CN116102442A - 一种不对称催化制备α-芳基氨基酸酯的方法 - Google Patents
一种不对称催化制备α-芳基氨基酸酯的方法 Download PDFInfo
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- CN116102442A CN116102442A CN202310026574.5A CN202310026574A CN116102442A CN 116102442 A CN116102442 A CN 116102442A CN 202310026574 A CN202310026574 A CN 202310026574A CN 116102442 A CN116102442 A CN 116102442A
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- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
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- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
- C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
- C07C227/08—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid by reaction of ammonia or amines with acids containing functional groups
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- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
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Abstract
本发明公开了一种不对称催化制备α‑芳基氨基酸酯的方法，其制备过程为：在手性醛催化剂和碱存在的条件下，将α‑氨基酸酯与芳烃衍生物在溶剂中充分反应，经后处理得到芳基氨基酸酯；其中，芳烃衍生物为苯环上具有相邻卤原子和吸电子基团的芳烃衍生物；碱选自Cs2CO3、K2CO3和K3PO4中任意一种；反应温度T为10℃～100℃。本发明的合成方法反应条件温和，路线简短，反应原料选择范围宽，反应过程氨基无保护，直接得到具有光学活性的芳基氨基酸酯化合物，产率较高。
Description
技术领域
本发明属于化合物制备技术领域，具体涉及一种不对称催化制备α-芳基氨基酸酯的方法。
背景技术
具有光学活性的α-芳基氨基酸化合物存在于一些重要的天然产物中，也广泛作为生物活性分子在药物、农用化学品和功能材料中使用。不对称合成α-氨基酸的方法已经有很多种，主要包括酶合成法、α,β-脱氢氨基酸氢化或环加成法、Strecker型反应、亲电或亲核氨基化法以及亲电或亲核烷基化法，这些反应都涉及α-碳的手性控制，其中手性辅基方法占多数，手性试剂方法较少。α-芳基氨基酸由于具有芳香基团的存在，其合成存在一些特殊性。目前，该类结构化合物的手性合成主要通过手性相转移催化剂完成，而且必须使用N-保护的醛亚胺酯。专利文献CN108569978A公开了一种制备α-芳基取代氨基酸衍生物的方法，过程为：将噁唑烷酮类化合物溶于溶剂中，加入碱，加入芳基化试剂，-78℃反应2小时，室温反应12小时，得到芳基取代的噁唑烷酮类化合物；将得到的芳基取代的噁唑烷酮类化合物经三氟乙酸水解即可以得到α-芳基取代的氨基酸衍生物。但这种方法制备的是氨基上连接有取代基的氨基酸衍生物。目前还未见到直接采用氨基无保护的氨基酸作为原料来制备芳基氨基酸酯的方法。
发明内容
有鉴于此，本发明目的之一在于提供一种不对称催化制备α-芳基氨基酸酯的方法，该方法具有反应条件温和，成本低的特点，且产物的产率较高。
其技术方案如下：
一种不对称催化制备α-芳基氨基酸酯的方法，其关键在于制备过程为：在手性醛催化剂和碱存在的条件下，将α-氨基酸酯与芳烃衍生物在溶剂中充分反应，经后处理得到芳基氨基酸酯；
其中，所述碱选自Cs2CO3、K2CO3、Na3PO4和K3PO4中任意一种；
反应温度T为10℃～100℃；
所述α-氨基酸酯结构如式(I)，
其中R1选自H、C1～C7的烷基、含有芳基或烯基或醚键或亚磺酰基取代的C1～C5烷基、C1～C5脂肪酸酯基；
其中R2选自tBu、iPr、Bn、Et或Me基团中的任意一种；
所述芳烃衍生物为
或结构如式(II)的化合物，
其中X为卤原子，
其中R3为H或苯环上X的邻位、间位或对位的取代基，R3为取代基时个数为1～2个，选自甲基、甲氧基、取代或无取代的苯基、卤原子、硝基、氰基、三氟甲基、酯基；
得到的芳基氨基酸酯为
或结构如式(III)的化合物，
所述手性醛催化剂结构如式(IV)，
在一种实施方式中，所述α-氨基酸酯结构中，R1选自H、C1～C6的链烷基、C3～C6环烷基取代的甲基或乙基、苯基或吲哚基取代的甲基或乙基、甲酸酯基或乙酸酯基、醚键或硫醚键取代的甲基或乙基、亚磺酰基取代的甲基或乙基、烯丙基。
在一种实施方式中，所述芳烃衍生物中，当X为氟原子时，R3为H或苯环上X的邻位、间位或对位的取代基，R3为取代基时个数为1～2个，R3为取代基时选自甲基、甲氧基、取代或无取代的苯基、氟、氯、溴、碘；
当X为氯原子时，R3为苯环上X的间位或对位的取代基，选自硝基、氰基、三氟甲基、酯基中的一种。
在一种实施方式中，所述芳烃衍生物为以下化合物中的任意一种：
在一种实施方式中，所述反应温度T为20℃≤T≤90℃。
在一种实施方式中，所述反应温度T为30℃≤T≤60℃。
在一种实施方式中，所述反应温度T或为30℃≤T<35℃，或35℃≤T<40℃，或40℃≤T<45℃，或45℃≤T<50℃，或50℃≤T<55℃，或55℃≤T≤60℃。
在一种实施方式中，反应体系中，所述芳烃衍生物的浓度为0.025～0.2mol/L，所述芳烃衍生物与碱的物质的量之比为1:(1-15)。
在一种实施方式中，所述溶剂为均三甲苯、六氟苯、二氯甲烷、三氯甲烷、四氯化碳、氟苯、氯苯、甲醇、乙醚、四氢呋喃、丁醚中的一种，或能够互溶的两种或两种以上的混合。
本发明目的之二在于提供一种α-芳基氨基酸酯。其技术方案为：
一种α-芳基氨基酸酯，其关键在于结构如式(III)：
其中R1选自H、C1～C7的烷基、含有芳基或烯基或醚键或亚磺酰基取代的甲基或乙基、甲酸酯基或乙酸酯基，
其中R2选自tBu、iPr、Bn、Et或Me基团中的任意一种；
其中R3为H或苯环上硝基的间位或对位的取代基，R3为取代基时个数为1～2个，选自甲基、甲氧基、取代或无取代的苯基、卤原子、硝基、氰基、三氟甲基、酯基。
与现有技术相比，本发明的有益效果：
(1)反应条件温和，合成路线简短；
(2)反应原料选择范围宽，能够制备具有不同功能基团的芳基氨基酸酯；
(3)反应过程氨基无保护，直接得到具有光学活性的芳基氨基酸酯化合物，产率较高。
附图说明
图1为本发明的方法反应示意图，以及部分典型实施例的反应条件、产物分子结构、收率和对映体过量百分率。
具体实施方式
以下结合实施例对本发明作进一步说明。
