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• γ-吡喃酮和3(2H)-呋喃酮等作为基本的结构单元广泛存在于天然产物中^[1].据报道, 具有这些结构的化合物具有广泛的生物活性^[2]和药理活性^[3].此外, 它们也是有价值的有机合成砌块^[4].近十多年来, 官能团化的γ-吡喃酮和3(2H)-呋喃酮衍生物的构建和合成应用已经引起极大的关注. γ-吡喃酮和3(2H)-呋喃酮衍生物的基本结构单元通常由不同的原料经两种完全不同的途径构建.到目前为止, 大量的合成方法已经被报道^[5].然而, 它们普遍存在某些缺点, 如非原子经济性、使用昂贵金属作为催化剂、苛刻的反应条件或官能团不相容性.

  1, 3-二羰基化合物SM是重要的有机合成原料^[6n].羰基氧对炔键的亲核进攻, 经6-endo-dig环化构建γ-吡喃酮(Scheme 1, Path a), 经5-exo-dig环化构建3(2H)-呋喃酮(Scheme 1, Path b).这种由同一原料制备两种不同的杂环化合物的策略具有100%原子经济性.为了实现这个目标, 化学工作者们已经进行了许多尝试, 如碱酸催化转化^[6a~6m].然而, 在相关报道中, γ-吡喃酮始终是主要产物, 3(2H)-呋喃酮总是次要产物^[6d].迄今, 试图通过酸碱催化实现其区域选择性逆转环化, 选择性构建3(2H)-呋喃酮的任何努力都未获得成功.

  图式 1

  

  图式 1.  1, 3-二羰基前体环化的可能方式

  Scheme 1.  Possible mode of the cyclization of 1, 3-dicarbonyl precursors

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  重氮官能团具有多方面的反应性能, 因此, 重氮化合物是重要的有机合成中间体^[7].重氮γ-吡喃酮和重氮3(2H)-呋喃酮是不同寻常的官能团化杂环化合物, 它们的选择性构建是我们探索的目标.最近, 我们报道了Ag(Ⅰ)催化2-重氮-3, 5-二氧代-6-炔酯/炔酮/炔酰胺区域选择性逆转合成重氮γ-吡喃酮和重氮3(2H)-呋喃酮衍生物的方法(Scheme 1)^[8].虽然这种Ag(Ⅰ)催化环化是一种实用且有效的方法, 但无过渡金属催化的区域选择性逆转环化一直是化学工作者探索的目标(Scheme 1).我们最近还报道了三乙胺介入2-重氮-3, 5-二氧代-6-炔酯的环化, 得到吡喃骈[3, 2-c]吡唑-7(1H)-酮衍生物(Scheme 1)^[9].此外, 在HSbF₆-MeOH反应体系中, 2-重氮-3, 5-二氧代-6-炔酯转化为重氮γ-吡喃酮; 在HOAc-1, 2-二氯乙烷(DCE)反应体系中, 则生成重氮3(2H)-呋喃酮^[8].但这种酸催化形成重氮3(2H)-呋喃酮的效率低下, 反应时间长达数天.特别需要指出的是, 在延长反应时间的情况下, 重氮3(2H)-呋喃酮可以逆向转化为相应的重氮γ-吡喃酮.在长时间存放过程中, 也发现重氮3(2H)-呋喃酮的这种自发转化.因此, 有必要提高这种酸催化合成重氮3(2H)-呋喃酮的反应活性.在此, 我们报道酸调控的2-重氮-3, 5-二氧代-6-炔酯(炔酮, 炔酰胺)区域选择性逆转环化的结果.

  1.   结果与讨论

  采用文献报道方法制备2-重氮-3, 5-二氧代-6-炔酮/炔酯/炔酰胺1a~1s^[8].首先, 使用2-重氮-3, 5-二氧代-7-对甲苯基-6-庚炔酯1b作为底物, 对反应条件进行优化(表 1).在60 ℃条件下, MeOH作溶剂, HSbF₆催化的底物1b的环化反应产生重氮吡喃酮2b, 但没有观察到相应的重氮3(2H)-呋喃酮(3b)和吡喃骈[3, 2-c]吡唑-7(1H)-酮(4b) (表 1, Entry 1).此外, 还考察了TsOH、H₂SO₄、HCl、三氟醋酸(TFA)、H₃PO₄、TfOH、HOAc等多种质子酸, 均获得了较好的产率(表 1, Entries 1~8).在考察的酸中, HSbF₆具有最好的反应活性和选择性, 用于有效地构建重氮γ-吡喃酮2b.然后, 考察了溶剂对形成重氮γ-吡喃酮2b的影响.通过薄层色谱(TLC)监测, 当使用四氢呋喃(THF)、CH₃CN和EtOAc作为溶剂时, 没有发现目标产物形成(表 1, Entries 9~11).基于反应活性, 在考察的溶剂中, EtOH最有利于重氮γ-吡喃酮2b的形成(表 1, Entry 12).最后, 当温度升高到80 ℃时, 反应时间进一步缩短, 而且对反应选择性没有影响(表 1, Entry 13).因此, 形成重氮γ-吡喃酮2b的最优反应条件是: 80 ℃, EtOH作为溶剂, HSbF₆作为催化剂.

