CN102516217B - 手性二氢色原酮骨架化合物及不对称合成 - Google Patents

手性二氢色原酮骨架化合物及不对称合成 Download PDF

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CN102516217B
CN102516217B CN201110420499.8A CN201110420499A CN102516217B CN 102516217 B CN102516217 B CN 102516217B CN 201110420499 A CN201110420499 A CN 201110420499A CN 102516217 B CN102516217 B CN 102516217B
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陈应春
李俊龙
蕫琳
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Sichuan University
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Abstract

本发明提供了一种制备含有多手性中心二氢色原酮骨架化合物的合成方法。该方法是一种能有效利用手性胺--特别是a,a-二芳基脯胺醇O-硅醚--催化色酮缺电子二烯化合物和烯醛在温和反应条件下发生高区域选择性、高立体选择性的不对称反电子需求的Diels-Alder反应及串联插烯Aldol或串联半缩醛化反应，用于合成一类具有多手性中心二氢色原酮骨架的化合物。该不对称合成方法为首次报道并具有多种优越性，例如催化剂廉价易得、催化活性高、反应条件温和、操作简单、底物适用范围广、产物区域和对映选择性高，更重要的是通过该方法学制备的各类含有二氢色原酮骨架化合物可能具有特殊生理活性或成为天然产物的重要合成中间体。

Description

手性二氢色原酮骨架化合物及不对称合成
技术领域
本发明设计一种由手性胺催化的色酮缺电子二烯化合物和烯醛在温和反应条件下发生高区域选择性、高立体选择性的不对称的反电子需求的Diels-Alder反应及串联插烯Aldol或串联半缩醛化反应，用于合成一类具有多手性中心二氢色原酮骨架的化合物。该类手性化合物可能具有多种特殊生理活性或成为天然产物的重要合成中间体。
背景技术
二氢色原酮骨架，尤其是基于此类骨架的三环和多环化合物广泛存在于天然产物及药物中间体中，鉴于这类化合物在医药学上的的重要作用，已经引起越来越多的化学家的兴趣。近年来来，对此类化合物的取代基修饰，结构类似物的合成及其生物活性的研究成为了研究热点。[a) S. Bräse, A. Encinas, J. Keck, C. F. Nising, Chem. Rev. 2009, 109, 3903; b) W. Zhang, K. Krohn, Z. Ullah, U. Flörke, G. Pescitelli, L. Di Bari, S. Antus, T. Kurtán, J. Rheinheimer, S. Draeger, B. Schulz, Chem. Eur. J. 2008, 14, 4913; c) C. A. Parish, et al. J. Am. Chem. Soc. 2008, 130, 7060; d) J. S. E. Holker, E. O’Brien, T. J. Simpson, J. Chem. Soc. Perkin Trans. 1 1983, 1365; e) J. C. Liermann, H. Kolshorn, T. Opatz, E. Thines, H. Anke, J. Nat. Chem. 2009, 72, 1905; f) M. M. Wagenaar, J. Clardy, J. Nat. Chem. 2001, 64, 1006.]。近五年来，通过色酮缺电子二烯化合物合成此类三环产物及其它更多有用化合物已经有大量文献报道[ (a) A.-T. Dang, D. O. Miller, L. N. Dawe, G. J. Bodwell, Org. Lett. 2008, 10, 233. b) S. Kumar, B. K. Singh, A. K. Pandey, A. Kumar, S. K. Sharma, H. G. Raj, A. K. Prasad, E. Van der Eycken, V. S. Parmar, B. Ghosh, Biorg. Med. Chem. 2007, 15, 2952; c) T. Patonay, A. Kiss-Szikszai, V. M. L. Silva, A. M. S. Silva, D. C. G. A. Pinto, J. A. S. Cavaleiro, J. Jek, Eur. J. Org. Chem. 2008, 1937; d) J. Gong, F. Xie, H. Chen, Y. Hu, Org. Lett. 2010, 12, 3848; e) H. Chen, F. Xie, J. Gong, Y. Hu, J. Org. Chem. 2011, 76, 8495; f) D. Kim, S. Hong, Org. Lett. 2011, 13, 4466. ]。但是，通过不对称催化此类缺电子二烯制备手性二氢色原酮三环化合物还几乎没有文献报道，尤其是通过绿色环保的有机小分子催化方式更是没有相关报道。因此，发展一种操作简便，环境友好，而且高对映选择性的合成一种具有取代二氢色原酮骨架多样性且具有潜在药用活性的手性化合物库的方法有着重要的意义。
发明内容
本发明的目的是提供一种具有多种潜在生物学活性的二氢色原酮骨架多环化合物的合成方法。
本发明的另一个目的是提供一系列光学纯的具有多种潜在活性的二氢色原酮骨架多环化合物。
本发明的二氢色原酮骨架多环化合物，是具有如下结构的几类手性化合物：
Figure 992223DEST_PATH_IMAGE001
，其中*为手性碳原子。其中*为手性碳原子。R1任意选自C1-C16的烷基、芳杂环或者
Figure 918591DEST_PATH_IMAGE002
取代的芳环，其中R1、R2、R3、R4或R5任意选自H、F、Cl、Br、C1-C16的烃氧基、C1-C16的烷基，R2、R3、R4、R5选自H、 C1-C16的烷基或者芳基，R6、R7、R8、R9任意选自H、F、Cl、Br、C1-C16的烃氧基、C1-C16的烷基或者芳基；
Figure 393348DEST_PATH_IMAGE003
，其中*为手性碳原子。R1任意选自具有吸电子效应的官能团（例如酯基、氰基、砜基、硝基），R2、R3、R4、R5选自H，C1-C16的烷基或者芳基，R6、R7、R8、R9任意选自H、F、Cl、Br、C1-C16的烃氧基、C1-C16的烷基或者芳基；
Figure 887915DEST_PATH_IMAGE004
，其中*为手性碳原子。R1任意选自C1-C16的烷基或者芳基，R2任意选自氮、氧等杂原子或氮、氧被保护基保护的官能团，其中保护基可以是苄基、甲烷磺酰基，对甲基苯磺酰胺基，对硝基苯磺酰胺基等， R3、R4、R5选自H、C1-C16的烷基或者芳基，R6、R7、R8、R9任意选自H、F、Cl、Br、C1-C16的烃氧基、C1-C16的烷基或者芳基。
