CN111233881B - 具橙酮骨架类化合物作为受体进行反-Micheal加成反应的方法 - Google Patents
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Abstract
本发明提供一种具橙酮骨架类化合物作为受体进行反‑Micheal加成反应的方法，属于化学合成技术领域。所述方法可在Sc(OTf)3催化下、温度为80℃、溶剂为二氯甲烷的条件下进行反应。本发明提出的方法，实现了路易斯酸催化下将橙酮骨架类化合物共轭的羰基与双键作为Michael加成的受体，通过负氢迁移/芳构化/去芳构化/环化反应得到氧杂二烯的α‑官能化反‑Michael加成产物。该方法操作简单实用，反应高效便捷，底物适用性广，具有极高的原子经济性。
Description
技术领域
本发明属于化学合成技术领域，具体涉及一种具橙酮骨架类化合物作为受体进行反-Micheal加成反应。
背景技术
螺旋环结构广泛存在于生物活性天然产物和药物中，由于其固有的三维性和结构新颖性，通常是新药开发的理想结构。在各种螺环结构中，如以下结构所示的[6,5]–哌啶螺呋喃结构是非常重要的一类，存在于烟碱乙酰胆碱受体(nAChR)调节剂、CCR1拮抗剂、乙酰辅酶a羧化酶(ACC)抑制剂中。因此，相关的螺环骨架的合成近年来引起了相当大的兴趣。
橙酮是植物体内的次生代谢产物，属于类黄酮，可看作为取代的苯并呋喃酮衍生物，是黄酮的同分异构体，同时也是一类稀有类黄酮化合物，在自然界中分布很少，含量较低，大多存在于玄参科、菊科、苦苣苔科以及单子叶植物中的莎草科。橙酮类化合物具有广泛的生物活性和药理作用，如抗肿瘤和细胞毒性、抗炎和抑菌、白细胞介素-5抑制剂、抗氧化等。
橙酮作为一类重要的天然产物，被广泛地用作构建杂环体系的合成材料。通过杂二烯(α,β-不饱和酮)的迈克尔加成得到β-官能化的酮的方法已得到很好的发展。在已有的反应中，杂二烯通过环加成一步得到复杂多环骨架是众多构建复杂多环骨架的策略之一(如下所示)。以杂二烯作为4π电子体(双烯)进行1,4-环加成反应,可以得到苯并呋喃稠和的6至8元环。此外，He组还开发了橙酮的1,2-环加成，得到了螺4-恶唑烷酮(J.Org.Chem.2017,82,10680-10686)。特别值得注意的是，相当大的努力已经致力于开发3,4-环加成法来产生[6,5]或[5,5]螺环体系(Chin.Chem.Lett.2018,29,1209-1211)。然而，通过迈克尔途径实现杂二烯的α-官能化仍是一个挑战。事实上，合成含有苯并呋喃-3(2H)-部分的螺环主要依赖于环加成。因此，探索构建这类结构的新方法势在必行。
作为众多生物活性分子母核的具橙酮骨架类化合物多被作为环加成反应的2π、4π电子体而被用于合成各种并环、螺环结构，主要用作[4+n]、[3+2]、[2+n]环加成反应等，而其它反应类型较少。与现有橙酮骨架的[4+n]、[3+2]、[2+n]环加成反应不同，将共轭的羰基与双键作为Michael加成的受体，通过负氢迁移/芳构化/去芳构化/环化反应得到氧杂二烯的α-官能化反-Michael加成产物。该反应不仅增加了橙酮类化合物在有机合成中的反应类型，也为反-Michael加成反应提供一种新方法。
发明内容
针对上述技术问题，本发明提供一种基于橙酮骨架类化合物为受体进行反-Micheal加成反应的方法，旨在探索一种新的橙酮类化合物的有机合成反应类型。技术方案如下：
一种具橙酮骨架类化合物作为受体进行反-Micheal加成反应的方法，是以具橙酮骨架类化合物作为受体，在路易斯酸作为催化剂的作用下，将共轭的羰基与双键作为Michael加成的受体，通过负氢迁移、芳构化、去芳构化、环化反应得到氧杂二烯的α-官能化反-Michael加成产物。
在上述方案的基础上，所述具橙酮骨架类化合物结构式如下：
其中，
X为O、S或N中的一种；
R1为氢、甲基、甲氧基、氰基、三氟甲基、卤素、苯基或者亚硝基中的一种；
R2为卤素或者甲氧基；
R3、R4可构成成环结构，成环时，包括五元环、六元环、七元环、并环以及杂环；不成环时，R3、R4为C1-C3烷基。
在上述方案的基础上，所述催化剂为Sc(OTf)3、Cu(OTf)2、Zn(OTf)2、Mg(OTf)2、TsOH·H2O、(-)-CSA以及TfOH中的一种。
在上述方案的基础上，所述催化剂的浓度为1-20mol％
在上述方案的基础上，所述反应是在溶剂中完成的，所述溶剂为二氯甲烷、二氯乙烷、乙醇、甲苯、四氢呋喃以及乙腈中的一种。
在上述方案的基础上，所述反应的温度为60-120℃。
在上述方案的基础上，所述反应的时间为1.5-3.5h。
在上述方案的基础上，所述具橙酮骨架类化合物作为受体进行反-Micheal加成反应的方法，其化学反应式如下：
在上述方案的基础上，所述具橙酮骨架类化合物还包括：
在上述方案的基础上，所述具橙酮骨架类化合物作为受体进行反-Micheal加成反应的方法，具体步骤为：
取原料橙酮类化合物0.1mmol，于催化剂Sc(OTf)3 2％、溶剂二氯甲烷(1mL)、温度为80℃的反应体系条件下进行反应。通过TLC法检测反应，待原料消耗完后(1.5-3.5h)减压旋干，硅胶柱色谱分离，洗脱剂石油醚：乙酸乙酯为50:1。
化学反应式如下：
化合物Ⅰ和化合物Ⅱ中，
X为O、S或N；
R1为氢、甲基、甲氧基、氰基、三氟甲基、卤素、苯基或者亚硝基；
R2为卤素或者甲氧基；
R3、R4可构成成环结构，成环时，包括五元环、六元环、七元环、并环以及杂环；不成环时，R3、R4为C1-C3烷基。