  表 1

  

  表 1  环化反应的条件优化^a

  Table 1.  Optimization of the cyclization

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  Entry	Catalyst	Base	Solvent	T/℃	t/h	Yieldb/%	n(2b):n(3b):n(4b)c
  1	HSbF6	—	MeOH	60	22	95	100:0:0
  2	TsOH	—	MeOH	60	34	90	100:0:0
  3	H2SO4	—	MeOH	60	35	84	100:0:0
  4	HCl	—	MeOH	60	24	90	100:0:0
  5	TFA	—	MeOH	60	34	87	100:0:0
  6	H3PO4	—	MeOH	60	26	85	100:0:0
  7	TfOH	—	MeOH	60	34	93	100:0:0
  8	HOAc	—	MeOH	60	37	89	100:0:0
  9	HSbF6	—	THF	60	0.5	NRd	—
  10	HSbF6	—	MeCN	60	9.5	NRd	—
  11	HSbF6	—	EtOAc	60	9.5	NRd	—
  12	HSbF6	—	EtOH	60	9	95	100:0:0
  13	HSbF6	—	EtOH	80	6	95	100:0:0
  14	HOAc	—	DCE	25	144	94	7:93:0[8]
  15	HOAc	DBU (1 equiv.)	DCE	25	1	80	0:0:100
  16	HOAc	DIPAE (1 equiv.)	DCE	25	7	72	11:89:0
  17	HOAc	Et3N (1 equiv.)	DCE	25	1	96	2:98:0
  18	HOAc	Et3N (1 equiv.)	DCM	25	1.5	88	4:96:0
  19	HOAc	Et3N (1 equiv.)	DMF	25	8	63	0:0:100
  20	HOAc	Et3N (1 equiv.)	THF	25	24	NRd	—
  21	HOAc	Et3N (1 equiv.)	MeCN	25	0.5	NRd	—
  22	HOAc	Et3N (0.5 equiv.)	DCE	25	16	80	15:85:0
  23	HOAc	Et3N (0.1 equiv.)	DCE	25	34	75	21:79:0
  a Reaction conditions: ethyl 2-diazo-3, 5-dioxo-7-p-tolylhept-6-ynoate (1b, 0.2 mmol), catalyst (10 mol%), solvent (4 mL). b Total yield of isolated products (2b+ 3b+4b). c The ratio was determined by 1H NMR spectroscopic analysis (500 MHz) and was confirmed by separation by column chromatography. d Starting material was recovered.

  随后, 我们对合成重氮3(2H)-呋喃酮3b的反应条件进行了探讨.在室温下, DCE作为溶剂, HOAc作为催化剂, 主要得到重氮3(2H)-呋喃酮3b及很少量的2b, 没有观察到4b的形成; 其不足之处在于反应时间长(表 1, Entry 14).基于基本反应原理, 我们推测, 碱也许能够增强该反应活性.当1, 8-二氮杂二环[5.4.0]十一碳-7-烯(DBU, 1 equiv.)被用作碱时, 正如预期的那样, 反应活性增强, 反应时间大大缩短; 然而, 这种DBU介入的反应只得到4b, 没有观察到目标产物3b的形成(表 1, Entry 15).幸运地是, 当用i-Pr₂NEt (DIPEA)代替DBU时, 3b成为主要产物(表 1, Entry 16). Et₃N是形成3b的最合适的碱(表 1, Entry 17).然后, 以Et₃N作为碱, 在25 ℃下, 进一步考察溶剂对形成3b的影响.二氯甲烷(DCM)作溶剂时, 需要稍长的反应时间(表 1, Entry 18); N, N-二甲基甲酰胺(DMF)作溶剂时, 只生成产物4b (表 1, Entry 19);当THF和CH₃CN作溶剂时, 则无反应发生(表 1, Entries 20, 21).此外, 我们还发现Et₃N的用量对形成3b的反应活性及选择性有明显影响:小于1 equiv.的Et₃N不仅降低了反应活性, 也降低了3b的选择性(表 1, Entries 22, 23).因此, 制备3b的最佳条件是: 25 ℃, DCE作溶剂, HOAc (10 mol%)作催化剂和Et₃N (1 equiv.)作为碱(Table 1, Entry 17).

  基于形成2b的优化条件, 考察了不同底物1转换成重氮γ-吡喃酮2的情况, 其结果见表 2中Method A.当R¹＝OEt时, 不同的R (芳基、芳香族杂环、乙烯基、环丙基和脂肪基)均可得到较好的产率, 其产率和反应时间没有明显变化(表 2, Method A, Entries 1~12).当R¹＝NEt₂时, 由于有未知副产物的生成, 2n的产率较低(表 2, Method A, Entry 14).当R¹＝Ph时, R为各种芳芳香取代基, 同样获得相应的γ-吡喃酮2, 产率较高(表 2, Method A, Entries 15~18).