本发明的二氢色原酮骨架多环化合物是以色酮缺电子二烯化合物和烯醛为原料，在有机溶剂的存在下，以手性alfa,alfa-二芳基脯胺醇硅醚作为催化剂进行反电子需求的Diels-Alder反应或串联Diels-Alder/插烯Aldol、串联Diels-Alder/半缩醛化反应。可用如下反应通式表示：
Figure 686106DEST_PATH_IMAGE005
该反应的进一步描述是在有机溶剂中和温度在25oC，以色酮缺电子二烯化合物和烯醛为原料，以alfa,alfa-二芳基脯胺醇硅醚作为催化剂进行反电子需求的Diels-Alder反应或串联Diels-Alder/插烯Aldol、串联Diels-Alder/半缩醛化反应24到48小时不等。其中所述的色酮缺电子二烯化合物、烯醛、手性alfa,alfa-二芳基脯胺醇硅醚、酸性添加剂的摩尔比为1:2:0.2:0.2。
色酮缺电子二烯化合物的结构式为：
Figure 557110DEST_PATH_IMAGE006
，其中：R1任意选H、C1-C16的烷基或者
Figure 898093DEST_PATH_IMAGE007
取代的芳环，其中R3、R4、R5、R6或R7任意选自H、F、Cl、Br、C1-C16的烃氧基，C1-C16的烷基，R2任意选自C1-C16的烷基、具有吸电子效应的官能团（例如酯基、氰基、砜基、硝基）、芳杂环或者
Figure 422615DEST_PATH_IMAGE007
取代的芳环，R3、R4、R5、R6或R7任意选自H、F、Cl、Br、C1-C16的烃氧基，C1-C16的烷基；烯醛的结构式为：
Figure 849048DEST_PATH_IMAGE008
其中，R3、R4、R5任意选自H或者C1-C16的烷基或者
Figure 992585DEST_PATH_IMAGE007
取代的芳环，其中R3、R4、R5、R6或R7任意选自H、F、Cl、Br、C1-C16的烃氧基；催化剂的结构通式为(为任意光学纯的结构，不受图示所限)：
Figure 312708DEST_PATH_IMAGE009
，其中: R1 、R2任意选自H、CH3、tBu、OCH3, R3任意选自TMS、TES、TBS，R4任意选自H, OTBS。
酸性添加剂任意选自质子酸。
本发明所提到的烷基，烃氧基等，除非另外说明，均推荐为碳数为1-16的基团，进一步推荐碳数为1-10的基团，尤其推荐碳数为1-4的基团. 本发明所提到的芳基，除非另外说明，均指苯基或萘基，推荐为苯基，所述的杂环为C5-C10的含N，O，S的杂环基。
本发明中所述水为蒸馏水，所述有机溶剂可以是极性溶剂或非极性溶剂，如：苯、甲苯、二氯甲烷、氯仿、乙腈、1,4-二氧六环、四氢呋喃、石油醚、乙酸乙酯等。
采用本发明所制得的产物可以经过柱层析的方法加以分离。所用的展开剂和洗脱剂为极性溶剂和非极性溶剂的混合溶剂。推荐溶剂：石油醚/乙酸乙酯。
本发明提供了一种有效的以手性的a,a-二芳基脯胺醇硅醚作为催化剂，由色酮缺电子二烯化合物和烯醛为原料，高效率、高立体选择性的合成一种具有多种潜在活性的二氢色原酮骨架多环化合物的方法。该方法催化剂易得，催化活性高，反应条件温和，操作简单，底物适用范围广，产物结构多样，原子经济性好，具有环境友好性，收率可达中等到很好（最高可到93% yield），非对映选择性较高（大于95% de），对映选择性高（一般为90%-98% ee）。
本发明所得到的具有多取代的二氢色原酮骨架多环化合物可以用于合成如下结构的化合物：
1，
Figure 414656DEST_PATH_IMAGE010
，其中R1任意选自C1-C16的烷基或者芳基，其中 R2、R3任意选自H、C1-C16的烷基或者芳基，R4、R5、R6、R7任意选自H、F、Cl、Br、C1-C16的烃氧基、C1-C16的烷基或者芳基，可用如下方程式表示：
Figure 328385DEST_PATH_IMAGE011
2，
Figure 134667DEST_PATH_IMAGE012
，其中R1任意选自具有吸电子效应的官能团（例如酯基、氰基、砜基、硝基），R2、R3任意选自H、C1-C16的烷基或者芳基，R4、R5、R6、R7任意选自H、F、Cl、Br、C1-C16的烃氧基、C1-C16的烷基或者芳基，可用如下方程式表示：
Figure 450242DEST_PATH_IMAGE013
具体实施方式
通过下述实施例将有助于理解本发明，但并不限制本发明的内容。
实施例1：a,a-二芳基脯胺醇硅醚催化的色酮缺电子二烯化合物和烯醛的不对称反电子需求Diels-Alder反应及串联反应。
在一干净的反应管中，依次加入手性脯胺醇硅醚催化剂（0. 02mmol），色酮缺电子二烯化合物（0.1mmol），烯醛（0.2mmol），酸性添加剂（0.02 mmol）和1,4-二氧六环（1 mL），在25oC下搅拌反应相应的时间，TLC监测反应结束后，减压回收溶剂，剩余物通过柱层析分离得到目标产物。
Figure 191933DEST_PATH_IMAGE014
P1, 89% yield, 94% ee, 手性测试条件：HPLC analysis on Chiralpak IC column (20% 2-propanol/n-hexane, 1 mL/min), UV 220 nm, tmajor = 23.47 min, tminor = 25.67 min. [α]D 20 = -21.3 (c = 0.79 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.01 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.52 (td, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.30 (s, 1H), 7.09 (t, J = 8.0 Hz, 1H), 6.97 (d, J = 8.4 Hz, 1H), 4.59 (d, J = 7.6 Hz, 1H), 4.36 (dd, J = 10.0 Hz, J = 3.2 Hz, 1H), 4.20 (q, J = 7.2 Hz, 2H), 2.21 (dd, J = 13.6 Hz, J = 8.0 Hz, 1H), 2.06-1.99 (m, 1H), 1.54 (dd, J = 14.0 Hz, J = 3.2 Hz, 1H), 1.49 (s, 3H), 1.40 (dt, J = 13.6 Hz, J = 3.2 Hz, 1H), 1.32 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 192.8, 164.7, 161.0, 142.6, 136.2, 134.5, 128.0, 122.1, 119.7, 117.8, 77.9, 67.3, 60.6, 55.4, 46.9, 40.5, 37.3, 22.6, 14.1 ppm; 高分辨质谱计算值：C19H20O5+Na 351.1208, 实测值：351.1207.