本发明有益效果：
为解决现有橙酮骨架反应类型有限、多用作[4+n]、[3+2]、[2+n]环加成反应的问题，本发明将共轭的羰基与双键作为Michael加成的受体，通过负氢迁移/芳构化/去芳构化/环化反应得到氧杂二烯的α-官能化反-Michael加成产物。该反应不仅增加了橙酮类化合物在有机合成中的反应类型，也为反-Michael加成反应提供一种新方法。反应高效便捷，底物适用性广，具有极高的原子经济性。
本发明研究的杂二烯的反-迈克尔碳氢化反应，实现了螺呋喃/噻吩-哌啶的一步合成。这种方法提供了一个另一种思路，即氢化物作为亲核试剂进行反-迈克尔加成。这种转化是由芳香化驱动的[1,5]-氢迁移引发的，氢化物可以在C4位置进行亲核攻击。3-烷基化是通过分子内环化实现的，并参与螺旋环的形成。这项工作不仅为[6,5]螺旋环的合成提供了有效的方法，而且为进一步设计具有氧化还原中性和原子经济性的反-迈克尔加成反应提供了一种新的策略。
具体实施方式
在本发明中所使用的术语，除非有另外说明，一般具有本领域普通技术人员通常理解的含义。
下面结合具体实施例，并参照数据进一步详细的描述本发明。以下实施例只是为了举例说明本发明，而非以任何方式限制本发明的范围。
实施例1
橙酮类化合物1a(0.1mmol)在催化剂(20mol％,0.02mmol)的作用下，于溶剂(1.0mL)中经过反-Michael加成获得加成产物2a，其催化剂、溶剂以及温度等条件如表1所示：
表1
| 序号 | 催化剂 | 溶剂 | 温度(℃) | 时间(h) | 产率(％) |
| 1 | Cu(OTf)<sub>2</sub> | DCE | 120 | 1.5 | 23 |
| 2 | Zn(OTf)<sub>2</sub> | DCE | 120 | 1.5 | 42 |
| 3 | Mg(OTf)<sub>2</sub> | DCE | 120 | 1.5 | n.r. |
| 4 | Sc(OTf)<sub>3</sub> | DCE | 120 | 1.5 | 94 |
| 5 | TsOH·H<sub>2</sub>O | DCE | 120 | 1.5 | 39 |
| 6 | (-)-CSA | DCE | 120 | 1.5 | 72 |
| 7 | TfOH | DCE | 120 | 1.5 | 57 |
| 8 | Sc(OTf)<sub>3</sub> | EtOH | 120 | 1.5 | 84 |
| 9 | Sc(OTf)<sub>3</sub> | DCM | 120 | 1.5 | 94 |
| 10 | Sc(OTf)<sub>3</sub> | toluene | 120 | 1.5 | 75 |
| 11 | Sc(OTf)<sub>3</sub> | THF | 120 | 1.5 | 43 |
| 12 | Sc(OTf)<sub>3</sub> | CH<sub>3</sub>CN | 120 | 1.5 | 60 |
| 13 | Sc(OTf)<sub>3</sub> | DCM | 80 | 3.5 | 89 |
| 14 | Sc(OTf)<sub>3</sub> | DCM | 60 | 5.0 | 81 |
| 15 | Sc(OTf)<sub>3</sub> | DCM | 80 | 3.5 | 95 |
| 16 | Sc(OTf)<sub>3</sub> | DCM | 80 | 3.5 | 95 |
| 17 | Sc(OTf)<sub>3</sub> | DCM | 80 | 3.5 | 94 |
| 18 | Sc(OTf)<sub>3</sub> | DCM | 80 | 3.5 | 55 |
| 19 | - | DCM | 80 | 3.5 | n.r. |
注：表1中产率为纯化后的分离产率；序号15的催化剂浓度为10mol％；序号16的催化剂浓度为5mol％；序号17的催化剂浓度为2mol％；序号18的催化剂浓度为1mol％。
由实验结果可知，反应体系中，当催化剂Sc(OTf)3的浓度为2mol％时，在80℃的条件下，于二氯甲烷(DCM)中，橙酮类化合物1a即可通过加成反应获得较高产率的产物2a，产率与序号15、16相差不大，但是催化剂用量低。
化合物2a的核磁共振数据，如下：
1H NMR(500MHz,CDCl3)δ7.69(d,J＝7.8Hz,1H),7.56(t,J＝7.8Hz,1H),7.16(t,J＝7.8Hz,1H),7.11–7.04(m,2H),7.02(d,J＝7.4Hz,1H),6.63(t,J＝7.4Hz,1H),6.57(d,J＝8.1Hz,1H),3.82(dd,J＝10.0,5.6Hz,1H),3.58–3.48(m,1H),3.37–3.18(m,2H),2.78(d,J＝16.5Hz,1H),1.99(dt,J＝14.2,7.4Hz,1H),1.96–1.85(m,1H),1.76–1.67(m,1H),1.42–1.30(m,1H)；13C NMR(126MHz,CDCl3)δ202.11,172.09,143.40,138.13,129.19,127.99,124.24,122.06,121.33,117.56,116.02,113.63,111.04,84.18,61.52,47.62,36.01,25.56,23.66；HRMS(ESI-TOF)m/z calcd for C19H18NO2[M+H]+:292.1332；found:292.1335.