  表 2

  

  表 2  重氮γ-吡喃酮2和重氮3(2H)-呋喃酮3的区域选择性合成^a

  Table 2.  Regioselective synthesis of diazo γ-pyrones 2 and diazo 3(2H)-furanones 3

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  Entry	R/R1 (1)	Method A				Method B
  		t/h	Yieldb/%	n(2):n(3):n(4)c		t//h	Yieldb/%	n(2):n(3):n(4)c
  1	Ph/OEt (1a)	9.0	88	100:0:0		1.5	92	5:95:0
  2	p-MeC6H4/OEt (1b)	6.0	95	100:0:0		1.0	96	2:98:0
  3	p-nPrC6H4/OEt (1c)	4.0	95	100:0:0		6.0	92	6:94:0
  4	3, 5-tBu2C6H3/OEt (1d)	6.5	95	100:0:0		7.5	89	8:92:0
  5	p-MeOC6H4/OEt (1e)	2.0	93	100:0:0		7.0	88	11:89:0
  6	p-ClC6H4/OEt (1f)	4.0	91	100:0:0		3.0	89	10:90:0
  7	p-FC6H4/OEt (1g)	2.0	90	100:0:0		2.5	92	9:91:0
  8	3-Thienyl//OEt (1h)	2.5	90	100:0:0		6.0	94	10:90:0
  9	(E)-Me(CH2)6CH＝CH/OEt (1i)	3.5	88	100:0:0		3.5	88	10:90:0
  10	Me2C＝CH/OEt (1j)	10	85	100:0:0		5.0	83	12:88:0
  11	Cyclopropyl/OEt (1k)	2.0	86	100:0:0		7.5	85	15:85:0
  12	n-Bu/OEt (1l)	6.0	96	100:0:0		8.0	92	98:2:0
  13	Et3Si/OEt (1m)	—d				—d
  14	Ph/NEt2 (1n)	1.5	60	100:0:0		4.0	80	12:88:0
  15	Ph/Ph (1o)	1.5	88	100:0:0		1.5	94	7:93:0
  16	p-nPrC6H4/Ph (1p)	3.0	90	100:0:0		5.5	87	12:88:0
  17	p-MeOC6H4/Ph (1q)	4.5	89	100:0:0		6.0	85	11:89:0
  18	p-FC6H4/Ph (1r)	2.0	85	100:0:0		2.0	83	5:95:0
  19	n-Bu/Ph (1s)	3.0	94	0:0:100		4.0	93	0:0:100
  a Method A: The reaction was carried out by using 1 (0.2 mmol) and HSbF6 (10 mol%) in EtOH (4 mL) at 80 ℃. Method B: The reaction was carried out by using 1 (0.2 mmol), Et3N (0.2 mmol) and HOAc (10 mol%) in DCE (4 mL) at 25 ℃. b Isolated total yield (2+3+4). c The ratio was determined by 1H NMR spectroscopic analysis (500 MHz) and was confirmed by separation by column chromatography. d No anticipated product was observed.

  基于形成3b的优化条件, 探讨了各种底物1a~1s转化为相应重氮3(2H)-呋喃酮3的可能性, 其结果见表 2中Method B.当R¹＝OEt, 且R为芳基、芳香杂环、烯基和环丙基时, 均获得相应的重氮3(2H)-呋喃酮3, 产率80%~96% (表 2, Method B, Entries 1~11).令人奇怪的是, 底物1l (R¹＝OEt, R＝Bu)得到的并不是预期的产物3l, 而是相应的重氮γ-吡喃酮衍生物2l, 产率为98% (表 2, Method B, Entry 12).当底物为1n时, 获得预期的产物3n, 选择性好且产率高(表 2, Method B, Entry 14).类似地, 当R¹＝Ph和R＝Ar时, 得到期望的重氮3(2H)-呋喃酮衍生物3o~3r, 选择性较高(表 2, Method B, Entries 15~18).

  值得注意的是, 无论Method A还是Method B, 底物1m (R＝Et₃Si, R¹＝OEt)并不形成预期的产物2m或3m, 只有未知的荧光物质产生(表 2, Method A and Method B, Entry 13). Et₃Si导致这些环化反应不能进行的原因目前尚不清楚.此外, 无论Method A还是Method B, 底物1s (R＝n-Bu, R¹＝Ph)的环化反应仅仅形成3-苯甲酰基-5-丁基吡喃骈[3, 2-c]吡唑-7(1H)-酮(4s), 而没有预期产物2s和3s (Table 2, Method A and Method B, Entry 19), 其原因也不清楚.