Figure 717593DEST_PATH_IMAGE015
P2 ，88% yield, 96% ee, 手性测试条件：HPLC analysis on Chiralpak IC column (20% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tmajor = 25.09 min, tminor = 27.84 min. [α]D 20 = -15.2 (c = 0.90 in CHCl3); 1H NMR (400 MHz, CDCl3): 7.81 (s, 1H), 7.33 (dd, J = 8.4 Hz, J = 2.0 Hz, 1H), 7.30 (s, 1H), 6.88 (d, J = 8.4 Hz, 1H), 4.58 (d, J = 6.8 Hz, 1H), 4.33 (dd, J = 10.0 Hz, J = 2.8 Hz, 1H), 4.20 (q, J = 7.2 Hz, 2H), 2.34 (s, 3H ), 2.21 (dd, J = 13.6 Hz, J = 8.4 Hz, 1H), 2.05-1.98 (m, 1H), 1.54 (dd, J = 14.0 Hz, J = 3.2 Hz, 1H), 1.50 (s, 3H), 1.40 (dt, J = 13.6 Hz, J = 2.8 Hz, 1H), 1.33 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 193.1, 164.7, 159.2, 142.8, 137.4, 134.6, 131.7, 127.6, 119.4, 117.6, 77.9, 67.5, 60.6, 55.5, 47.0, 40.6, 37.3, 22.6, 20.4, 14.2 ppm; 高分辨质谱计算值：C20H22O5+H 343.1545, 实测值：343.1546.
Figure 202932DEST_PATH_IMAGE016
P3 ，67% yield, 90% ee, 手性测试条件：HPLC analysis on Chiralpak OD column (10% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tminor = 18.12 min, tmajor = 20.51 min. [α]D 20 = -15.5 (c = 0.60 in CHCl3); 1H NMR (400 MHz, CDCl3): = 7.95 (d, J = 8.8 Hz, 1H), 7.29 (s, 1H), 6.65 (dd, J = 8.8 Hz, J = 2.4 Hz, 1H), 6.42 (d, J = 2.4 Hz, 1H), 4.55 (d, J = 7.6 Hz, 1H), 4.34 (dd, J = 10.0 Hz, J = 3.2 Hz, 1H), 4.20 (q, J = 7.2 Hz, 2H), 3.85 (s, 3H ), 2.18 (dd, J = 13.6 Hz, J = 8.4 Hz, 1H), 2.06-1.99 (m, 1H), 1.54-1.50 (m, 4H), 1.41 (dt, J = 13.6 Hz, J = 3.2 Hz, 1H), 1.32 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): = 191.7, 166.2, 164.7, 163.1, 142.5, 134.8, 129.7, 113.6, 110.7, 100.7, 78.2, 67.5, 60.6, 55.7, 55.1, 46.8, 40.5, 37.3, 22.6, 14.2 ppm; 高分辨质谱计算值：C20H22O6+H 381.1314, 实测值：381.1315.
Figure 232068DEST_PATH_IMAGE017
P4 ，92% yield, 90% ee, 手性测试条件： HPLC analysis on Chiralpak IC column (20% 2-propanol/n-hexane, 1 mL/min), UV 220 nm, tmajor = 19.51 min, tminor = 21.85 min. [α]D 20 = -18.2 (c = 1.17 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.04 (dd, J = 8.8 Hz, J = 6.4 Hz, 1H), 7.27 (d, J = 1.6 Hz, 1H), 6.82 (td, J = 8.8 Hz, J = 2.4 Hz, 1H), 6.67 (dd, J = 10.0 Hz, J = 2.4 Hz, 1H), 4.56 (dd, J = 8.0 Hz, J = 2.4 Hz, 1H), 4.37 (dd, J = 10.4 Hz, J = 3.2 Hz, 1H), 4.20 (q, J = 7.2 Hz, 2H), 2.22 (dd, J = 13.6 Hz, J = 8.4 Hz, 1H), 2.07-2.00 (m, 1H), 1.54 (dd, J = 13.6 Hz, J = 3.2 Hz, 1H), 1.50 (s, 3H), 1.41 (dt, J = 13.6 Hz, J = 3.2 Hz, 1H), 1.32 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 191.5, 168.8, 166.2, 164.6, 162.8, 142.9, 134.0, 130.6, 110.7, 110.5, 104.8, 104.6, 78.5, 67.4, 60.7, 55.2, 47.0, 40.4, 37.3, 22.6, 14.1 ppm; 高分辨质谱计算值：C19H19FO5+H 347.1295, 实测值：347.1286.
Figure 675818DEST_PATH_IMAGE018
P5 ，86% yield, 94% ee, 手性测试条件：HPLC analysis on Chiralpak OD column (10% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tminor = 10.95 min, tmajor = 13.87 min. [α]D 20 = -43.8 (c = 0.72 in CHCl3); 1H NMR (400 MHz, CDCl3): 7.96 (d, J = 2.4 Hz, 1H), 7.45 (dd, J = 8.8 Hz, J = 2.4 Hz, 1H), 7.27 (s, 1H), 6.95 (d, J = 8.8 Hz, 1H), 4.55-4.54 (m, 1H), 4.35 (dd, J = 10.0 Hz, J = 3.2 Hz, 1H), 4.20 (q, J = 7.2 Hz, 2H), 2.22 (dd, J = 13.6 Hz, J = 8.4 Hz, 1H), 2.06-1.99 (m, 1H), 1.54 (dd, J = 13.6 Hz, J = 3.2 Hz, 1H), 1.50 (s, 3H), 1.41 (dt, J = 13.6 Hz, J = 3.2 Hz, 1H), 1.33 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 191.6, 164.6, 159.5, 143.0, 136.0, 133.8, 127.6, 127.3, 120.6, 119.5, 78.3, 67.3, 60.7, 55.2, 47.1, 40.4, 37.4, 22.5, 14.2 ppm; 高分辨质谱计算值：C19H19ClO5+H 363.0999, 实测值：363.0997.
