,116.4(d,JC‑F＝22.1Hz),115.0
19
(d,JC‑F＝21.1Hz),64.0(d,JC‑F＝1.6Hz),48.5, 35.4,35.4,34.6,34.5,21.7. F NMR
(376MHz,CDCl3)δ‑112.6.HPLC:Chiracel IA column,254 nm, 30℃,n‑Hexane/i‑PrOH＝
90/10,flow＝1.0mL/min,retention time 6.4min(major)and 7.2min.HRMS: Calculated
+
for C33H32FNaNO2S[M+Na]548.2030,found:548.2061.
136℃,new compound,Rf＝0.43
(m,2H),
13
3.06‑2.89(m,4H),2.57‑2.46(m,1H),2.51(s,3H),2.46‑2.37(m,1H). C NMR(100MHz,
CDCl3)δ162.7(d,JC‑F＝246.7Hz),143.8,143.5(d,JC‑F＝6.6Hz),140.2,139.6,139.2,
138.7,138.5, 136.2,136.1,133.8,133.7,132.7,132.6,132.3,131.4,130.4,129.8(d,
JC‑F＝8.0Hz),129.8,128.1,125.1 (d,JC‑F＝2.8Hz),117.4,116.4(d,JC‑F＝22.1Hz),115.0
19
(d,JC‑F＝21.1Hz),64.0(d,JC‑F＝1.6Hz),48.5, 35.4,35.4,34.6,34.5,21.7. F NMR
(376MHz,CDCl3)δ‑112.6.HPLC:Chiracel IA column,254 nm, 30℃,n‑Hexane/i‑PrOH＝
90/10,flow＝1.0mL/min,retention time 6.4min(major)and 7.2min.HRMS: Calculated
+
for C33H32FNaNO2S[M+Na]548.2030,found:548.2061.
[0062] (‑)‑N‑Tosyl[2.2]paracyclophane‑4‑methanimine(1a):Kinetic resolution from the addition of [2.2]paracyclophane aldimine 1a with 3‑
fluorophenylboronic acid,31.9mg,41％yield,97.4％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.2min and 18.3min(major).
fluorophenylboronic acid,31.9mg,41％yield,97.4％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.2min and 18.3min(major).
[0063] (+)‑N‑Allyl‑N‑{[2.2]paracyclophan‑4‑yl(3‑chlorophenyl)methyl}‑4‑methylbenzenesulfonamide (2i):54.4mg,50％yield,>20:1 dr,white solid,mp＝56‑58
℃,new compound,Rf＝0.41(hexanes/ethyl
MHz,
CDCl3)δ143.9,142.9,140.2,139.6,139.1,138.6,138.4,136.2,136.1,134.3,133.8,
133.7,132.7, 132.6,132.3,131.4,130.4,129.9,129.6,129.5,128.2,128.1,127.4,
117.6,64.0,48.6,35.4,35.4,34.6, 34.5,21.7.HPLC:Chiracel IC column,254nm,30℃,
n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min, retention time 11.2min and 13.2
+
(major)min.HRMS:Calculated for C33H36ClN2O2S[M+NH4] 559.2181,found:559.2175
35 37
( Cl),561.2155( Cl).
℃,new compound,Rf＝0.41(hexanes/ethyl
MHz,
CDCl3)δ143.9,142.9,140.2,139.6,139.1,138.6,138.4,136.2,136.1,134.3,133.8,
133.7,132.7, 132.6,132.3,131.4,130.4,129.9,129.6,129.5,128.2,128.1,127.4,
117.6,64.0,48.6,35.4,35.4,34.6, 34.5,21.7.HPLC:Chiracel IC column,254nm,30℃,
n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min, retention time 11.2min and 13.2
+
(major)min.HRMS:Calculated for C33H36ClN2O2S[M+NH4] 559.2181,found:559.2175
35 37
( Cl),561.2155( Cl).
[0064] (‑)‑N‑Tosyl[2.2]paracyclophane‑4‑methanimine(1a):Kinetic resolution from the addition of [2.2]paracyclophane aldimine 1a with 3‑
chlorophenylboronic acid,32.7mg,42％yield,98.4％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.3min and 18.5min(major).
chlorophenylboronic acid,32.7mg,42％yield,98.4％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.3min and 18.5min(major).