  基于这些实验结果, 我们提出了Method A中形成重氮γ-吡喃酮2和Method B中形成重氮3(2H)-呋喃酮3的合理机理, 分别见Schemes 2和3.强酸催化通常倾向于形成γ-吡喃酮^{[6i, 10]}.在HSbF₆作为催化剂的情况下, 2-重氮-3, 5-二氧代-6-炔酮(炔酯、炔酰胺)1首先质子化形成双正离子活性中间体5.随后, 羰基氧原子进攻双正离子活性中间体中带正电荷的烯基碳^[11], 经6-exo-dig环化提供重氮γ-吡喃酮2 (Method A, Scheme 2).在HOAc/DCE的弱酸反应体系中, 2-重氮-3, 5-二氧代-6-炔酮(炔酯、炔酰胺)1首先质子化形成𨦡盐5A^[12].我们推测𨦡盐5A有利于发生5-exo-dig环化, 从而主要产生重氮3(2H)-呋喃酮3.在Et₃N (1 equiv.)作用下, 𨦡盐5A转化为中间体6.中间体6中烯醇氧负离子的亲核性明显强于𨦡盐5A中的羰基氧原子.因此, 后续的5-exo- dig环化速率明显加快, 导致反应时间大大缩短(Method B, Scheme 3).在上述选择性环化反应中, 溶剂效应和酸性扮演重要的角色.溶剂也能导致反应体系酸性改变^[13], 从而影响该环化反应的区域选择性.不过, 其原因目前并不很清楚.

  图式 2

  

  图式 2.  重氮γ-吡喃酮2形成的合理机理

  Scheme 2.  Possible mechanism for the formation of diazo γ-pyrone 2

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  图式 3

  

  图式 3.  重氮3(2H)-呋喃酮3形成的合理机理及Et₃N的促进环化作用

  Scheme 3.  Proposed mechanism for the formation of diazo 3(2H)-furanone 3 and Et₃N-promoted cyclization

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  重氮化合物已经被广泛应用于有机合成中^[7], 但重氮γ-吡喃酮和重氮3(2H)-呋喃酮的合成应用则很少探讨^[8].我们发现, 这些重氮杂环化合物能在温和条件下与烯烃发生环丙烷反应, 形成新颖的α-环丙基γ-吡喃酮和α-环丙基3(2H)-呋喃酮.例如, 在DCE中, Rh₂(OAc)₄ (5 mol%)催化重氮γ-吡喃酮2b与对甲基苯乙烯反应, 形成相应的α-环丙基γ-吡喃酮7; 类似地, 重氮3(2H)-呋喃酮3b与对甲基苯乙烯的环丙烷化反应, 生成α-环丙基3(2H)-呋喃酮8 (Scheme 4).这些分子间环丙烷化反应都具有高的化学选择性.

  图式 4

  

  图式 4.  重氮γ-吡喃酮和重氮3(2H)-呋喃酮的环丙烷化

  Scheme 4.  Cyclopropanation of diazo γ-pyrone and diazo 3(2H)-furanone

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  2.   结论

  提供一种无过渡金属催化的有效方法, 由同一种原料区域选择性逆转构建重氮γ-吡喃酮和重氮3(2H)-呋喃酮.在HSbF₆/EtOH体系中, 强酸HSbF₆促进分子内6-endo-dig环化, 获得系列重氮γ-吡喃酮.在HOAc/ Et₃N/DCE反应体系中, 有利于5-exo-dig环化, 构建系列重氮3(2H)-呋喃酮.在该区域选择性切换的环化反应中, 溶剂和酸性扮演重要角色.基于实验结果, 提出了合理的反应机理.同时, 首次探讨了重氮γ-吡喃酮和重氮3(2H)-呋喃酮环丙烷化反应, 提供新颖的α-环丙基γ-吡喃酮和α-环丙基3(2H)-呋喃酮.

  3.   实验部分

  3.1   仪器与试剂

  所有¹H NMR和¹³C NMR均由Bruker Varian-500型核磁共振仪检测(用四甲基硅烷作为内标, CDCl₃作溶剂). HRMS光谱使用Thermo Scientific LTQ Orbitrap XL检测.使用Merck 25 TLC铝板(硅胶60 GF254, 0.25 mm), 通过薄层色谱法(TLC)监测反应进程.所有的反应都在具有搅拌子的圆底烧瓶中进行.除非另有说明, 否则所有的实验都是在空气环境下进行的.除非特别说明, 否则所有试剂和溶剂都是从阿拉丁购买, 且未经处理. DCM和THF使用前分别经CaH₂和金属钠分别处理, 使用前进行重蒸.柱层析硅胶(300~400目)购自青岛海阳化工有限公司.

  3.2   实验方法

  3.2.1   重氮γ-吡喃酮2的一般合成方法(Method A)

  在80 ℃下, 将底物1a (0.2 mmol, 57 mg)滴加到六氟锑酸(10 mol%)的乙醇(4 mL)溶液中, 然后搅拌9 h.将反应混合物抽滤, 浓缩, 残渣柱层析分离, 得到2-重氮-2-(2-氧代-6-苯基-4H-吡喃-2-基)乙酸乙酯(2a)^[8], 黄色固体, 产率88%. m.p. 149~150 ℃ (lit.^[8] 149~150 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.64~7.48 (m, 5H), 6.97 (d, J＝2.0 Hz, 1H), 6.66 (d, J＝2.0 Hz, 1H), 4.37 (q, J＝7.0 Hz, 2H), 1.36 (t, J＝7.0 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 178.13, 161.50, 153.14, 131.42, 131.11, 130.78, 129.15, 125.51, 110.81, 110.79, 62.15, 14.35.

