CN116444386A - 一种手性的炔丙基氨基酸酯化合物的合成方法 - Google Patents

一种手性的炔丙基氨基酸酯化合物的合成方法 Download PDF

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CN116444386A
CN116444386A CN202211478500.7A CN202211478500A CN116444386A CN 116444386 A CN116444386 A CN 116444386A CN 202211478500 A CN202211478500 A CN 202211478500A CN 116444386 A CN116444386 A CN 116444386A
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chiral
amino acid
acid ester
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propargyl amino
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郭其祥
朱芳
文巍
刘克垒
陈婷婷
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Jiangsu Yongan Pharmaceutical Co ltd
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Abstract

本发明公开了一种手性的炔丙基氨基酸酯化合物的合成方法，通过手性醛催化剂和单一金属的手性配合物，催化化合物1和化合物2生成炔丙基氨基酸酯。本发明手性醛催化剂能够与单一金属的手性配合物联合催化，实现单金属一步法对N‑无保护氨基酸酯催化反应得到炔丙基氨基酸酯，具有更好的经济性和步骤经济性。

Description

一种手性的炔丙基氨基酸酯化合物的合成方法
技术领域
本发明属于有机合成技术领域，具体的说，涉及一种手性的炔丙基氨基酸酯化合物的合成方法。
背景技术
近年来，双金属催化作为一种高效可靠的策略，实现了一系列新的对映选择性转化，提供目前无法实现的反应途径。但是氨基酸酯的炔丙基化反应仍然存在很大挑战。近日，中国科学技术大学郭昌教授研究团队发展了一种全新的Ni/Cu双金属催化体系，得到了具有出色的区域和对映选择性的α-季碳炔丙基氨基酸酯。
但是双金属催化的立体选择反应对于许多药物的合成具有重大影响。尽管炔丙基官能团具有碳-碳三键的合成潜能以及广泛的应用，但合成方法都需要多步转化，其原子经济性和步骤经济性有待提高。
发明内容
为解决以上技术问题，本发明的目的在于提供一种手性的炔丙基氨基酸酯化合物的合成方法，能够实现一步法催化反应得到手性的炔丙基氨基酸酯化合物。
本发明目的是这样实现的：
一种手性的炔丙基氨基酸酯化合物的合成方法，其关键在于：
通过手性醛催化剂和单一金属的手性配合物，催化化合物1和化合物2生成炔丙基氨基酸酯；
所述化合物1具有如下所示的结构通式：
所述R1基具有5a～5o所示的结构式之一：
所述化合物2具有如下所示的结构：
所述LG基团为OBz、OAc、OBoc、OCO2Me、OPO(OEt)2中的一种。
优选的，所述手性醛催化剂具有如下所示的结构：
所述R基为H、TMS、C6H5、4-CF3C6H4、4-FC6H4、4-ClC6H4、4-MeOC6H3、3,5-(MeO)2C6H3、CH3、3,5-(Me)2C6H3、CN中的一种。
优选的，所述单一金属为有机镍化合物。
优选的，所述手性配合物具有如下L1～L4所示的结构式：
优选的，所述化合物2中的Ph基团4a可采用4b～4x所示的基团替换：
其中n＝2，
优选的，所述合成方法包括：
步骤一：准备反应体系：在干燥的反应容器中加入所述单一金属、手性配合物和溶剂，得到反应体系溶液；
步骤二：催化反应：将反应体系溶液冷却至室温，搅拌，向反应容器中加入所述化合物1、化合物2、手性催化剂、酸和碱，继续在50℃下反应至化合物2完全消失，反应混合物通过减压浓缩后，经柱层析获得炔丙基氨基酸酯。
优选的，所述手性醛与所述反应体系溶液中的单一金属及手性配合物及溶剂的物质的量之比为1:1:1.2。
优选的，所述化合物1与化合物2的物质的量之比为3:2。
优选的，所述酸为氯化锌，所述溶剂为甲苯，所述碱为四甲基胍。
优选的，所述氯化锌与四甲基胍的物质的量之比为0.4:(1～1.6)。
有益效果：