[0065] (+)‑N‑Allyl‑N‑{[2.2]paracyclophan‑4‑yl(4‑methoxyphenyl)methyl}‑4‑methylbenzenesulfonamide (2j):51.6mg,48％yield,13:1 dr,white solid,mp＝65‑67
℃,new compound,Rf＝0.25(hexanes/ethyl
2.49(s,
13
3H). C NMR(100MHz,CDCl3)δ159.2,143.4,140.0,139.5,139.3,139.0,138.7,137.4,
136.0, 134.3,133.7,133.1,132.7,132.3,132.2,131.5,130.6,130.5,129.7,128.2,
117.2,113.6,64.1,55.3,48.5, 35.5,35.4,34.6,34.6,21.7.HPLC:Chiracel AD‑H
column,254 nm,30℃,n‑Hexane/i‑PrOH＝80/20, flow＝1.0mL/min,retention time
+
6.5min and 7.2min(major).HRMS:Calculated for C34H35KNO3S [M+K]576.1969,found:
576.1959.
℃,new compound,Rf＝0.25(hexanes/ethyl
2.49(s,
13
3H). C NMR(100MHz,CDCl3)δ159.2,143.4,140.0,139.5,139.3,139.0,138.7,137.4,
136.0, 134.3,133.7,133.1,132.7,132.3,132.2,131.5,130.6,130.5,129.7,128.2,
117.2,113.6,64.1,55.3,48.5, 35.5,35.4,34.6,34.6,21.7.HPLC:Chiracel AD‑H
column,254 nm,30℃,n‑Hexane/i‑PrOH＝80/20, flow＝1.0mL/min,retention time
+
6.5min and 7.2min(major).HRMS:Calculated for C34H35KNO3S [M+K]576.1969,found:
576.1959.
[0066] (‑)‑N‑Tosyl[2.2]paracyclophane‑4‑methanimine(1a):Kinetic resolution from the addition of [2.2]paracyclophane aldimine 1a with 4‑
methoxyphenylboronic acid,35.1mg,45％yield,83.9％ee. HPLC:Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.3min and 18.5min(major).
methoxyphenylboronic acid,35.1mg,45％yield,83.9％ee. HPLC:Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.3min and 18.5min(major).
[0067] (+)‑N‑Allyl‑N‑{[2.2]paracyclophan‑4‑yl(2‑naphthyl)methyl}‑4‑methylbenzenesulfonamide(2k): 54.0mg,48％yield,12:1 dr,white solid,mp＝66‑68
℃,new compound,Rf＝0.38(hexanes/ethyl
3 .31‑
13
3.20(m,2H),3.12‑2.96(m,3H),2.95‑2.85(m,1H),2.54(s,3H),2.48‑2.39(m,2H). C NMR
(100 MHz,CDCl3)δ143.5,140.1,139.6,139.2,138.9,138.7,138.2,136.9,136.1,134.1,
133.8,133.0,132.9, 132.7,132.5,132.3,131.6,130.5,129.8,128.5,128.3,128.1,
128.1,127.7,127.3,126.4,126.3,117.4, 64.7,48.7,35.5,35.4,34.6,21.7.HPLC:
Chiracel AD‑3 column,254nm,30℃,n‑Hexane/i‑PrOH＝ 90/10,flow＝1.0mL/min,
+
retention time 9.0min and 13.8min(major).HRMS:Calculated for C37H35NaNO2S[M+Na]
580.2281,found:580.2279.
℃,new compound,Rf＝0.38(hexanes/ethyl
3 .31‑
13
3.20(m,2H),3.12‑2.96(m,3H),2.95‑2.85(m,1H),2.54(s,3H),2.48‑2.39(m,2H). C NMR
(100 MHz,CDCl3)δ143.5,140.1,139.6,139.2,138.9,138.7,138.2,136.9,136.1,134.1,
133.8,133.0,132.9, 132.7,132.5,132.3,131.6,130.5,129.8,128.5,128.3,128.1,
128.1,127.7,127.3,126.4,126.3,117.4, 64.7,48.7,35.5,35.4,34.6,21.7.HPLC:
Chiracel AD‑3 column,254nm,30℃,n‑Hexane/i‑PrOH＝ 90/10,flow＝1.0mL/min,
+
retention time 9.0min and 13.8min(major).HRMS:Calculated for C37H35NaNO2S[M+Na]
580.2281,found:580.2279.
[0068] (‑)‑N‑Tosyl[2.2]paracyclophane‑4‑methanimine(1a):Kinetic resolution from the addition of [2.2]paracyclophane aldimine 1a with 2‑
naphthaleneboronic acid,31.9mg,41％yield,82.3％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.3min and 18.5min(major).
naphthaleneboronic acid,31.9mg,41％yield,82.3％ee.HPLC: Chiralcel AD‑3
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.3min and 18.5min(major).