  2-重氮-2-(6-氧代-6-对甲苯基-4H-吡喃酮-2-基)乙酸乙酯(2b)^[8]:黄色固体, 产率95%. m.p. 136~137 ℃ (lit.^[8] 136~137 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.43 (d, J＝8.0 Hz, 2H), 7.20 (d, J＝8.0 Hz, 2H), 6.87 (d, J＝2.0 Hz, 1H), 6.53 (d, J＝2.0 Hz, 1H), 4.29 (q, J＝7.1 Hz, 2H), 2.33 (s, 3H), 1.28 (t, J＝7.1 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 178.09, 161.31, 157.80, 152.67, 133.07, 127.65, 125.67, 124.43, 110.77, 110.2, 62.12, 14.32.

  2-重氮-2-[4-氧代-6-(4-正丙基苯基)-4H-吡喃-2-基]乙酸乙酯(2c)^[8]:黄色固体, 产率95%. m.p. 129~130 ℃ (lit.^[8] 129~130 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.53 (d, J＝8.0 Hz, 2H), 7.27 (d, J＝8.0 Hz, 2H), 6.94 (d, J＝2.0 Hz, 1H), 6.61 (d, J＝2.0 Hz, 1H), 4.36 (q, J＝7.1 Hz, 2H), 2.63 (t, J＝7.6 Hz, 1H), 1.68~1.61 (m, 2H), 1.35 (t, J＝7.1 Hz, 3H), 0.94 (t, J＝7.1 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 178.13, 161.74, 161.39, 152.89, 146.72, 129.24, 128.24, 125.46, 110.80, 110.18, 64.46, 62.08, 37.78, 24.11, 14.32, 13.63.

  2-[6-(3, 5-二叔丁基苯基)-4-氧代-4H-吡喃酮-2-基]-2-重氮乙酸乙酯(2d)^[8]:黄色固体, 产率95%. m.p. 164~166 ℃ (lit.^[8] 164~166 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.57~7.49 (m, 3H), 6.97 (d, J＝2.1 Hz, 1H), 6.69 (d, J＝2.1 Hz, 1H), 4.38 (q, J＝7.0 Hz, 2H), 1.36 (t, J＝7.0 Hz, 3H), 1.34 (s, 18H); ¹³C NMR (125.8 MHz, CDCl₃) δ: 178.35, 162.39, 161.38, 152.94, 151.87, 130.10, 125.81, 119.89, 110.78, 110.45, 62.07, 35.49, 31.23, 14.32.

  2-重氮-2-[6-(4-甲氧基苯基)-4-氧代-4H-吡喃-2-基]乙酸乙酯(2e)^[8]:黄色固体, 产率93%. m.p. 153~154 ℃ (lit.^[8] 153~154 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.58 (d, J＝9.0 Hz, 2H), 6.98 (d, J＝9.0 Hz, 2H), 6.93 (d, J＝2.2 Hz, 1H), 6.57 (d, J＝2.2 Hz, 1H), 4.37 (q, J＝7.1 Hz, 2H), 3.86 (s, 3H), 1.36 (t, J＝7.1 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 178.28, 162.14, 161.61, 152.77, 127.21, 123.07, 114.58, 110.65, 109.28, 62.14, 55.47, 14.36.

  2-[6-(4-氯苯基)-4-氧代-4H-吡喃-2-基]-2-重氮乙酸乙酯(2f)^[8]:黄色固体, 产率91%. m.p. 180~182 ℃ (lit.^[8] 180~182 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.56 (d, J＝8.7 Hz, 2H), 7.45 (d, J＝8.7 Hz, 1H), 6.95 (d, J＝2.1 Hz, 1H), 6.62 (d, J＝2.1 Hz, 1H), 4.36 (q, J＝7.1 Hz, 2H), 1.35 (t, J＝7.1 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 177.88, 161.24, 160.47, 153.23, 137.70, 129.51, 129.25, 126.78, 110.99, 110.82, 62.22, 14.34.

  2-重氮-2-[6-(4-氟苯基)-4-氧代-4H-吡喃-2-基]乙酸乙酯(2g)^[8]:黄色固体, 产率90%. m.p. 175~176 ℃ (lit.^[8] 175~176 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.65~7.16 (m, 4H), 6.95 (d, J＝2.2 Hz, 1H), 6.60 (d, J＝2.2 Hz, 1H), 4.38 (q, J＝7.1 Hz, 2H), 1.36 (t, J＝7.2 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 177.90, 165.52, 163.51, 160.97 (d, J＝77.7 Hz), 153.13, 127.75 (d, J_C-F＝8.8 Hz), 127.07, 116.4 (d, J_C-F＝22.2 Hz), 110.80, 110.67, 62.19, 14.33.