一种不对称催化制备α-芳基氨基酸酯的方法，制备过程为：在手性醛催化剂和碱存在的条件下，将α-氨基酸酯(化合物1)与芳烃衍生物(化合物2)在溶剂中充分反应，得到含有芳基氨基酸酯(化合物3)的混合物，再经过后处理得到化合物3。其中，所述碱选自Cs2CO3、K2CO3、Na3PO4和K3PO4中任意一种。反应温度T为10℃～100℃；优选为20℃≤T≤90℃；进一步优选为30℃≤T≤60℃。溶剂为均三甲苯、六氟甲苯、二氯甲烷、三氯甲烷、四氯化碳、氟苯、氯苯、甲醇、乙醚、四氢呋喃、丁醚中的一种，或以能够互溶的比例相混合的两种溶剂或两种以上溶剂组成的混合溶剂。反应体系中，所述芳烃衍生物的浓度为0.025～0.2mol/L，所述芳烃衍生物与碱的物质的量之比为1:(1-15)。
所述手性醛催化剂结构如式(IV)：
所述α-氨基酸酯结构如式(I)，
其中R1选自H、C1～C7的烷基、含有芳基或烯基或醚键或亚磺酰基取代的C1～C5烷基、C1～C5脂肪酸酯基；
其中R2选自tBu、iPr、Bn、Et或Me基团中的任意一种；
所述芳烃衍生物为
或结构如式(II)的化合物，
其中X为卤原子，
其中R3为H或苯环上X的邻位、间位或对位的取代基，R3为取代基时个数为1～2个，选自甲基、甲氧基、取代或无取代的苯基、卤原子、硝基、氰基、三氟甲基、酯基；
得到的芳基氨基酸酯为
或结构如式(III)的化合物，
芳烃衍生物的苯环上具有相邻的卤原子和吸电子基团，因此以卤原子作为反应的活性位点。
下面结合具体实例说明本方法的制备过程和效果，并分别研究了不同反应条件对反应结果的影响。各实施例和对照例所用试剂均采用市售的分析纯试剂，产物经分离纯化后使用核磁共振波谱分析法(NMR)确认，产物纯度通过手性高效液相色谱分析测定，以对映体过量百分率ee％表示。
(一)不同碱的添加对反应的影响
在封管中加入搅拌磁子，将0.01mmol的手性醛催化剂和0.20mmol的化合物1a加入封管中，加入1mL的甲苯作为溶剂，加入1mmol的碱试剂，室温下搅拌10min，然后加入0.10mmol的化合物2a，在50℃下反应48h。也即，该反应体系中化合物2a与碱试剂的物质的量之比为1:10，或碱试剂的用量为化合物2a的10当量。反应过程中，通过薄层色谱(TLC)监测反应进程，至化合物2a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芳基氨基酸酯化合物3a。其中化合物1a为
化合物2a为
该反应的反应式为：
各个实施例和对照例的区别在于，反应体系中加入的碱不同，如表1所示；各个反应的目标物质产率和对映体过量百分率ee值如表1。对比对照例1～9和实施例1～3可知，常用的碱试剂中，仅Cs2CO3、K2CO3和K3PO4能够促进反应进行，其中又以Cs2CO3和K3PO4的效果更好。后续试验均选择K3PO4作为碱试剂。
表1反应体系中加入不同碱对反应的影响
注：b纯化产率；c通过手性HPLC分析测定；d 1,1,3,3-四甲基胍；e N.R.＝不反应；fN.D.＝未测定；g 1,8-二氮杂双环[5.4.0]十一碳-7-烯。
(二)不同反应温度对反应的影响
实验过程同第(一)部分，不同之处在于：所用碱试剂为K3PO4，反应温度分别为30～120℃的不同温度。该反应的反应式为：
从表2可以看出，保持其他反应条件不变的情况下，随着反应温度的升高，产率先增大后减小；反应温度达到100℃时，产率非常低。反应温度在50℃时，产率最高。
表2不同反应温度对反应的影响
注：b纯化产率；c通过手性HPLC分析测定。
(三)不同溶剂对反应的影响
实验过程同第(一)部分，不同之处在于：所用碱试剂为K3PO4，实施例9～21中所用溶剂分别为均三甲苯(mesitylene)、六氟苯(C6F6)、三氯甲烷(CHCl3)、氟苯(PhF)、氯苯(PhCl)、甲醇(CH3OH)、N,N-二甲基甲酰胺(DMF)、二氯甲烷(CH2Cl2)、四氯化碳(CCl4)、二氯甲烷与甲苯的混合溶剂(CH2Cl2:PhMe＝1:4体积比)、乙醚(Et2O)、四氢呋喃(THF)、丁醚(nBu2O)；对照例10～13所用溶剂分别为乙腈(CH3CN)、乙酸乙酯(EA)、乙二醇二甲醚(1,2-dimethoxyethane)和1,4-二氧六环(1,4-dioxane)。该反应的反应式为：
反应结果如表3所示。可以看出，以乙醚作为反应溶剂时，产率明显高于使用其他溶剂。在给定的实验条件下，对照例的几组反应几乎不能进行。
表3不同溶剂对反应的影响
(四)碱当量对反应的影响
实验过程同第(一)部分，不同之处在于：所用碱试剂为K3PO4，其用量为化合物2a的1～15当量；反应溶剂为乙醚。该反应的反应式如下：
从表2可以看出，随着K3PO4当量的增大，产率先升高后降低；K3PO4当量为5～10时，反应产率最高。
表4不同碱当量对反应的影响
(五)反应物浓度对反应的影响
实验过程同第(四)部分，不同之处在于：所用碱试剂为K3PO4，其用量为化合物2a的5当量；反应溶剂乙醚的用量为0.5～4mL，对应的化合物2a的浓度为0.025～0.2mol/L。该反应的反应式如下：
从表5可以看出，虽然在较宽的浓度范围内，反应都能够进行，但适当的反应浓度有助于提高产物收率。
表5反应物浓度(溶剂用量)对反应的影响
(六)不同α-氨基酸酯作为反应原料制备芳基氨基酸酯
根据上述实验确定的最适反应条件，按照第(一)部分的操作进行实验。不同之处在于，将0.02mmol的醛催化剂和0.4mmol的化合物1加入封管中，加入2mL的乙醚，1mmol的K3PO4，室温下搅拌10min，然后加入0.2mmol的化合物2，在50℃下反应，根据TLC检测结果，反应进行24h、48h或72h。实施例32～50中，反应使用不同的化合物1作为原料α-氨基酸酯，使用化合物2a作为原料芳烃衍生物，得到的产物分别为化合物3a～3r，如图1(a)所示。实施例50与实施例32的不同之处在于，实施例50的反应时间为72h，较实施例32的反应时间更长，但产物收率降低。
实验发现，α-氨基酸酯分子上R1基团影响目标反应转化率。虽然R1基团可以是烷烃基或含有酯或醚键等取代基团的烷烃基，但当R1基团中与α碳直接相连的C链长度为1和2时，反应转化率更高；与α碳直接相连的C链长度为3～7时，反应转化率降低。
(七)不同芳烃衍生物作为反应原料制备芳基氨基酸酯
实验过程参照第(六)部分，不同之处在于，将化合物1a作为原料α-氨基酸酯，使用不同化合物2作为原料芳烃衍生物，分别为实施例51～68，得到的产物分别为化合物3s～3z以及3aa～3aj，如图1(b)和1(c)所示。对于图1(b)示意的这类反应，化合物2中X为氟原子，苯环上第3个取代基R为卤原子或者甲基、甲氧基、取代或无取代的苯基。实验发现，当R为卤原子中的氯原子时，目标反应转化率不及R为其他几种卤原子的反应体系。
(八)特殊芳烃衍生物作为反应原料制备芳基氨基酸酯
实验过程参照第(七)部分，不同之处在于，原料α-氨基酸酯选择化合物1a或化合物
分别为实施例69～71，得到的产物分别为3ak～3am，如图1(d)所示。
上述实施例32～71制备得到的芳基氨基酸酯的量、产率、对映体过量百分率ee％以及核磁共振分析数据如下。
tert-Butyl(S)-2-amino-2-(2-nitrophenyl)propanoate(3a):