本发明手性醛催化剂能够与单一金属的手性配合物联合催化，实现单金属一步法对N-无保护氨基酸酯催化反应得到炔丙基氨基酸酯，具有更好的经济性和步骤经济性。
附图说明
图1为本申请一示例性的实施例所示的一种手性的炔丙基氨基酸酯化合物的合成方法的反应通式；
图2为本申请一示例性的实施例所示的一种手性的炔丙基氨基酸酯化合物的合成方法的反应通式。
具体实施方式
下面结合实施例和附图对本发明作进一步说明。
图1为本申请一示例性的实施例所示的合成方法的反应式。所述手性醛催化剂具有如下所示的结构：
所述R基为3a为H、3b为TMS、3c为C6H5、3d为4-CF3C6H4、3e为4-FC6H4、3f为4-ClC6H4、3g为4-MeOC6H3、3h为3,5-(MeO)2C6H3、3i为CH3、3j为3,5-(Me)2C6H3、3k为CN中的一种。本示例中R基以3i-CH3为例进行说明。
如图1所示的反应式：在氮气氛围下，在干燥的反应容器中加入0.01mmol的有机镍化合物双(1,5-环辛二烯)镍、0.012mmol的手性配合物和0.5mL的甲苯溶剂，得到反应体系溶液；将反应体系溶液冷却至室温，搅拌5min左右，向反应容器中加入0.3mmol的化合物1、0.2mmol的化合物2、0.01mmol的手性催化剂、0.08mmol的氯化锌和0.32mmol的四甲基胍，继续在50℃下反应24小时，高相液相色谱(TLC)检测反应进程，至化合物2完全消失，反应混合物通过减压浓缩后，经柱层析获得炔丙基氨基酸酯。并对反应产物炔丙基氨基酸酯进行检测，结果如表1所示：
表1为不同的R2基团制备得到的炔丙基氨基酸酯的ee值检测结果
在该体系中，给电子可以表现出更好的结果，但是对于邻甲基取代的产物，因为位阻影响，使得产率有所下降。吸电子也能表现出较好的收率，像三氟甲基这种强吸电子的取代基，在提高醛催化剂用量的情况下，也能得到目标产物。饱和脂肪烷烃在该催化提下，以优秀的产率及对应选择性能得到目标产物。综上可知，该催化体系应用范围广泛。
图2为本申请一示例性的实施例所示的合成方法的反应式。所述手性醛催化剂具有如下所示的结构：
所述R基为3a为H、3b为TMS、3c为C6H5、3d为4-CF3C6H4、3e为4-FC6H4、3f为ClC6H4、3g为MeOC6H3、3h为3,5-(MeO)2C6H3、3i为CH3、3j为3,5-(Me)2C6H3、3k为CN中的一种。本示例中R基以3i-CH3为例进行说明。
如图2所示的反应式：氮气(N2)氛围下，在干燥的反应管中加入金属催化剂(0.01mmol)，配体(0.012mmol)和甲苯(0.5mL)，将反应体系在室温下搅拌5min。一次加入0.3mmol化合物1、0.2mmol化合物2、0.01mmol手性醛催化剂、0.04mmol氯化锌和0.16mmol四甲基胍。继续在50℃下反应，高相液相色谱(TLC)检测反应进程，至化合物2完全消失，反应混合物通过减压浓缩后，经柱层析获得光学活性的α-炔丙基氨基酸化合物。不同的R1基团制备得到的炔丙基氨基酸酯的ee值检测结果如表2所示：
表2为不同的R1基团制备得到的炔丙基氨基酸酯的ee值检测结果
另外，本示例结合无色油状液体(48.6mg，92％)；Rf＝0.26(石油醚/乙酸乙酯＝2.5:1)；通过HPLC分析确定对映体过量为96％(正己烷/异丙醇＝95/5,流速0.6mL/min,T＝30℃),UV 254nm,tR(major)9.866min,tR(minor)9.126min；[α]D20＝-20.45(c＝0.92,CH2Cl2)；1H NMR(600MHz,CDCl3)δ7.38-7.37(m,2H),7.28-7.27(m,3H),2.84(d,J＝18.0Hz,1H),2.62(d,J＝18.0Hz,1H),1.87(s,2H),1.49(s,9H),1.39(s,3H).13C NMR(151MHz,CDCl3)δ175.38,131.62,128.20,127.87,123.40,85.53,83.23,81.26,57.97,32.09,27.94,25.9.HRMS(ESI)m/z:[M+H]+Calculated for C16H22NO2 +260.1645found 260.1645。
在该催化体系下，苯丙氨基酸衍生的酯和苯甘氨酸衍生的酯也可以得到目标产物。含脂肪族烷基，烯丙基，硫烷基，酯烷基取代的氨基酸衍生的酯均可得到目标产物。综上可知，该催化体系应用范围广。
最后需要说明的是，上述描述仅仅为本发明的优选实施例，本领域的普通技术人员在本发明的启示下，在不违背本发明宗旨及权利要求的前提下，可以做出多种类似的表示，这样的变换均落入本发明的保护范围之内。

Claims (10)