  2-重氮-2-[4-氧代-6-(噻吩-3-基)-4H-吡喃-2-基]乙酸乙酯(2h)^[8]:黄色固体, 产率90%. m.p. 132~134 ℃ (lit.^[8] 132~134 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.65 (d, J＝3.0, 1H), 7.42 (dd, J＝5.0, 3.0 Hz, 1H), 7.28 (d, J＝5.0 Hz, 0H), 6.90 (d, J＝1.5, 1H), 6.49 (d, J＝1.5, 1H), 4.35 (q, J＝7.1 Hz, 1H), 1.34 (t, J＝7.2 Hz, 1H); ¹³C NMR (125.8 MHz, CDCl₃) δ: 178.06, 161.23, 157.77, 152.68, 132.96, 127.61, 125.67, 124.37, 110.63, 110.09, 62.07, 14.27.

  (E)-2-重氮-2-(4-氧代-6-苯乙烯基-4H-吡喃-2-基)乙酸乙酯(2i)^[8]:黄色固体, 产率88%. m.p. 128~130 ℃ (lit.^[8] 128~130 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 6.82 (s, 1H), 6.35 (dt, J＝15.5, 7.0 Hz, 1H), 5.98 (d, J＝15.5 Hz, 1H), 5.96 (s, 1H), 4.32 (q, J＝7.0 Hz, 2H), 2.18~2.09 (m, 2H), 1.42~1.34 (m, 2H), 1.31~1.23 (m, 11H), 0.84 (t, J＝7.0 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 178.34, 161.31, 159.75, 152.35, 140.31, 121.64, 111.89, 110.47, 61.95, 32.69, 31.60, 28.96, 28.91, 28.37, 22.47, 14.23, 13.92.

  2-重氮-2-[6-(2-甲基丙烯-1-基)-4-氧代-4H-吡喃-2-基]乙酸乙酯(2j)^[8]:黄色液体, 产率85%. ¹H NMR (500 MHz, CDCl₃) δ: 6.83 (s, 1H), 5.99 (d, J＝2.0 Hz, 1H), 5.77 (s, 1H), 4.32 (q, J＝7.0 Hz, 2H), 1.93 (s, 3H), 1.91 (s, 3H), 1.29 (t, J＝7.0 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 178.22, 161.40, 161.32, 153.01, 146.71, 116.92, 113.68, 110.42, 61.92, 27.70, 20.79, 14.22.

  2-重氮-2-(6-环丙基-4-氧代-4H-吡喃-2-基)乙酸乙酯(2k)^[8]:黄色固体, 产率86%. m.p. 94~95 ℃ (lit.^[8] 94~95 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 6.81 (s, 1H), 6.04 (s, 1H), 4.31 (q, J＝7.1 Hz, 2H), 1.80~1.72 (m, 1H), 1.31 (t, J＝7.1 Hz, 3H), 1.05~0.99 (m, 2H), 0.95~0.87 (m, 2H); ¹³C NMR (125.8 MHz, CDCl₃) δ: 177.78, 167.43, 161.31, 152.19, 110.68, 110.44, 61.92, 14.23, 13.56, 7.82.

  2-(6-正丁基-4-氧代-4H-吡喃-2-基)-2-重氮乙酸乙酯(2l)^[8]:黄色液体, 产率96%. ¹H NMR (500 MHz, CDCl₃) δ: 6.84 (d, J＝2.2 Hz, 1H), 6.00 (d, J＝2.2 Hz, 1H), 4.32 (q, J＝7.2 Hz, 2H), 2.46 (t, J＝7.5 Hz, 2H), 1.58~1.54 (m, 2H), 1.39~1.30 (m, 5H), 0.91 (t, J＝7.5 Hz, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ: 178.01, 166.88, 161.20, 153.03, 112.67, 109.98, 64.04, 61.74, 32.64, 28.24, 21.66, 14.09, 13.37.

  2-重氮-N, N-二乙基-2-(4-氧代-6-苯基-4H-吡喃-2-基)乙酰胺(2n):黄色固体, 产率60%. m.p. 102~104 ℃; ¹H NMR (500 MHz, CDCl₃) δ: 7.67~7.48 (m, 5H), 6.67 (d, J＝2.0 Hz, 1H), 6.41 (d, J＝2.0 Hz, 1H), 3.44 (q, J＝7.1 Hz, 4H), 1.23 (t, J＝7.1 Hz, 6H); ¹³C NMR (125.8 MHz, CDCl₃) δ: 178.11, 161.89, 160.06, 155.80, 131.44, 130.85, 129.15, 125.59, 110.65, 109.97, 61.99, 42.00, 13.19; HRMS (ESI) calcd for C₁₇H₁₈N₃O₃ (M+H)312.1343, found 312.1343.

  2-(1-重氮-2-氧代-2-苯乙基)-6-苯基-4H-吡喃-4-酮(2o)^[8]:黄色固体, 产率88%. m.p. 128~129 ℃ (lit.^[8] 128~129 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.67~7.42 (m, 10H), 7.07 (d, J＝2.2 Hz, 1H), 6.69 (d, J＝2.2 Hz, 1H); ¹³C NMR (125 MHz, CDCl₃) δ: 185.12, 178.23, 161.88, 153.23, 136.54, 132.70, 131.43, 130.59, 129.07, 128.89, 127.35, 125.47, 112.46, 110.96, 72.21.