70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)7.186min；[α]D 25＝-58.93(c＝0.67,CHCl3)；1H NMR(600MHz,CDCl3)δ7.91(d,J＝6.0Hz,1H),7.87(d,J＝6.0Hz,1H),7.60(t,J＝6.0Hz,1H),7.42(t,J＝6Hz,1H),2.02(s,2H),1.77(s,3H),1.41(s,9H)；13C NMR(151MHz,CDCl3)δ173.81,148.84,138.88,132.82,128.45,128.03,124.95,82.10,60.27,27.87,27.59.HRMS(ESI)m/z:[M+H]+Calculated for C14H21N2O4 +267.1334；found 267.1349。
Isopropyl(S)-2-amino-2-(2-nitrophenyl)propanoate(3b):
70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于98％,UV 254nm,tR(major)8.362min,tR(minor)14.792min；[α]D 25＝-65.85(c＝0.33,CHCl3)；1H NMR(600MHz,CDCl3)δ7.93(d,J＝6.0Hz,1H),7.89(d,J＝6.0Hz,1H),7.62(t,J＝9.0Hz,1H),7.43(t,J＝9.0Hz,1H),4.99–5.05(m,1H),2.09(s,2H),1.79(s,3H),1.18–1.21(m,6H).13C NMR(151MHz,CDCl3)δ174.26,148.66,138.69,132.97,128.40,128.21,125.12,69.33,59.85,27.80,21.43,21.39.HRMS(ESI)m/z:[M+H]+Calculated for C11H17N2O4 +253.1183；found 283.1189.
Benzyl(S)-2-amino-2-(2-nitrophenyl)propanoate(3c):
70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于97％,UV 254nm,tR(major)19.592min,tR(minor)12.693min；[α]D 25＝-77.13(c＝0.36,CHCl3)；1H NMR(600MHz,CDCl3)δ7.92(d,J＝12.0Hz,1H),7.88(d,J＝6.0Hz,1H),7.60(t,J＝9.0Hz,1H),7.43(t,J＝9.0Hz,1H),7.34–7.24(m,5H),5.12(s,2H),1.99(s,2H),1.80(s,3H)；13C NMR(151MHz,CDCl3)δ174.64,148.69,138.50,135.49,133.04,128.53,128.40,128.36,128.32,125.15,67.28,59.94,27.79；HRMS(ESI)m/z:[M+H]+Calculated forC16H17N2O4 +301.1183；found 301.1189.
Ethyl(S)-2-amino-2-(2-nitrophenyl)propanoate(3d):
70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于98％,UV 254nm,tR(major)11.767min,tR(minor)25.945min；[α]D 25＝-105.0(c＝0.30,CHCl3)；1H NMR(600MHz,CDCl3)δ7.94(d,J＝6.0Hz,1H),7.89(d,J＝6.0Hz,1H),7.62(t,J＝6.0Hz,1H),7.44(t,J＝6.0Hz,1H),4.18–4.14(m,2H),2.13(s,2H),1.81(s,3H),1.22(t,J＝6.0Hz,3H)；13C NMR(151MHz,CDCl3)174.70,148.70,138.45,133.00,128.40,128.32,125.09,61.64,59.79,27.77,13.89；HRMS(ESI)m/z:[M+H]+Calculated for C11H15N2O4 +239.1026；found 239.1038.
Methyl(S)-2-amino-2-(2-nitrophenyl)propanoate(3e):
70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于96％,UV 254nm,tR(major)11.973min,tR(minor)28.145min；[α]D 25＝-85.43(c＝0.30,CHCl3)；1H NMR(600MHz,CDCl3)δ7.93(d,J＝6.0Hz,1H),7.88(d,J＝6.0Hz,1H),7.62(t,J＝9.0Hz,1H),7.45(t,J＝9.0Hz,1H),3.70(s,3H),1.97(s,2H),1.80(s,3H)；13C NMR(151MHz,CDCl3)δ175.31,148.71,138.49,132.99,128.35,128.27,125.09,59.75,52.42,27.86；HRMS(ESI)m/z:[M+H]+Calculated for C10H13N2O4 +225.0870；found 225.0878.
tert-Butyl(S)-2-amino-2-(2-nitrophenyl)butanoate(3f):
70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)7.077min；[α]D 25＝-38.53(c＝0.78,CHCl3)；1H NMR(600MHz,CDCl3)δ7.83–7.77(m,2H),7.57(t,J＝6.0Hz,1H),7.40(t,J＝6.0Hz,1H),2.23–2.29(m,1H),2.13–2.60(m,1H),2.08(s,2H),1.42(s,9H),0.90(t,J＝6.0Hz,3H)；13C NMR(151MHz,CDCl3)δ172.92,149.79,136.97,132.09,129.25,127.96,124.95,82.28,63.29,32.00,27.69,8.23；HRMS(ESI)m/z:[M+H]+Calculated for C14H21N2O4 +281.1496；found281.1501.Ethyl(S)-2-amino-2-(2-nitrophenyl)butanoate(3g):
体过量百分率大于95％,UV 254nm,tR(major)11.379min,tR(minor)20.724min；[α]D 25＝-6.18(c＝0.36,CHCl3)；1H NMR(600MHz,CDCl3)δ7.83–7.80(m,2H),7.59(t,J＝6.0Hz,1H),7.42(t,J＝6.0Hz,1H),4.21–4.12(m,2H),2.22–2.11(m,2H),1.97(s,2H),1.36–1.26(m,2H),1.22(t,J＝6.0Hz,3H),1.17–1.10(m,1H),0.89(t,J＝6.0Hz,3H)；13CNMR(151MHz,CDCl3)δ174.17,149.53,137.01,132.29,129.07,128.17,125.01,62.60,61.50,38.88,25.94,22.89,13.94,13.85.HRMS(ESI)m/z:[M+H]+Calculated forC14H21N2O4 +281.1496；found 281.1502.
