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• 5-(1-苯基-3-苯基丙基-2-炔基)-2, 2-二甲基-1, 3-二噁烷-4, 6-二酮分子内存在麦氏酸结构, 通过开环可以合成γ-烷基丁内酯^{[1, 2]}、β-炔基脂肪酸或其衍生物^{[3, 4]}.它是制备黄陂酰胺生物碱的关键中间体^[5].此外, 它也是有机合成中非常重要的合成砌块.

  目前, 5-(1-苯基-3-苯基丙基-2-炔基)-2, 2-二甲基- 1, 3-二噁烷-4, 6-二酮的合成方法主要有: (1)有机炔基盐如炔基锂、炔基铝、炔基锌等参与的共轭加成反应(Eq. 1)^[6~10]; (2)碱性条件下三氟甲基磺酸锌促进的5-烯基米氏酸与苯乙炔发生共轭加成反应(Eq. 2)^[11]; (3)水相醋酸铜促进5-烯基米氏酸与苯乙炔发生共轭加成反应(Eq. 3)^[12]; (4)两步法, 即在乙醇溶剂中2, 2-二甲基-1, 3-二噁烷-4, 6-二酮与芳香醛发生Knoevenagel缩合反应制备5-烯基米氏酸, 再与苯乙炔发生Conjugate加成反应得到目标产物(Eq. 4)^[4].方法(1)、(2)无水无氧条件下需要加入促进剂t-BuMe₂SiOTf进行反应, 且后处理工艺复杂、反应时间长、收率较低.方法(3)、(4)也存在反应时间长、反应副产物较多、需柱层析分离产品等不足.因此, 发展绿色、简便及高效合成的新方法显得极为迫切.

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  与分步进行的单分子反应和双分子反应相比较, 多组分反应具有简单、高效、高选择性和原子经济性等特点, 被认为是最接近理想的合成方法.它是当今有机化学的研究重点之一, 已广泛应用于天然产物的全合成、杂环化合物的合成、组合化学领域.我们课题组^{[13, 14]}曾通过Yonemitsu反应、Biginelli-like反应成功制备了具有潜在生物活性的含吲哚环、螺环或双螺环结构的杂环化合物.基于此, 本文报道以醋酸铜和抗坏血酸钠为催化体系, 用2, 2-二甲基-1, 3-二噁烷-4, 6-二酮、醛和苯乙炔发生三组分反应合成5-(1-苯基-3-苯基丙基-2-炔基)-2, 2-二甲基-1, 3-二噁烷-4, 6-二酮衍生物, 合成路线见Eq. 5.

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  1.   结果与讨论

  1.1   反应条件的优化

  以苯甲醛、2, 2-二甲基-1, 3-二噁烷-4, 6-二酮及苯乙炔为标准反应, 探索了不同过渡金属盐、铜源、还原剂、溶剂和反应时间对反应的影响, 实验结果见表 1.首先对不同过渡金属盐进行了筛选, 发现金属铜盐具有一定的催化效果, 但不同金属铜盐的催化活性表现出较大的差异性.硫酸铜、氯化铜、碱式碳酸铜被抗坏血酸钠还原后, 由于阴离子配位效果较差, 亚铜离子不稳定易发生歧化反应. Cu(acac)₂、Cu(NH₃)₄SO₄还原后亚铜离子不稳定易被氧化形成更稳定二价铜离子配合物, 因此, 催化效果较差. CuI在中性及无强配体时不能解离出亚铜离子, 不能生成苯乙炔基铜, 因此, 仅得到5, 5-(苯基亚甲基)双(2, 2-二甲基-1, 3-二噁烷-4, 6-二酮)[¹H NMR (400 MHz, CDCl₃) δ: 1.68 (s, 6H), 1.81 (s, 6H), 4.61~4.68 (m, 3H), 7.29~7.37 (m, 3H), 7.53 (d, J＝7.6 Hz, 2H)]副产物, 而Cu(OAc)₂•(H₂O)的催化效果最好(表 1, Entries 1~12).然后考察了不同还原剂对反应的影响, 当还原剂为NH₂OH•HCl时未检测到目标产物.当还原剂为抗坏血酸钠时产品收率可达76%(表 1, Entries 12~14).接着对溶剂进行了筛选, 此反应在PEG400/H₂O (V:V＝1:1)混合溶剂中的反应效果最优(表 1, Entries 15~17).最后对反应时间也进行了考察, 实验结果表明最佳反应时间为6.0 h.综上所述, 优化的反应条件是:在醋酸铜催化作用下, 以抗坏血酸钠为还原剂, 以PEG400/H₂O (V:V＝1:1)为反应溶剂, 溶剂用量4.0 mL, 反应原料(苯甲醛、2, 2-二甲基-1, 3-二噁烷-4, 6-二酮与苯乙炔)的物质的量之比为2:1:1.5, 反应温度为室温, 最佳反应时间为6.0 h.

