Diastereoselective addition of lithium enolate of γ-substituted α-diazoacetoacetate to N-sulfinyl imines

英文原文与中文译文逐段对照 · English original with Chinese translation

MO FanYang, LI Fei &WANG JianBo ${}^{ * }$

莫凡洋, 李飞 & 王剑波 ${}^{ * }$

Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China

北京分子科学国家实验室(BNLMS)及教育部生物有机化学与分子工程重点实验室，北京大学化学与分子工程学院，北京 100871，中国

Received September 10, 2009; accepted December 1, 2009

2009年9月10日收到；2009年12月1日接受

Highly diastereoselective addition of lithium enolate of $\gamma$ -substituted $\alpha$ -diazoacetoacetate to chiral $N$ -sulfinyl imines has been developed. The addition products were further subjected to photo-induced Wolff rearrangement or Rh(II)-catalyzed intramolecular N-H insertion to afford chiral 4,5-disubstituted 2-oxo and 3-oxo pyrrolidines, respectively.

已开发出将$\gamma$-取代的$\alpha$-重氮乙酰乙酸酯的烯醇锂对映选择性地加成到手性$N$-亚磺酰亚胺的方法。加成产物进一步进行光诱导的沃尔夫重排或铑(II)催化的分子内N-H插入反应，分别得到手性4,5-二取代的2-氧代和3-氧代吡咯烷。

diazo compound, pyrrolidine, $N$ -sulfinyl imine, rhodium, diastereoselective addition

重氮化合物，吡咯烷，$N$-亚磺酰亚胺，铑，非对映选择性加成

Citation: Mo F Y, Li F, Wang J B. Diastereoselective addition of lithium enolate of $\gamma$ -substituted $\alpha$ -diazoacetoacetate to $N$ -sulfinyl imines. Chinese Sci Bull,2010, 55: 2847-2854, doi: 10.1007/s11434-010-3140-5

引用:Mo F Y, Li F, Wang J B. 将$\gamma$-取代的$\alpha$-重氮乙酰乙酸酯的烯醇锂对映选择性地加成到$N$-亚磺酰亚胺上。《中国科学通报》，2010，55:2847 - 2,854，doi: 10.1007/s11434-010-3140-5

The importance of 2-oxo and 3-oxo pyrrolidines as common structure features of many alkaloid natural products, bioac-tive compounds, drugs, and drug candidates is well recognized [1-3]. As a consequence, numerous methodologies have been developed for their synthesis over the years [4-14]. Among various methods, the application of chiral sulfinimines is practical and reliable [13]. Davis’s N-p-tolylsulfinimines [15-26] and Ellman’s N-tert-butyl derivatives [27-30] are the two representatives which have been successfully utilized in a variety of transformations. We have recently developed a new synthesis of 2-oxo and 3-oxo pyrrolidines based on the nucleophilic addition of the lithium enolate of $\alpha$ -diazoacetoacetate to chiral $N$ -sulfinyl imines, followed by photo-induced Wolff rearrangement or Rh(II)-catalyzed intramolecular N-H insertion (Scheme 1) [31].

2-氧代和3-氧代吡咯烷作为许多生物碱天然产物、生物活性化合物、药物和候选药物的常见结构特征的重要性已得到广泛认可[1-3]。因此，多年来已经开发了许多用于其合成的方法[4-14]。在各种方法中，手性亚磺酰亚胺的应用是实用且可靠的[13]。戴维斯的N-对甲苯基亚磺酰亚胺[15-26]和埃尔曼的N-叔丁基衍生物[27-30]是已成功用于各种转化的两个代表。我们最近基于$\alpha$-重氮乙酰乙酸酯的烯醇锂对手性$N$-亚磺酰亚胺的亲核加成，开发了一种新的2-氧代和3-氧代吡咯烷的合成方法，随后进行光诱导的沃尔夫重排或Rh(II)催化的分子内N-H插入(方案1)[31]。

Here we report the further extension of this methodology to the diastereoselective addition reaction when there is a substituent in the $\gamma$ -position of $\alpha$ -diazoacetoacetate. We found that when the size of the substituted group is small, such as methyl or ethyl, the addition reaction could proceed smoothly. The addition product could be further transformed to the pyrrolidine derivatives by the previously established approach. However, when the substituent is phenyl group, no addition reaction occurs. The diastereoselectivity of the reaction has distinct solvent effect (Figure 1).

在此，我们报告了该方法在$\alpha$-重氮乙酰乙酸酯的$\gamma$-位存在取代基时对非对映选择性加成反应的进一步扩展。我们发现，当取代基的尺寸较小时，如甲基或乙基，加成反应可以顺利进行。加成产物可以通过先前建立的方法进一步转化为吡咯烷衍生物。然而，当取代基为苯基时，不发生加成反应。该反应的非对映选择性具有明显的溶剂效应(图1)。

Scheme 1

方案1

Figure 1 $\gamma$ -Substituted $\alpha$ -diazoacetoacetates.

图1 $\gamma$ -取代的$\alpha$ -重氮乙酰乙酸酯。

*Corresponding author ()

*通讯作者()

1 Experimental

1 实验

1.1 General

1.1 一般情况

All reactions were performed under a nitrogen atmosphere in a flame-dried reaction flask. All solvents were distilled prior to use. ${\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}$ was distilled over calcium hydride, and THF was distilled over sodium. For chromatography, 200-300 mesh silica gel (Qindao, China) was employed. ${}^{1}\mathrm{H}$ and ${}^{13}\mathrm{C}$ NMR spectra were recorded at 300 and ${75}\mathrm{{MHz}}$ with Varian Mercury 300 spectrometer. Chemical shifts are reported in ppm using tetramethylsilane as internal standard. IR spectra were recorded with a Nicolet Avatar 330 FT-IR infrared spectrometer.

所有反应均在氮气气氛下于火焰干燥的反应烧瓶中进行。所有溶剂在使用前均进行蒸馏。${\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}$ 经氢化钙蒸馏，四氢呋喃经钠蒸馏。柱色谱使用200 - 300目硅胶(中国青岛)。${}^{1}\mathrm{H}$ 和 ${}^{13}\mathrm{C}$ NMR谱在Varian Mercury 300光谱仪上于300和${75}\mathrm{{MHz}}$ 下记录。化学位移以ppm为单位报告，以四甲基硅烷作为内标。红外光谱用Nicolet Avatar 330傅里叶变换红外光谱仪记录。

1.2 General procedure for the diastereoselective addi- tion of ethyl 2-diazo-3-oxopentanoate 1a with $N$ -sulfinyl- imine 2

1.2 用2-重氮-3-氧代戊酸乙酯1a与$N$-亚磺酰亚胺2进行非对映选择性加成的通用步骤

To a solution of $2\left( {{0.5}\mathrm{{mmol}}}\right)$ in ${\mathrm{{Et}}}_{2}\mathrm{O}\left( {{20}\mathrm{\;{mL}}}\right)$ was added LiHMDS (2 mmol of ${1.0}\mathrm{\;{mol}}{\mathrm{\;L}}^{-1}$ in hexane) at $- {78}^{ \circ }\mathrm{C}$ and then $1\mathrm{a}\left( {{1.5}\mathrm{{mmol}}}\right)$ in ${\mathrm{{Et}}}_{2}\mathrm{O}\left( {5\mathrm{\;{mL}}}\right)$ was dropped in the solution in $5\mathrm{\;{min}}$ . After stirring for another $5 - {10}\mathrm{\;{min}}$ , the reaction was quenched with saturated aqueous ${\mathrm{{NH}}}_{4}\mathrm{{Cl}}$ at $- {78}^{ \circ }\mathrm{C}$ and then warmed quickly to room temperature. The organic layer was separated and the aqueous layer was extracted with EtOAc $\left( {2 \times {15}\mathrm{\;{mL}}}\right)$ . The organic layers were then combined and dried over ${\mathrm{{Na}}}_{2}{\mathrm{{SO}}}_{4}$ . The crude product was purified by flash silica gel column chromatography to yield the addition products 3a-3j.

在${\mathrm{{Et}}}_{2}\mathrm{O}\left( {{20}\mathrm{\;{mL}}}\right)$中加入LiHMDS(2 mmol的${1.0}\mathrm{\;{mol}}{\mathrm{\;L}}^{-1}$溶于己烷)至$2\left( {{0.5}\mathrm{{mmol}}}\right)$的溶液中，于$- {78}^{ \circ }\mathrm{C}$加入，然后将$1\mathrm{a}\left( {{1.5}\mathrm{{mmol}}}\right)$溶于${\mathrm{{Et}}}_{2}\mathrm{O}\left( {5\mathrm{\;{mL}}}\right)$的溶液滴入$5\mathrm{\;{min}}$中的上述溶液。再搅拌$5 - {10}\mathrm{\;{min}}$后，于$- {78}^{ \circ }\mathrm{C}$用饱和${\mathrm{{NH}}}_{4}\mathrm{{Cl}}$水溶液淬灭反应，然后迅速升温至室温。分离有机层，水层用乙酸乙酯萃取$\left( {2 \times {15}\mathrm{\;{mL}}}\right)$。然后合并有机层，用${\mathrm{{Na}}}_{2}{\mathrm{{SO}}}_{4}$干燥。粗产物通过快速硅胶柱色谱法纯化，得到加成产物3a - 3j。

1.3 Characterization data

1.3 表征数据

Ethyl 2-diazo-4-methyl-5-(4-methylphenylsulfinamido)-3- oxo-5-phenylpentanoate (3a). Yellow oil. ${}^{1}\mathrm{H}$ NMR (300 MHz, CDCl ${}_{3}$ ) 7.51-7.48 (m, 2H), 7.37-7.36 (m, 4H), ${7.28} - {7.25}\left( {\mathrm{\;m},3\mathrm{H}}\right) ,{5.24}\left( {\mathrm{\;d},1\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ,{4.55}(\mathrm{t},1\mathrm{H}, J = \; {7.2}\mathrm{\;{Hz}}),{4.25}\left( {\mathrm{q},2\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{4.16} - {4.06}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.40}(\mathrm{\;s}$ , 3H), ${1.29}\left( {\mathrm{t},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{1.00}\left( {\mathrm{\;d},3\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}$ NMR (75 MHz, CDCl3) 195.0, 160.9, 141.9, 141.0, 140.5, 129.2, 128.4, 127.6, 127.4, 125.3, 61.4, 61.2, 47.2, 21.1, 15.4, 14.1; IR (film) 2922, 2137, 1713, 1654, 1375, 1300, 1205, 1092, 1068, 1017, 976, 842, 811, 754, 699, 683 c ${\mathrm{m}}^{-1}$ ; EI-MS $\left( {m/z\text{ , relative intensity): }{385}\left( {12}\right) ,{369}\left( 5\right) ,{278}\left( {18}\right) }\right)$ , 246(42), 220(15), 199(22), 173(30), 139(61), 123(59), 91(100), 77(59), 69(34), 30(43). HRMS (EI) calcd for ${\mathrm{C}}_{21}{\mathrm{H}}_{23}{\mathrm{\;N}}_{3}{\mathrm{O}}_{4}\mathrm{\;S}{413.14093}$ , found 413.14082.