为了探讨这一反应的机理，在标准条件下进行了氘代实验。当氘代底物[D]-1a进行反应时，产物[D]-2a在C4位置的氘代说明了分子内[1,5]氢迁移的发生。此外，通过底物1a和[D]-1a之间的竞争性反应，得到氘动力学同位素效应(DKIE)值为1.5，这表明，分子内[1,5]氢化物转移可能不是决速步骤。这些结果说明，芳构化使橙酮更容易发生[1,5]-氢迁移。根据上述控制实验和以往文献(Chem Sci 2018,9,8253-8259；J.Org.Chem.2019,84,1833-1844)，提出了一个合理的机理来解释该反应，如下所示。在Lewis酸催化作用下，苯并呋喃-3(2H)-酮I的芳香化倾向作为引发[1,5]-氢迁移的驱动力，实现了杂二烯的反-迈克尔加成。合成的芳香族中间体II随后参与分子内3-烷基化，以产生所需的螺环。
实施例2-24所述化合物的制备方法为：取原料橙酮类化合物1 0.1mmol，于催化剂Sc(OTf)3 2％、溶剂二氯甲烷(1mL)、温度为80℃的反应体系条件下进行反应。
实施例2
产物化学式：C20H20NO2
分子量：306.15
结构式：
产率：43％
1H NMR(500MHz,CDCl3)δ7.70(dd,J＝7.9,1.5Hz,1H),7.61–7.58(m,1H),7.13–7.07(m,2H),6.94(d,J＝7.5Hz,1H),6.49(dd,J＝7.5,1.6Hz,1H),6.42(d,J＝1.7Hz,1H),3.83(dd,J＝10.0,5.6Hz,1H),3.55(td,J＝8.7,2.1Hz,1H),3.35–3.23(m,2H),2.79(d,J＝16.3Hz,1H),2.33(s,3H),2.05–1.97(m,1H),1.97–1.89(m,1H),1.77–1.69(m,1H),1.42–1.32(m,1H)；
13C NMR(126MHz,CDCl3)δ202.30,172.09,143.16,138.08,137.73,129.04,124.21,121.97,121.30,116.92,114.56,113.65,111.65,84.32,61.49,47.58,35.72,25.54,23.65,21.70；
实施例3
产物化学式：C20H20NO3
分子量：322.14
结构式：
产率：71％
1H NMR(500MHz,CDCl3)δ7.70(d,J＝7.8Hz,1H),7.59(t,J＝7.8Hz,1H),7.09(dt,J＝7.4,3.1Hz,2H),6.95(d,J＝8.2Hz,1H),6.24(dd,J＝8.2,2.4Hz,1H),6.16(d,J＝2.5Hz,1H),3.80(s,4H),3.52(t,J＝8.7Hz,1H),3.27(dt,J＝16.6,5.1Hz,2H),2.77(d,J＝16.2Hz,1H),2.06–1.97(m,1H),1.97–1.87(m,1H),1.76–1.66(m,1H),1.42–1.31(m,1H)；13CNMR(126MHz,CDCl3)δ202.16,172.07,159.85,144.25,138.10,129.70,124.22,122.01,121.27,113.64,110.28,100.88,97.34,84.38,61.44,55.20,47.56,35.42,25.55,23.57；
实施例4
产物化学式：C20H17N2O2
分子量：317.13
结构式：
产率：82％
1H NMR(500MHz,CDCl3)δ7.72(dd,J＝7.8,1.4Hz,1H),7.66-7.60(m,1H),7.13(t,J＝7.5Hz,1H),7.09(dd,J＝8.0,2.7Hz,2H),6.92(dd,J＝7.6,1.6Hz,1H),6.77(d,J＝1.6Hz,1H),3.88-3.82(m,1H),3.55(td,J＝8.8,1.8Hz,1H),3.33(dt,J＝16.8,1.5Hz,1H),3.25(td,J＝9.5,7.0Hz,1H),2.84(d,J＝16.8Hz,1H),2.11-2.03(m,1H),2.03-1.92(m,1H),1.79-1.72(m,1H),1.45-1.35(m,1H)；13C NMR(126MHz,CDCl3)δ202.16,172.07,159.85,144.25,138.10,129.70,124.22,122.01,121.27,113.64,110.28,100.88,97.34,84.38,61.44,55.20,47.56,35.42,25.55,23.57；
实施例5
产物化学式：C20H17F3NO2
分子量：360.12
结构式：
产率：62％
1H NMR(500MHz,CDCl3)δ7.72(dd,J＝7.8,1.4Hz,1H),7.65–7.59(m,1H),7.15–7.06(m,3H),6.88(dd,J＝7.8,1.8Hz,1H),6.76(d,J＝1.8Hz,1H),3.91–3.83(m,1H),3.59(td,J＝8.8,1.9Hz,1H),3.39–3.25(m,2H),2.85(d,J＝16.7Hz,1H),2.10–2.02(m,1H),2.02–1.91(m,1H)1.79–1.72(m,1H),1.45–1.35(m,1H)；13C NMR(126MHz,CDCl3)δ201.61,171.94,143.38,138.37,130.21(q,J＝31.3Hz),129.83,129.34,124.53(q,J＝270.0Hz),123.45,122.29,121.08,121.06,113.59,112.26(q,J＝3.7Hz),107.14(q,J＝3.7Hz),83.21,61.54,47.53,35.81,25.51,23.55；19F NMR(471MHz,CDCl3)δ-62.53(s)；
实施例6
产物化学式：C19H17ClNO2
分子量：326.09
结构式：
产率：74％
1H NMR(500MHz,CDCl3)δ7.71(dd,J＝7.8,1.5Hz,1H),7.64–7.57(m,1H),7.15–7.06(m,2H),6.94(d,J＝7.9Hz,1H),6.61(dd,J＝8.0,2.0Hz,1H),6.55(d,J＝2.0Hz,1H),3.83(dd,J＝10.2,5.5Hz,1H),3.52(td,J＝8.9,1.9Hz,1H),3.30–3.19(m,2H),2.78(d,J＝16.4Hz,1H),2.08–1.99(m,1H),1.99–1.87(m,1H),1.78–1.70(m,1H),1.42–1.32(m,1H)；13CNMR(126MHz,CDCl3)δ201.73,171.96,144.21,138.26,133.53,129.98,124.30,122.19,121.12,115.93,115.67,113.59,110.65,83.58,61.42,47.55,35.52,25.48,23.55；
实施例7
产物化学式：C19H17BrNO2
分子量：370.04
结构式：
产率：73％