Figure 32981DEST_PATH_IMAGE019
P6 ，71% yield, 88% ee, 手性测试条件：HPLC analysis on Chiralpak OD column (20% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tminor = 6.89 min, tmajor = 8.46 min. [α]D 20 = -23.1 (c = 1.30 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.11 (s, 1H), 7.59 (dd, J = 8.8 Hz, J = 2.4 Hz, 1H), 7.27 (s, 1H), 6.89 (d, J = 8.8 Hz, 1H), 4.55 (dd, J = 8.4 Hz, J = 2.4 Hz, 1H), 4.35 (dd, J = 10.0 Hz, J = 2.8 Hz, 1H), 4.20 (q, J = 7.2 Hz, 2H), 2.22 (dd, J = 13.6 Hz, J = 8.0 Hz, 1H), 2.06-1.99 (m, 1H), 1.54 (dd, J = 14.0 Hz, J = 3.2 Hz, 1H), 1.50 (s, 3H), 1.41 (dt, J = 13.6 Hz, J = 3.2 Hz, 1H), 1.32 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 191.6, 164.6, 159.9, 143.0, 138.8, 133.8, 130.4, 121.1, 119.9, 114.8, 78.2, 67.3, 60.7, 55.2, 47.0, 40.4, 37.4, 22.5, 14.2 ppm; 高分辨质谱计算值：C19H19BrO5+H 407.0494 (79Br), 409.0474 (81Br), 实测值：407.0495, 409.0483.
P7 ，74% yield, 94% ee, 手性测试条件： HPLC analysis on Chiralpak OD column (10% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tminor = 11.45 min, tmajor = 15.48 min. [α]D 20 = -18.6 (c = 0.87 in CHCl3); 1H NMR (400 MHz, CDCl3): 7.84 (s, 1H), 7.27 (s, 1H), 7.24 (s, 1H), 4.55 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 4.33 (dd, J = 10.0 Hz, J = 2.8 Hz, 1H), 4.20 (q, J = 7.2 Hz, 2H), 2.38 (s, 3H), 2.21 (dd, J = 13.6 Hz, J = 8.4 Hz, 1H), 2.05-1.98 (m, 1H), 1.52 (dd, J = 14.0 Hz, J = 2.8 Hz, 1H), 1.49 (s, 3H), 1.40 (dt, J = 13.6 Hz, J = 2.8 Hz, 1H), 1.32 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 192.3, 164.6, 159.1, 142.9, 134.1, 133.4, 132.1, 128.7, 121.6, 118.7, 78.3, 67.4, 60.7, 55.4, 47.0, 40.5, 37.4, 22.6, 21.9, 14.2 ppm; 高分辨质谱计算值：C20H21BrO5+Na 443.0470 (79Br), 445.0450 (81Br), 实测值：443.0473, 445.0470.
Figure 471233DEST_PATH_IMAGE021
P8 ，72% yield, 82% ee, 手性测试条件：HPLC analysis on Chiralpak AD column (20% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tminor = 8.95 min, tmajor = 12.47 min. [α]D 20 = -34.0 (c = 2.00 in CHCl3); 1H NMR (400 MHz, CDCl3): 11.71 (s, 1H), 7.39 (t, J = 8.0 Hz, 1H), 7.25 (s, 1H), 6.57 (d, J = 8.4 Hz, 1H), 6.44 (d, J = 8.0 Hz, 1H), 4.62 (d, J = 6.8 Hz, 1H), 4.33 (dd, J = 10.0 Hz, J = 2.8 Hz, 1H), 4.21 (q, J = 7.2 Hz, 2H), 2.23 (dd, J = 13.6 Hz, J = 8.0 Hz, 1H), 2.04-1.98 (m, 1H), 1.52 (dd, J = 14.0 Hz, J = 3.2 Hz, 1H), 1.50 (s, 3H), 1.40 (dt, J = 14.0 Hz, J = 3.2 Hz, 1H), 1.33 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 198.9, 164.6, 162.8, 161.0, 143.1, 138.3, 133.4, 110.2, 107.4, 107.0, 77.6, 68.1, 60.8, 55.2, 47.1, 40.2, 37.4, 22.6, 14.2 ppm; 高分辨质谱计算值：C19H20O6+Na 367.1158, 实测值：367.1157.
Figure 944940DEST_PATH_IMAGE022
P9 ，93% yield, 97% ee, 手性测试条件：HPLC analysis on Chiralpak IA column (10% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tmajor = 17.04 min, tminor = 19.23 min. [α]D 20 = -46.9 (c = 1.76 in CHCl3); 1H NMR (400 MHz, CDCl3): 9.54 (d, J = 8.8 Hz, 1H), 7.95 (d, J = 9.2 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.67 (t, J = 7.2 Hz, 1H), 7.46 (t, J = 7.2 Hz, 1H), 7.42 (s, 1H), 7.08 (d, J = 9.2 Hz, 1H), 4.60 (d, J = 6.4 Hz, 1H), 4.45 (dd, J = 10.0 Hz, J = 3.2 Hz, 1H), 4.21 (q, J = 7.2 Hz, 2H), 2.18 (dd, J = 13.6 Hz, J = 8.0 Hz, 1H), 2.07-2.01 (m, 1H), 1.59 (dd, J = 13.6 Hz, J = 3.2 Hz, 1H), 1.51 (s, 3H), 1.42 (dt, J = 13.6 Hz, J = 3.2 Hz, 1H), 1.33 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 194.2, 164.7, 163.4, 142.2, 137.8, 135.3, 131.8, 129.9, 129.5, 128.5, 125.9, 125.1, 118.4, 111.4, 77.7, 67.8, 60.6, 55.6, 46.9, 40.4, 37.2, 22.6, 14.2 ppm; 高分辨质谱计算值：C23H22O5+H 379.1545, 实测值：379.1546.
Figure 54978DEST_PATH_IMAGE023
P10, 90% yield, 94% ee, 手性测试条件：HPLC analysis on Chiralpak OD column (20% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tmajor = 13.43 min, tminor = 17.43 min. [α]D 20 = -56.4 (c = 1.85 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.03 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.55-7.51 (m, 1H), 7.38-7.26 (m, 5H), 7.20 (s, 1H), 7.10 (t, J = 8.0 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 4.71 (d, J = 8.0 Hz, 1H), 4.51 (dd, J = 10.0 Hz, J = 2.8 Hz, 1H), 3.87 (q, J = 7.2 Hz, 2H), 2.66-2.56 (m, 2H), 2.28 (br s, 1H), 1.98-1.93 (m, 2H), 0.91 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 192.4, 165.7, 161.0, 145.3, 143.0, 136.2, 132.0, 128.3, 128.0, 126.8, 126.2, 122.2, 119.7, 117.8, 77.8, 67.3, 60.6, 55.5, 45.4, 44.7, 39.3, 13.5 ppm; 高分辨质谱计算值：C24H22O5+H 391.1545, 实测值：391.1544.