2-重氮基-4-甲基-5-(4-甲基苯基亚磺酰胺基)-3-氧代-5-苯基戊酸乙酯(3a)。黄色油状物。${}^{1}\mathrm{H}$核磁共振氢谱(300兆赫，CDCl${}_{3}$) 7.51 - 7.48(多重峰，2H)，7.37 - 7.36(多重峰，4H)，${7.28} - {7.25}\left( {\mathrm{\;m},3\mathrm{H}}\right) ,{5.24}\left( {\mathrm{\;d},1\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ,{4.55}(\mathrm{t},1\mathrm{H}, J = \; {7.2}\mathrm{\;{Hz}}),{4.25}\left( {\mathrm{q},2\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{4.16} - {4.06}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.40}(\mathrm{\;s}$，3H)，${1.29}\left( {\mathrm{t},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{1.00}\left( {\mathrm{\;d},3\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}$核磁共振碳谱(75兆赫，CDCl3) 195.0，160.9，141.9，141.0，140.5，129.2，128.4，127.6，127.4，125.3，61.4，61.2，47.2，21.1，15.4，14.1；红外光谱(薄膜)2922，2137，1713，1654，1375，1300，1205，1092，1068，1017，976，842，811，754，699，683 c${\mathrm{m}}^{-1}$；电子轰击质谱$\left( {m/z\text{ , relative intensity): }{385}\left( {12}\right) ,{369}\left( 5\right) ,{278}\left( {18}\right) }\right)$，246(42)，220(15)，199(22)，173(30)，139(61)，123(59)，91(100)，77(59)，69(34)，30(43)。高分辨质谱(电子轰击)计算值为${\mathrm{C}}_{21}{\mathrm{H}}_{23}{\mathrm{\;N}}_{3}{\mathrm{O}}_{4}\mathrm{\;S}{413.14093}$，实测值为413.14082。

Ethyl 5-(4-chlorophenyl)-2-diazo-4-methyl-5-(4-methy-lphenylsulfinamido)-3-oxopentanoate (3b). Yellow oil. ${}^{1}\mathrm{H}$ NMR (300 MHz, CDCl ${}_{3}$ ) 7.57-7.43 (m, 2H), 7.36-7.24 (m, 6H), 5.30 (d, 1H, J = 7.2 Hz), 4.45 (t, 1H, J = 7.5 Hz), 4.25 $\left( {\mathrm{q},2\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{4.09} - {4.00}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.41}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.30}(\mathrm{t}$ , $3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}),{1.00}\left( {\mathrm{\;d},3\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}$ NMR (75 MHz, CDCl3) 194.9, 160.9, 141.5, 141.2, 139.3, 133.3, 129.3, 128.8, 128.6, 125.4, 61.5, 60.3, 47.1, 21.2, 15.5, 14.1; IR (film) 2978, 2138, 1713, 1300, 1140, 1090, 1014, 812 ${\mathrm{{cm}}}^{-1}$ ; EI-MS ( $m/z$ , relative intensity): 419 (6),294 (14),278 (31), 139 (100), 51 (60), 29 (55); HRMS (EI) calcd for ${\mathrm{C}}_{21}{\mathrm{H}}_{22}{\mathrm{\;N}}_{3}{\mathrm{O}}_{4}{\mathrm{\;S}}^{35}\mathrm{{Cl}}$ 447.10196, found 447.10115.

5-(4-氯苯基)-2-重氮基-4-甲基-5-(4-甲基苯基亚磺酰胺基)-3-氧代戊酸乙酯(3b)。黄色油状物。${}^{1}\mathrm{H}$核磁共振(300兆赫，CDCl${}_{3}$) 7.57 - 7.43(多重峰，2H)，7.36 - 7.24(多重峰，6H)，5.30(双峰，1H，J = 7.2赫兹)，4.45(三重峰，1H，J = 7.5赫兹)，4.25$\left( {\mathrm{q},2\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{4.09} - {4.00}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.41}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.30}(\mathrm{t}$，$3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}),{1.00}\left( {\mathrm{\;d},3\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}$核磁共振(75兆赫，CDCl3) 194.9，160.9，141.5，141.2，139.3，133.3，129.3，128.8，128.6，125.4，61.5，60.3，47.1，21.2，15.5，14.1；红外(薄膜)光谱2978，2138，1713，1300，1140，1090，1014，812${\mathrm{{cm}}}^{-1}$；电子轰击质谱($m/z$，相对强度):419(6)，294(14)，278(31)，139(100)，51(60)，29(55)；高分辨质谱(电子轰击)计算值为${\mathrm{C}}_{21}{\mathrm{H}}_{22}{\mathrm{\;N}}_{3}{\mathrm{O}}_{4}{\mathrm{\;S}}^{35}\mathrm{{Cl}}$ 447.10196，实测值为447.10115。

Ethyl 5-(3-bromophenyl)-2-diazo-4-methyl-5-(4-met-hylphenylsulfinamido)-3-oxopentanoate (3c). Yellow oil. ${}^{1}\mathrm{H}$ NMR (300 MHz, CDCl3) 7.50-7.40 (m, 4H), 7.30-7.22 (m, 4H), 5.30(d, 1H, J = 7.2 Hz), 4.45 (t, 1H, J = 7.5 Hz), 4.25 $\left( {\mathrm{q},2\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{4.10} - {4.00}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.41}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.30}(\mathrm{t}$ , $3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}),{1.01}\left( {\mathrm{\;d},3\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}$ NMR (75 MHz, CDCl3) 194.8, 161.0, 143.2, 141.2, 130.8, 130.4, 130.0, 129.4, 126.2, 125.4, 122.5, 61.6, 60.5, 47.0, 21.3, 15.6, 14.1; IR (film) 2975, 2139, 1712, 1652, 1375, 1301, 1204,1091,1017,811 ${\mathrm{\;{cm}}}^{-1}$ ; EI-MS $(m/z$ , relative intensity): 465 (9), 324 (29), 278 (31), 184 (58), 139 (100), 91 (86), 29 (96); HRMS (EI) calcd for ${\mathrm{C}}_{21}{\mathrm{H}}_{22}{\mathrm{\;N}}_{3}{\mathrm{O}}_{4}{\mathrm{\;S}}^{79}\mathrm{{Br}}{491.05144}$ , found 491.04966.

5-(3-溴苯基)-2-重氮基-4-甲基-5-(4-甲基苯基亚磺酰胺基)-3-氧代戊酸乙酯(3c)。黄色油状物。${}^{1}\mathrm{H}$核磁共振氢谱(300兆赫兹，氘代氯仿)7.50 - 7.40(多重峰，4H)，7.30 - 7.22(多重峰，4H)，5.30(双峰，1H，J = 7.2赫兹)，4.45(三重峰，1H，J = 7.5赫兹)，4.25 $\left( {\mathrm{q},2\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{4.10} - {4.00}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.41}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.30}(\mathrm{t}$ ，$3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}),{1.01}\left( {\mathrm{\;d},3\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}$核磁共振碳谱(75兆赫兹，氘代氯仿)194.8，161.0，143.2，141.2，130.8，130.4，130.0，129.4，126.2，125.4，122.5，61.6，60.5，47.0，21.3，15.6，14.1；红外光谱(薄膜)2975，2139，1712，1652，1375，1301，1204，1091，1017，811 ${\mathrm{\;{cm}}}^{-1}$ ；电子轰击质谱$(m/z$ ，相对强度):465(9)，324(29)，278(31)，184(58)，139(100)，91(86)，29(96)；高分辨质谱(电子轰击)计算值为${\mathrm{C}}_{21}{\mathrm{H}}_{22}{\mathrm{\;N}}_{3}{\mathrm{O}}_{4}{\mathrm{\;S}}^{79}\mathrm{{Br}}{491.05144}$ ，实测值491.04966。

(E)-ethyl 2-diazo-4-methyl-5-(4-methylphenylsulfin-amido)- 3-oxo-7-phenylhept-6-enoate (3d). Yellow oil. ${}^{1}\mathrm{H}$ NMR $\left( {{300}\mathrm{{MHz}},{\mathrm{{CDCl}}}_{3}}\right) {7.59} - {7.57}\left( {\mathrm{\;m},2\mathrm{H}}\right) ,{7.41} - {7.20}\left( {\mathrm{\;m},7\mathrm{H}}\right)$ , ${6.62} - {6.57}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{6.25} - {6.18}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{5.02}(\mathrm{\;d},1\mathrm{H}, J = {6.9}$ Hz), 4.26(q, 2H, J = 7.2 Hz), 4.17-4.12 (m, 1H), 3.93-3.84 $\left( {\mathrm{m},1\mathrm{H}}\right) ,{2.40}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.29}\left( {\mathrm{t},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{1.15}(\mathrm{\;d},3\mathrm{H}$ , $J = {7.2}\mathrm{\;{Hz}});{}^{13}\mathrm{C}\mathrm{{NMR}}\left( {{75}\mathrm{{MHz}},{\mathrm{{CDCl}}}_{3}}\right) {195.0},{160.8}$ , 142.0, 141.0 136.3, 132.8, 129.3, 128.6, 128.4, 128.4, 127.7, 126.6, 126.5, 125.5, 125.4, 61.5, 59.3, 46.2, 21.2, 15.0, 14.1; IR (film) 2979, 2137, 1713, 1645, 1374, 1299, 1201, 1091, 1016,808 ${\mathrm{\;{cm}}}^{-1}$ ; EI-MS ( $m/z$ , relative intensity): 411 (10), 289 (24), 278 (54), 139 (98), 123 (100), 91 (96), 77 (55), 29 (36); HRMS(EI) calcd for ${\mathrm{C}}_{23}{\mathrm{H}}_{25}{\mathrm{\;N}}_{3}{\mathrm{O}}_{4}\mathrm{\;S}$ 439.15658, found 439.15688.

(E)-2-重氮基-4-甲基-5-(4-甲基苯基亚磺酰胺基)-3-氧代-7-苯基庚-6-烯酸乙酯(3d)。黄色油状物。${}^{1}\mathrm{H}$核磁共振$\left( {{300}\mathrm{{MHz}},{\mathrm{{CDCl}}}_{3}}\right) {7.59} - {7.57}\left( {\mathrm{\;m},2\mathrm{H}}\right) ,{7.41} - {7.20}\left( {\mathrm{\;m},7\mathrm{H}}\right)$，${6.62} - {6.57}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{6.25} - {6.18}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{5.02}(\mathrm{\;d},1\mathrm{H}, J = {6.9}$赫兹)，4.26(四重峰，2H，J = 7.2赫兹)，4.17 - 4.12(多重峰，1H)，3.93 - 3.84$\left( {\mathrm{m},1\mathrm{H}}\right) ,{2.40}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.29}\left( {\mathrm{t},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{1.15}(\mathrm{\;d},3\mathrm{H}$，$J = {7.2}\mathrm{\;{Hz}});{}^{13}\mathrm{C}\mathrm{{NMR}}\left( {{75}\mathrm{{MHz}},{\mathrm{{CDCl}}}_{3}}\right) {195.0},{160.8}$，142.0，141.0 136.3，132.8，129.3，128.6，128.4，128.4，127.7，126.6，126.5，125.5，125.4，61.5，59.3，46.2，21.2，15.0，14.1；红外光谱(薄膜)2979，2137，1713，1645，1374，1299，1201，1091，1016，808${\mathrm{\;{cm}}}^{-1}$；电子轰击质谱($m/z$，相对强度):411(10)，289(24)，278(54)，139(98)，123(100)，91(96)，77(55)，29(36)；高分辨电子轰击质谱计算值为${\mathrm{C}}_{23}{\mathrm{H}}_{25}{\mathrm{\;N}}_{3}{\mathrm{O}}_{4}\mathrm{\;S}$439.15658，实测值为439.15688。

Ethyl 2-diazo-4-methyl-5-(4-methylphenylsulfin-amido)- 3- oxo-5-o-tolylpentanoate (3e). Yellow oil. ${}^{1}\mathrm{H}$ NMR (300 MHz, CDCl3) 7.57-7.38 (m, 3H), 7.27-7.15 (m, 5H), 5.20 $\left( {\mathrm{d},1\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ,{4.81}\left( {\mathrm{t},1\mathrm{H}, J = {8.1}\mathrm{\;{Hz}}}\right) ,{4.22}(\mathrm{q},2\mathrm{H}, J = \; {7.2}\mathrm{\;{Hz}}),{4.16} - {4.07}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.40}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{2.39}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.28}$ (t, $3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}$ ), ${1.04}\left( {\mathrm{\;d},3\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}$ NMR (75 MHz, CDCl3) 195.2, 161.0, 142.0, 141.0, 138.7, 135.8, 130.4, 129.3, 127.4, 126.8, 126.2, 125.4, 61.4, 56.8, 46.6, 21.2, 19.5, 15.0, 14.1; IR (film) 2971, 2138, 1713, 1650, 1374,1300,1203,1056,1017,812,763 ${\mathrm{{cm}}}^{-1}$ ; EI-MS ( $m/z$ , relative intensity): 338 (9), 310 (13), 278 (22), 259 (24), 198 (32), 151 (64), 139 (100), 120 (67), 91 (91), 69 (42), 57 (47), 42 (44), 29 (92); HRMS(EI) calcd for ${\mathrm{C}}_{22}{\mathrm{H}}_{25}{\mathrm{\;N}}_{3}{\mathrm{O}}_{4}\mathrm{\;S}$ 427.15658, found 427.15454.