1H NMR(500MHz,CDCl3)δ7.70(dd,J＝7.8,1.5Hz,1H),7.63–7.57(m,1H),7.14–7.06(m,2H),6.91–6.85(m,1H),6.75(dd,J＝7.9,1.9Hz,1H),6.70(d,J＝1.9Hz,1H),3.82(dd,J＝10.2,5.5Hz,1H),3.51(td,J＝8.8,1.9Hz,1H),3.28–3.19(m,2H),2.76(d,J＝16.4Hz,1H),2.07–1.98(m,1H),1.98–1.88(m,1H),1.77–1.69(m,1H),1.42–1.32(m,1H)；13CNMR(126MHz,CDCl3)δ201.73,171.95,144.43,138.30,130.31,124.31,122.22,121.68,121.10,118.57,116.42,113.60,113.48,83.47,61.42,47.55,35.57,25.48,23.57；
实施例8
产物化学式：C19H17ClNO2
分子量：326.09
结构式：
产率：73％
1H NMR(500MHz,CDCl3)δ7.73(dd,J＝7.7,1.8Hz,1H),7.62(td,J＝7.8,7.1,1.6Hz,1H),7.29–7.21(m,1H),7.18–7.06(m,2H),6.96(d,J＝7.5Hz,1H),6.79(td,J＝7.7,1.5Hz,1H),4.40–4.29(m,1H),3.83(d,J＝8.0Hz,1H),3.42–3.27(m,2H),2.83(d,J＝17.2Hz,1H),2.06–1.95(m,1H),1.92–1.81(m,2H),1.50–1.41(m,1H)；13C NMR(126MHz,CDCl3)δ202.39,171.97,142.32,138.11,129.64,127.84,124.32,123.72,123.48,122.17,121.54,120.52,113.41,86.42,61.33,53.32,36.40,26.39,24.30；
实施例9
产物化学式：C19H17FNO2
分子量：310.12
结构式：
产率：61％
1H NMR(500MHz,CDCl3)δ7.71(d,J＝7.7Hz,1H),7.66–7.57(m,1H),7.17–7.07(m,2H),6.89(td,J＝8.7,3.0Hz,1H),6.79(dd,J＝8.9,2.9Hz,1H),6.50(dd,J＝8.9,4.6Hz,1H),3.81(dd,J＝9.8,5.7Hz,1H),3.52(td,J＝8.6,2.3Hz,1H),3.33(d,J＝16.6Hz,1H),3.25(td,J＝9.0,7.0Hz,1H),2.77(d,J＝16.7Hz,1H),2.11–1.87(m,2H),1.81–1.69(m,1H),1.46–1.32(m,1H)；13C NMR(126MHz,CDCl3)δ201.85,171.98,155.66,153.79,139.94,138.23,124.28,122.17,121.18,118.63(d,J＝6.25Hz),115.71(d,J＝22.5Hz),114.27(d,J＝22.5Hz),113.58,111.57(d,J＝7.5Hz),83.95,61.51,48.07,35.96,25.49,23.59；19FNMR(471MHz,CDCl3)δ-129.56(s)；
实施例10
产物化学式：C19H17ClNO2
分子量：326.09
结构式：
产率：57％
1H NMR(500MHz,CDCl3)δ7.75–7.68(m,1H),7.65–7.57(m,1H),7.15–6.97(m,4H),6.50(d,J＝8.6Hz,1H),3.82(dd,J＝10.0,5.6Hz,1H),3.52(td,J＝8.7,2.1Hz,1H),3.36–3.20(m,2H),2.76(d,J＝16.6Hz,1H),2.07–1.98(m,1H),1.98–1.88(m,1H),1.77–1.67(m,1H),1.44–1.31(m,1H)；13C NMR(126MHz,CDCl3)δ201.73,171.95,141.98,138.29,128.77,127.72,124.31,122.22,121.12,120.52,119.04,113.58,111.97,83.56,61.53,47.75,35.74,25.48,23.58；
实施例11
产物化学式：C19H17BrNO2
分子量：370.04
结构式：
产率：75％
1H NMR(500MHz,CDCl3)δ7.71(dd,J＝7.7,1.4Hz,1H),7.63–7.59(m,1H),7.27–7.22(m,1H),7.16–7.06(m,3H),6.45(d,J＝8.7Hz,1H),3.82(dd,J＝10.0,5.6Hz,1H),3.52(td,J＝8.7,2.0Hz,1H),3.30(dq,J＝16.6,1.3Hz,1H),3.23(td,J＝9.4,7.0Hz,1H),2.76(d,J＝16.5Hz,1H),2.07–1.98(m,1H),1.98–1.88(m,1H),1.76–1.70(m,1H),1.41–1.32(m,1H)；13C NMR(126MHz,CDCl3)δ201.72,171.94,142.37,138.30,131.53,130.59,124.32,122.22,121.10,119.55,113.59,112.45,107.55,83.45,61.52,47.68,35.67,25.46,23.57；
实施例12
产物化学式：C19H17FNO2
分子量：310.12
结构式：
产率：89％
1H NMR(500MHz,CDCl3)δ7.71(dd,J＝7.6,1.5Hz,1H),7.64–7.58(m,1H),7.16–7.06(m,3H),6.44–6.34(m,2H),3.80(dd,J＝9.9,5.7Hz,1H),3.55(td,J＝8.8,2.2Hz,1H),3.30(td,J＝9.3,7.1Hz,1H),3.06(s,2H),2.05–1.97(m,1H),1.97–1.87(m,1H),1.79–1.72(m,1H),1.47–1.35(m,1H)；13C NMR(126MHz,CDCl3)δ201.88,172.02,162.50,160.58,144.73(d,J＝7.5Hz),138.27,128.29(d,J＝10.0Hz),124.33,122.18,121.18,113.58,106.60(d,J＝2.5Hz),104.95(d,J＝21.2Hz),102.59(d,J＝22.5Hz),83.17,60.95,47.76,29.17,29.13,25.52,23.50；19F NMR(471MHz,CDCl3)δ-117.85(s)；
实施例13
产物化学式：C19H17ClNO2
分子量：326.09
结构式：
产率：73％
1H NMR(500MHz,CDCl3)δ7.72(dd,J＝7.7,1.4Hz,1H),7.65–7.58(m,1H),7.10(dt,J＝12.3,7.4Hz,3H),6.72(d,J＝7.9Hz,1H),6.50(d,J＝8.2Hz,1H),3.79(dd,J＝9.8,5.7Hz,1H),3.53(td,J＝8.9,2.3Hz,1H),3.31(td,J＝9.2,7.1Hz,1H),3.14(d,J＝2.6Hz,2H),2.08–1.98(m,1H),1.98–1.88(m,1H),1.79–1.72(m,1H),1.46–1.35(m,1H)；13C NMR(126MHz,CDCl3)δ201.65,172.04,144.55,138.26,134.66,128.20,124.35,122.17,121.19,116.66,115.77,113.60,109.49,83.87,60.88,47.65,33.86,25.47,23.58；