P11 ，82% yield, 86% ee, 手性测试条件：HPLC analysis on Chiralpak OD column (20% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tmajor = 18.54 min, tminor = 35.13 min. [α]D 20 = -38.5 (c = 1.30 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.04 (d, J = 7.6 Hz, 1H), 7.55-7.51 (m, 1H), 7.22 (d, J = 8.8 Hz, 2H), 7.18 (s, 1H), 7.11 (t, J = 7.6 Hz, 1H), 6.99 (d, J = 8.0 Hz, 1H), 6.90 (d, J = 8.8 Hz, 2H), 4.71 (d, J = 7.2 Hz, 1H), 4.51 (dd, J = 10.0 Hz, J = 2.8 Hz, 1H), 3.91 (q, J = 7.2 Hz, 2H), 3.81(s, 3H), 2.63-2.55 (m, 2H), 2.22 (br s, 1H), 1.94-1.90 (m, 2H), 0.98 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 192.6, 165.6, 161.1, 158.3, 145.6, 136.3, 134.9, 131.7, 128.1, 127.3, 122.3, 119.8, 117.9, 113.6, 77.9, 67.4, 60.7, 55.5, 55.2, 45.6, 44.1, 39.5, 13.8 ppm; 高分辨质谱计算值：C25H24O6+Na 443.1471, 实测值：443.1472.
Figure 761214DEST_PATH_IMAGE025
P12, 76% yield, 97% ee, 手性测试条件：HPLC analysis on Chiralpak OD column (20% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tmajor = 7.46 min, tminor = 13.07 min. [α]D 20 = -25.1 (c = 0.59 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.01 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.51 (td, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.22 (s, 1H), 7.08 (t, J = 8.0 Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 4.58 (dd, J = 8.0 Hz, J = 2.4 Hz, 1H), 4.28-4.18 (m, 2H), 3.85 (d, J = 3.2 Hz, 1H), 2.81-2.78 (m, 1H), 2.16-2.12 (m, 1H), 1.85 (d, J = 13.2 Hz, 1H), 1.74-1.72 (m, 2H), 1.59 (dt, J = 12.8 Hz, J = 3.6 Hz, 1H), 1.42 (dd, J = 13.6 Hz, J = 2.8 Hz, 1H), 1.33 (t, J = 7.6 Hz, 3H), 1.28-1.20 (m, 3H), 0.97 (dd, J = 13.2 Hz, J = 3.2 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): 192.7, 165.9, 161.3, 141.6, 136.2, 133.3, 128.0, 122.0, 119.8, 117.8, 84.1, 67.5, 60.8, 55.3, 48.0, 47.3, 42.5, 32.3, 31.6, 25.8, 23.4, 14.2 ppm; 高分辨质谱计算值：C22H24O5+H 369.1702, 实测值：369.1703.
Figure 281188DEST_PATH_IMAGE026
P13, 72% yield, 94% ee, 手性测试条件：HPLC analysis on Chiralpak AD column (20% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tmajor = 6.54 min, tminor = 7.64 min. [α]D 20 = -37.8 (c = 0.70 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.02 (dd, J = 8.0 Hz, J = 1.2 Hz, 1H), 7.51 (td, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.35 (s, 1H), 7.10 (t, J = 7.6 Hz, 1H), 6.96 (d, J = 8.4 Hz, 1H), 4.40 (d, J = 3.2 Hz, 1H), 4.29-4.20 (m, 2H), 2.98-2.93 (m, 1H), 2.55 (d, J = 18.0 Hz, 1H), 2.33-2.19 (m, 4H), 2.00-1.90 (m, 2H), 1.57-1.49 (m, 1H), 1.34 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 204.4, 189.1, 164.2, 160.6, 142.7, 136.3, 132.5, 127.5, 122.4, 120.9, 118.0, 83.1, 66.9, 61.0, 53.5, 50.8, 45.8, 30.3, 28.9, 23.5, 14.2 ppm; 高分辨质谱计算值：C21H20O5+Na 375.1208, 实测值：375.1207.
Figure 3157DEST_PATH_IMAGE027
P14, 54% yield, 95% ee, 手性测试条件：HPLC analysis on Chiralpak AD column (10% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tminor = 9.53 min, tmajor = 12.80 min. [α]D 20 = -36.3 (c = 0.60 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.00 (d, J = 7.6 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), 7.20 (s, 1H), 7.08 (t, J = 7.6 Hz, 1H), 6.96 (d, J = 8.4 Hz, 1H), 5.14 (br s, 1H), 4.59 (d, J = 6.8 Hz, 1H), 4.36 (dd, J = 10.0 Hz, J = 2.8 Hz, 1H), 4.20 (q, J = 7.2 Hz, 2H), 2.27 (dd, J = 13.6 Hz, J = 8.4 Hz, 1H), 2.10-2.03 (m, 1H), 1.98-1.91 (m, 4H), 1.69 (s, 3H), 1.60 (s, 3H), 1.56-1.53 (m, 1H), 1.43-1.39 (m, 1H), 1.31 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 192.8, 165.3, 161.1, 143.1, 136.3, 134.0, 131.6, 128.1, 124.2, 122.1, 119.8, 117.8, 77.9, 67.4, 60.8, 55.3, 44.4, 41.0, 38.0, 34.9, 25.7, 23.8, 17.7, 14.2 ppm; 高分辨质谱计算值：C24H28O5+Na 419.1834, 实测值：419.1832.
Figure 306093DEST_PATH_IMAGE028
P15, 27% yield, 94% ee, 手性测试条件：HPLC analysis on Chiralpak AS column (10% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tmajor = 7.10 min, tminor = 13.26 min. [α]D 20 = -42.9 (c = 0.45 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.02 (d, J = 7.6 Hz, 1H), 7.52 (t, J = 7.2 Hz, 1H), 7.28 (s, 1H), 7.09 (t, J = 8.0 Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 5.08-5.06 (m, 1H), 4.56 (d, J = 5.6 Hz, 1H), 4.21 (q, J = 7.2 Hz, 2H), 3.91 (d, J = 2.4 Hz, 1H), 2.41-2.36 (m, 1H), 2.24 (dd, J = 13.6 Hz, J = 8.0 Hz, 1H), 1.78-1.67 (m, 1H), 1.65 (s, 3H), 1.53 (s, 3H), 1.45 (s, 3H), 1.42 (dd, J = 13.2 Hz, J = 2.4 Hz, 1H), 1.33 (t, J = 7.2 Hz, 3H), 1.26 (d, J = 12.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): 193.0, 165.0, 161.4, 141.6, 136.3, 133.9, 133.5, 128.0, 122.0, 120.7, 119.8, 117.9, 83.2, 67.2, 60.6, 55.6, 50.5, 48.1, 40.8, 29.8, 25.8, 20.9, 18.0, 14.2 ppm; 高分辨质谱计算值：C24H28O5+Na 419.1834, 实测值：419.1835.