2-重氮基-4-甲基-5-(4-甲基苯基亚磺酰胺基)-3-氧代-5-(邻甲苯基)戊酸乙酯(3e)。黄色油状物。${}^{1}\mathrm{H}$核磁共振氢谱(300兆赫兹，氘代氯仿)7.57 - 7.38(多重峰，3个氢)，7.27 - 7.15(多重峰，5个氢)，5.20$\left( {\mathrm{d},1\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ,{4.81}\left( {\mathrm{t},1\mathrm{H}, J = {8.1}\mathrm{\;{Hz}}}\right) ,{4.22}(\mathrm{q},2\mathrm{H}, J = \; {7.2}\mathrm{\;{Hz}}),{4.16} - {4.07}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.40}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{2.39}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.28}$(三重峰，$3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}$)，${1.04}\left( {\mathrm{\;d},3\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}$核磁共振碳谱(75兆赫兹，氘代氯仿)195.2，161.0，142.0，141.0，138.7，135.8，130.4，129.3，127.4，126.8，126.2，125.4，61.4，56.8，46.6，21.2，19.5，15.0，14.1；红外光谱(薄膜)2971，2138，1713，1650，1374，1300，1203，1056，1017，812，763${\mathrm{{cm}}}^{-1}$；电子轰击质谱($m/z$，相对强度):338(9)，310(13)，278(22)，259(24)，198(32)，151(64)，139(100)，120(67)，91(91)，69(42)，57(47)，42(44)，29(92)；高分辨电子轰击质谱计算值为${\mathrm{C}}_{22}{\mathrm{H}}_{25}{\mathrm{\;N}}_{3}{\mathrm{O}}_{4}\mathrm{\;S}$427.15658，实测值为427.15454。

Ethyl 2-diazo-5-(4-fluorophenyl)-4-methyl-5-(4-methy-lphenylsulfinamido)-3-oxopentanoate (3f). Yellow oil. ${}^{1}\mathrm{H}$ NMR (300 MHz, CDC1, ${\text{ J }}_{2}$ . ${\text{ J }}_{3}$ . ${\text{ H }}_{2}$ M $\left( {\text{ M },\text{ 2 H }}\right) ,$ 7.35-7.26 (m, 4H), 7.07-7.01 (m, 2H), 5.23 (d, 1H, J = 6.9 Hz), 4.49 (t, $1\mathrm{H}, J = {7.5}\mathrm{\;{Hz}}),{4.25}\left( {\mathrm{q},2\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{4.09} - {4.00}\left( {\mathrm{\;m},1\mathrm{H}}\right)$ , ${2.41}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.30}\left( {\mathrm{t},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{0.98}(\mathrm{\;d},3\mathrm{H}, J = {6.9}$ Hz); ${}^{13}\mathrm{C}$ NMR (75 MHz, ${\mathrm{{CDCl}}}_{3}$ ) 194.9,163.7,161.0,160.4, 141.5, 141.2, 136.3, 136.3, 129.3, 129.2, 129.1, 125.4, 115.5, 115.2, 61.5, 60.3, 47.3, 21.2, 15.4, 14.1; IR (film) 2979, 2136, 1713, 1651, 1509, 1300, 1204, 1091, 1064, 1016,812 ${\mathrm{{cm}}}^{-1}$ ; EI-MS $(m/z$ , relative intensity): 403 (7), 429 (8), 262 (43), 218 (25), 139 (100), 124 (58), 91 (39), 29 (47); HRMS(EI) calcd for ${\mathrm{C}}_{21}{\mathrm{H}}_{22}{\mathrm{{NFO}}}_{4}\mathrm{\;S}\left( {-{\mathrm{N}}_{2}}\right)$ 403.12536, found 403.12531.

2-重氮基-5-(4-氟苯基)-4-甲基-5-(4-甲基苯基亚磺酰胺基)-3-氧代戊酸乙酯(3f)。黄色油状物。${}^{1}\mathrm{H}$核磁共振(300兆赫，CDC1，${\text{ J }}_{2}$。${\text{ J }}_{3}$。${\text{ H }}_{2}$M$\left( {\text{ M },\text{ 2 H }}\right) ,$7.35 - 7.26(多重峰，4H)，7.07 - 7.01(多重峰，2H)，5.23(双峰，1H，J = 6.9赫兹)，4.49(三重峰，$1\mathrm{H}, J = {7.5}\mathrm{\;{Hz}}),{4.25}\left( {\mathrm{q},2\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{4.09} - {4.00}\left( {\mathrm{\;m},1\mathrm{H}}\right)$，${2.41}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.30}\left( {\mathrm{t},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{0.98}(\mathrm{\;d},3\mathrm{H}, J = {6.9}$赫兹)；${}^{13}\mathrm{C}$核磁共振(75兆赫，${\mathrm{{CDCl}}}_{3}$)194.9，163.7，161.0，160.4，141.5，141.2，136.3，136.3，129.3，129.2，129.1，125.4，115.5，115.2，61.5，60.3，47.3，21.2，15.4，14.1；红外光谱(薄膜)2979,2136,1713,1651,1509,1300,1204,1091,1064,1016,812${\mathrm{{cm}}}^{-1}$；电子轰击质谱$(m/z$，相对强度):403(7)，429(8)，262(43)，218(25)，139(100)，124(58)，91(39)，29(47)；高分辨质谱(电子轰击)计算值为${\mathrm{C}}_{21}{\mathrm{H}}_{22}{\mathrm{{NFO}}}_{4}\mathrm{\;S}\left( {-{\mathrm{N}}_{2}}\right)$403.12536，实测值为403.12531。

Ethyl 2-diazo-4-methyl-5-(4-methylphenylsulfin-amido)- 3-oxohept-6-enoate (3g). Yellow oil. ${}^{1}\mathrm{H}$ NMR (300 MHz, ${\mathrm{{CDCl}}}_{3}){7.56}\left( {\mathrm{\;d},2\mathrm{H}, J = {8.4}\mathrm{\;{Hz}}}\right) ,{7.29}\left( {\mathrm{\;d},2\mathrm{H}, J = {8.1}\mathrm{\;{Hz}}}\right)$ , 5.95-5.84 (m, 1H), 5.30-5.21 (m, 2H), 5.05 (d, 1H, J = 7.5 $\mathrm{{Hz}}),{4.28}\left( {\mathrm{q},1\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{3.92}(\mathrm{{dd}},1\mathrm{H},{J}_{1} = {6.6}\mathrm{\;{Hz}},{J}_{2} \; = {7.5}\mathrm{\;{Hz}}),{3.84} - {3.75}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.40}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.31}(\mathrm{t},3\mathrm{H}, J \; = {7.2}\mathrm{\;{Hz}}),{1.09}\left( {\mathrm{\;d},3\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}\mathrm{{NMR}}({75}\mathrm{{MHz}}$ , ${\mathrm{{CDCl}}}_{3}){195.1},{160.8},{141.5},{141.0},{137.6},{129.2},{125.6}$ , 117.5, 61.5, 59.3, 45.5, 21.2, 14.8, 14.1; EI-MS (m/z, relative intensity): 335 (96), 278 (40), 246 (28), 196 (42), 150 (52), 139 (100), 123 (45), 91 (37), 29 (25); HRMS(EI) calcd for ${\mathrm{C}}_{17}{\mathrm{H}}_{21}{\mathrm{\;N}}_{3}{\mathrm{O}}_{4}\mathrm{\;S}$ 363.12528, found 363.12541.

2-重氮基-4-甲基-5-(4-甲基苯基亚磺酰胺基)-3-氧代庚-6-烯酸乙酯(3g)。黄色油状物。${}^{1}\mathrm{H}$核磁共振(300兆赫，${\mathrm{{CDCl}}}_{3}){7.56}\left( {\mathrm{\;d},2\mathrm{H}, J = {8.4}\mathrm{\;{Hz}}}\right) ,{7.29}\left( {\mathrm{\;d},2\mathrm{H}, J = {8.1}\mathrm{\;{Hz}}}\right)$ ，5.95 - 5.84(多重峰，1H)，5.30 - 5.21(多重峰，2H)，5.05(双峰，1H，J = 7.5 $\mathrm{{Hz}}),{4.28}\left( {\mathrm{q},1\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{3.92}(\mathrm{{dd}},1\mathrm{H},{J}_{1} = {6.6}\mathrm{\;{Hz}},{J}_{2} \; = {7.5}\mathrm{\;{Hz}}),{3.84} - {3.75}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.40}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.31}(\mathrm{t},3\mathrm{H}, J \; = {7.2}\mathrm{\;{Hz}}),{1.09}\left( {\mathrm{\;d},3\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}\mathrm{{NMR}}({75}\mathrm{{MHz}}$ ，${\mathrm{{CDCl}}}_{3}){195.1},{160.8},{141.5},{141.0},{137.6},{129.2},{125.6}$ ，117.5，61.5，59.3，45.5，21.2，14.8，14.1；电子轰击质谱(质荷比，相对强度):335(96)，278(40)，246(28)，196(42)，150(52)，139(100)，123(45)，91(37)，29(25)；高分辨电子轰击质谱计算值为${\mathrm{C}}_{17}{\mathrm{H}}_{21}{\mathrm{\;N}}_{3}{\mathrm{O}}_{4}\mathrm{\;S}$ 363.12528，实测值为363.12541。

Ethyl 2-diazo-5-(furan-2-yl)-4-methyl-5-(4-methylph-en-ylsulfinamido)-3-oxopentanoate (3h). Yellow oil. ${}^{1}\mathrm{H}$ NMR (300 MHz, CDCl ${}_{3}$ ) 7.52-7.49 (m, 2H), 7.38-7.26 (m, 3H), ${6.32} - {6.31}\left( {\mathrm{\;m},2\mathrm{H}}\right) ,{5.23}\left( {\mathrm{\;d},1\mathrm{H}, J = {8.1}\mathrm{\;{Hz}}}\right) ,{4.58}(\mathrm{t},1\mathrm{H}, J = \; {7.8}\mathrm{\;{Hz}}),{4.28}\left( {\mathrm{q},2\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{4.22} - {4.15}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.39}(\mathrm{\;s}$ , 3H), ${1.32}\left( {\mathrm{t},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{1.00}\left( {\mathrm{\;d},3\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}$ NMR (75 MHz, CDCl ${}_{3}$ ) 194.6, 160.8, 153.0, 142.0, 141.5, 141.0, 129.2, 125.4, 110.2, 108.2, 61.4, 54.5, 45.0, 21.2, 14.9, 14.1; IR (film) 2984, 2137, 1714, 1650, 1375, 1302, 1210,1092,1015,812,734 ${\mathrm{{cm}}}^{-1}$ ; EI-MS $(m/z$ , relative intensity): 375 (6), 264 (12), 234 (23), 190 (25), 139 (100), 124 (43), 29 (68); HRMS(EI) calcd for ${\mathrm{C}}_{19}{\mathrm{H}}_{21}{\mathrm{\;N}}_{3}{\mathrm{O}}_{5}\mathrm{\;S}$ 403.1202, found 403.1210.