实施例14
产物化学式：C19H17BrNO2
分子量：370.04
结构式：
产率：75％
1H NMR(500MHz,CDCl3)δ7.64(dd,J＝7.8,1.5Hz,1H),7.58–7.49(m,1H),7.10–6.99(m,2H),6.94(t,J＝8.0Hz,1H),6.82(dd,J＝8.0,1.1Hz,1H),6.51–6.42(m,1H),3.71(dd,J＝9.8,5.7Hz,1H),3.44(td,J＝8.9,2.4Hz,1H),3.23(td,J＝9.2,7.2Hz,1H),3.06(d,J＝3.3Hz,2H),1.99–1.92(m,1H),1.92–1.80(m,1H),1.72–1.65(m,1H),1.38–1.27(m,1H)；13C NMR(126MHz,CDCl3)δ201.55,172.05,144.65,138.29,128.64,125.45,124.36,122.20,121.18,119.87,117.34,113.62,110.15,84.12,60.96,47.61,36.76,25.44,23.63；
实施例15
产物化学式：C20H20NO3
分子量：322.14
结构式：
产率：58％
1H NMR(500MHz,CDCl3)δ7.70(dd,J＝7.9,1.5Hz,1H),7.62–7.54(m,1H),7.13(t,J＝8.2Hz,1H),7.11–7.04(m,2H),6.29(dd,J＝9.5,8.3Hz,2H),3.76(s,4H),3.53(td,J＝8.7,2.5Hz,1H),3.31(td,J＝9.1,7.1Hz,1H),3.09(d,J＝17.3Hz,1H),2.96(dt,J＝17.2,1.3Hz,1H),2.07–1.95(m,1H),1.95–1.85(m,1H),1.78–1.70(m,1H),1.44–1.33(m,1H)；13CNMR(126MHz,CDCl3)δ202.46,172.12,157.86,144.20,138.00,127.89,124.20,121.90,121.41,113.60,105.82,104.75,98.73,84.32,60.74,55.38,47.77,30.12,25.53,23.55；
实施例16
产物化学式：C21H22NO2
分子量：320.16
结构式：
产率：88％
1H NMR(500MHz,CDCl3)δ7.74(dd,J＝7.9,1.5Hz,1H),7.66–7.59(m,1H),7.20(td,J＝7.9,1.7Hz,1H),7.15–7.10(m,2H),7.07(dd,J＝7.3,1.5Hz,1H),6.75(d,J＝8.3Hz,1H),6.69(td,J＝7.3,1.1Hz,1H),4.15–4.08(m,H),3.48(d,J＝17.3Hz,1H),3.38–3.32(m,1H),3.32–3.14(m,1H),2.75(dd,J＝17.5,1.8Hz,1H),2.27–2.12(m,2H),1.74–1.63(m,3H),1.62–1.46(m,3H).；13C NMR(126MHz,CDCl3)δ201.22,170.86,142.53,138.11,129.62,127.99,124.50,121.86,121.00,115.93,115.79,113.96,110.28,86.86,62.71,50.32,31.49,30.23,27.23,26.03,25.83；
实施例17
产物化学式：C20H20NO2
分子量：306.15
结构式：
产率：62％
1H NMR(500MHz,CDCl3)δ7.69(dd,J＝7.9,1.4Hz,1H),7.64–7.58(m,1H),7.17(t,J＝8.2Hz,2H),7.09(t,J＝7.4Hz,1H),6.98(dd,J＝11.5,7.9Hz,2H),6.73(t,J＝7.4Hz,1H),4.16–4.09(m,1H),3.46–3.28(m,2H),2.79(td,J＝12.4,2.9Hz,1H),2.71(d,J＝16.4Hz,1H),1.82–1.71(m,2H),1.70–1.59(m,1H),1.46–1.39(m,1H),1.39–1.30(m,1H)；13CNMR(126MHz,CDCl3)δ202.02,172.42,145.20,138.33,129.66,127.80,124.33,122.03,121.06,119.94,118.26,113.91,113.59,88.25,59.93,48.73,36.03,25.72,25.41,23.41；
实施例18
产物化学式：C24H20NO2
分子量：354.15
结构式：
产率：95％
1H NMR(500MHz,CDCl3)δ7.47–7.42(m,1H),δ7.40–7.34(m,1H),7.24–7.19(m,1H),7.14–7.06(m,2H),6.99–6.91(m,3H),6.87(dd,J＝14.4,7.7Hz,3H),6.78(td,J＝7.4,1.1Hz,1H),4.81(s,1H),4.04–3.98(m,1H),3.68(dd,J＝17.4,1.3Hz,1H),3.40(td,J＝11.5,2.9Hz,1H),3.31–3.17(m,1H),2.90(d,J＝17.5Hz,1H),2.69(dt,J＝14.7,2.7Hz,1H)；13C NMR(126MHz,CDCl3)δ202.46,171.49,145.86,137.51,137.17,131.04,129.30,128.47,127.82,127.42,127.18,125.68,123.89,121.65,121.42,119.43,117.73,113.99,112.49,89.61,60.95,45.24,36.13,30.49；
实施例19
产物化学式：C19H18NO3
分子量：308.13
结构式：
产率：52％
1H NMR(500MHz,CDCl3)δ7.71(d,J＝7.7Hz,1H),7.67–7.61(m,1H),7.23–7.15(m,2H),7.13(t,J＝7.5Hz,1H),7.01(d,J＝7.5Hz,1H),6.93(d,J＝8.4Hz,1H),6.80(t,J＝7.4Hz,1H),3.99(dd,J＝11.5,3.6Hz,1H),3.80(dd,J＝12.1,2.8Hz,1H),3.70(td,J＝11.8,2.9Hz,1H),3.66–3.57(m,2H),3.39(d,J＝16.9Hz,1H),3.28(t,J＝10.4Hz,1H),3.03(td,J＝12.0,3.7Hz,1H),2.76(d,J＝16.9Hz,1H)；13C NMR(126MHz,CDCl3)δ200.55,171.90,144.25,138.69,129.84,127.88,124.50,122.49,120.61,119.62,119.20,113.93,112.62,85.93,66.66,65.85,57.81,46.53,36.06；
实施例20