Figure 898749DEST_PATH_IMAGE029
P16, 47% yield, 91% ee, 手性测试条件：HPLC analysis on Chiralpak AD column (10% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tminor = 12.91 min, tmajor = 13.78 min. [α]D 20 = -30.0 (c = 0.65 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.01 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.52 (td, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.40 (s, 1H), 7.09 (t, J = 7.6 Hz, 1H), 6.99 (d, J = 8.0 Hz, 1H), 4.58 (dd, J = 7.6 Hz, J = 2.4 Hz, 1H), 4.27-4.21 (m, 2H), 3.84 (d, J = 3.2 Hz, 1H), 3.33 (s, 1H), 2.44-2.38 (m, 1H), 1.79-1.76 (m, 1H), 1.41-1.26 (m, 6H), 0.99 (t, J = 7.6 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 192.9, 164.4, 161.4, 139.6, 136.3, 134.2, 128.0, 122.1, 119.8, 117.9, 83.7, 66.6, 60.9, 56.2, 46.4, 38.7, 34.5, 27.8, 14.2, 11.6 ppm; 高分辨质谱计算值：C20H22O5+Na 365.1365, 实测值：365.1364.
Figure 792886DEST_PATH_IMAGE030
P17, 38% yield, 98% ee, 手性测试条件：HPLC analysis on Chiralpak AD column (20% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tminor = 21.95 min, tmajor = 28.23 min. [α]D 20 = -22.9 (c = 0.70 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.06 (dd, J = 8.0 Hz, J = 1.2 Hz, 1H), 7.57 (td, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.50-7.44 (m, 3H), 7.37 (t, J = 8.0 Hz, 2H), 7.29-7.28 (m, 1H), 7.13 (t, J = 7.2 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 4.90 (s, 1H), 4.46 (dd, J = 10.0 Hz, J = 3.6 Hz, 1H), 4.28 (q, J = 7.2 Hz, 2H), 3.43 (s, 1H), 2.74 (s, 1H), 2.06-2.01 (m, 1H), 1.95-1.88 (m, 1H), 1.79 (br s, 1H), 1.36 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 192.4, 164.0, 161.3, 141.7, 139.6, 136.5, 135.2, 128.6, 128.5, 128.1, 126.9, 122.4, 119.9, 118.0, 78.1, 70.8, 61.1, 56.6, 54.7, 36.9, 25.8, 14.2 ppm; 高分辨质谱计算值：C24H22O5+H 391.1545, 实测值：391.1547.
Figure 877517DEST_PATH_IMAGE031
P18, 36% yield, 97% ee, 手性测试条件：HPLC analysis on Chiralpak OD column (20% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tmajor = 6.51 min, tminor = 7.95 min. [α]D 20 = +62.2 (c = 1.25 in EtOH); Since some decomposition was observed for P18 in deuterated reagents, NMR data of its oxide P18` was provided, 1H NMR (400 MHz, CDCl3): 7.98 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.51 (td, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.44 (s, 1H), 7.06 (t, J = 8.0 Hz, 1H), 6.93 (d, J = 8.4 Hz, 1H), 3.77 (s, 3H), 2.31-2.28 (m, 3H), 2.031-1.99 (m, 1H), 1.57 (s, 3H), 1.28 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): 204.3, 189.1, 164.6, 158.1, 142.2, 136.1, 132.4, 126.9, 121.9, 121.2, 118.4, 85.7, 69.5, 51.9, 50.4, 45.8, 39.3, 22.6, 22.1 ppm; 高分辨质谱计算值：C19H20O5+Na 351.1208, 实测值：351.1204.
Figure 436674DEST_PATH_IMAGE032
P19, 89% yield, 85% ee, 手性测试条件：HPLC analysis on Chiralpak AD column (40% 2-propanol/n-hexane, 1 mL/min), UV 220 nm, tminor = 8.95 min, tmajor = 18.01 min. [α]D 20 = -67.2 (c = 0.50 in CHCl3); 1H NMR (400 MHz, CDCl3): 7.96 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 7.6 Hz, 2H), 7.62-7.59 (m, 1H), 7.54-7.49 (m, 4H), 7.07 (t, J = 7.6 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 4.59 (d, J = 6.8 Hz, 1H), 4.36 (dd, J = 10.0 Hz, J = 2.4 Hz, 1H), 2.34 (br s, 1H), 2.11-1.98 (m, 2H), 1.52 (dd, J = 13.6 Hz, J = 2.4 Hz, 1H), 1.28 (s, 3H), 1.21 (d, J = 13.6 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): 191.9, 160.9, 148.8, 139.8, 137.0, 136.4, 133.5, 129.2, 128.0, 127.8, 122.3, 119.4, 117.8, 77.2, 67.4, 56.5, 46.5, 40.9, 38.2, 20.5 ppm; 高分辨质谱计算值：C22H20O5S+Na 419.0929, 实测值：419.0929.
Figure 290361DEST_PATH_IMAGE033
P20, 85% yield, 80% ee, 手性测试条件：HPLC analysis on Chiralpak AD column (10% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tminor = 23.59 min, tmajor = 26.61 min. [α]D 20 = -22.8 (c = 0.90 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.00 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.55 (td, J = 8.0 Hz, J = 2.0 Hz, 1H), 7.32 (s, 1H), 7.12 (t, J = 8.0 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 4.65 (dd, J = 8.0 Hz, J = 2.0 Hz, 1H), 4.39 (dd, J = 10.0 Hz, J = 3.2 Hz, 1H), 2.29 (dd, J = 13.6 Hz, J = 8.4 Hz, 1H), 2.08-1.96 (m, 1H), 1.65 (dd, J = 14.0 Hz, J = 3.2 Hz, 1H), 1.46 (s, 3H), 1.38 (dt, J = 14.0 Hz, J = 3.2 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): 191.6, 160.9, 141.8, 136.6, 128.1, 125.2, 122.5, 119.5, 117.9, 115.1, 77.5, 67.5, 55.8, 45.3, 39.4, 37.2, 22.2 ppm; 高分辨质谱计算值：C17H15NO3+Na 304.0950, 实测值：304.0947.