2 - 重氮 - 5 - (呋喃 - 2 - 基) - 4 - 甲基 - 5 - (4 - 甲基苯基亚磺酰胺基) - 3 - 氧代戊酸乙酯 (3h)。黄色油状物。${}^{1}\mathrm{H}$ 核磁共振谱 (300 MHz, CDCl ${}_{3}$ ) 7.52 - 7.49 (m, 2H), 7.38 - 7.26 (m, 3H), ${6.32} - {6.31}\left( {\mathrm{\;m},2\mathrm{H}}\right) ,{5.23}\left( {\mathrm{\;d},1\mathrm{H}, J = {8.1}\mathrm{\;{Hz}}}\right) ,{4.58}(\mathrm{t},1\mathrm{H}, J = \; {7.8}\mathrm{\;{Hz}}),{4.28}\left( {\mathrm{q},2\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{4.22} - {4.15}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.39}(\mathrm{\;s}$ , 3H), ${1.32}\left( {\mathrm{t},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{1.00}\left( {\mathrm{\;d},3\mathrm{H}, J = {6.9}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}$ 核磁共振谱 (75 MHz, CDCl ${}_{3}$ ) 194.6, 160.8, 153.0, 142.0, 141.5, 141.0, 129.2, 125.4, 110.2, 108.2, 61.4, 54.5, 45.0, 21.2, 14.9, 14.1；红外光谱 (薄膜) 2984, 2137, 1714, 1650, 1375, 1302, 1210,1092,1015,812,734 ${\mathrm{{cm}}}^{-1}$ ；电子轰击质谱 $(m/z$ ,相对强度): 375 (6), 264 (12), 234 (23), 190 (25), 139 (100), 124 (43), 29 (68)；高分辨质谱 (电子轰击) 计算值 ${\mathrm{C}}_{19}{\mathrm{H}}_{21}{\mathrm{\;N}}_{3}{\mathrm{O}}_{5}\mathrm{\;S}$ 403.1202，实测值 403.1210。

Ethyl 5-(biphenyl-4-yl)-2-diazo-4-methyl-5-(4-methyl-phenylsulfinamido)-3-oxopentanoate (3i). Yellow oil. ${}^{1}\mathrm{H}$ NMR (300 MHz, CDCl ${}_{3}$ ) 7.60-7.51 (m, 6H), 7.44-7.39 (m, 4H), 7.35-7.26 (m, 3H), 5.31 (d, 1H, J = 6.9 Hz), 4.58 (t, $1\mathrm{H}, J = {7.5}\mathrm{\;{Hz}}),{4.23}\left( {\mathrm{q},2\mathrm{H}, J = {7.5}\mathrm{\;{Hz}}}\right) ,{4.18} - {4.09}\left( {\mathrm{\;m},1\mathrm{H}}\right)$ , ${2.39}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.27}\left( {\mathrm{t},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{1.04}(\mathrm{\;d},3\mathrm{H}, J = {6.9}$ Hz); ${}^{13}\mathrm{C}$ NMR (75MHz, ${\mathrm{{CDCl}}}_{3}$ ) 195.1, 161.0, 141.9, 141.0, 140.4, 140.3, 139.6, 129.3, 128.6, 127.9, 127.1, 127.1, 126.8, 125.4, 61.4, 60.9, 47.2, 21.2, 15.6, 14.1; IR (film) 2926, 2138, 1715, 1650, 1375, 1301, 1204, 1091, 1068, 1017,909,733 ${\mathrm{{cm}}}^{-1}$ ; EI-MS $\left( {m/z}\right.$ , relative intensity): 461 (4), 445 (5), 339 (45), 323 (81), 396 (57), 246 (58), 182 (100), 139 (65), 91 (49), 29 (44); HRMS(EI) calcd for ${\mathrm{C}}_{27}{\mathrm{H}}_{27}{\mathrm{{NO}}}_{4}\mathrm{\;S}\left( {-{\mathrm{N}}_{2}}\right) {461.1661}$ , found 461.1674.

5-(联苯-4-基)-2-重氮基-4-甲基-5-(4-甲基苯基亚磺酰胺基)-3-氧代戊酸乙酯(3i)。黄色油状物。${}^{1}\mathrm{H}$核磁共振(300兆赫，CDCl${}_{3}$)7.60 - 7.51(多重峰，6H)，7.44 - 7.39(多重峰，4H)，7.35 - 7.26(多重峰，3H)，5.31(双峰，1H，J = 6.9赫兹)，4.58(三重峰，$1\mathrm{H}, J = {7.5}\mathrm{\;{Hz}}),{4.23}\left( {\mathrm{q},2\mathrm{H}, J = {7.5}\mathrm{\;{Hz}}}\right) ,{4.18} - {4.09}\left( {\mathrm{\;m},1\mathrm{H}}\right)$，${2.39}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{1.27}\left( {\mathrm{t},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{1.04}(\mathrm{\;d},3\mathrm{H}, J = {6.9}$赫兹)；${}^{13}\mathrm{C}$核磁共振(75兆赫，${\mathrm{{CDCl}}}_{3}$)195.1，161.0，1,41.9，141.0，140.4，140.3，139.6，129.3，128.6，127.9，127.1，127.1，126.8，125.4，61.4，60.9，47.2，21.2,15.6，14.1；红外光谱(薄膜)2926，2138，1715，1650，1375，1301，1204，1091，1068，1017，909，733${\mathrm{{cm}}}^{-1}$；电子轰击质谱$\left( {m/z}\right.$，相对强度):461(4)，445(5)，339(45)，323(81)，396(57)，246(58)，182(100)，139(65)，91(49)，29(44)；高分辨质谱(电子轰击)计算值为${\mathrm{C}}_{27}{\mathrm{H}}_{27}{\mathrm{{NO}}}_{4}\mathrm{\;S}\left( {-{\mathrm{N}}_{2}}\right) {461.1661}$，实测值为461.1674。

Ethyl 2-diazo-4-methyl-5-(4-methylphenylsulfin-amido)-5- (6-methylpyridin-2-yl)-3-oxopentanoate (3j). Yellow oil. ${}^{1}\mathrm{H}$ NMR (300 MHz, CDCl ${}_{3}$ ) 7.54-7.49 (m, 3 H), 7.29-7.27(m, 2H), 7.13-7.10 (m, 1 H), 7.01-6.98 (m, 1 H), 5.95 (d, 1 H, J = 9.6 Hz), 4.45 (dd, 1 H, J = 9.6, 2.1 Hz), 4.27(q, 2 H, J = ${7.2}\mathrm{\;{Hz}}),{4.20} - {4.10}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.49}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{2.41}\left( {\mathrm{\;s},3\mathrm{H}}\right)$ , ${1.32}\left( {\mathrm{t},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{0.88}\left( {\mathrm{\;d},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}\mathrm{N}\mathrm{M}\mathrm{R}$ (75 MHz, CDCl3) 195.2, 160.8, 159.4, 157.7, 141.2, 140.9, 136.4, 129.2, 125.7, 121.7, 119.3, 61.3, 60.1, 45.6, 24.2, 21.2, 14.8, 14.2; IR (film) 3289, 2957, 2928, 2131, 1718, 1649, 1458, 1374, 1301, 1206, 1124, 1093, 1072, 1017, 814, ${748}{\mathrm{\;{cm}}}^{-1}$ ; EI-MS (m/z, relative intensity): 428 (5),400 (6), 337 (44), 259 (20), 151 (74), 139 (100), 121 (62), 91 (40), 65 (30), 57 (25), 39 (23), 29 (68); HRMS (EI) calcd for ${\mathrm{C}}_{21}{\mathrm{H}}_{24}{\mathrm{\;N}}_{4}{\mathrm{O}}_{4}\mathrm{\;S}{428.1518}$ , found 428.1516.

2-重氮-4-甲基-5-(4-甲基苯基亚磺酰胺基)-5-(6-甲基吡啶-2-基)-3-氧代戊酸乙酯 (3j)。黄色油状物。${}^{1}\mathrm{H}$ NMR (300 MHz, CDCl ${}_{3}$ ) 7.54 - 7.49 (m, 3 H), 7.29 - 7.27 (m, 2 H), 7.13 - 7.10 (m, 1 H), 7.01 - 6.98 (m, 1 H), 5.95 (d, 1 H, J = 9.6 Hz), 4.45 (dd, 1 H, J = 9.6, 2.1 Hz), 4.27 (q, 2 H, J = ${7.2}\mathrm{\;{Hz}}),{4.20} - {4.10}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.49}\left( {\mathrm{\;s},3\mathrm{H}}\right) ,{2.41}\left( {\mathrm{\;s},3\mathrm{H}}\right)$ , ${1.32}\left( {\mathrm{t},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ,{0.88}\left( {\mathrm{\;d},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right) ;{}^{13}\mathrm{C}\mathrm{N}\mathrm{M}\mathrm{R}$ (75 MHz, CDCl3) 195.2, 160.8, 159.4, 157.7, 141.2, 140.9, 136.4, 129.2, 125.7, 121.7, 119.3, 61.3, 60.1, 45.6, 24.2, 21.2, 14.8, 14.2；红外光谱(薄膜)3289, 2957, 2928, 2131, 1718, 1649, 1458, 1374, 1301, 1206, 1124, 1093, 1072, 1017, 814, ${748}{\mathrm{\;{cm}}}^{-1}$；电子轰击质谱(m/z，相对强度):428 (5), 400 (6), 337 (44), 259 (20), 151 (74), 139 (100), 121 (62), 91 (40), 65 (30), 57 (25), 39 (23), 29 (68)；高分辨质谱(电子轰击)计算值为 ${\mathrm{C}}_{21}{\mathrm{H}}_{24}{\mathrm{\;N}}_{4}{\mathrm{O}}_{4}\mathrm{\;S}{428.1518}$，实测值 428.1516。

Allyl 5-(4-chlorophenyl)-2-diazo-4-methyl-5-(4-meth-yl-phenylsulfinamido)-3-oxopentanoate (5). Yellow oil. ${}^{1}\mathrm{H}$ NMR (300 MHz, CDCl ${}_{3}$ ) 7.55 (d, 2H, $J = {8.4}\mathrm{\;{Hz}}$ ), 7.34-7.27 (m, 6H), 5.96-5.85 (m, 1H), 5.41-5.27 (m, 3H), ${4.69} - {4.67}\left( {\mathrm{\;m},2\mathrm{H}}\right) ,{4.46}\left( {\mathrm{t},1\mathrm{H}, J = {7.5}\mathrm{\;{Hz}}}\right) ,{4.15} - {3.92}(\mathrm{\;m}$ , 1H), 2.41 (s, 3H), 0.99 (d, 3H, J = 6.9 Hz); ${}^{13}\mathrm{C}$ NMR (75 MHz, CDCl3) 194.8, 160.7, 141.4, 141.3, 139.3, 133.4, 131.1, 129.4, 128.8, 128.7, 125.5, 119.4, 66.0, 60.4, 47.2, 21.3, 15.6; IR (film) 2978, 2141, 1715, 1649, 1491, 1377, 1301,1204,1090,987,811,732 ${\mathrm{{cm}}}^{-1}$ ; EI-MS $(m/z$ , relative intensity): 431 (3), 364 (3), 278 (8), 139 (55), 124 (97), 91 (100), 57 (12); HRMS (EI) calcd for ${\mathrm{C}}_{22}{\mathrm{H}}_{22}{\mathrm{{NO}}}_{4}{\mathrm{\;S}}^{35}\mathrm{{Cl}}\left( {\mathrm{M} - {\mathrm{N}}_{2}}\right)$ 431.096, found ${431.096}.{\left\lbrack \alpha \right\rbrack }_{\mathrm{D}}{}^{20} = {176.6}^{ \circ }\left( {c = {1.55}\text{ in }{\mathrm{{CHCl}}}_{3}}\right)$ .