  表 1

  

  表 1  化合物4a反应条件的优化^a

  Table 1.  Optimization of reaction conditions for the synthesis of 4a

  下载: 导出CSV

  Entry	Copper(Ⅱ) source	Reductant	Solvent (mL)	Time/h	Yieldb/%
  1	Fe(OAc)2	Sodium ascorbate	PEG400/H2O (1:1)	12	6
  2	Zn(OAc)2(H2O)2	Sodium ascorbate	PEG400/H2O (1:1)	12	0
  3	Ni(OAc)2	Sodium ascorbate	PEG400/H2O (1:1)	12	0
  4	Mn(OAc)2	Sodium ascorbate	PEG400/H2O (1:1)	12	0
  5	CuSO4(H2O)5	Sodium ascorbate	PEG400/H2O (1:1)	12	49
  6	CuCl2(H2O)2	Sodium ascorbate	PEG400/H2O (1:1)	12	36
  7	Cu2(CO3)(OH)2	Sodium ascorbate	PEG400/H2O (1:1)	12	12
  8	Cu(acac)2	Sodium ascorbate	PEG400/H2O (1:1)	12	9
  9	Cu(NH3)4SO4	Sodium ascorbate	PEG400/H2O (1:1)	12	20
  10c	CuI	—	PEG400/H2O (1:1)	20	0
  11d	CuOAc	—	PEG400/H2O (1:1)	6	48
  12	Cu(OAc)2(H2O)	Sodium ascorbate	PEG400/H2O (1:1)	6	76
  13c	Cu(OAc)2(H2O)	NH2OH•HCl	PEG400/H2O (1:1)	6	0
  14	Cu(OAc)2(H2O)	Na2SO3	PEG400/H2O (1:1)	6	42
  15	Cu(OAc)2(H2O)	Sodium ascorbate	TBA/H2O (1:10)	8	61
  16	Cu(OAc)2(H2O)	Sodium ascorbate	Ethanol/H2O (1:1)	12	55
  17c	Cu(OAc)2(H2O)	Sodium ascorbate	H2O	12	0
  18	Cu(OAc)2(H2O)	Sodium ascorbate	PEG400/H2O (1:1)	8	76
  19	Cu(OAc)2(H2O)	Sodium ascorbate	PEG400/H2O (1:1)	5	68
  a The reaction conditions were conducted using 20 mol% Cu(Ⅱ) salt, 1.5 equiv. of PhC≡CH, and 40 mol% reductant in 4 mL of solvent at room temperature; b Isolated yield; c The products were 5, 5-(phenylmethylene)bis(2, 2-dimethyl-1, 3-dioxane-4, 6-dione); d The reaction conditions: CuOAc was synthesized from a solution of 20 mol% Cu(Ⅱ) salt and 40 mol% reductant in 4 mL of PEG400)/H2O (V:V＝1:1), subsequently. 1.5 equiv. of PhC≡CH, 2.0 equiv. of benzaldehyde and 1 mmol of 2, 2-dimethyl-1, 3-dioxane-4, 6-dione were added.

  1.2   反应底物的拓展

  在上述优化反应条件下, 系统考察了不同的醛、2, 2-二甲基-1, 3-二噁烷-4, 6-二酮与苯乙炔的三组分反应(表 2).从表 2可看出该反应体系无论脂肪醛还是芳香醛反应均可顺利进行, 并以63%~86%较高收率得到相应的目标产物.对芳香环上的取代基的电性也不是很敏感, 不同取代的芳香醛参与该反应均可获得较高收率, 但反应底物的电子效应对反应速度有显著的影响, 带吸电子基的芳香醛反应速度一般快于带供电子基的芳香醛, 对于芳杂醛如呋喃甲醛也能得到较好的反应效果.