  2-(1-重氮-2-氧代-2-苯乙基)-6-(4-正丙基苯基)-4H-吡喃-4-酮(2p)^[8]:黄色固体, 产率90%. m.p. 115~116 ℃ (lit.^[8] 115~1116 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.67~7.24 (m, 9H), 7.05 (d, J＝2.2 Hz, 1H), 6.67 (d, J＝2.2 Hz, 1H), 2.62 (t, J＝7.5 Hz, 2H), 1.68~1.61 (m, 2H), 0.93 (t, J＝7.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 185.13, 178.32, 162.10, 153.03, 146.77, 136.55, 132.65, 129.17, 128.86, 127.98, 127.34, 125.41, 112.39, 110.29, 72.24, 37.71, 24.10, 13.62.

  2-(1-重氮-2-氧代-2-苯乙基)-6-(4-甲氧基苯基)-4H-吡喃-4-酮(2q)^[8]:黄色固体, 产率89%. m.p. 125~126 ℃ (lit.^[8] 125~126 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.67~6.92 (m, 9H), 7.00 (d, J＝2.0 Hz, 1H), 6.58 (d, J＝2.0 Hz, 2H), 3.84 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 185.16, 178.28, 162.15, 161.97, 152.84, 136.65, 132.67, 128.88, 127.38, 127.17, 122.91, 114.50, 112.37, 109.46, 72.20, 55.42.

  2-(1-重氮-2-氧代-2-苯乙基)-6-(4-氟苯基)-4H-吡喃- 4-酮(2r)^[8]:黄色固体, 产率85%. m.p. 114~115 ℃ (lit.^[8] 114~115 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.66~7.10 (m, 9H), 7.04 (d, J＝2.0 Hz, 1H), 6.64 (d, J＝2.0 Hz, 1H); ¹³C NMR (125 MHz, CDCl₃) δ: 185.04, 178.13, 165.43, 163.41, 161.01, 153.33, 136.50, 132.73, 128.92 (d, J_C-F＝8.5 Hz), 127.70 (d, J_C-F＝8.8 Hz), 127.37 (d, J_C-F＝5.3 Hz), 116.33 (d, J_C-F＝22.3 Hz), 112.25, 110.71, 72.11.

  5-叔丁基-3-苯基吡喃骈[3, 2-c]吡唑-7(1H)-酮(4s)^[9]:白色固体, 产率94%. m.p. 220~221 ℃ (lit.^[8] 220~221 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 14.08 (s, 1H), 8.34~7.51 (m, 5H), 6.35 (s, 1H), 2.79 (t, J＝7.5 Hz, 2H), 1.81~1.41 (m, 4H), 0.97 (t, J＝7.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 186.15, 171.99, 170.62, 147.72, 136.62, 133.27, 130.55, 128.37, 110.71, 33.91, 29.28, 22.14, 13.69.

  3.2.2   重氮3(2H)-呋喃酮3的一般合成方法(Method B)

  在室温下, 将1a (0.2 mmol, 57 mg)和HOAc (10 mol%)溶于DCE (4 mL)溶剂中, 然后将Et₃N (0.2 mmol)缓慢滴加到上述搅拌的混合物中.继续搅拌1 h, 然后抽滤, 浓缩.残渣柱层析分离, 得到白色固体3a (49.8 mg, 产率87.4%)及白色固体2a (2.6 mg, 产率4.6%), n(3a):n(2a)＝95:5.

  (Z)-2-(5-苯亚甲基-4-氧代-4, 5-二氢呋喃-2-基)-2-重氮乙酸乙酯(3a)^[8]:黄色固体, m.p. 143~144 ℃ (lit.^[8] 143~144 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.70~7.38 (m, 5H), 6.73 (s, 1H), 6.33 (s, 1H), 4.39 (q, J＝7.1 Hz, 2H), 1.38 (t, J＝7.1 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 184.64, 166.65, 160.81, 144.99, 131.72, 131.07, 129.81, 128.88, 111.69, 103.86, 62.54, 14.24.

  (Z)-2-重氮-2-[5-(4-甲氧基苯亚甲基)-4-氧代-4, 5-二氢呋喃-2-基]乙酸乙酯(3b)^[8]:黄色固体, 产率94%, n(3b):n(2b)＝98:2. m.p. 120~121 ℃ (lit.^[8] 120~121 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.55 (d, J＝7.8 Hz, 2H), 7.22 (d, J＝7.8 Hz, 2H), 6.70 (s, 1H), 6.31 (s, 1H), 4.38 (q, J＝7.1 Hz, 2H), 2.37 (s, 3H), 1.37 (t, J＝7.1 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 184.66, 166.26, 160.87, 144.60, 140.43, 131.09, 129.67, 128.87, 111.92, 103.90, 62.49, 30.83, 14.23.