烯丙基 5-(4-氯苯基)-2-重氮基-4-甲基-5-(4-甲基苯基亚磺酰胺基)-3-氧代戊酸酯(5)。黄色油状物。${}^{1}\mathrm{H}$核磁共振氢谱(300兆赫兹，CDCl${}_{3}$) 7.55(双峰，2H，$J = {8.4}\mathrm{\;{Hz}}$)，7.34 - 7.27(多重峰，6H)，5.96 - 5.85(多重峰，1H)，5.41 - 5.27(多重峰，3H)，${4.69} - {4.67}\left( {\mathrm{\;m},2\mathrm{H}}\right) ,{4.46}\left( {\mathrm{t},1\mathrm{H}, J = {7.5}\mathrm{\;{Hz}}}\right) ,{4.15} - {3.92}(\mathrm{\;m}$，1H)，2.41(单峰，3H)，0.99(双峰，3H，J = 6.9赫兹)；${}^{13}\mathrm{C}$核磁共振碳谱(75兆赫兹，CDCl3) 194.8，160.7，141.4，141.3，139.3，133.4，131.1，129.4，128.8，128.7，125.5，119.4，66.0，60.4，47.2，21.3，15.6；红外光谱(薄膜)2978，2141，1715，1649，1491，1377，1301，1204，1090，987，811，732${\mathrm{{cm}}}^{-1}$；电子轰击质谱$(m/z$，相对强度):431(3)，364(3)，278(8)，139(55)，124(97)，91(100)，57(12)；高分辨质谱(电子轰击)计算值为${\mathrm{C}}_{22}{\mathrm{H}}_{22}{\mathrm{{NO}}}_{4}{\mathrm{\;S}}^{35}\mathrm{{Cl}}\left( {\mathrm{M} - {\mathrm{N}}_{2}}\right)$ 431.096，实测值${431.096}.{\left\lbrack \alpha \right\rbrack }_{\mathrm{D}}{}^{20} = {176.6}^{ \circ }\left( {c = {1.55}\text{ in }{\mathrm{{CHCl}}}_{3}}\right)$。

Allyl 5-(tert-butoxycarbonylamino)-5-(4-chlorophenyl)-2- diazo-4-methyl-3-oxopentanoate (6). The addition product 5 (302 mg,0.7 mmol) was treated by TFA (400 mg,3.5 mmol, 5.0 equiv.) in $\mathrm{{MeOH}}\left( {5\mathrm{\;{mL}}}\right)$ at ${0}^{ \circ }\mathrm{C}$ . Monitored by TLC, the sulfinyl group in5was removed in about $2\mathrm{\;h}$ to give the corresponding amine salt. The solution was concentrated, and then was dissolved in THF. The solution was treated at ${0}^{ \circ }\mathrm{C}$ with ${\mathrm{{Boc}}}_{2}\mathrm{O}\left( {{180}\mathrm{{mg}},{0.84}\mathrm{{mmol}},{1.2}\text{ equiv.) }/{\mathrm{{Et}}}_{3}\mathrm{\;N}\text{ (424 }}\right.$ mg, 4.2 mmol, 6 equiv.) and a catalytic amount of DMAP ( $4\mathrm{{mg}},{0.035}\mathrm{{mmol}},{0.05}$ equiv.). After stirred for about $2\mathrm{\;h}$ , the solution was concentrated and purified by flash chromatography (Petroleum ether: EtOAc = 10/1) to give the $N$ -Boc protected product $6\left( {{280}\mathrm{{mg}},{95}\% }\right.$ for the two steps). Yellow oil. ${}^{1}\mathrm{H}$ NMR (300 MHz, ${\mathrm{{CDCl}}}_{3}$ ) 7.27-7.19 (m,4H), ${6.14}\left( {\mathrm{\;d},1\mathrm{H}, J = {8.7}\mathrm{\;{Hz}}}\right) ,{5.97} - {5.84}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{5.35} - {5.25}(\mathrm{\;m}$ , 2H), ${4.83}\left( {\mathrm{t},1\mathrm{H}, J = {6.6}\mathrm{\;{Hz}}}\right) ,{4.68}\left( {\mathrm{\;d},2\mathrm{H}, J = {5.7}\mathrm{\;{Hz}}}\right)$ , ${4.20} - {4.03}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{1.41}\left( {\mathrm{\;s},9\mathrm{H}}\right) ,{1.21}\left( {\mathrm{\;d},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right)$ ; ${}^{13}\mathrm{C}\;\mathrm{{NMR}}\left( {{75}\mathrm{{MHz}},{\mathrm{{CDCl}}}_{3}}\right) \;{195.6},\;{160.5},\;{155.4},\;{139.9},$ 132.7, 131.0, 128.4, 127.7, 119.3, 79.4, 77.4, 76.9, 76.5, 65.9, 56.7, 45.3, 28.2, 15.4, IR (film) 3416, 2977, 2141, 1713, 1650, 1491, 1366, 1301, 1166, 1091, 993, 736 cm ${}^{-1}$ ; EI-MS $\left( {m/z\text{ , relative intensity): 421 (3),348 (5),293 (12), }}\right)$ 252 (48), 240 (46), 208 (35), 184 (95), 166 (46), 142 (44), 140 (100), 138 (48), 57 (62), 41 (34), 39 (13); HRMS (EI) calcd for ${\mathrm{C}}_{20}{\mathrm{H}}_{24}{\mathrm{\;N}}_{3}{\mathrm{O}}_{5}{}^{35}\mathrm{{Cl}}{421.1404}$ , found ${421.1407}.{\left\lbrack \alpha \right\rbrack }_{\mathrm{D}}{}^{20} \; = + {79.2}^{ \circ }\left( {c = {0.85}\text{ in }{\mathrm{{CHCl}}}_{3}}\right)$ .

烯丙基 5-(叔丁氧羰基氨基)-5-(4-氯苯基)-2-重氮-4-甲基-3-氧代戊酸酯(6)。在$\mathrm{{MeOH}}\left( {5\mathrm{\;{mL}}}\right)$中于${0}^{ \circ }\mathrm{C}$用三氟乙酸(400 mg,3.5 mmol,5.0当量)处理加成产物5(302 mg,0.7 mmol)。通过薄层层析监测，5中的亚磺酰基在约$2\mathrm{\;h}$内被除去，得到相应的胺盐。将溶液浓缩，然后溶于四氢呋喃。该溶液在${0}^{ \circ }\mathrm{C}$用${\mathrm{{Boc}}}_{2}\mathrm{O}\left( {{180}\mathrm{{mg}},{0.84}\mathrm{{mmol}},{1.2}\text{ equiv.) }/{\mathrm{{Et}}}_{3}\mathrm{\;N}\text{ (424 }}\right.$mg(4.2 mmol,6当量)和催化量的4-(二甲氨基)吡啶($4\mathrm{{mg}},{0.035}\mathrm{{mmol}},{0.05}$当量)处理。搅拌约$2\mathrm{\;h}$后，将溶液浓缩并通过快速柱色谱法(石油醚:乙酸乙酯 = 10/1)纯化，得到两步反应的$N$-Boc保护产物$6\left( {{280}\mathrm{{mg}},{95}\% }\right.$。黄色油状物。${}^{1}\mathrm{H}$核磁共振(300兆赫，${\mathrm{{CDCl}}}_{3}$)7.27 - 7.19(多重峰，4H)，${6.14}\left( {\mathrm{\;d},1\mathrm{H}, J = {8.7}\mathrm{\;{Hz}}}\right) ,{5.97} - {5.84}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{5.35} - {5.25}(\mathrm{\;m}$(2H)，${4.83}\left( {\mathrm{t},1\mathrm{H}, J = {6.6}\mathrm{\;{Hz}}}\right) ,{4.68}\left( {\mathrm{\;d},2\mathrm{H}, J = {5.7}\mathrm{\;{Hz}}}\right)$，${4.20} - {4.03}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{1.41}\left( {\mathrm{\;s},9\mathrm{H}}\right) ,{1.21}\left( {\mathrm{\;d},3\mathrm{H}, J = {7.2}\mathrm{\;{Hz}}}\right)$；${}^{13}\mathrm{C}\;\mathrm{{NMR}}\left( {{75}\mathrm{{MHz}},{\mathrm{{CDCl}}}_{3}}\right) \;{195.6},\;{160.5},\;{155.4},\;{139.9},$132.7、131.0、128.4、127.7、119.3、79.4、77.4、76.9、76.5、65.9、56.7、45.3、28.2、15.4，红外光谱(薄膜)3416、2977、2141、1713、1650、1491、1366、1301、1166、1091、993、736厘米${}^{-1}$；电子轰击质谱$\left( {m/z\text{ , relative intensity): 421 (3),348 (5),293 (12), }}\right)$252(48)、240(46)、208(35)、184(95)、166(46)、142(44)、140(100)、138(48)、57(62)、41(34)、39(13)；高分辨质谱(电子轰击)计算值为${\mathrm{C}}_{20}{\mathrm{H}}_{24}{\mathrm{\;N}}_{3}{\mathrm{O}}_{5}{}^{35}\mathrm{{Cl}}{421.1404}$，实测值为${421.1407}.{\left\lbrack \alpha \right\rbrack }_{\mathrm{D}}{}^{20} \; = + {79.2}^{ \circ }\left( {c = {0.85}\text{ in }{\mathrm{{CHCl}}}_{3}}\right)$。

(4S,5R)-3-allyl 1-tert-butyl 5-(4-chlorophenyl)-4-methyl- 2-oxopyrrolidine-1,3-dicarboxylate (7). A solution of 6 (109 mg, 0.26 mmol) in benzene (30 mL) in a Pyrex tube was irradiated with a 500-W Hg lamp with a water-cooled tube inserted into the solvent. The reaction temperature was kept at about ${35}^{ \circ }\mathrm{C}$ . The reaction was complete in about ${1.5}\mathrm{\;h}$ (monitored by IR and TLC). The solution was concentrated under reduced pressure to give the crude product, which was purified by flash chromatography (Petroleum ether: EtOAc = 5/1) to yield the diastereomeric mixture of the corresponding 3-allyloxycarbonyl-2-oxo pyrrolidines 7, 85 mg (yield 84%). The diastereomeric mixture could not be separated by column chromatography because of the isomerization of the products on silica gel. Yellow oil. ${}^{1}\mathrm{H}$ NMR (300 MHz, CDCl ${}_{3}$ ) 7.36 (d, 2H, J = 8.4 Hz), 7.24 (d, 2H, J $= {8.4}\mathrm{\;{Hz}}),{5.99} - {5.86}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{5.41} - {5.24}\left( {\mathrm{\;m},2\mathrm{H}}\right) ,{4.77} - {4.63} \; \left( {\mathrm{m},2\mathrm{H}}\right) ,{4.43}\left( {\mathrm{\;d},1\mathrm{H}, J = {8.7}}\right) ,{3.33}\left( {\mathrm{\;d},1\mathrm{H}, J = {11.0}\mathrm{\;{Hz}}}\right)$ , 2.59-2.33 (m, 1H), 1.23 (s, 9H), 1.16(1.08) (d, 3H, J = 6.6 Hz); ${}^{13}\mathrm{C}$ NMR (75 MHz, ${\mathrm{{CDCl}}}_{3}$ ) 168.4,167.5,148.6,139.1, 133.6, 131.2, 131.0, 128.8, 128.8, 127.3, 127.1, 119.1, 118.7, 83.5, 83.4, 67.4, 66.8, 66.2, 66.0, 56.6, 54.3, 40.1, 39.3, 27.4, 15.9, 12.3; IR (film) 2980, 1786, 1732, 1493, 1369, 1318, 1246, 1145, 1074, 990, 827, 734 cm ${}^{-1}$ ; EI-MS $\left( {m/z,\text{ relative intensity): }{393}\left( 4\right) ,{339}\left( {13}\right) ,{337}\left( {35}\right) ,{293}}\right)$ (36), 254 (33), 252 (100), 234 (45), 208 (22), 140 (32), 56 (58),41 (63), 39 (26); HRMS (EI) calcd for ${\mathrm{C}}_{20}{\mathrm{H}}_{24}{\mathrm{{NO}}}_{5}{}^{35}\mathrm{{Cl}}$ 393.1343, found 393.1348.