Figure 11192DEST_PATH_IMAGE034
P21, 62% yield, 84% ee, 手性测试条件：HPLC analysis on Chiralpak OD column (30% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tminor = 8.70 min, tmajor = 9.55 min. [α]D 20 = +97.3 (c = 1.50 in CHCl3); 1H NMR (400 MHz, CDCl3): 9.59 (d, J = 1.6 Hz, 1H), 8.02 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.52 (td, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.33-7.26 (m, 3H), 7.18-7.16 (m, 2H), 7.11-7.06 (m, 2H), 7.02 (d, J = 8.8 Hz, 1H), 5.11-5.08 (m, 1H), 3.56 (s, 1H), 2.31 (dd, J = 13.6 Hz, J = 8.4 Hz, 1H), 2.20-2.05 (m, 3H), 1.31 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): 201.4, 182.0, 161.6, 138.7, 137.9, 135.9, 132.2, 130.0, 128.6, 128.0, 127.8, 122.3, 122.0, 118.0, 73.8, 52.7, 52.4, 36.3, 35.2, 25.5 ppm; 高分辨质谱计算值：C22H20O3+MeOH+Na 387.1572, 实测值：387.1571.
Figure 583119DEST_PATH_IMAGE035
P22, 75% yield, 94% ee, 手性测试条件：HPLC analysis on Chiralpak AD column (20% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tminor = 10.96 min, tmajor = 12.09 min. [α]D 20 = +109.1 (c = 2.25 in CHCl3); 1H NMR (400 MHz, CDCl3): 9.63 (d, J = 1.6 Hz, 1H), 8.00 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.51 (td, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.29-7.26 (m, 2H), 7.11-7.06 (m, 3H), 7.01-6.99 (m, 2H), 5.09-5.06 (m, 1H), 3.58-3.57 (m, 1H), 2.26-2.02 (m, 4H), 1.29 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): 201.1, 181.9, 161.5, 138.0, 136.4, 136.0, 133.7, 132.4, 131.2, 128.7, 127.9, 122.1, 122.0, 118.0, 73.6, 52.4, 51.4, 36.1, 35.2, 25.2 ppm; 高分辨质谱计算值：C22H19ClO3+MeOH+Na 421.1183, 实测值：421.1185.
Figure 555754DEST_PATH_IMAGE036
P23, 44% yield, 86% ee, 手性测试条件：HPLC analysis on Chiralpak AD column (10% 2-propanol/n-hexane, 1 mL/min), UV 220 nm, tmajor = 15.14 min, tminor = 16.65 min. [α]D 20 = +115.1 (c = 0.95 in CHCl3); 1H NMR (400 MHz, CDCl3): 9.59 (t, J = 1.6 Hz, 1H), 8.02 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.52 (td, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.13-7.09 (m, 3H), 7.06-7.01 (m, 4H), 5.11-5.07 (m, 1H), 3.53-3.51 (m, 1H), 2.32 (s, 3H), 2.30-2.26 (m, 1H), 2.19-2.05 (m, 3H), 1.30 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): 201.6, 182.0, 161.5, 139.0, 137.6, 135.8, 134.7, 131.9, 129.9, 129.2, 128.0, 122.2, 122.0, 118.0, 73.8, 52.7, 51.9, 36.2, 35.1, 25.5, 21.0 ppm; 高分辨质谱计算值：C23H22O3+Na 369.1467, 实测值：369.1465.
Figure 388581DEST_PATH_IMAGE037
P24, 74% yield, 94% ee, 手性测试条件：HPLC analysis on Chiralpak AD column (40% 2-propanol/n-hexane, 1 mL/min), UV 220 nm, tmajor = 10.14 min, tminor = 13.60 min. [α]D 20 = +51.9 (c = 0.75 in CHCl3); 1H NMR (400 MHz, CDCl3): 9.68 (s, 1H), 8.55 (d, J = 4.0 Hz, 1H), 8.49 (s, 1H), 8.02 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.55-7.50 (m, 2H), 7.29-7.26 (m, 1H), 7.10 (t, J = 7.6 Hz, 1H), 7.03-6.99 (m, 2H), 5.12-5.09 (m, 1H), 3.65-3.64 (m, 1H), 2.30-2.15 (m, 3H), 2.08-2.04 (m, 1H), 1.34 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): 200.7, 181.8, 161.4, 151.0, 149.1, 137.2, 137.1, 136.1, 133.7, 133.1, 128.0, 123.4, 122.2, 122.1, 118.1, 73.5, 52.1, 49.6, 36.1, 35.3, 25.1 ppm; 高分辨质谱计算值：C21H19NO3+Na 356.1263, 实测值：356.1264.
实施例2： 具有多功能官能团的转化（应用实例1）
Figure 686838DEST_PATH_IMAGE038
将P22(37 mg, 0.1 mmol) 称入一干燥的反应管中，用1mL氯仿溶解，再于室温下分别加入如上图所示的卡宾催化剂(7.3 mg, 0.02 mmol)、乙酸钠(9.8 mg, 0.12 mmol)，升温至40℃搅拌至薄层层析检测P22消失。柱层析分离石油醚/乙酸乙酯：8/1）得如题化合物，92% yield，90% ee, 手性测试条件： HPLC analysis on Chiralpak OD column (20% 2-propanol/n-hexane, 1 mL/min), UV 220 nm, tminor = 11.96 min, tmajor = 17.04 min. [α]D 20 = +128.8 (c = 0.90 in CHCl3); 1H NMR (400 MHz, CDCl3): 7.92 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.50 (td, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.27-7.25 (m, 2H), 7.07 (t, J = 8.0 Hz, 1H), 6.95-6.92 (m, 3H), 4.79-4.78 (m, 1H), 3.10 (t, J = 3.6 Hz, 1H), 2.99 (br s, 2H), 2.71 (d, J = 18.4 Hz, 1H), 2.45 (d, J = 15.2 Hz, 1H), 2.24-2.20 (m, 1H), 2.09 (d, J = 18.0 Hz, 1H), 1.01 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): 216.4, 191.4, 160.6, 137.7, 136.5, 132.9, 129.3, 128.5, 127.2, 122.3, 120.9, 118.3, 75.5, 58.1, 55.1, 54.9, 46.5, 45.8, 42.1, 24.4 ppm; 高分辨质谱计算值：C22H19ClO3+Na 389.0920, 实测值：389.0921.