Ethyl(S)-2-amino-2-(2-nitrophenyl)butanoate(3h):
70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)13.929min,tR(minor)25.271min；[α]D 25＝-13.13(c＝0.72,CHCl3)；1H NMR(600MHz,CDCl3)δ7.83–7.79(m,2H),7.59(t,J＝6.0Hz,1H),7.42(t,J＝6.0Hz,1H),4.16(m,2H),2.22–2.09(m,2H),2.06(s,2H),1.30(m,5H),1.21(t,J＝9.0Hz,3H),1.16(m,1H),0.89–0.83(m,3H)；13C NMR(151MHz,CDCl3)δ174.18,149.55,137.09,132.24,129.05,128.13,124.98,62.64,61.46,39.13,31.96,23.42,22.37,13.92,13.86.HRMS(ESI)m/z:[M+H]+Calculated for C15H23N2O4 +295.1652；found 295.1674.Ethyl(S)-2-amino-2-(2-nitrophenyl)butanoate(3i):
体过量百分率大于97％,UV 254nm,tR(major)10.527min,tR(minor)17.661min；[α]D 25＝-6.56(c＝0.43,CHCl3)；1H NMR(600MHz,CDCl3)δ7.81(m,2H),7.59(t,J＝6.0Hz,1H),7.42(t,J＝6.0Hz,1H),4.22–4.10(m,2H),2.16(m,2H),1.99(s,2H),1.34–1.19(m,11H),0.86(t,J＝6.8Hz,3H).13C NMR(151MHz,CDCl3)δ13C NMR(151MHz,Chloroform-d)δ174.19,149.55,137.08,132.25,129.05,128.14,125.01,62.65,61.49,39.19,31.56,29.46,23.74,22.50,13.94,13.93；HRMS(ESI)m/z:[M+H]+Calculated for C16H25N2O4 +309.1809；found309.1824.
tert-Butyl(S)-2-amino-4-methyl-2-(2-nitrophenyl)pentanoate(3j):
HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)7.437min,tR(minor)18.990min；[α]D25＝-39.58(c＝0.32,CHCl3)；1H NMR(600MHz,CDCl3)δ7.97(d,J＝6.0Hz,1H),7.80(d,J＝6.0Hz,1H),7.56(t,J＝6.0Hz,1H),7.40(t,J＝6.0Hz,1H),2.17(dd,J＝18.0,6.0Hz,1H),2.04(dd,J＝18.0,6.0Hz,1H),1.86(s,2H),1.72–1.65(m,1H),1.41(s,9H),0.95(d,J＝6.0Hz,3H),0.70(d,J＝6.0Hz,3H)；13C NMR(151MHz,CDCl3)δ173.24,149.42,137.82,131.98,129.29,127.90,124.87,82.08,63.50,46.92,27.68,24.81,24.38,23.91；HRMS(ESI)m/z:[M+H]+Calculated for C16H25N2O4+309.1809；found309.1812.
Methyl(S)-2-amino-3-cyclohexyl-2-(2-nitrophenyl)propanoate(3k):
(hexane/isopropanol＝70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于92％,UV 254nm,tR(major)9.234min,tR(minor)7.983min；[α]D 25＝8.05(c＝0.29,CHCl3)；1H NMR(600MHz,CDCl3)δ7.91(d,J＝6.0Hz,1H),7.80(d,J＝6.0Hz,1H),7.59(t,J＝6.0Hz,1H),7.48(t,J＝6.0Hz,1H),3.68(s,3H),2.12–2.05(m,2H),1.70–1.62(m,2H),1.56–1.52(m,2H),1.37–1.27(m,2H),1.21–0.97(m,4H),0.91–0.85(m,1H)；13C NMR(151MHz,CDCl3)δ174.86,149.43,137.40,132.33,128.93,128.30,125.09,62.67,52.28,46.15,35.22,35.01,33.11,26.37,26.21,26.10；HRMS(ESI)m/z:[M+H]+Calculated for C16H23N2O4 +307.1652；found 307.1666.
tert-Butyl(S)-2-amino-2-(2-nitrophenyl)pent-4-enoate(3l):
70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)6.515min,tR(minor)13.024min；[α]D 25＝-78.53(c＝0.29,CHCl3)；1H NMR(600MHz,CDCl3)δ7.81–7.78(m,2H),7.56(t,J＝6.0Hz,1H),7.40(t,J＝6.0Hz,1H),5.69–5.70(m,1H),5.16–5.12(m,2H),2.98–2.89(m,2H),1.96(s,2H),1.42(s,9H)；13C NMR(151MHz,CDCl3)δ172.54,149.58,137.32,132.27,132.04,129.16,128.05,124.91,119.86,82.48,62.47,43.70,27.71；HRMS(ESI)m/z:[M+H]+Calculated forC15H21N2O4 +293.1496；found 293.1510.
tert-Butyl(S)-2-amino-2-(2-nitrophenyl)-4-phenylbutanoate(3m):
(hexane/isopropanol＝70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)7.404min,tR(minor)16.385min；[α]D 25＝-36.27(c＝0.82,CHCl3)；1H NMR(600MHz,CDCl3)δ7.88(d,J＝12.0Hz,1H),7.83(d,J＝12.0Hz,1H),7.58(t,J＝12.0Hz,1H),7.42(t,J＝9.0Hz,1H),7.27(t,J＝6.0Hz,2H),7.17(m,3H),2.72–2.61(m,1H),2.53–2.43(m,3H),2.16(s,2H),1.45(s,9H).13C NMR(151MHz,CDCl3)δ172.86,149.62,141.41,136.96,132.27,129.16,128.52,128.29,128.17,126.07,125.07,82.53,63.09,40.89,30.38,27.74；HRMS(ESI)m/z:[M+H]+Calculated for C20H25N2O4 +357.1809；found 357.1822.
di-tert-Butyl(S)-2-amino-2-(2-nitrophenyl)pentanedioate(3n):
(hexane/isopropanol＝70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于97％,UV 254nm,tR(major)10.283min,tR(minor)8.419min；[α]D 25＝-75.11(c＝0.29,CHCl3)；1H NMR(600MHz,CDCl3)δ7.93(d,J＝6.0Hz,1H),7.86(d,J＝6.0Hz,1H),7.59(t,J＝6.0Hz,1H),7.42(t,J＝6.0Hz,1H),2.51(t,J＝6.0Hz,2H),2.26–2.33(m,1H),2.11–2.15(m,1H),1.80(s,2H),1.42(s,9H),1.41(s,9H)；13C NMR(151MHz,CDCl3)δ172.64,172.46,149.37,136.74,132.42,129.20,128.19,125.16,82.44,80.46,62.68,33.35,30.41,28.06,27.65；HRMS(ESI)m/z:[M+H]+Calculated.for C19H29N2O6 +381.2020；found 381.2031.