(4S,5R)-3-烯丙基 1-叔丁基 5-(4-氯苯基)-4-甲基-2-氧代吡咯烷-1,3-二羧酸酯(7)。将6(109毫克，0.26毫摩尔)溶于苯(30毫升)的溶液置于派热克斯管中，用500瓦汞灯照射，同时往溶剂中插入一根水冷管。反应温度保持在约${35}^{ \circ }\mathrm{C}$。反应在约${1.5}\mathrm{\;h}$内完成(通过红外光谱和薄层色谱监测)。溶液在减压下浓缩得到粗产物，通过快速柱色谱法(石油醚:乙酸乙酯 = 5/1)纯化，得到相应的3-烯丙氧基羰基-2-氧代吡咯烷7的非对映体混合物，85毫克(产率84%)。由于产物在硅胶上异构化，该非对映体混合物无法通过柱色谱法分离。黄色油状物。${}^{1}\mathrm{H}$核磁共振(300兆赫，CDCl${}_{3}$) 7.36(双峰，2H，J = 8.4赫兹)，7.24(双峰，2H，J$= {8.4}\mathrm{\;{Hz}}),{5.99} - {5.86}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{5.41} - {5.24}\left( {\mathrm{\;m},2\mathrm{H}}\right) ,{4.77} - {4.63} \; \left( {\mathrm{m},2\mathrm{H}}\right) ,{4.43}\left( {\mathrm{\;d},1\mathrm{H}, J = {8.7}}\right) ,{3.33}\left( {\mathrm{\;d},1\mathrm{H}, J = {11.0}\mathrm{\;{Hz}}}\right)$，2.59 - 2.33(多重峰，1H)，1.23(单峰，9H)，1.16(1.08)(双峰，3H，J = 6.6赫兹);${}^{13}\mathrm{C}$核磁共振(75兆赫，${\mathrm{{CDCl}}}_{3}$) 168.4,167.5,148.6,139.1, 133.6, 131.2, 131.0, 128.8, 128.8, 127.3, 127.1, 119.1, 118.7, 83.5, 83.4, 67.4, 66.8, 66.2, 66.0, 56.6, 54.3, 40.1, 39.3, 27.4, 15.9, 12.3;红外光谱(薄膜)2980, 1786, 1732, 1493, 13, 1318, 1246, 1145, 1074, 990, 827, 734厘米${}^{-1}$;电子轰击质谱$\left( {m/z,\text{ relative intensity): }{393}\left( 4\right) ,{339}\left( {13}\right) ,{337}\left( {35}\right) ,{293}}\right)$(36)，254(33)，252(100)，234(45)，208(22)，140(32)，56(58)，41(63)，39(26);高分辨质谱(电子轰击)计算值为${\mathrm{C}}_{20}{\mathrm{H}}_{24}{\mathrm{{NO}}}_{5}{}^{35}\mathrm{{Cl}}$ 393.1343，实测值为393.1348。

(2R,3S)-tert-butyl 2-(4-chlorophenyl)-3-methyl-5-ox-opy-rrolidine-1-carboxylate (8). 7 (112 mg, 0.28 mmol) was dissolved in THF ${\left( 8\mathrm{\;{mL}}\right) }_{1},\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}$ (16 mg, 0.014 mmol,5 mol%), and morpholine (37 mg, 0.42 mmol, 1.5 equiv.) wasere added at room temperature. When the reaction was complete as monitored by TLC, the solution was concentrated under reduced pressure and purified by flash column chromatography with silica gel to afford the pyrrolidine derivative $8\left( {{76}\mathrm{{mg}}\text{ , yield }{86}\% }\right)$ . White solid. mp. 137-139°C $\left( {{\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}}\right)$ . ${}^{1}\mathrm{H}$ NMR (300 MHz, ${\mathrm{{CDCl}}}_{3}$ ) 7.34 (d, $2\mathrm{H}, J = {8.4}\mathrm{\;{Hz}}),{7.17}\left( {\mathrm{\;d},2\mathrm{H}, J = {8.4}\mathrm{\;{Hz}}}\right) ,{4.55}(\mathrm{\;d},1\mathrm{H}, J = \; {5.4}\mathrm{\;{Hz}}),{2.83} - {2.74}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.27} - {2.10}\left( {\mathrm{\;m},2\mathrm{H}}\right) ,{1.25}(\mathrm{\;s}$ , 9H), 1.19 (d, 3H, J = 6.6 Hz); ${}^{13}\mathrm{C}$ NMR (75 MHz, CDCl ${}_{3}$ ) 173.8, 149.2, 140.2, 133.3, 128.8, 126.6, 83.0, 68.6, 39.3, 35.6, 27.5, 18.6; IR (film) 2974, 1785, 1752, 1719, 1492, 1367,1303,1252,1142,1089,1014,807 ${\mathrm{{cm}}}^{-1}$ ; EI-MS $(m/z$ , relative intensity): 309 (5), 253 (25), 236 (15), 209 (60), 174 (93), 140 (100), 138 (62), 56 (20), 41 (22); HRMS (EI) calcd for ${\mathrm{C}}_{16}{\mathrm{H}}_{20}{\mathrm{{NO}}}_{3}\mathrm{{Cl}}{309.1132}$ , found ${309.1135}.{\left\lbrack \alpha \right\rbrack }_{\mathrm{D}}{}^{20} = \; + {35.5}^{ \circ }\left( {c = {0.85}\text{ in }{\mathrm{{CHCl}}}_{3}}\right)$ .

(2R,3S)-叔丁基 2-(4-氯苯基)-3-甲基-5-氧代吡咯烷-1-羧酸酯(8)。将7(112毫克，0.28毫摩尔)溶解于四氢呋喃${\left( 8\mathrm{\;{mL}}\right) }_{1},\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}$(16毫克，0.014毫摩尔，5摩尔%)中，并于室温下加入吗啉(37毫克，0.42毫摩尔，1.5当量)。通过薄层层析监测反应完成后，将溶液减压浓缩，并通过硅胶快速柱色谱法纯化，得到吡咯烷衍生物$8\left( {{76}\mathrm{{mg}}\text{ , yield }{86}\% }\right)$。白色固体。熔点137 - 139°C$\left( {{\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}}\right)$。${}^{1}\mathrm{H}$核磁共振(300兆赫，${\mathrm{{CDCl}}}_{3}$)7.34(双峰，$2\mathrm{H}, J = {8.4}\mathrm{\;{Hz}}),{7.17}\left( {\mathrm{\;d},2\mathrm{H}, J = {8.4}\mathrm{\;{Hz}}}\right) ,{4.55}(\mathrm{\;d},1\mathrm{H}, J = \; {5.4}\mathrm{\;{Hz}}),{2.83} - {2.74}\left( {\mathrm{\;m},1\mathrm{H}}\right) ,{2.27} - {2.10}\left( {\mathrm{\;m},2\mathrm{H}}\right) ,{1.25}(\mathrm{\;s}$，9H)，1.19(双峰，3H，J = 6.6赫兹)；${}^{13}\mathrm{C}$核磁共振(75兆赫，CDCl${}_{3}$)173.8，149.2，140.2，133.3，128.8，126.6，83.0，68.6，39.3，35.6，27.5，18.6；红外光谱(薄膜)2974，1785，1752，1719，1492，1367，1303，1252，1142，1089，1014，807${\mathrm{{cm}}}^{-1}$；电子轰击质谱$(m/z$(相对强度):309(5)，253(25)，236(15)，209(60)，174(93)，140(100)，138(62)，56(20)，41(22)；高分辨质谱(电子轰击)计算值为${\mathrm{C}}_{16}{\mathrm{H}}_{20}{\mathrm{{NO}}}_{3}\mathrm{{Cl}}{309.1132}$，实测值为${309.1135}.{\left\lbrack \alpha \right\rbrack }_{\mathrm{D}}{}^{20} = \; + {35.5}^{ \circ }\left( {c = {0.85}\text{ in }{\mathrm{{CHCl}}}_{3}}\right)$。

(2R,3R)-tert-butyl 2-(4-chlorophenyl)-3-methyl-4-ox-opy-rrolidine-1-carboxylate (9). A solution of8(195 mg,0.46 mmol) and ${\mathrm{{Rh}}}_{2}{\left( \mathrm{{OAc}}\right) }_{4}\left( {2\mathrm{{mg}},{0.0046}\mathrm{{mmol}},1\mathrm{\;{mol}}\% }\right)$ in benzene $\left( {{12}\mathrm{\;{mL}}}\right)$ was heated to reflux. The reflux was continued for about ${10}\mathrm{\;{min}}$ and then the solution was cooled to room temperature. $\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}\left( {{26}\mathrm{{mg}},{0.023}\mathrm{{mmol}},5\mathrm{{mol}}\% }\right)$ and morpholine ( ${60}\mathrm{{mg}},{0.69}\mathrm{{mmol}},{1.5}$ equiv.) were added and the mixture was stirred for about $1\mathrm{\;h}$ under argon. When the reaction was complete as monitored by TLC, the solution was concentrated under reduced pressure and purified by flash column chromatography with silica gel (Petroleum ether : EtOAc = 5/1) to afford the 3-oxo pyrrolidines 9 (120 mg, 84%). ${}^{1}\mathrm{H}$ NMR (300 MHz, CDCl3) 7.33(d, 2H, J = 8.4 $\mathrm{{Hz}}),{7.18}\left( {\mathrm{\;d},2\mathrm{H}, J = {8.4}\mathrm{\;{Hz}}}\right) ,{4.62}\left( {\mathrm{\;d},1\mathrm{H}, J = {4.8}\mathrm{\;{Hz}}}\right) ,{4.06}(\mathrm{\;s}$ , 2H), 2.54-2.45 (m, 1H), 1.30 (s, 9H), 1.26 (d, 3H, J = 7.2 Hz); ${}^{13}\mathrm{C}$ NMR (75 MHz, ${\mathrm{{CDCl}}}_{3}$ ) 211.3, 154.3, 141.4,133.0, 128.8, 126.7, 80.7, 65.8, 53.4, 52.4, 28.0, 13.7; IR (film) 2976, 1759, 1696, 1492, 1391, 1366, 1155, 1089, 1015, 859, 827, 790, ${732},{682}{\mathrm{\;{cm}}}^{-1}$ ; EI-MS (m/z, relative intensity): 309 (4),253 (25), 209 (17), 152 (100), 117 (46), 57 (25); HRMS (EI) calcd for ${\mathrm{C}}_{16}{\mathrm{H}}_{20}{\mathrm{{NO}}}_{3}\mathrm{{Cl}}{309.1132}$ , found 309.1136. ${\left\lbrack \alpha \right\rbrack }_{\mathrm{D}}^{20} = \; + {21.2}^{ \circ }\left( {c = {0.98}\text{ in }{\mathrm{{CHCl}}}_{3}}\right)$ .

(2R,3R)-叔丁基 2-(4-氯苯基)-3-甲基-4-氧代吡咯烷-1-羧酸酯(9)。将8(195毫克，0.46毫摩尔)和${\mathrm{{Rh}}}_{2}{\left( \mathrm{{OAc}}\right) }_{4}\left( {2\mathrm{{mg}},{0.0046}\mathrm{{mmol}},1\mathrm{\;{mol}}\% }\right)$在苯$\left( {{12}\mathrm{\;{mL}}}\right)$中的溶液加热至回流。继续回流约${10}\mathrm{\;{min}}$，然后将溶液冷却至室温。加入$\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}\left( {{26}\mathrm{{mg}},{0.023}\mathrm{{mmol}},5\mathrm{{mol}}\% }\right)$和吗啉(${60}\mathrm{{mg}},{0.69}\mathrm{{mmol}},{1.5}$当量)，混合物在氩气下搅拌约$1\mathrm{\;h}$。通过TLC监测反应完成后，将溶液减压浓缩，并用硅胶进行快速柱色谱纯化(石油醚:乙酸乙酯=5/1)，得到3-氧代吡咯烷9(120毫克，84%)。${}^{1}\mathrm{H}$核磁共振(300兆赫，CDCl3) 7.33(d，2H，J = 8.4$\mathrm{{Hz}}),{7.18}\left( {\mathrm{\;d},2\mathrm{H}, J = {8.4}\mathrm{\;{Hz}}}\right) ,{4.62}\left( {\mathrm{\;d},1\mathrm{H}, J = {4.8}\mathrm{\;{Hz}}}\right) ,{4.06}(\mathrm{\;s}$，2H)，2.54 - 2.45(m，1H)，1.30(s，9H)，1.26(d，3H，J = 7.2赫兹)；${}^{13}\mathrm{C}$核磁共振(75兆赫，${\mathrm{{CDCl}}}_{3}$) 211.3，154.3，141.4，133.0，128.8，126.7，80.7，65.8，53.4，52.4，28.0，13.7；红外光谱(薄膜)2976，1759，1696，1492，1391，1366，1155，1089，1015，859，827，790，${732},{682}{\mathrm{\;{cm}}}^{-1}$；电子轰击质谱(质荷比，相对强度):309(4)，253(25)，209(17)，152(100)，117(46)，57(25)；高分辨质谱(电子轰击)计算值为${\mathrm{C}}_{16}{\mathrm{H}}_{20}{\mathrm{{NO}}}_{3}\mathrm{{Cl}}{309.1132}$，实测值为309.1136。${\left\lbrack \alpha \right\rbrack }_{\mathrm{D}}^{20} = \; + {21.2}^{ \circ }\left( {c = {0.98}\text{ in }{\mathrm{{CHCl}}}_{3}}\right)$。