  表 2

  

  表 2  化合物4a~4j的合成^a

  Table 2.  Synthesis of compounds 4a~4j

  下载: 导出CSV

  Entry	R	Time/h	Product	Yieldb/%
  1	C6H5	6.0	4a	76
  2	4-FC6H4	4.0	4b	72
  3	4-ClC6H4	5.0	4c	75
  4	4-CH3C6H4	8.0	4d	69
  5	4-O2NC6H4	5.0	4e	68
  6	4-CH3OC6H4	12.0	4f	81
  7	2-Furyl	16.0	4g	80
  8	PhCH＝CH	20.0	4h	86
  9	CH3CH2	16.0	4i	63
  10	CH3(CH2)2	16.0	4j	71
  a The reaction conditions were conducted using 20 mol% Cu(OAc)2, 1.5 equiv. of PhC≡CH, and 40 mol% sodium ascorbate in 4 mL of PEG400/H2O (V: V＝1:1) at room temperature; b Isolated yield.

  1.3   反应机理探讨

  依据已有的文献报道^{[12, 15~17]}和实验探索结果, 对该反应提出了如Scheme 1所示的可能机理.以4a的形成为反应模型对此机理进行阐述.一方面, 极性质子溶剂中苯甲醛(2a)与2, 2-二甲基-1, 3-二噁烷-4, 6-二酮(1)发生Knoevenagel缩合反应产生中间体5; 另一方面, 醋酸铜被抗坏血酸钠还原, 再与苯乙炔形成苯乙炔基亚铜中间体6; 最后, 中间体5与苯乙炔基亚铜中间体6发生Conjugate加成反应得到目标产物4a.

  图式 1

  

  图式 1.  生成化合物4a可能的机理

  Scheme 1.  Proposed mechanism for the imformation of 4a

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  2.   结论

  在PEG400/H₂O (V:V＝1:1)反应溶剂中, 以醋酸铜和抗坏血酸钠为催化体系, 以醛、2, 2-二甲基-1, 3-二噁烷-4, 6-二酮与苯乙炔发生Knoevenagel缩合与Conjugate加成反应的多组分反应有效地合成了10种5-(1-苯基-3-苯基丙基-2-炔基)-2, 2-二甲基-1, 3-二噁烷-4, 6-二酮衍生物, 并确定了较好的反应条件: 20 mol% Cu(OAc)₂- (H₂O), 40 mol%抗坏血酸钠, 4.0 mL PEG400)/H₂O (V:V＝1:1), 反应原料(醛、2, 2-二甲基-1, 3-二噁烷-4, 6-二酮与苯乙炔)的物质的量之比为2:1:1.5, 室温反应4.0~20.0 h, 产品收率为63%~86%.该反应具有反应温和、操作简单及环境友好等优点, 为合成5-(3-苯基-1-苯基丙基-2-炔基)-2, 2-二甲基-1, 3-二噁烷-4, 6-二酮衍生物提供了一种有效的方法.

  3.   实验部分

  3.1   仪器与试剂

  瑞士BuchiB-540型显微熔点仪(温度计未经校正); 德国Bruker 400 MHz型核磁共振仪(CDCl₃为溶剂, TMS为内标); MS谱由ABI公司API3200三重四级杆质谱仪记录.

  2, 2-二甲基-1, 3-二噁烷-4, 6-二酮按文献[18]制备; 苯甲醛、4-甲基苯甲醛、4-氯苯甲醛、4-氟苯甲醛、2-氯苯甲醛、4-硝基苯甲醛、4-甲氧基苯甲醛、2-呋喃甲醛及肉桂醛(西陇化工股份有限公司, 分析纯); 其它试剂均为化学纯, 天津市永大化学试剂有限公司生产.

  3.2   化合物4a~4j的合成

  在20 mL试管中加入PEG400)/H₂O (V:V＝1:1)的混合溶剂4 mL、Cu(OAc)₂•(H₂O) 0.2 mmol、2, 2-二甲基-1, 3-二噁烷-4, 6-二酮1 mmol、芳香醛2 mmol和抗坏血酸钠0.4 mol, 于室温磁力搅拌反应4.0~20.0 h.反应完毕, 加入二氯甲烷和氯化铵饱和溶液, 分出有机层, 水层用二氯甲烷萃取两次.再合并有机层, 无水硫酸镁干燥, 过滤.减压回收二氯甲烷得粗产品, 再用无水乙醇重结晶、干燥得目标化合物4a~4j.