Diethyl(R)-2-amino-2-(2-nitrophenyl)succinate(3o):
(hexane/isopropanol＝70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于96％,UV 254nm,tR(major)16.689min,tR(minor)12.347min；[α]D 25＝-57.86(c＝0.58,CHCl3)；1H NMR(600MHz,CDCl3)δ7.91(d,J＝6.0Hz,1H),7.77(d,J＝6.0Hz,1H),7.58(t,J＝9.0Hz,1H),7.45(t,J＝9.0Hz,1H),4.19(q,J＝6.0Hz,2H),4.11(q,J＝6.0Hz,1H),3.25(d,J＝18.0Hz,1H),3.12(d,J＝18.0Hz,1H),2.61(s,2H),1.25–1.20(m,6H)；13C NMR(151MHz,CDCl3)δ172.73,170.80,149.24,136.29,132.22,128.80,128.77,124.94,62.20,61.95,60.75,42.76,14.03,13.84；HRMS(ESI)m/z:[M+H]+Calculated for C14H19N2O6 +311.1238；found 311.1248.
Ethyl(2S)-2-amino-4-(methylsulfinyl)-2-(2-nitrophenyl)butanoate(3p):
行HPLC分析，确定对映体过量百分率大于94％,UV 254nm,tR(major)16.443min,tR(minor)22.888min；[α]D 25＝-54.76(c＝0.45,CHCl3)；1H NMR(600MHz,CDCl3)δ7.92(d,J＝6.0,1H),7.87(d,J＝6.0Hz,1H),7.62(t,J＝6.0Hz,1H),7.46(t,J＝9.0Hz,1H),4.17(q,J＝6.0Hz,2H),2.55–2.48(m,3H),2.30–2.26(m,1H),2.08(s,3H),1.61(s,2H),1.22(t,J＝7.1Hz,3H)；13C NMR(151MHz,CDCl3)δ173.59,149.21,136.29,132.59,128.99,128.51,125.28,62.59,61.71,38.49,28.68,15.55,13.92；HRMS(ESI)m/z:[M+Na]+Calculated forC13H19N2O5SNa+315.1009；found 315.1010.
tert-Butyl(S)-2-amino-3-(tert-butoxy)-2-(2-nitrophenyl)propanoate(3q):
(hexane/isopropanol＝70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于96％,UV 254nm,tR(major)8.820min,tR(minor)27.267min；[α]D 25＝-58.86(c＝0.25,CHCl3)；1H NMR(600MHz,CDCl3)δ7.67–7.69(m,2H),7.51(t,J＝6.0Hz,1H),7.38(t,J＝6.0Hz,1H),3.92(d,J＝6.0Hz,1H),3.83(d,J＝6.0Hz,1H),2.01(s,2H),1.44(s,9H),1.18(s,9H)；13C NMR(151MHz,CDCl3)δ171.79,150.11,135.95,131.55,129.47,128.06,124.69,82.39,73.66,67.09,63.85,27.81,27.45；HRMS(ESI)m/z:[M+H]+Calculated for C17H27N2O5 +339.1914；found 339.1914.
Ethyl(S)-2-amino-3-(1H-indol-3-yl)-2-(2-nitrophenyl)propanoate(3r):
行HPLC分析，确定对映体过量百分率大于95％,UV 254nm,tR(major)14.276min,tR(minor)15.798min；[α]D 25＝-24.15(c＝0.43,CHCl3)；1H NMR(600MHz,CDCl3)δ8.04(s,1H),7.70(d,J＝6.0Hz,1H),7.64(d,J＝6.0Hz,1H),7.36–7.28(m,3H),7.22(d,J＝6.0Hz,1H),7.06(t,J＝9.0Hz,1H),6.95(t,J＝6.0Hz,1H),6.83(s,1H),4.04–3.97(m,2H),3.65(dd,J＝24.0,12.0Hz,2H),1.94(s,1H),1.05(t,J＝6.0Hz,3H)；13C NMR(151MHz,CDCl3)δ173.78,149.54,137.46,135.85,131.90,129.32,128.52,128.20,124.75,124.09,122.02,119.62,118.90,110.98,109.61,63.72,61.63,34.77,13.79；HRMS(ESI)m/z:[M+H]+Calculatedfor C19H20N3O4 +354.1448；found 354.1469.
tert-Butyl(S)-2-amino-2-(4-fluoro-2-nitrophenyl)propanoate(3s):
行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)8.586min；[α]D 25＝-77.35(c＝0.75,CHCl3)；1H NMR(600MHz,CDCl3)δ7.94(dd,J＝12.0,6.0Hz,1H),7.59(dd,J＝8.3,2.8Hz,1H),7.34–7.26(m,1H),2.06(s,2H),1.75(s,3H),1.41(s,9H)；13CNMR(151MHz,CDCl3)δ173.44,161.81,160.15,149.24,134.88,130.42,130.37,119.75,119.61,112.59,112.41,82.34,60.03,27.86,27.56；HRMS(ESI)m/z:[M+H]+Calculatedfor C13H18FN2O4 +285.1245；found 285.1259.
tert-Butyl(S)-2-amino-2-(4-bromo-2-nitrophenyl)propanoate(3t):
行HPLC分析，确定对映体过量百分率大于94％,UV 254nm,tR(major)10.941min,tR(minor)8.513min；[α]D 25＝-81.92(c＝0.78,CHCl3)；1H NMR(600MHz,CDCl3)δ7.98(s,1H),7.82(d,J＝12.0Hz,1H),7.70(d,J＝12.0Hz,1H),1.98(s,2H),1.74(s,3H),1.41(s,9H)；13CNMR(151MHz,CDCl3)δ173.23,149.29,138.13,135.66,130.15,127.75,121.11,82.42,60.16,27.76,27.58；HRMS(ESI)m/z:[M+H]+Calculated for C13H18BrN2O4 +345.0444；found345.0458.