产物化学式：C19H19BrNO2
分子量：372.06
结构式：
产率：93％
1H NMR(500MHz,CDCl3)δ7.67(dt,J＝7.7,2.2Hz,1H),7.63–7.55(m,1H),7.15–7.01(m,2H),6.92–6.82(m,2H),6.81–6.72(m,1H),3.59–3.48(m,1H),3.37–3.22(m,3H),2.62(dd,J＝17.4,2.0Hz,1H),1.31–1.17(m,6H)；13C NMR(126MHz,CDCl3)δ200.80,170.65,143.21,138.28,131.05,124.56,122.09,121.67,119.42,118.65,115.57,113.73,86.15,57.39,45.31,30.62,14.92,12.94；
实施例21
产物化学式：C23H20NO2
分子量：342.15
结构式：
产率：64％
1H NMR(500MHz,CDCl3)δ7.80–7.67(m,3H),7.67–7.55(m,2H),7.43–7.36(m,2H),7.20(t,J＝7.4Hz,1H),7.15–7.02(m,3H),3.92–3.84(m,1H),3.72(td,J＝8.5,2.7Hz,1H),3.51–3.39(m,2H),3.31(d,J＝16.8Hz,1H),2.08–2.00(m,1H),2.00–1.91(m,1H),1.88–1.80(m,1H),1.52–1.41(m,1H).；13C NMR(126MHz,CDCl3)δ202.59,172.13,140.90,138.17,133.05,128.64,128.25,126.79,126.66,124.25,122.07,121.53,121.44,121.18,115.21,113.58,108.21,84.68,60.66,48.05,32.39,25.57,23.75；
实施例22
产物化学式：C18H17N2O2
分子量：293.13
结构式：
产率：69％
1H NMR(500MHz,CDCl3)δ8.12(dt,J＝5.2,1.5Hz,1H),7.72(dd,J＝7.9,1.4Hz,1H),7.65–7.59(m,1H),7.28–7.21(m,1H),7.17–7.07(m,2H),6.55(dd,J＝7.2,5.1Hz,1H),3.95(dd,J＝10.1,5.5Hz,1H),3.87–3.79(m,1H),3.56(td,J＝10.3,7.1Hz,1H),3.31(dq,J＝16.5,1.4Hz,1H),2.79(d,J＝16.4Hz,1H),2.06–1.98(m,1H),1.98–1.86(m,1H),1.79–1.72(m,1H),1.47–1.37(m,1H)；13C NMR(126MHz,CDCl3)δ201.49,171.93,153.88,146.96,138.38,135.97,124.35,122.27,121.05,113.59,113.07,111.75,83.16,61.64,46.61,35.63,25.83,23.45；
实施例23
产物化学式：C20H20NO3
分子量：322.14
结构式：
产率：75％
1H NMR(500MHz,CDCl3)δ7.22(dd,J＝9.0,2.9Hz,1H),7.20–7.15(m,1H),7.08(d,J＝2.8Hz,1H),7.06–7.02(m,1H),7.01(d,J＝9.0Hz,1H),6.65(td,J＝7.4,1.2Hz,1H),6.59(dd,J＝8.3,1.1Hz,1H),3.81(s,4H),3.55(td,J＝8.7,2.1Hz,1H),3.33(dd,J＝16.4,1.4Hz,1H),3.26(td,J＝9.3,7.0Hz,1H),2.80(d,J＝16.4Hz,1H),2.06–1.97(m,1H),1.97–1.87(m,1H),1.76–1.69(m,1H),1.42–1.32(m,1H)；13C NMR(126MHz,CDCl3)δ202.42,167.50,155.03,143.35,129.15,128.25,127.97,121.14,117.59,115.96,114.53,110.97,103.82,84.82,61.56,55.94,47.59,36.07,25.52,23.62；
实施例24
产物化学式：C19H17BrNO2
分子量：370.04
结构式：
产率：54％
1H NMR(500MHz,CDCl3)δ7.82(d,J＝2.2Hz,1H),7.66(dd,J＝8.8,2.2Hz,1H),7.19(td,J＝7.6,7.0,1.2Hz,1H),7.04(d,J＝7.4Hz,1H),6.99(d,J＝8.7Hz,1H),6.66(td,J＝7.4,1.1Hz,1H),6.60(d,J＝8.1Hz,1H),3.83(dd,J＝10.0,5.6Hz,1H),3.56(td,J＝8.7,2.1Hz,1H),3.33(dd,J＝16.6,1.5Hz,1H),3.26(td,J＝9.3,7.1Hz,1H),2.82(d,J＝16.4Hz,1H),2.06–1.99(m,1H),1.99–1.89(m,1H),1.78–1.70(m,1H),1.40–1.29(m,1H)；13CNMR(126MHz,CDCl3)δ200.75,170.72,143.20,140.63,129.16,128.09,126.73,123.00,117.15,116.09,115.38,114.64,111.04,85.22,61.49,47.56,36.00,25.53,23.59；
确定了反应条件后，对该反应的合成潜力进行了评价，结果如实施例2-24：无论氢化物供体的性质和苯基上取代基的性质如何，在高立体控制(>20:1dr)条件下，目标螺环的分离产率可达43-94％。一开始，我们试图研究Ar1的反应范围。令人满意的是，在4位上安装有供电子或吸电子取代基如甲氧基、氰基、三氟甲基、卤化物等的芳基环，反应效率高。氯的位置由4位(实施例6)变为3位(实施例8)对反应产率没有明显影响。此外，一系列在Ar1的5位或6位上含有卤化物的杂二烯顺利地进行了预期的反应，以57-89％的收率得到了相应的产物。值得一提的是，其他杂环取代基如氮杂环(实施例16)、哌啶(实施例17)、四氢异喹啉(实施例18)和吗啉(实施例19)也是可行的，虽然非对映选择性较低，但也得到了相应的螺环。更重要的是，非环胺也是该反应的良好氢供体，生成的产物实施例20的收率为93％。随后，对其他类型的Ar1进行了测试，以检验该策略的通用性。令人欣喜的是，含萘和吡啶的杂二烯反应平稳，实施例21和实施例22产物的产率适中，具有良好的非对映选择性。对苯并呋喃-3(2H)-酮的Ar2部分进行了供电子取代基(OMe)和吸电子取代基(Br)的测试，结果表明，吸电子取代基(实施例24)对转化略有削弱。
实施例25-34所述化合物的制备方法为：取原料橙酮类化合物3 0.1mmol，于催化剂Sc(OTf)3 2％、溶剂二氯甲烷(1mL)、温度为80℃的反应体系条件下进行反应。
实施例25
产物化学式：C19H18NOS
分子量：308.11
结构式：
产率：84％