  5-(1-苯基-3-苯基丙基-2-炔基)-2, 2-二甲基-1, 3-二噁烷-4, 6-二酮(4a):白色固体, m.p. 160~162 ℃ (Lit.^[12] 159~161 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 1.63 (s, 3H), 1.75 (s, 3H), 4.01 (d, J＝2.8 Hz, 1H), 5.16 (d, J＝2.8 Hz, 1H), 7.26~7.33 (m, 3H), 7.36~7.40 (m, 2H), 7.47~7.51 (m, 2H), 7.63 (d, J＝7.2 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 27.82, 28.37, 37.09, 52.89, 85.55, 86.21, 105.33, 122.75, 127.87, 128.27, 128.41, 128.53, 128.73, 131.91, 137.16, 163.18, 163.86.

  5-[1-(4-氟苯基)-3-苯基丙基-2-炔基)]-2, 2-二甲基- 1, 3-二噁烷-4, 6-二酮(4b):白色固体, m.p. 141~143 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 1.65 (s, 3H), 1.74 (s, 3H), 3.97 (d, J＝2.8 Hz, 1H), 5.13 (d, J＝2.8 Hz, 1H), 7.01~7.07 (m, 2H), 7.36~7.40 (m, 2H), 7.44~7.50 (m, 2H), 7.57~7.63 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 27.74, 28.34, 36.33, 52.88, 85.58, 86.18, 105.34, 115.26, 115.47, 122.59, 128.29 128.51, 130.62 (d, J＝8.0 Hz), 131.87, 132.81 (d, J＝3.0 Hz), 161.11 (d, J＝246.5 Hz), 163.19, 163.57; HRMS calcd for C₂₁H₁₇FNaO₄ [M+Na]⁺ 375.1009, found 375.1002.

  5-[1-(4-氯苯基)-3-苯基丙基-2-炔基)]-2, 2-二甲基- 1, 3-二噁烷-4, 6-二酮(4c):白色固体, m.p. 124~126 ℃(Lit.^[12] 124~127 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 1.66 (s, 3H), 1.73 (s, 3H), 4.01 (d, J＝2.8 Hz, 1H), 5.13 (d, J＝2.8 Hz, 1H), 7.26~7.34 (m, 5H), 7.42~7.51 (m, 2H), 7.58 (d, J＝8.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 27.68, 28.36, 36.89, 52.77, 85.60, 85.86, 105.24, 122.38, 128.17, 128.40, 128.46, 130.11, 131.78, 135.42, 162.91, 163.31.

  5-[1-(4-甲基苯基)-3-苯基丙基-2-炔基)]-2, 2-二甲基- 1, 3-二噁烷-4, 6-二酮(4d):白色固体, m.p. 129~131 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 1.62 (s, 3H), 1.73 (s, 3H), 2.34 (s, 3H), 3.97 (d, J＝2.4 Hz, 1H), 5.12 (d, J＝2.4 Hz, 1H), 7.17 (d, J＝8.0 Hz, 2H), 7.29~7.32 (m, 3H), 7.46~7.51 (m, 4H); ¹³C NMR (100 MHz, CDCl₃) δ: 21.10, 27.83, 28.36, 36.83, 52.94, 85.38, 85.49, 105.27, 122.84, 128.24, 128.34, 128.60, 129.24, 131.89, 134.14, 137.60, 163.21, 163.89; HRMS calcd for C₂₂H₂₀NaO₄ [M+Na]⁺ 371.1259, found 371.1272.

  5-[(4-硝基苯基)-3-苯基丙基-2-炔基)]-2, 2-二甲基- 1, 3-二噁烷-4, 6-二酮(4e):淡黄色固体, m.p. 140~142 ℃ (Lit.^[12] 142~145 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 1.73 (s, 3H), 1.79 (s, 3H), 4.02 (d, J＝2.4 Hz, 1H), 5.16 (d, J＝2.4 Hz, 1H), 7.29~7.36 (m, 3H), 7.42~7.51 (m, 2H), 7.81 (d, J＝8.8 Hz, 2H), 8.24 (d, J＝8.8 Hz, 2 H); ¹³C NMR (100 MHz, CDCl₃) δ: 27.63, 28.41, 36.90, 52.74, 84.83, 86.47, 105.53, 121.96, 123.59, 128.30, 128.72, 129.83, 131.91, 144.32, 147.69, 162.84, 163.20.