tert-Butyl(S)-2-amino-2-(4-iodo-2-nitrophenyl)propanoate(3u):
(hexane/isopropanol＝70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于91％,UV 254nm,tR(major)9.297min,tR(minor)8.154min；[α]D 25＝-51.67(c＝0.33,CHCl3)；1H NMR(600MHz,CDCl3)δ8.14(s,1H),7.89(d,J＝6.0Hz,1H),7.66(d,J＝6.0Hz,1H),2.02(s,2H),1.73(s,3H),1.40(s,9H)；13C NMR(151MHz,CDCl3)δ173.22,149.17,141.66,138.77,133.34,130.25,91.62,82.44,60.20,27.71,27.59；HRMS(ESI)m/z:[M+Na]+Calculated for C13H17IN2NaO4 +415.0125；found415.0123.
tert-Butyl(S)-2-amino-2-(4-methyl-2-nitrophenyl)propanoate(3v):
进行HPLC分析，确定对映体过量百分率大于97％,UV 254nm,tR(major)8.375min,tR(minor)13.806min；[α]D 25＝-27.6(c＝0.51,CHCl3)；1H NMR(600MHz,CDCl3)δ7.75(d,J＝6.0Hz,1H),7.68(s,1H),7.39(d,J＝12.0Hz,1H),2.41(s,3H),1.97(s,2H),1.74(s,3H),1.40(s,9H)；13C NMR(151MHz,CDCl3)δ174.03,148.62,138.44,135.86,133.52,128.29,125.35,81.99,60.04,27.86,27.59,20.53；HRMS(ESI)m/z:[M+H]+Calculated forC14H21N2O4 +281.1496；found281.1495.
tert-Butyl(S)-2-amino-2-(4-methoxy-2-nitrophenyl)propanoate(3w):
进行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)16.487min；[α]D 25＝-30.6(c＝0.25,CHCl3)；1H NMR(600MHz,CDCl3)δ7.77(d,J＝12.0Hz,1H),7.38(s,1H),7.10(d,J＝6.0Hz,1H),3.86(s,3H),2.19(s,2H),1.74(s,3H),1.40(s,9H)；13C NMR(151MHz,CDCl3)δ174.09,158.80,149.32,130.63,129.51,118.70,110.10,82.00,59.87,55.79,27.90,27.60；HRMS(ESI)m/z:[M+H]+Calculated for C14H21N2O5 +297.1445；found 297.1447.tert-Butyl(S)-2-amino-2-(3-nitro-[1,1'-biphenyl]-4-yl)propanoate(3x):
行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)10.551min,tR(minor)8.497min；[α]D 25＝-31.17(c＝0.80,CHCl3)；1H NMR(600MHz,CDCl3)δ8.09(s,1H),7.96(d,J＝12.0Hz,1H),7.81(d,J＝6.0Hz,1H),7.61(d,J＝6.0Hz,2H),7.49–7.40(m,3H),2.04(s,2H),1.80(s,3H),1.43(s,9H)；13CNMR(151MHz,CDCl3)δ173.85,149.20,141.38,138.22,137.49,130.97,129.10,129.01,128.45,126.99,123.35,82.19,60.20,27.90,27.64；HRMS(ESI)m/z:[M+H]+Calculated for C19H23N2O4 +343.1652；found 343.1652.
tert-Butyl(S)-2-amino-2-(4'-fluoro-3-nitro-[1,1'-biphenyl]-4-yl)propanoate(3y):
30℃)进行HPLC分析，确定对映体过量百分率大于98％,UV 254nm,tR(major)8.648min,tR(minor)12.074min；[α]D 25＝-40.20(c＝0.60,CHCl3)；1H NMR(600MHz,CDCl3)δ8.03(s,1H),7.96(d,J＝6.0Hz,1H),7.75(d,J＝6.0Hz,1H),7.59–7.56(m,2H),7.17(t,J＝9.0Hz,2H),2.08(s,2H),1.80(s,3H),1.43(s,9H)；13C NMR(151MHz,CDCl3)δ173.69,163.93,162.29,149.20,140.40,137.36,134.32,130.84,129.17,128.74,128.69,123.18,116.17,116.02,82.31,60.18,27.80,27.62；HRMS(ESI)m/z:[M+H]+Calculated forC19H22FN2O4 +361.1558；found 361.1557.
tert-Butyl(S)-2-amino-2-(5-methyl-2-nitrophenyl)propanoate(3z):
(hexane/isopropanol＝70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)8.396min；[α]D 25＝-11.95(c＝0.66,CHCl3)；1H NMR(600MHz,CDCl3)δ7.82(d,J＝6.0Hz,1H),7.70(s,1H),7.20(d,J＝12.0Hz,1H),2.45(s,3H),2.06(s,2H),1.75(s,3H),1.40(s,9H)；13C NMR(151MHz,CDCl3)δ173.97,146.50,144.09,138.75,128.95,128.46,125.28,81.99,60.26,27.61,27.59,21.64；HRMS(ESI)m/z:[M+H]+Calculated for C14H21N2O4 +281.1496；found 281.1496.
tert-Butyl(S)-2-amino-2-(5-methoxy-2-nitrophenyl)propanoate(3aa):
进行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)10.975min；[α]D 25＝-31.47(c＝0.62,CHCl3)；1H NMR(600MHz,CDCl3)δ8.03(d,J＝12.0Hz,1H),7.48(s,1H),6.85(d,J＝12.0Hz,1H),3.91(s,3H),2.09(s,2H),1.74(s,3H),1.40(s,9H)；13C NMR(151MHz,CDCl3)δ173.70,163.35,142.04,141.61,127.97,114.38,111.85,81.87,60.53,55.79,27.60,27.21；HRMS(ESI)m/z:[M+H]+Calculated for C14H21N2O5 +297.1445；found 297.1445.tert-Butyl(S)-2-amino-2-(2-fluoro-6-nitrophenyl)propanoate(3ab):
映体过量百分率大于96％,UV 254nm,tR(major)8.250min,tR(minor)6.601min；[α]D 25＝85.05(c＝0.66,CHCl3)；1H NMR(600MHz,CDCl3)δ7.35(m,1H),7.30–7.25(m,1H),7.23–7.17(m,1H),1.86(s,2H),1.76(d,J＝6.0Hz,3H),1.44(s,9H)；13C NMR(151MHz,CDCl3)δ173.00,161.16,159.50,151.06,128.90,128.84,126.14,126.03,119.76,119.74,118.75,118.59,82.09,59.74,27.59,26.03,25.99；HRMS(ESI)m/z:[M+H]+Calculated forC13H18N2O4 +285.1245；found 285.1247.