1.4 Allyl 2-diazo-5-methoxy-3-oxopentanoate(1d)

1.4 烯丙基 2-重氮基-5-甲氧基-3-氧代戊酸酯(1d)

To 1.80 g (45 mmol) of NaH (60% in mineral oil) was added ${10}\mathrm{\;{mL}}$ of dry hexane under a nitrogen atmosphere. The mixture was stirred briefly and allowed to settle, and the hexane was carefully decanted off to remove most of the mineral oil. The NaH was then suspended in ${40}\mathrm{\;{mL}}$ of dry THF and with stirring at ${0}^{ \circ }\mathrm{C}$ . A solution of allyl acetoacetate $\left( {{5.68}\mathrm{\;g},{40}\mathrm{{mmol}}}\right)$ in ${15}\mathrm{\;{mL}}$ of THF was added dropwise over ${0.5}\mathrm{\;h}$ . The mixture was stirred for ${0.5}\mathrm{\;h}$ after the addition and then cooled to $- {25}^{ \circ }\mathrm{C}$ , and ${18}\mathrm{\;{mL}}\left( {{45}\mathrm{{mmol}}}\right)$ solution of $n$ -butyl lithium ( ${2.5}\mathrm{\;{mol}}{\mathrm{\;L}}^{-1}$ in hexane) was added dropwise over 15 min. The mixture was stirred for ${0.5}\mathrm{\;h}$ after the addition, and then a solution of ${6.25}\mathrm{\;g}$ (50 mmol) of bromo (methoxy) methane in ${10}\mathrm{\;{mL}}$ of THF was added slowly. The mixture was stirred at $- {25}^{ \circ }\mathrm{C}$ for $1\mathrm{\;h}$ , and then ${50}\mathrm{\;{mL}}$ of cold $1\mathrm{\;{mol}}{\mathrm{\;L}}^{-1}\mathrm{{HCl}}$ was added slowly, followed by ${50}\mathrm{\;{mL}}$ of ${\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}$ . The phases were separated, and the aqueous layer was extracted again with ${50}\mathrm{\;{mL}}$ of ${\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}$ . The combined organic extract was dried over ${\mathrm{{Na}}}_{2}{\mathrm{{SO}}}_{4}$ , filtered, and concentrated to give the crude product allyl 5-methoxy-3-oxopentanoate which was used in the next step without further purification. This compound was added ${100}\mathrm{\;{mL}}{\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}$ ,4-acetamidobenzenesulfonyl azide (9.60 g,40 mmol) and ${\mathrm{{Et}}}_{3}\mathrm{\;N}{4.04}\mathrm{\;g}\left( {{40}\mathrm{{mmol}}}\right)$ successively. The mixture was stirred overnight. The resulting suspension was filtered and the filter cake was washed with ${\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}$ . The combined filtrate was concentrated and the residue was purified by chromatography (Petroleum ether: EtOAc 10/1) to afford the title compound (4.20 g, 50%) as yellow liquid. (Scheme 2) ${}^{1}\mathrm{H}$ NMR (300 MHz, ${\mathrm{{CDCl}}}_{3}$ ) 6.01-5.88 (m,1H), 5.39-5.28 (m, 2H), 4.75-4.72 (m, 2H), 3.72 (t, 2H, J = 6.0 Hz), 3.36 (s, 3H), 3.14 (t, 2H, J = 6.0 Hz); ${}^{13}\mathrm{C}$ NMR (75 MHz, ${\mathrm{{CDCl}}}_{3}){190.4},{160.8},{131.3},{119.0},{67.2},{65.7},{58.7},{40.0}$ ; IR (film) 2922, 2136, 1716, 1655, 1369, 1302, 1215, 1115, 1071, 997,743 ${\mathrm{{cm}}}^{-1}$ ; EI-MS $(m/z$ , relative intensity): ${169}\left( {10}\right) ,{153} \; \left( {12}\right) ,{143}\left( {12}\right) ,{108}\left( {23}\right) ,{98}\left( {24}\right) ,{85}\left( {43}\right) ,{58}\left( {77}\right) ,{45}\left( {90}\right) ,{40}$ (100), 29 (52), 27 (50); Anal. Calcd for ${\mathrm{C}}_{9}{\mathrm{H}}_{12}{\mathrm{\;N}}_{2}{\mathrm{O}}_{4}$ : C, 50.94; H, 5.70; N, 13.20. Found: C, 51.12; H, 5.71; N, 13.19.

在氮气氛围下，向1.80 g(45 mmol)氢化钠(60%于矿物油中)中加入${10}\mathrm{\;{mL}}$干燥己烷。混合物搅拌片刻后静置，小心倾析出己烷以除去大部分矿物油。然后将氢化钠悬浮于${40}\mathrm{\;{mL}}$干燥四氢呋喃中，并在${0}^{ \circ }\mathrm{C}$搅拌。将$\left( {{5.68}\mathrm{\;g},{40}\mathrm{{mmol}}}\right)$烯丙基乙酰乙酸酯于${15}\mathrm{\;{mL}}$四氢呋喃中的溶液在${0.5}\mathrm{\;h}$内逐滴加入。加完后混合物搅拌${0.5}\mathrm{\;h}$，然后冷却至$- {25}^{ \circ }\mathrm{C}$，并在15分钟内逐滴加入${18}\mathrm{\;{mL}}\left( {{45}\mathrm{{mmol}}}\right)$ $n$ -丁基锂(${2.5}\mathrm{\;{mol}}{\mathrm{\;L}}^{-1}$于己烷中)溶液。加完后混合物搅拌${0.5}\mathrm{\;h}$，然后缓慢加入${6.25}\mathrm{\;g}$(50 mmol)溴(甲氧基)甲烷于${10}\mathrm{\;{mL}}$四氢呋喃中的溶液。混合物在$- {25}^{ \circ }\mathrm{C}$搅拌$1\mathrm{\;h}$，然后缓慢加入${50}\mathrm{\;{mL}}$冷的$1\mathrm{\;{mol}}{\mathrm{\;L}}^{-1}\mathrm{{HCl}}$，接着加入${50}\mathrm{\;{mL}}$的${\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}$。分层，水层再用${50}\mathrm{\;{mL}}$的${\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}$萃取。合并的有机萃取液用${\mathrm{{Na}}}_{2}{\mathrm{{SO}}}_{4}$干燥，过滤并浓缩得到粗产物烯丙基5-甲氧基-3-氧代戊酸酯，直接用于下一步无需进一步纯化。向此化合物中依次加入${100}\mathrm{\;{mL}}{\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}$、4-乙酰氨基苯磺酰叠氮(9.60 g，40 mmol)和${\mathrm{{Et}}}_{3}\mathrm{\;N}{4.04}\mathrm{\;g}\left( {{40}\mathrm{{mmol}}}\right)$。混合物搅拌过夜。所得悬浮液过滤，滤饼用${\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}$洗涤。合并滤液浓缩后，残余物通过柱色谱法(石油醚:乙酸乙酯10/1)纯化，得到标题化合物(4.20 g，50%)，为黄色液体。(方案2)${}^{1}\mathrm{H}$核磁共振(300 MHz，${\mathrm{{CDCl}}}_{3}$)6.01 - 5.88(m，1H)，5.39 - 5.28(m，2H)，4.75 - 4.72(m，2H)，3.72(t，2H，J = 6.0 Hz)，3.36(s，3H)，3.14(t，2H，J = 6.0 Hz)；${}^{13}\mathrm{C}$核磁共振(75 MHz，${\mathrm{{CDCl}}}_{3}){190.4},{160.8},{131.3},{119.0},{67.2},{65.7},{58.7},{40.0}$；红外光谱(薄膜)2922，2136，1716，1655，1369，1302，1215，1115，1071，997，743 ${\mathrm{{cm}}}^{-1}$；电子轰击质谱$(m/z$，相对强度):${169}\left( {10}\right) ,{153} \; \left( {12}\right) ,{143}\left( {12}\right) ,{108}\left( {23}\right) ,{98}\left( {24}\right) ,{85}\left( {43}\right) ,{58}\left( {77}\right) ,{45}\left( {90}\right) ,{40}$(100)，29(52)，27(50)；分析计算值${\mathrm{C}}_{9}{\mathrm{H}}_{12}{\mathrm{\;N}}_{2}{\mathrm{O}}_{4}$:C，50.94；H，5.70；N，13.20。实测值:C，51.12；H，5.71；N，13.19。

2 Results and discussion

2结果与讨论

$N$ -Sulfinylimines 2a-2j have been obtained by condensation of the corresponding aldehydes with $N$ -p-tolylsulfinylamide following the Davis’ protocol [32] with slight modifications in the work-up [33]. Diazo compounds 1a-1e were prepared according to the literature procedures [34-36].

$N$-亚磺酰亚胺2a - 2j是通过相应的醛与$N$-对甲苯亚磺酰胺按照戴维斯方法[32]缩合得到的，后处理略有修改[33]。重氮化合物1a - 1e按照文献方法[34 - 36]制备。

Scheme 2

方案2

Figure 2 $N$ -Sulfinylimines.

图2 $N$-亚磺酰亚胺

As a model study for the optimization of the reaction conditions, we first choose the phenyl $N$ -p-tolylsulfinimine 2a and ethyl 2-diazo-3-oxopentanoate 1a as substrates for test. Initially, we found that dropwise addition of diazo 1a to the mixture of imine 2a and LiHMDS in ethyl ether smoothly at $- {78}^{ \circ }\mathrm{C}$ afforded corresponding $\delta$ -amino- $\alpha$ -diazo-β-carbonyl ester $3\mathrm{a}$ with ${56}\%$ yield and 5.5:1 dr value (Table 1, entry 1). By careful examination we observed that this addition reaction was reversible. Consequently, prolonging reaction time from ${15}\mathrm{\;{min}}$ to $1\mathrm{\;h}$ could not improve the reaction (Table 1, entry 2). To our delight, by increasing the amount of nucleophile the diastereoselectivity could be remarkably improved, while the yield had no obvious change (Table 1, entry 4). Carrying out the reaction at $- {94}^{ \circ }\mathrm{C}$ or prolonging the reaction time afforded similar result (Table 1, entry 5). To our surprise, when diethyl ether was replaced by THF as the solvent, the reaction gave essentially no diastereo-selectivity (Table 1, entry 3). Finally, with mixed solvent (ethyl ether and hexane) the reaction afforded a reasonable yield and moderate dr value (Table 1, entry 6).

作为优化反应条件的模型研究，我们首先选择苯基$N$-对甲苯亚磺酰亚胺2a和2 - 重氮 - 3 - 氧代戊酸乙酯1a作为测试底物。最初，我们发现将重氮化合物1a滴加到乙醚中2a与LiHMDS的混合物中，在$- {78}^{ \circ }\mathrm{C}$时顺利得到相应的$\delta$-氨基 - $\alpha$-重氮-β-羰基酯$3\mathrm{a}$，产率为${56}\%$，非对映选择性为5.5:1(表1，第1项)。通过仔细观察，我们发现该加成反应是可逆的。因此，将反应时间从${15}\mathrm{\;{min}}$延长到$1\mathrm{\;h}$并不能改善反应(表1，第2项)。令我们高兴的是，通过增加亲核试剂的量，非对映选择性可以显著提高，而产率没有明显变化(表1，第4项)。在$- {94}^{ \circ }\mathrm{C}$进行反应或延长反应时间得到类似结果(表1，第5项)。令我们惊讶的是，当用THF代替乙醚作为溶剂时，反应基本没有非对映选择性(表1，第3项)。最后，使用混合溶剂(乙醚和己烷)时，反应产率合理，非对映选择性适中(表1,第6项)。

The ratios of the syn- and anti-3a were determined by integration of the characteristic doublets of the amino proton resonances in the ${}^{1}\mathrm{H}$ NMR of the crude product 3a. In syn-3a the ${\mathrm{H}}^{\mathrm{a}}$ and ${\mathrm{H}}^{\mathrm{b}}$ appear at $\delta$ 5.23 ppm and $\delta$ 4.55, respectively, while in anti-3a they appear at ${\delta 4.83}$ and ${\delta 4.90}$ (Figure 3) [37].