  5-[1-(4-甲氧基苯基)-3-苯基丙基-2-炔基)]-2, 2-二甲基-1, 3-二噁烷-4, 6-二酮(4f):淡黄色固体, m.p. 88~90 ℃ (Lit.^[12] 88~91 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 1.62 (s, 3H), 1.73 (s, 3H), 3.85 (s, 3H), 4.00 (d, J＝2.4 Hz, 1H), 5.11 (d, J＝2.4 Hz, 1H), 6.88 (d, J＝8.8 Hz, 1H), 7.29~7.33 (m, 3H), 7.46~7.51 (m, 2H), 7.57 (d, J＝8.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 27.80, 28.34, 36.92, 52.97, 55.38, 85.17, 86.20, 105.13, 113.66, 122.63, 128.11, 128.29, 129.01, 129.80, 131.76, 158.69, 163.12, 163.52.

  5-[1-(2-呋喃基)-3-苯基丙基-2-炔基)]-2, 2-二甲基- 1, 3-二噁烷-4, 6-二酮(4g):灰色固体, m.p. 131~132 ℃(1it.^[12] 129~131 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 1.75 (s, 3H), 1.82 (s, 3H), 4.18 (d, J＝2.4 Hz, 1H), 5.16 (d, J＝2.4 Hz, 1H), 6.38 (dd, J＝1.9, 3.2 Hz, 1H), 6.53~6.59 (m, 1 H), 7.30~7.38 (m, 4H), 7.44~7.50 (m, 4H); ¹³C NMR (100 MHz, CDCl₃) δ: 27.61, 28.27, 31.53, 49.65, 83.84, 84.65, 105.37, 108.45, 110.11, 122.38, 128.23, 128.59, 131.96, 141.87, 150.00, 162.44, 163.31.

  5-(1-苯乙烯基-3-苯基丙基-2-炔基)-2, 2-二甲基-1, 3-二噁烷-4, 6-二酮(4h):黄色固体, m.p. 128~130 ℃(1it.^[12] 129~132 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 1.765 (s, 3H), 1.81 (s, 3H), 3.92 (d, J＝3.2 Hz, 1H), 4.56~4.62 (m, 1H), 6.52 (dd, J＝7.2, 15.6 Hz, 1H), 6.82 (d, J＝15.6 Hz, 1H), 7.24~7.38 (m, 6H), 7.42~7.51 (m, 4H); ¹³C NMR (100 MHz, CDCl₃) δ: 27.32, 28.44, 34.73, 52.01, 84.42, 86.23, 105.17, 122.69, 124.97, 126.56, 127.83, 128.20, 128.47, 131.76, 133.68, 136.10, 163.09, 163.22.

  5-(1-乙基-3-苯基丙基-2-炔基)-2, 2-二甲基-1, 3-二噁烷-4, 6-二酮(4i):白色固体, m.p. 140~142 ℃ (Lit.^[12] 139~140 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 1.16 (t, J＝7.5 Hz, 3H), 1.68~1.82 (m, 1H), 1.76 (s, 6H), 2.06~2.17 (m, 1H), 3.48~3.57 (m, 1H), 3.65 (d, J＝2.4 Hz, 1H), 7.24~7.31 (m, 3H), 7.36~7.44 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 12.78, 26.22, 27.63, 28.57, 34.12, 49.80, 83.77, 87.64, 105.19, 122.86, 127.89, 128.20, 131.76, 163.51, 164.39.

  5-(1-丙基-3-苯基丙基-2-炔基)-2, 2-二甲基-1, 3-二噁烷-4, 6-二酮(4j):白色固体, m.p. 122~124 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 0.99 (t, J＝7.2 Hz, 3H), 1.44~1.55 (m, 1H), 1.59~1.75 (m, 2H), 1.78 (s, 6H), 2.10~2.18 (m, 1H), 3.65~3.70 (m, 2H), 7.25~7.30 (m, 3H), 7.37~7.41 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 13.60, 21.22, 27.65, 28.54, 32.09, 34.76, 50.06, 83.66, 88.02, 105.22, 122.99, 128.11, 128.17, 131.82, 163.73, 164.45; HRMS calcd for C₁₈H₂₀NaO₄ [M+Na]⁺ 323.1259, found 323.1276.