实施例3： 具有多功能官能团的转化（应用实例2）
Figure 746061DEST_PATH_IMAGE039
将P22(33 mg, 0.09 mmol) 称入一干燥的反应管中，用1mL二氯甲烷溶解，再有机碱DBU (15.2 mg, 0.1 mmol)，室温搅拌至薄层层析检测P22消失。柱层析分离石油醚/乙酸乙酯：10/1）得如题化合物半固体，88% yield，94% ee, 手性测试条件： HPLC analysis on Chiralpak AD column (20% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tmajor = 11.14 min, tminor = 19.03 min. [α]D 20 = -17.0 (c = 0.50 in CHCl3); 1H NMR (400 MHz, CDCl3): 8.03 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.52 (td, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.31 (d, J = 8.4 Hz, 2H), 7.12-7.07 (m, 3H), 6.99 (d, J = 8.4 Hz, 1H), 6.33 (s, 1H), 4.60 (t, J = 6.0 Hz, 1H), 4.48 (dd, J = 10.0 Hz, J = 2.8 Hz, 1H), 2.30 (dd, J = 13.6 Hz, J = 8.0 Hz, 1H), 2.12-2.05 (m, 1H), 1.65 (dd, J = 13.6 Hz, J = 3.2 Hz, 1H), 1.43 (dt, J = 13.6 Hz, J = 3.2 Hz, 1H), 1.15 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): 193.8, 161.3, 152.8, 137.3, 136.1, 133.4, 129.5, 128.2, 128.1, 122.2, 122.0, 119.9, 117.8, 78.6, 67.4, 55.2, 47.4, 40.8, 38.3, 23.3 ppm; 高分辨质谱计算值：C22H19ClO3+Na 389.0920, 实测值：389.0922.
实施例4： 具有多功能官能团的转化（应用实例3）
Figure 647021DEST_PATH_IMAGE040
将P1(38 mg, 0.12 mmol) 称入一干燥的反应管中，用2mL二氯甲烷溶解，再氧化剂PCC(77.8 mg, 0.36 mmol)和硅胶（78 mg），室温搅拌至薄层层析检测P1消失。柱层析分离（石油醚/乙酸乙酯：10/1）得氧化产物；将该氧化产物直接以二氯甲烷溶解后于-78℃通入臭氧搅拌至薄层层析检测原料消失，加入20 uL二甲硫醚并于室温搅拌4小时，柱层析分离（石油醚/乙酸乙酯：10/1）得氧化产物，82% yield，90% ee, 手性测试条件： HPLC analysis on Chiralpak AD column (10% 2-propanol/n-hexane, 1 mL/min), UV 254 nm, tmajor = 10.59 min, tminor = 11.92 min. [α]D 20 = -23.5 (c = 0.95 in CHCl3); 1H NMR (400 MHz, CDCl3): 14.76 (s, 1H), 7.83 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.43 (td, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H), 5.00-4.96 (m, 1H), 4.38-4.31 (m, 2H), 2.96-2.91 (m, 2H), 2.41-2.36 (m, 1H), 2.03 (dd, J = 12.8 Hz, J = 10.8 Hz, 1H), 1.49 (s, 3H), 1.36 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): 197.9, 181.0, 179.6, 162.3, 159.9, 135.3, 126.6, 122.0, 121.2, 117.4, 103.4, 72.0, 62.5, 46.0, 38.7, 37.4, 24.8, 14.0 ppm; 高分辨质谱计算值：C19H18O7-CHO+Na 353.1001, 实测值：353.0995。

Claims (3)

1.一种二氢色原酮骨架多环化合物，是具有如下结构的手性化合物：
Figure DEST_PATH_IMAGE001
，其中*为手性碳原子，R1任意选自C1-C4的烷基、C5-C10的含N、S、O的杂环基，R2、R3、R4、R5为H、C1-C4的烷基或者苯基，R6、R7、R8、R9 为H、F、Cl、Br、C1-C4的烃氧基、C1-C4的烷基或者苯基；
Figure 2011104204998100001DEST_PATH_IMAGE002
，其中*为手性碳原子，R1为酯基、氰基、砜基、硝基，R2、R3、R4、R5 为H，C1-C4的烷基或者苯基，R6、R7、R8、R9 为H、F、Cl、Br、C1-C4的烃氧基、C1-C4的烷基或者苯基。
2.一种权利要求1所述的二氢色原酮骨架多环化合物的合成方法，其特征是在0oC～50oC的条件下在有机溶剂苯或甲苯或二氯甲烷或氯仿或乙腈或1,4-二氧六环或四氢呋喃中，酸性添加剂下，以色酮缺电子二烯化合物和烯醛为原料，以手性胺a,a-二芳基脯胺醇硅醚作为催化剂进行反电子需求的Diels-Alder反应或串联Diels-Alder/插烯Aldol、串联Diels-Alder/半缩醛化反应，其中所述的色酮缺电子二烯化合物、烯醛、手性a,a-二芳基脯胺醇硅醚、酸性添加剂的摩尔比为1:2:0.2:0.2；上述手性的脯胺醇硅醚催化剂的结构通式为：
Figure 2011104204998100001DEST_PATH_IMAGE004
，其中: R1 、R2任意选自H、CH3、tBu、OCH3, R3任意选自TMS、TES、TBS，R4任意选自H, OTBS。
3.一种如权利要求1所述的二氢色原酮骨架多环化合物的用途，其特征是该二氢色原酮骨架多环化合物用于合成基于二氢色原酮骨架结构多样性的类天然产物或复杂化合物，具有如下结构：
Figure DEST_PATH_IMAGE005
，其中R1 为C1-C4的烷基；其中 R2、R3任意选自H、 C1-C4的烷基或者苯基，R4、R5、R6、R7 为H、F、Cl、Br、C1-C4的烃氧基、C1-C4的烷基或者苯基；
Figure 2011104204998100001DEST_PATH_IMAGE006
，其中R1为酯基、氰基、砜基、硝基，R2、R3 为H、 C1-C4的烷基或者苯基，R4、R5、R6、R7任意选自H、F、Cl、Br、C1-C4的烃氧基、C1-C4的烷基或者苯基。
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