通过对粗产物3a的${}^{1}\mathrm{H}$ NMR中氨基质子共振的特征双峰积分来确定顺式和反式3a的比例。在顺式3a中，${\mathrm{H}}^{\mathrm{a}}$和${\mathrm{H}}^{\mathrm{b}}$分别出现在$\delta$ 5.23 ppm和$\delta$ 4.55处，而在反式3a中它们出现在${\delta 4.83}$和${\delta 4.90}$处(图3)[37]。

Based on the previous studies, we have conceived that the absolute stereochemistry for addition product is controlled by the $N$ -sulfinyl group and can be predicted by a six-membered chairlike transition state [17]. The addition of the $E$ - and $Z$ -enolate of $\mathbf{{1a}}$ to sulfinimines $\mathbf{{2a}}$ results in exclusive re face addition, which affords the syn-3a and anti-3a $\delta$ -amino $\alpha$ -diazo- $\beta$ -carbonyl ester via transition states TS-1 and TS-2, respectively (Scheme 3). The fact that syn-3a is favored in nearly all cases suggests that the $E$ -enolate of $1\mathrm{a}$ is more selectively formed in the above conditions and more reactive toward addition to the sulfinimine than the Z-enolate is. As the 1, 3-axial interacts in TS-2 Z-enolate, TS-1 E-enolate is favored to give the corresponding product syn-3a. As mentioned above, when THF is involved as a solvent, the diastereoselectivity of the reaction is very low (close to 1:1, see Table 1, entry 3). This may be due to non-selective formation of $E$ - and $Z$ -enolate in THF. It has been reported by Davis et al. that $E$ -enolate is favored in LiHMDS/diethyl ether as compared to LiHMDS/ THF [17]. This is consistent with the observation made in this study. Moreover, in the transition structure, ${\mathrm{{Li}}}^{ + }$ plays an important role in forming the relatively ordered chelation structure. The low selectivity observed in THF, which is known to coordinate to ${\mathrm{{Li}}}^{ + }$ , could be the result of the failure of the formation of such ordered chelation structure.

基于先前的研究，我们设想加成产物的绝对立体化学受$N$ -亚磺酰基控制，并且可以通过六元椅状过渡态预测[17]。将$\mathbf{{1a}}$的$E$ -和$Z$ -烯醇锂加成到亚磺酰亚胺$\mathbf{{2a}}$上会导致专一的从Re面加成，分别通过过渡态TS - 1和TS - 2得到顺式-3a和反式-3a $\delta$ -氨基$\alpha$ -重氮-$\beta$ -羰基酯(方案3)。几乎在所有情况下顺式-3a都占优势，这一事实表明在上述条件下$1\mathrm{a}$ 的$E$ -烯醇锂更具选择性地形成，并且比Z -烯醇锂对亚磺酰亚胺加成反应更具活性。由于在TS - 2的Z -烯醇锂中存在1,3 -轴向相互作用，所以TS - 1的E -烯醇锂有利于生成相应产物顺式-3a。如上所述，当使用四氢呋喃作为溶剂时，反应的非对映选择性非常低(接近1:1，见表1，第3项)。这可能是由于在四氢呋喃中$E$ -和$Z$ -烯醇锂的形成缺乏选择性。Davis等人报道，与LiHMDS/四氢呋喃相比，在LiHMDS/乙醚中$E$ -烯醇锂更占优势[17]。这与本研究中的观察结果一致。此外，在过渡结构中，${\mathrm{{Li}}}^{ + }$在形成相对有序的螯合结构中起重要作用。在已知与${\mathrm{{Li}}}^{ + }$配位的四氢呋喃中观察到的低选择性可能是由于未能形成这种有序的螯合结构。

Next, we proceeded to explore the scope of this addition reaction (Table 2). The reaction proceeded with a high degree of stereo-control and moderate yields with various aryl substituted $N$ -sulfinyl imines (2a-2j). The substituents on the aromatic ring had little influence on the reaction. Both electron-donating and electron-withdrawing groups gave similar results. Based on the similarity of the ${}^{1}\mathrm{H}$ NMR spectra, it was concluded that all the reactions gave the major products with syn selectivity.

接下来，我们着手探索该加成反应范围(表2)。该反应在各种芳基取代的$N$ -亚磺酰亚胺(2a - 2j)中以高度的立体控制和中等产率进行。芳环上的取代基对反应影响很小。供电子基团和吸电子基团都给出了相似的结果。基于${}^{1}\mathrm{H}$ NMR光谱的相似性，得出所有反应都给出了具有顺式选择性的主要产物。

Figure 3 Determination of dr value by ${}^{1}\mathrm{H}$ NMR.

图3通过${}^{1}\mathrm{H}$ NMR测定dr值。

Table 1 Optimization of reaction conditions

表1反应条件的优化

a) Isolated yield. b) Ratio was determined by ${}^{1}\mathrm{H}$ NMR (300 MHz) of the crude product.

a)分离产率。b)比例通过粗产物的${}^{1}\mathrm{H}$ NMR(300 MHz)确定。

Scheme 3

方案3

We further attempted to explore diazo compounds $\mathbf{{1b}} - \mathbf{{1d}}$ as the substrates (Scheme 4). In the case of ethyl $\gamma$ -substituted of $\alpha$ -diazoacetoacetate $\mathbf{{1b}}$ , the addition reaction can proceed smoothly, giving corresponding product 4b in 58% yield and $\mathrm{{dr}} > {19} : 1$ . However, in the cases of $\alpha$ -diazoacetoacetates 1c and 1d, the reaction could not occur, presumably due to the steric bulky of the substituents.

我们进一步尝试探索将重氮化合物$\mathbf{{1b}} - \mathbf{{1d}}$用作底物(方案4)。对于乙基$\gamma$-取代的$\alpha$-重氮乙酰乙酸酯$\mathbf{{1b}}$，加成反应能够顺利进行，以58%的产率得到相应产物4b和$\mathrm{{dr}} > {19} : 1$。然而，对于$\alpha$-重氮乙酰乙酸酯1c和1d，反应无法发生，推测是由于取代基的空间位阻较大。

Finally, we synthesized 4,5-disubsitituted 2-oxo and 3-oxo pyrrolidines diastereoselectively by using our newly developed methodology (Scheme 5). Starting from chiral $N$ - sulfinyl imine 2b, addition of lithium enolate with allyl 2-diazo-3-oxopentanoate 1e to it gave the corresponding product 5 in 60% yield and 10:1 dr value. Because $N$ -sulfinyl group was not compatible with the photochemical condition according to our previous study [31], 5 was converted to $N$ -Boc protected diazo compound 6 before photolysis. With compound 6 in hand, we proceeded to convert these chiral diazo compounds to 2-oxo and 3-oxo pyrrolidines by the reaction sequence that we have been reported previously. First, photolysis by high-pressure Hg lamp $\left( {\lambda > {300}\mathrm{\;{nm}}}\right)$ was carried out, and the diazo compound 6 underwent Wolff rearrangement to form ketene intermediate [38-41], which was followed by intramolecular nucleophilic attack by the amino group, affording 2-oxo- 3-allyloxycarbonyl pyrrolidine 7 in excellent yield. However, the diastereoselectivity of this reaction was poor due to the easy epimerization at C3. Consequently, the ally-loxycarbonyl was removed by Pd(0)-catalyzed reaction [42,43] and 4,5-disubstituted 2-oxo pyrrolidine 8 was obtained.

最后，我们使用新开发的方法(方案5)非对映选择性地合成了4,5-二取代的2-氧代和3-氧代吡咯烷。从手性$N$-亚磺酰亚胺2b开始，将烯醇锂与烯丙基2-重氮-3-氧代戊酸酯1e加成，得到相应产物5，产率为60%，非对映体比例为10:1。根据我们之前的研究[31]，由于$N$-亚磺酰基与光化学条件不兼容，因此在光解之前将5转化为$N$-Boc保护的重氮化合物6。得到化合物6后，我们按照之前报道的反应顺序将这些手性重氮化合物转化为2-氧代和3-氧代吡咯烷。首先，用高压汞灯$\left( {\lambda > {300}\mathrm{\;{nm}}}\right)$进行光解，重氮化合物6发生沃尔夫重排形成烯酮中间体[38 - 41]，随后氨基进行分子内亲核进攻，以优异的产率得到2-氧代-3-烯丙氧基羰基吡咯烷7。然而，由于C3位容易发生差向异构化，该反应的非对映选择性较差。因此，通过钯(0)催化的反应[42,43]除去烯丙氧基羰基，得到4,5-二取代的2-氧代吡咯烷8。

Table 2 Reaction scope

表2反应范围

a) Isolated yield after chromatography. b) Ratio was determined by ${}^{1}\mathrm{H}$ NMR (400 MHz) of the crude product.

a) 柱色谱分离后的产率。b) 比例通过粗产物的${}^{1}\mathrm{H}$核磁共振(400兆赫)确定。

Scheme 4

方案4

Scheme 5

方案5

On the other hand, $N$ -Boc protected $\delta$ -amino diazo compound6was subjected to ${\mathrm{{Rh}}}_{2}{\left( \mathrm{{OAc}}\right) }_{4}$ catalysis, and the expected intramolecular $\mathrm{N} - \mathrm{H}$ insertion product was obtained as a mixture of diastereoisomers and tautomers. The mixture was further catalyzed with $\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}$ to remove the alloxycarbonyl group. 4-Methyl-5-(4-chlorophenyl) disubstituted 3-oxo pyrrolidine 9 was thus obtained in 84% overall yield from 6 .

另一方面，将$N$-Boc保护的$\delta$-氨基重氮化合物6进行${\mathrm{{Rh}}}_{2}{\left( \mathrm{{OAc}}\right) }_{4}$催化，得到预期的分子内$\mathrm{N} - \mathrm{H}$插入产物，为非对映异构体和互变异构体的混合物。用$\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}$进一步催化该混合物以除去脲羰基。由此从6以84%的总收率得到4-甲基-5-(4-氯苯基)二取代的3-氧代吡咯烷9。

3 Conclusions

3 结论

In summary, the highly diastereoselective addition of lithium enolate of $\gamma$ -substituted $\alpha$ -diazoacetoacetate to $N$ -sulfi-nylimines has been achieved to afford $\delta - N$ -sulfinylamino $\alpha$ - diazo- $\beta$ -ketoesters. Two chiral carbon centers were formed selectively in one step. The chiral $\delta - N$ -sulfinylamino $\alpha$ -diazo $\beta$ -ketoesters can be easily converted into 4,5-disubstituted 2-oxo and 3-oxo pyrrolidines.

总之，已实现将$\gamma$ -取代的$\alpha$ -重氮乙酰乙酸酯的烯醇锂对$N$ -亚磺酰亚胺进行高度非对映选择性加成，得到$\delta - N$ -亚磺酰氨基$\alpha$ -重氮$\beta$ -酮酯。一步中选择性地形成了两个手性碳中心。手性$\delta - N$ -亚磺酰氨基$\alpha$ -重氮$\beta$ -酮酯可轻松转化为4,5 -二取代的2 -氧代和3 -氧代吡咯烷。

This paper is dedicated to Professor LIU YouCheng on the occasion of his 90th birthday. This work was supported by the National Natural Science Foundation of China (20832002, 20772003, 20821062), the Ministry of Education of the People’s Republic of China, and National Basic Research Program of China (2009CB825300).

本文谨献给刘有成教授九十华诞。本工作得到了中国国家自然科学基金(20832002、20772003、20821062)、中华人民共和国教育部以及中国国家基础研究计划(2009CB825300)的支持。

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