tert-Butyl(S)-2-amino-2-(2-fluoro-3-methoxy-6-nitrophenyl)propanoate(3ac):
进行HPLC分析，确定对映体过量百分率大于96％,UV 254nm,tR(major)10.031min,tR(minor)8.852min；[α]D 25＝116.16(c＝0.30,CHCl3)；1H NMR(600MHz,CDCl3)δ7.44(d,J＝6.0Hz,1H),6.90(t,J＝9.0Hz,1H),3.94(s,3H),1.89(s,2H),1.82(d,J＝6.0Hz,3H),1.44(s,9H)；13C NMR(151MHz,CDCl3)δ173.96,168.25,154.38,135.47,131.26,125.17,124.24,123.42,119.20,117.46,116.46,79.63,61.78,59.82,30.96,28.44,24.11,23.97,14.05；HRMS(ESI)m/z:[M+H]+Calculated for C14H20FN2O5 +315.1351；found315.1352.
tert-Butyl(S)-2-amino-2-(4-fluoro-5-methyl-2-nitrophenyl)propanoate(3ad):
进行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)6.792min；[α]D 25＝-39.38(c＝0.77,CHCl3)；1H NMR(600MHz,CDCl3)δ7.77(d,J＝6.0Hz,1H),7.60(d,J＝12.0Hz,1H),2.36(s,3H),2.12(s,2H),1.74(s,3H),1.40(s,9H)；13C NMR(151MHz,CDCl3)δ173.68,160.02,158.37,146.90,146.85,134.66,134.63,131.45,131.42,130.83,130.72,112.38,112.20,82.15,60.03,27.65,27.56,14.81,14.79.；HRMS(ESI)m/z:[M+H]+Calculated for C14H20FN2O4 +299.1402；found 299.1405.
tert-Butyl(S)-2-amino-2-(5-chloro-4-methyl-2-nitrophenyl)propanoate(3ae):
进行HPLC分析，确定对映体过量百分率大于94％,UV 254nm,tR(major)7.353min,tR(minor)9.440min；[α]D 25＝-44.03(c＝0.54,CHCl3)；1H NMR(600MHz,CDCl3)δ7.91(s,1H),7.79(s,1H),2.42(s,3H),2.19(s,2H),1.74(s,3H),1.40(s,9H)；13C NMR(151MHz,CDCl3)δ173.32,146.63,139.48,138.04,136.50,129.21,127.20,82.33,60.03,27.58,27.48,19.43；HRMS(ESI)m/z:[M+H]+Calculated for C14H20ClN2O4 +315.1106；found315.1109.
tert-Butyl(S)-2-amino-2-(2,4-dinitrophenyl)propanoate(3af):
进行HPLC分析，确定对映体过量百分率大于91％,UV 254nm,tR(major)14.257min,tR(minor)11.888min；[α]D 25＝-130.02(c＝0.37,CHCl3)；1H NMR(600MHz,CDCl3)δ8.67(d,J＝2.4Hz,1H),8.41(dd,J＝6.0,2.4Hz,1H),8.22(d,J＝12.0Hz,1H),1.97(s,2H),1.81(s,3H),1.42(s,9H)；13C NMR(151MHz,CDCl3)δ172.45,149.05,146.93,145.99,130.36,126.67,120.30,83.08,60.64,27.85,27.62；HRMS(ESI)m/z:[M+Na]+Calculated for C13H17N3NaO6 +334.1010；found 334.1011.
tert-Butyl(S)-2-amino-2-(4-cyano-2-nitrophenyl)propanoate(3ag):
进行HPLC分析，确定对映体过量百分率大于96％,UV 254nm,tR(major)9.585min,tR(minor)7.666min；[α]D 25＝-178.52(c＝0.72,CHCl3)；1H NMR(600MHz,CDCl3)δ8.15–8.12(m,2H),7.86(d,J＝12.0Hz,1H),2.02(s,2H),1.78(s,3H),1.41(s,9H)；13C NMR(151MHz,CDCl3)δ172.52,149.08,144.36,135.54,130.03,128.31,116.39,112.52,82.90,60.52,27.71,27.56；HRMS(ESI)m/z:[M+H]+Calculated for C14H18N3O4 +292.1292；found292.1294.
tert-Butyl(S)-2-amino-2-(2-nitro-4-(trifluoromethyl)phenyl)propanoate(3ah):
进行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)4.819min；[α]D 25＝-113.01(c＝0.50,CHCl3)；1H NMR(600MHz,CDCl3)δ8.13(d,J＝12.0Hz,1H),8.11(s,1H),7.84(d,J＝12.0Hz,1H),2.07(s,2H),1.79(s,3H),1.42(s,9H)；13C NMR(151MHz,CDCl3)δ172.91,148.91,143.04,131.10,130.87,130.64,129.68,129.16,129.14,129.12,129.09,125.51,123.71,122.18,122.15,122.12,122.10,121.90,82.67,60.41,27.78,27.57；HRMS(ESI)m/z:[M+H]+Calculated for C14H18F3N2O4 +335.1213；found 335.1215.
Methyl(S)-4-(2-amino-1-(tert-butoxy)-1-oxopropan-2-yl)-3-nitrobenzoate(3ai):
(hexane/isopropanol＝70/30,flow rate 1.0mL/min,T＝30℃)进行HPLC分析，确定对映体过量百分率大于96％,UV 254nm,tR(major)32.480min,tR(minor)17.663min；[α]D 25＝-82.76(c＝0.71,CHCl3)；1H NMR(600MHz,CDCl3)δ8.47(s,1H),8.22(d,J＝6.0Hz,1H),8.02(d,J＝6.0Hz,1H),3.96(s,3H),2.04(s,2H),1.78(s,3H),1.41(s,9H)；13C NMR(151MHz,CDCl3)δ173.16,164.87,148.93,143.58,133.30,130.43,129.02,126.03,82.54,60.47,52.64,27.86,27.62；HRMS(ESI)m/z:[M+H]+Calculated for C15H21N2O6 +325.1394；found 325.1395.
tert-Butyl(S)-2-amino-2-(2-nitro-5-(trifluoromethyl)phenyl)propanoate(3aj):
进行HPLC分析，确定对映体过量百分率大于99％,UV 254nm,tR(major)6.259min,tR(minor)9.549min；[α]D 25＝-92.15(c＝0.45,CHCl3)；1H NMR(600MHz,CDCl3)δ8.26(s,1H),7.93(d,J＝6.0Hz,1H),7.69(d,J＝12.0Hz,1H),2.06(s,2H),1.80(s,3H),1.42(s,9H)；13C NMR(151MHz,CDCl3)δ172.88,150.82,140.35,134.58,134.36,134.14,133.92,126.19,126.17,126.14,126.12,125.36,125.26,125.24,125.21,125.19,123.97,122.17,82.68,60.37,27.77,27.55；HRMS(ESI)m/z:[M+H]+Calculated for C14H18F3N2O4 +335.1213；found 335.1215.