1H NMR(500MHz,CDCl3)δ7.78(dd,J＝7.8,1.3Hz,1H),7.56–7.48(m,1H),7.32(d,J＝7.9Hz,1H),7.18(dt,J＝18.8,7.4Hz,2H),7.06(d,J＝7.4Hz,1H),6.64(t,J＝7.4Hz,1H),6.54(d,J＝8.1Hz,1H),3.94(dd,J＝9.4,5.8Hz,1H),3.60(d,J＝15.6Hz,1H),3.49(td,J＝8.7,2.2Hz,1H),3.24(td,J＝9.1,6.9Hz,1H),2.98(d,J＝15.6Hz,1H),2.08–2.00(m,1H),2.00–1.90(m,1H),1.88–1.81(m,1H),1.64–1.56(m,1H).；13C NMR(126MHz,CDCl3)δ203.54,152.47,143.04,135.86,131.75,129.18,128.15,126.44,124.69,124.18,119.09,115.94,111.05,64.12,63.41,47.25,40.44,27.23,23.53；
实施例26
产物化学式：C20H17N2OS
分子量：333.11
结构式：
产率：84％
1H NMR(500MHz,CDCl3)δ7.79(dd,J＝7.9,1.4Hz,1H),7.60–7.52(m,1H),7.35(d,J＝7.9Hz,1H),7.24(t,J＝7.6Hz,1H),7.11(d,J＝7.6Hz,1H),6.90(dd,J＝7.6,1.8Hz,1H),6.73(d,J＝1.7Hz,1H),3.95(dd,J＝9.6,5.9Hz,1H),3.59(d,J＝16.1Hz,1H),3.48(td,J＝8.8,1.9Hz,1H),3.22(td,J＝9.3,7.1Hz,1H),3.00(dd,J＝16.4,1.6Hz,1H),2.13–2.05(m,1H),2.05–1.94(m,1H),1.91–1.82(m,1H),1.67–1.57(m,2H)；13C NMR(126MHz,CDCl3)δ202.62,151.88,143.20,136.22,131.36,129.70,126.67,125.05,124.27,124.22,119.68,119.31,113.53,111.62,64.06,61.80,47.26,40.36,27.17,23.44；
实施例27
产物化学式：C19H17BrNOS
分子量：386.02
结构式：
产率：93％
1H NMR(500MHz,CDCl3)δ7.70(dd,J＝7.8,1.4Hz,1H),7.49–7.43(m,1H),7.26(d,J＝8.0Hz,1H),7.17–7.11(m,1H),6.82(d,J＝7.9Hz,1H),6.66(dd,J＝7.9,1.9Hz,1H),6.58(d,J＝1.9Hz,1H),3.84(dd,J＝9.6,5.7Hz,1H),3.46–3.34(m,2H),3.13(td,J＝9.3,7.0Hz,1H),2.85(d,J＝15.7Hz,1H),2.01–1.93(m,1H),1.92–1.82(m,1H),1.80–1.72(m,1H),1.58–1.47(m,1H)；13C NMR(126MHz,CDCl3)δ203.08,152.22,144.12,136.04,131.58,130.35,126.56,124.87,124.25,121.82,118.61,118.01,113.62,64.01,62.77,47.30,39.99,27.20,23.49；
实施例28
产物化学式：C20H20NO2S
分子量：338.12
结构式：
产率：87％
1H NMR(500MHz,CDCl3)δ7.77(d,J＝7.7Hz,1H),7.57–7.47(m,1H),7.32(d,J＝7.9Hz,1H),7.19(t,J＝7.5Hz,1H),7.12(t,J＝8.2Hz,1H),6.26(dd,J＝12.2,8.2Hz,2H),3.88(dd,J＝9.3,5.8Hz,1H),3.77(s,3H),3.47(td,J＝8.7,2.4Hz,1H),3.36–3.24(m,2H),3.20(d,J＝16.5Hz,1H),2.08–1.98(m,1H),1.98–1.91(m,1H),1.90–1.81(m,1H),1.63–1.57(m,2H)；13C NMR(126MHz,CDCl3)δ203.71,157.79,152.63,144.00,135.73,131.87,128.02,126.41,124.58,124.17,107.41,104.63,98.69,63.72,63.30,55.41,47.44,34.40,27.26,23.49；
实施例29
产物化学式：C19H17N2O3S
分子量：353.10
结构式：
产率：92％
1H NMR(500MHz,CDCl3)δ8.11(dd,J＝9.0,2.6Hz,1H),8.03(d,J＝2.6Hz,1H),7.83(dd,J＝8.0,1.3Hz,1H),7.60(td,J＝7.6,7.1,1.4Hz,1H),7.38(d,J＝7.9Hz,1H),7.28(t,J＝7.4Hz,2H),6.52(d,J＝9.1Hz,1H),4.05(dd,J＝9.9,5.6Hz,1H),3.68–3.58(m,2H),3.35(td,J＝10.0,7.1Hz,1H),3.05(d,J＝15.8Hz,1H),2.20–2.11(m,1H),2.10–1.98(m,1H),1.97–1.88(m,1H),1.76–1.65(m,1H)；13C NMR(126MHz,CDCl3)δ202.08,151.63,147.79,136.97,136.40,131.18,126.84,125.58,125.41,125.23,124.33,118.68,109.83,64.47,61.72,47.66,39.96,27.10,23.29；
实施例30
产物化学式：C23H20NOS
分子量：358.13
结构式：
产率：89％
1H NMR(500MHz,CDCl3)δ7.75(dd,J＝7.9,1.4Hz,1H),7.66–7.56(m,3H),7.44(td,J＝7.6,1.4Hz,1H),7.35–7.29(m,1H),7.22(d,J＝7.9Hz,1H),7.13(td,J＝7.5,4.5Hz,2H),6.93(d,J＝8.9Hz,1H),3.90(dd,J＝9.1,5.8Hz,1H),3.64–3.55(m,2H),3.48(d,J＝16.0Hz,1H),3.34(td,J＝8.8,7.0Hz,1H),2.05–1.95(m,1H),1.95–1.82(m,2H),1.64–1.54(m,1H)；13C NMR(126MHz,CDCl3)δ203.98,152.67,140.69,135.92,133.10,131.91,128.61,128.47,126.72,126.67,126.46,124.72,124.22,121.57,121.42,114.91,109.81,63.66,63.46,47.67,36.55,27.30,23.71；
实施例31
产物化学式：C24H20NOS
分子量：370.13
结构式：
产率：81％