  辅助材料(Supporting Information)   化合物4a, 4b, 4d, 4f, 4g, 4i的NMR谱.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

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• 

  图式 1  生成化合物4a可能的机理

  Scheme 1  Proposed mechanism for the imformation of 4a

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  表 1  化合物4a反应条件的优化^a

  Table 1.  Optimization of reaction conditions for the synthesis of 4a

  Entry	Copper(Ⅱ) source	Reductant	Solvent (mL)	Time/h	Yieldb/%
  1	Fe(OAc)2	Sodium ascorbate	PEG400/H2O (1:1)	12	6
  2	Zn(OAc)2(H2O)2	Sodium ascorbate	PEG400/H2O (1:1)	12	0
  3	Ni(OAc)2	Sodium ascorbate	PEG400/H2O (1:1)	12	0
  4	Mn(OAc)2	Sodium ascorbate	PEG400/H2O (1:1)	12	0
  5	CuSO4(H2O)5	Sodium ascorbate	PEG400/H2O (1:1)	12	49
  6	CuCl2(H2O)2	Sodium ascorbate	PEG400/H2O (1:1)	12	36
  7	Cu2(CO3)(OH)2	Sodium ascorbate	PEG400/H2O (1:1)	12	12
  8	Cu(acac)2	Sodium ascorbate	PEG400/H2O (1:1)	12	9
  9	Cu(NH3)4SO4	Sodium ascorbate	PEG400/H2O (1:1)	12	20
  10c	CuI	—	PEG400/H2O (1:1)	20	0
  11d	CuOAc	—	PEG400/H2O (1:1)	6	48
  12	Cu(OAc)2(H2O)	Sodium ascorbate	PEG400/H2O (1:1)	6	76
  13c	Cu(OAc)2(H2O)	NH2OH•HCl	PEG400/H2O (1:1)	6	0
  14	Cu(OAc)2(H2O)	Na2SO3	PEG400/H2O (1:1)	6	42
  15	Cu(OAc)2(H2O)	Sodium ascorbate	TBA/H2O (1:10)	8	61
  16	Cu(OAc)2(H2O)	Sodium ascorbate	Ethanol/H2O (1:1)	12	55
  17c	Cu(OAc)2(H2O)	Sodium ascorbate	H2O	12	0
  18	Cu(OAc)2(H2O)	Sodium ascorbate	PEG400/H2O (1:1)	8	76
  19	Cu(OAc)2(H2O)	Sodium ascorbate	PEG400/H2O (1:1)	5	68
  a The reaction conditions were conducted using 20 mol% Cu(Ⅱ) salt, 1.5 equiv. of PhC≡CH, and 40 mol% reductant in 4 mL of solvent at room temperature; b Isolated yield; c The products were 5, 5-(phenylmethylene)bis(2, 2-dimethyl-1, 3-dioxane-4, 6-dione); d The reaction conditions: CuOAc was synthesized from a solution of 20 mol% Cu(Ⅱ) salt and 40 mol% reductant in 4 mL of PEG400)/H2O (V:V＝1:1), subsequently. 1.5 equiv. of PhC≡CH, 2.0 equiv. of benzaldehyde and 1 mmol of 2, 2-dimethyl-1, 3-dioxane-4, 6-dione were added.

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  表 2  化合物4a~4j的合成^a

  Table 2.  Synthesis of compounds 4a~4j

  Entry	R	Time/h	Product	Yieldb/%
  1	C6H5	6.0	4a	76
  2	4-FC6H4	4.0	4b	72
  3	4-ClC6H4	5.0	4c	75
  4	4-CH3C6H4	8.0	4d	69
  5	4-O2NC6H4	5.0	4e	68
  6	4-CH3OC6H4	12.0	4f	81
  7	2-Furyl	16.0	4g	80
  8	PhCH＝CH	20.0	4h	86
  9	CH3CH2	16.0	4i	63
  10	CH3(CH2)2	16.0	4j	71
  a The reaction conditions were conducted using 20 mol% Cu(OAc)2, 1.5 equiv. of PhC≡CH, and 40 mol% sodium ascorbate in 4 mL of PEG400/H2O (V: V＝1:1) at room temperature; b Isolated yield.

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