tert-Butyl(S)-2-amino-2-(5-nitroquinolin-8-yl)propanoate(3ak):
进行HPLC分析，确定对映体过量百分率大于70％,UV 254nm,tR(major)17.301min,tR(minor)12.002min；[α]D 25＝-8.99(c＝0.46,CHCl3)；1H NMR(600MHz,CDCl3)δ9.04(d,J＝6.0Hz,1H),8.95(d,J＝6.0Hz,1H),8.38(d,J＝6.0Hz,1H),7.98(d,J＝12.0Hz,1H),7.62(dd,J＝12.0,6.0Hz 1H),2.40(s,2H),1.83(s,3H),1.25(s,9H)；13C NMR(151MHz,CDCl3)δ176.21,150.34,149.54,145.59,144.76,132.39,124.55,124.05,123.43,121.24,80.71,60.10,27.63,25.63；HRMS(ESI)m/z:[M+H]+Calculated for C16H20N3O4 +318.1448；found 318.1449.tert-Butyl(S)-1-methyl-5-nitro-3-oxoisoindoline-1-carboxylate(3al):
行HPLC分析，确定对映体过量百分率大于75％,UV 254nm,tR(major)22.616min,tR(minor)10.133min；[α]D 25＝-9.97(c＝0.49,CHCl3)；1H NMR(600MHz,CDCl3)δ8.65(d,J＝6.0Hz,1H),8.48(m,1H),7.85(d,J＝12.0Hz,1H),7.38(s,1H),1.84(s,3H),1.47(s,9H)；13CNMR(101MHz,CDCl3)δ168.63,167.22,152.01,149.08,132.58,127.25,124.51,119.49,84.21,65.45,27.78,25.53；HRMS(ESI)m/z:[M+H]+Calculated for C14H17N2O5 +293.1132；found 293.1131.tert-Butyl(S)-1-(2-(methylthio)ethyl)-5-nitro-3-oxoisoindoline-1-carboxylate(3am):
30℃)进行HPLC分析，确定对映体过量百分率大于67％,UV 254nm,tR(major)23.316min,tR(minor)20.853min；[α]D 25＝2.64(c＝0.32,CHCl3)；1H NMR(600MHz,CDCl3)δ8.65(s,1H),8.48(d,J＝6.0Hz,1H),7.85(d,J＝6.0Hz,1H),7.48(s,1H),2.67–2.62(m,1H),2.55–2.50(m,1H),2.37–2.33(m,1H),2.24–2.19(m,1H),2.08(s,3H),1.48(s,9H)；13CNMR(151MHz,CDCl3)δ167.81,167.46,150.46,149.28,132.84,127.34,124.44,119.60,84.64,68.58,37.81,28.82,27.82,15.63；HRMS(ESI)m/z:[M+H]+Calculated forC16H20N2NaO5S+375.0985；found 375.0986.
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)
1.一种不对称催化制备α-芳基氨基酸酯的方法，其特征在于制备过程为：在手性醛催化剂和碱存在的条件下，将α-氨基酸酯与芳烃衍生物在溶剂中充分反应，经后处理得到芳基氨基酸酯；
其中，所述碱选自Cs2CO3、K2CO3、Na3PO4和K3PO4中任意一种；
反应温度T为10℃～100℃；
所述α-氨基酸酯结构如式(I)，
其中R1选自H、C1～C7的烷基、含有芳基或烯基或醚键或亚磺酰基取代的C1～C5烷基、C1～C5脂肪酸酯基；
其中R2选自tBu、iPr、Bn、Et或Me基团中的任意一种；
所述芳烃衍生物为
或结构如式(II)的化合物，
其中X为卤原子，
其中R3为H或苯环上X的邻位、间位或对位的取代基，R3为取代基时个数为1～2个，选自甲基、甲氧基、取代或无取代的苯基、卤原子、硝基、氰基、三氟甲基、酯基；
得到的芳基氨基酸酯为
或结构如式(III)的化合物，
所述手性醛催化剂结构如式(IV)，
2.根据权利要求1所述的一种不对称催化制备α-芳基氨基酸酯的方法，其特征在于：所述α-氨基酸酯结构中，R1选自H、C1～C6的链烷基、C3～C6环烷基取代的甲基或乙基、苯基或吲哚基取代的甲基或乙基、甲酸酯基或乙酸酯基、醚键或硫醚键取代的甲基或乙基、亚磺酰基取代的甲基或乙基、烯丙基。
3.根据权利要求1所述的一种不对称催化制备α-芳基氨基酸酯的方法，其特征在于：所述芳烃衍生物中，当X为氟原子时，R3为H或苯环上X的邻位、间位或对位的取代基，R3为取代基时个数为1～2个，R3为取代基时选自甲基、甲氧基、取代或无取代的苯基、氟、氯、溴、碘；
当X为氯原子时，R3为苯环上X的间位或对位的取代基，选自硝基、氰基、三氟甲基、酯基中的一种。
4.根据权利要求1所述的一种不对称催化制备α-芳基氨基酸酯的方法，其特征在于：所述芳烃衍生物为以下化合物中的任意一种：
5.根据权利要求1～4任意一项所述的一种不对称催化制备α-芳基氨基酸酯的方法，其特征在于：所述反应温度T为20℃≤T≤90℃。
6.根据权利要求1～4任意一项所述的一种不对称催化制备α-芳基氨基酸酯的方法，其特征在于：所述反应温度T为30℃≤T≤60℃。
7.根据权利要求1～4任意一项所述的一种不对称催化制备α-芳基氨基酸酯的方法，其特征在于：所述反应温度T或为30℃≤T<35℃，或35℃≤T<40℃，或40℃≤T<45℃，或45℃≤T<50℃，或50℃≤T<55℃，或55℃≤T≤60℃。
8.根据权利要求1～4任意一项所述的一种不对称催化制备α-芳基氨基酸酯的方法，其特征在于：反应体系中，所述芳烃衍生物的浓度为0.025～0.2mol/L，所述芳烃衍生物与碱的物质的量之比为1:(1-15)。
9.根据权利要求1所述的一种不对称催化制备α-芳基氨基酸酯的方法，其特征在于：所述溶剂为均三甲苯、六氟苯、二氯甲烷、三氯甲烷、四氯化碳、氟苯、氯苯、甲醇、乙醚、四氢呋喃、丁醚中的一种，或能够互溶的两种或两种以上的混合。
10.一种α-芳基氨基酸酯，其特征在于结构如式(III)：
其中R1选自H、C1～C7的烷基、含有芳基或烯基或醚键或亚磺酰基取代的甲基或乙基、甲酸酯基或乙酸酯基，
其中R2选自tBu、iPr、Bn、Et或Me基团中的任意一种；
其中R3为H或苯环上硝基的间位或对位的取代基，R3为取代基时个数为1～2个，选自甲基、甲氧基、取代或无取代的苯基、卤原子、硝基、氰基、三氟甲基、酯基。
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