1.一种手性的炔丙基氨基酸酯化合物的合成方法，其特征在于：
通过手性醛催化剂和单一金属的手性配合物，催化化合物1和化合物2生成炔丙基氨基酸酯；
所述化合物1具有如下所示的结构通式：
所述R1基具有5a～5o所示的结构式之一：
所述化合物2具有如下所示的结构：
所述LG基团为OBz、OAc、OBoc、OCO2Me、OPO(OEt)2中的一种。
2.根据权利要求1所述的一种手性的炔丙基氨基酸酯化合物的合成方法，其特征在于，所述手性醛催化剂具有如下所示的结构：
所述R基为H、TMS、C6H5、4-CF3C6H4、4-FC6H4、4-ClC6H4、4-MeOC6H3、3,5-(MeO)2C6H3、CH3、3,5-(Me)2C6H3、CN中的一种。
3.根据权利要求1所述的一种手性的炔丙基氨基酸酯化合物的合成方法，其特征在于：所述单一金属为有机镍化合物。
4.根据权利要求1所述的一种手性的炔丙基氨基酸酯化合物的合成方法，其特征在于：所述手性配合物具有如下L1～L4所示的结构式：
5.根据权利要求1所述的一种手性的炔丙基氨基酸酯化合物的合成方法，其特征在于，所述化合物2中的Ph基团4a可采用4b～4x所示的基团替换：
其中n＝2，
6.根据权利要求1～5任一项所述的一种手性的炔丙基氨基酸酯化合物的合成方法，其特征在于，所述合成方法包括：
步骤一：准备反应体系：在干燥的反应容器中加入所述单一金属、手性配合物和溶剂，得到反应体系溶液；
步骤二：催化反应：将反应体系溶液冷却至室温，搅拌，向反应容器中加入所述化合物1、化合物2、手性催化剂、酸和碱，继续在50℃下反应至化合物2完全消失，反应混合物通过减压浓缩后，经柱层析获得炔丙基氨基酸酯。
7.根据权利要求6任一项所述的一种手性的炔丙基氨基酸酯化合物的合成方法，其特征在于：所述手性醛与所述反应体系溶液中的单一金属及手性配合物及溶剂的物质的量之比为1:1:1.2。
8.根据权利要求7所述的一种手性的炔丙基氨基酸酯化合物的合成方法，其特征在于：所述化合物1与化合物2的物质的量之比为3:2或2:3。
9.根据权利要求8所述的一种手性的炔丙基氨基酸酯化合物的合成方法，其特征在于：所述酸为氯化锌，所述溶剂为甲苯，所述碱为四甲基胍。
10.根据权利要求9所述的一种手性的炔丙基氨基酸酯化合物的合成方法，其特征在于：所述氯化锌与四甲基胍的物质的量之比为0.4:(1～1.6)。
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004285059A (ja) * 2003-03-03 2004-10-14 Japan Science & Technology Agency 光学活性なβ−ヒドロキシ−α−置換カルボン酸エステルの不斉合成方法
JP2007119399A (ja) * 2005-10-28 2007-05-17 Sumitomo Chemical Co Ltd Ｎ−保護−２−アミノペンタン酸誘導体の製造方法
CN112707840A (zh) * 2019-10-25 2021-04-27 华东师范大学 含多炔基的α,β-二氨基酸酯衍生物类化合物及其制备和应用
CN112979485A (zh) * 2021-03-25 2021-06-18 齐鲁工业大学 3a型分子筛在n-（4-乙炔苯羰基）氨基酸酯合成中的应用
CN113582865A (zh) * 2021-08-30 2021-11-02 西安交通大学 一种α,α-双取代手性氨基酸酯的制备方法
CN114516814A (zh) * 2020-11-19 2022-05-20 中国科学院大连化学物理研究所 一种手性季碳α-氨基酸酯类化合物的催化不对称制备方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004285059A (ja) * 2003-03-03 2004-10-14 Japan Science & Technology Agency 光学活性なβ−ヒドロキシ−α−置換カルボン酸エステルの不斉合成方法
JP2007119399A (ja) * 2005-10-28 2007-05-17 Sumitomo Chemical Co Ltd Ｎ−保護−２−アミノペンタン酸誘導体の製造方法
CN112707840A (zh) * 2019-10-25 2021-04-27 华东师范大学 含多炔基的α,β-二氨基酸酯衍生物类化合物及其制备和应用
CN114516814A (zh) * 2020-11-19 2022-05-20 中国科学院大连化学物理研究所 一种手性季碳α-氨基酸酯类化合物的催化不对称制备方法
CN112979485A (zh) * 2021-03-25 2021-06-18 齐鲁工业大学 3a型分子筛在n-（4-乙炔苯羰基）氨基酸酯合成中的应用
CN113582865A (zh) * 2021-08-30 2021-11-02 西安交通大学 一种α,α-双取代手性氨基酸酯的制备方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LI-BING ZHANG等: "Synthesis and Application of Enantioenriched Functionalized α- Tetrasubstituted α-Amino Acids from Biocatalytic Desymmetrization of Prochiral α-Aminomalonamides", J. ORG. CHEM., vol. 77, 18 June 2012 (2012-06-18), pages 5584 *
LINGZI PENG，等: "Cooperative Ni/Cu-Catalyzed Asymmetric Propargylic Alkylation of Aldimine Esters", ANGEW. CHEM. INT. ED., vol. 59, 19 May 2020 (2020-05-19), pages 14270 *

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