1H NMR(500MHz,CDCl3)δ7.71(dd,J＝7.9,1.2Hz,1H),7.39–7.33(m,1H),7.27–7.21(m,1H),7.19(d,J＝7.9Hz,1H),7.14(dd,J＝7.8,4.7Hz,2H),7.11–7.02(m,3H),6.94(td,J＝7.6,1.8Hz,1H),6.87(d,J＝8.3Hz,1H),6.81(t,J＝7.3Hz,1H),5.06(s,1H),4.10–3.97(m,2H),3.52–3.43(m,1H),3.22(td,J＝11.6,2.8Hz,1H),3.10(d,J＝16.9Hz,1H),2.76(dt,J＝15.1,2.6Hz,1H)；13C NMR(126MHz,CDCl3)δ203.89,152.54,145.22,137.22,135.43,132.34,131.79,129.23,128.63,128.20,127.46,126.93,126.28,125.58,124.38,123.66,120.50,117.60,112.03,69.33,62.80,42.73,41.65,30.18；
实施例32
产物化学式：C19H19N2O3S
分子量：355.11
结构式：
产率：86％
1H NMR(500MHz,CDCl3,major)δ8.10(dq,J＝9.3,2.5Hz,1H),8.00(dq,J＝3.6,2.2,1.7Hz,1H),7.81(dq,J＝7.7,1.4Hz,1H),7.63–7.56(m,1H),7.33(dt,J＝7.9,1.1Hz,1H),7.28–7.23(m,1H),6.67(d,J＝9.2Hz,1H),3.80–3.72(m,1H),3.72–3.60(m,2H),3.39(dq,J＝14.6,7.2Hz,1H),2.88(dq,J＝16.9,2.0Hz,1H),1.41–1.36(m,3H),1.34(td,J＝7.2,1.1Hz,3H)；13C NMR(126MHz,CDCl3,major)δ200.73,150.38,147.04,137.00,136.42,130.96,127.13,126.12,125.11,125.08,123.96,117.32,109.91,62.52,61.61,45.56,33.54,15.74,12.38；
实施例33
产物化学式：C19H18NOS2
分子量：340.08
结构式：
产率：69％
1H NMR(500MHz,CDCl3,major)δ7.77(dd,J＝7.8,1.3Hz,2H),7.58–7.51(m,2H),7.30(d,J＝7.9Hz,1H),7.24–7.15(m,3H),7.04(d,J＝7.4Hz,1H),6.82(d,J＝8.4Hz,1H),6.75(td,J＝7.4,3.2Hz,2H),4.48(d,J＝15.0Hz,1H),3.88–3.79(m,2H),3.64(d,J＝16.9Hz,1H),3.59–3.48(m,2H),3.05(td,J＝12.8,2.7Hz,1H),2.99–2.75(m,5H),2.13(d,J＝13.4Hz,1H)；13C NMR(126MHz,CDCl3,major)δ201.12,151.70,141.45,136.35,130.79,130.23,128.40,127.13,124.84,123.94,119.81,117.98,112.88,64.43,63.73,50.86,35.08,27.76,24.25；
实施例34
产物化学式：C21H21N2O2
分子量：333.16
结构式：
产率：63％
1H NMR(500MHz,CDCl3)δ7.73–7.50(m,3H),7.12(t,J＝7.5Hz,1H),7.06(td,J＝7.7,1.6Hz,1H),6.88(d,J＝7.4Hz,1H),6.54(td,J＝7.4,1.1Hz,1H),6.49(d,J＝8.1Hz,1H),4.65(dd,J＝10.2,5.2Hz,1H),4.10(d,J＝16.1Hz,1H),3.45(tt,J＝7.0,3.6Hz,1H),3.37–3.23(m,1H),2.64(d,J＝16.0Hz,1H),2.53(s,3H),1.89–1.73(m,3H),1.26–1.15(m,1H)；13C NMR(126MHz,CDCl3)δ197.26,168.79,151.51,143.92,136.42,128.80,127.40,124.45,124.32,124.03,117.29,116.27,115.93,110.84,69.90,58.66,47.81,32.63,27.53,26.94,23.35；
实施例25～34制备了苯并[b]噻吩衍生的杂二烯。由实施例25～34可知：在Ar1环上具有4-(实施例26,实施例27)、6-(实施例28)或5-缺电子和富电子取代基(实施例29)的苯并[b]噻吩衍生物都能很好地耐受，非对映选择性地得到相应的含硫螺环。此外，含萘的杂二烯在该反应中也能很好地分离(实施例30)。其他氢化物供体如四氢异喹啉(实施例31)、乙胺(实施例32)、硫咪唑啉(实施例33)等也在标准条件下进行了测试，得到了产率良好的多环化合物(69-86％)。特别值得注意的是，吲哚啉酮衍生的杂二烯类经过反应，以63％的收率得到产物(实施例34)。
以上所述实施例仅提供了本发明的几种实施方式，但并不能因此而理解为对本发明专利保护范围的限制。应当指出的是，对于本领域的普通技术人员来说看，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。
Claims (8)
1.一种具橙酮骨架类化合物作为受体进行反-Micheal加成反应的方法，其特征在于，是以具橙酮骨架类化合物作为受体，在路易斯酸作为催化剂的作用下，将共轭的羰基与双键作为Michael加成的受体，通过负氢迁移、芳构化、去芳构化、环化反应得到氧杂二烯的α-官能化反-Michael加成产物；
化学反应式如下：
式I和式II中：
X为O、S或N中的一种；
R1为氢、甲基、甲氧基、氰基、三氟甲基、卤素、苯基或者亚硝基中的一种；
R2为卤素或者甲氧基；
R3、R4可构成成环结构，成环时，包括五元环、六元环、七元环、并环以及杂环；不成环时，R3、R4为C1-C3烷基。
2.根据权利要求1所述具橙酮骨架类化合物作为受体进行反-Micheal加成反应的方法，所述催化剂为Sc(OTf)3、Cu(OTf)2、Zn(OTf)2、Mg(OTf)2、TsOH·H2O、(-)-CSA和TfOH中的任意一种。
3.根据权利要求2所述具橙酮骨架类化合物作为受体进行反-Micheal加成反应的方法，所述催化剂的浓度为1-20mol％
4.根据权利要求1所述具橙酮骨架类化合物作为受体进行反-Micheal加成反应的方法，所述反应是在溶剂中完成的，所述溶剂为二氯甲烷、二氯乙烷、乙醇、甲苯、四氢呋喃以及乙腈中的一种。
5.根据权利要求1所述具橙酮骨架类化合物作为受体进行反-Micheal加成反应的方法，所述反应的温度为60-120℃。
6.根据权利要求1所述具橙酮骨架类化合物作为受体进行反-Micheal加成反应的方法，其特征在于，所述反应的时间为1.5-3.5h。
7.权利要求1-6任一项所述具橙酮骨架类化合物作为受体进行反-Micheal加成反应的方法，其特征在于，化学反应式如下：
8.根据权利要求1～6任一项所述具橙酮骨架类化合物作为受体进行反-Micheal加成反应的方法，其特征在于，所述具橙酮骨架类化合物还包括：
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