[0069] (+)‑N‑Allyl‑N‑{7‑methyl[2.2]paracyclophan‑4‑yl(phenyl)methyl}‑4‑methylbenzenesulfonamide (2l):52.1mg,50％yield,8:1 dr,white solid,mp＝183‑185
℃,new compound,Rf＝0.50(hexanes/ethyl
1H),
3.40‑3.29(m,1H),3.19(t,J＝11.8Hz,1H),3.04‑2.74(m,4H),2.50(s,3H),2.41‑2.29(m,
13
2H), 2.13(s,3H). C NMR(100MHz,CDCl3)δ143.4,141.1,139.2,139.0,138.9,138.5,
138.2,138.1,136.6, 134.7,134.2,133.9,132.6,131.3,130.8,129.7,129.4,128.4,
128.2,128.0,127.8,117.2,64.5,48.4,34.3, 34.0,33.6,33.4,21.7,19.8.HPLC:
Chiracel IB column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow ＝0.8mL/min,
+
retention time 6.2min(major)and 7.1min.HRMS:Calculated for C34H35NaNO2S [M+Na]
544.2281,found:544.2262.
℃,new compound,Rf＝0.50(hexanes/ethyl
1H),
3.40‑3.29(m,1H),3.19(t,J＝11.8Hz,1H),3.04‑2.74(m,4H),2.50(s,3H),2.41‑2.29(m,
13
2H), 2.13(s,3H). C NMR(100MHz,CDCl3)δ143.4,141.1,139.2,139.0,138.9,138.5,
138.2,138.1,136.6, 134.7,134.2,133.9,132.6,131.3,130.8,129.7,129.4,128.4,
128.2,128.0,127.8,117.2,64.5,48.4,34.3, 34.0,33.6,33.4,21.7,19.8.HPLC:
Chiracel IB column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow ＝0.8mL/min,
+
retention time 6.2min(major)and 7.1min.HRMS:Calculated for C34H35NaNO2S [M+Na]
544.2281,found:544.2262.
[0070] (‑)‑N‑Tosyl‑7‑methyl[2.2]paracyclophane‑4‑methanimine(1b):Kinetic resolution from the addition of[2.2]paracyclophane aldimine 1b with
20
phenylboronic acid,32.2mg,40％yield,99.4％ee,[α] D＝ ‑400.28(c 0.65,CHCl3)
.HPLC:Chiralcel AD‑H column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20, flow＝0.8mL/
min,retention time 16.8min and 20.5min(major).
20
phenylboronic acid,32.2mg,40％yield,99.4％ee,[α] D＝ ‑400.28(c 0.65,CHCl3)
.HPLC:Chiralcel AD‑H column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20, flow＝0.8mL/
min,retention time 16.8min and 20.5min(major).
[0071] (+)‑N‑Allyl‑N‑{7‑methyl[2.2]paracyclophan‑4‑yl(4‑chlorophenyl)methyl}‑4‑methylbenzenesulfon amide(2m):52.3mg,47％yield,17:1 dr,white solid,
mp＝55‑57℃,new compound,Rf＝0.50
(s,3H),
13
2.41‑2.27(m,2H),2.12(s,3H). C NMR(100MHz,CDCl3)δ143.7,139.7,139.2,138.9,
138.8, 138.6,138.2,138.0,136.9,134.1,133.9,133.8,133.8,132.6,131.4,130.7,
130.7,129.8,128.6,128.1, 127.9,117.5,63.7,48.5,34.3,34.1,33.6,33.4,21.7,
19.8.HPLC:Chiracel IB column,254nm,30℃, n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/
min,retention time 6.4min(major)and 7.5min.HRMS: Calculated for C34H38ClN2O2S[M
+ 35 37
+NH4]573.2337,found:573.2376( Cl),575.2360( Cl).
mp＝55‑57℃,new compound,Rf＝0.50
(s,3H),
13
2.41‑2.27(m,2H),2.12(s,3H). C NMR(100MHz,CDCl3)δ143.7,139.7,139.2,138.9,
138.8, 138.6,138.2,138.0,136.9,134.1,133.9,133.8,133.8,132.6,131.4,130.7,
130.7,129.8,128.6,128.1, 127.9,117.5,63.7,48.5,34.3,34.1,33.6,33.4,21.7,
19.8.HPLC:Chiracel IB column,254nm,30℃, n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/
min,retention time 6.4min(major)and 7.5min.HRMS: Calculated for C34H38ClN2O2S[M
+ 35 37
+NH4]573.2337,found:573.2376( Cl),575.2360( Cl).
[0072] (‑)‑N‑Tosyl‑7‑methyl[2.2]paracyclophane‑4‑methanimine(1b):Kinetic resolution from the addition of[2.2]paracyclophane aldimine 1b with 4‑
chlorophenylboronic acid,33.8mg,42％yield,99.9％ee. HPLC:Chiralcel AD‑H
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.7min and 20.5min(major)。
chlorophenylboronic acid,33.8mg,42％yield,99.9％ee. HPLC:Chiralcel AD‑H
column,254nm,30℃,n‑Hexane/i‑PrOH＝80/20,flow＝0.8mL/min,retention time
16.7min and 20.5min(major)。