  (Z)-2-重氮-2-[4-氧代-5-(4-正丙基苯亚甲基)-4, 5-二氢呋喃-2-基]乙酸乙酯(3c)^[8]:黄色固体, 产率86%, n(3c):n(2c)＝98:2, m.p. 89~90 ℃ (lit.^[8] 88~89 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.56-7.21 (m, 4H), 6.69 (s, 1H), 6.29 (s, 1H), 4.36 (q, J＝7.0 Hz, 2H), 2.58 (t, J＝7.5 Hz, 2H), 1.67~1.59 (m, 2H), 1.35 (t, J＝7.0 Hz, 3H), 0.92 (t, J＝7.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 184.59, 166.23, 160.83, 145.15, 144.65, 131.10, 129.14, 129.05, 111.91, 103.89, 62.46, 37.86, 24.10, 14.20, 13.64.

  (Z)-2-[5-(3, 5-二叔丁基苯亚甲基)-4-氧代-4, 5-二氢呋喃-2-基]-2-重氮乙酸乙酯(3d)^[8]:黄色固体, 产率82%, n(3d):n(2d)＝94:6, m.p. 145~147 ℃ (lit.^[8] 145~147 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.56 (s, 2H), 7.47 (s, 1H), 6.78 (s, 1H), 6.35 (s, 1H), 4.40 (q, J＝7.0 Hz, 2H), 1.37 (t, J＝7.0 Hz, 3H), 1.34 (s, 18H); ¹³C NMR (125.8 MHz, CDCl₃) δ: 184.77, 166.16, 160.93, 151.41, 144.75, 130.98, 125.52, 124.55, 113.14, 104.14, 62.49, 34.83, 31.29, 14.25.

  (Z)-2-重氮-2-(5-(4-甲氧苯亚甲基)-4-氧代-4, 5-二氢呋喃-2-基)乙酸乙酯(3e)^[8]:黄色固体, 产率78%, n(3e):n(2e)＝89:11. m.p. 99~100 ℃ (lit.^[8] 99~100 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.58 (d, J＝9.0 Hz, 2H), 6.98 (d, J＝9.0 Hz, 2H), 6.93 (d, J＝2.2 Hz, 1H), 6.57 (d, J＝2.2 Hz, 1H), 4.37 (q, J＝7.1 Hz, 2H), 3.86 (s, 3H), 1.36 (t, J＝7.1 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 178.28, 162.14, 161.61, 152.77, 127.21, 123.07, 114.58, 110.65, 109.28, 62.14, 55.47, 14.36.

  (Z)-2-[5-(4-氯苯亚甲基)-4-氧代-4, 5-二氢呋喃-2-基]-2-重氮乙酸乙酯(3f)^[8]:黄色固体, 产率80%, n(3f):n(2f)＝90:10. m.p. 145~146 ℃ (lit.^[8] 145~146 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.57 (d, J＝8.5 Hz, 2H), 7.38 (d, J＝8.5 Hz, 2H), 6.65 (s, 1H), 6.32 (s, 1H), 4.39 (q, J＝7.1 Hz, 2H), 1.37 (t, J＝7.1 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 184.47, 166.77, 160.72, 145.10, 135.84, 132.14, 130.24, 129.22, 110.32, 103.87, 62.64, 14.27.

  (Z)-2-重氮-2-[5-(4-氟苯亚甲基)-4-氧代-4, 5-二氢呋喃-2-基]乙酸乙酯(3g)^[8]:黄色固体, 产率84%, n(3g):n(2g)＝91:9. m.p. 146~147 ℃ (lit.^[8] 146~147 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.66~7.09 (m, 4H), 6.68 (s, 1H), 6.32 (s, 1H), 4.39 (q, J＝7.1 Hz, 2H), 1.37 (t, J＝7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ: 184.46, 166.61, 164.27, 161.50 (d, J＝191.7 Hz), 144.64, 133.01 (d, J＝9.0 Hz), 128.03, 116.13 (d, J＝22.7 Hz), 110.45, 103.88, 62.57, 14.23.

  (Z)-2-重氮-2-[4-氧代-5-(噻吩-3-基亚甲基)-4, 5-二氢呋喃-2-基]乙酸乙酯(3h)^[8]:黄色固体, 产率85%, n(3h):n(2h)＝90:10. m.p. 142~144 ℃ (lit.^[8] 142~144 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.67 (s, 1H), 7.37 (dd, J＝5.0, 3.0 Hz, 1H), 7.35 (s, 1H), 6.82 (s, 1H), 6.34 (s, 1H), 4.32 (q, J＝7.0 Hz, 2H), 1.40 (t, J＝7.0 Hz, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ: 184.57, 166.07, 160.87, 144.25, 133.18, 130.16, 128.52, 126.67, 105.94, 104.33, 62.57, 14.28.

  2-重氮-2-((Z)-4-氧代-5-[(E)-3-苯基亚烯丙基)-4, 5-二氢呋喃-2-基]乙酸乙酯(3i)^[8]:黄色固体, 产率79%, n(3i):n(2i)＝90:10, m.p. 110~112 ℃ (lit.^[8] 110~112 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 6.44 (d, J＝12.0 Hz, 1H), 6.36 (dd, J＝15.0, 12.0 Hz, 1H), 6.25 (s, 1H), 6.24 (dt, J＝15.0, 7.0 Hz, 1H), 4.36 (q, J＝7.0 Hz, 2H), 2.22 (q, J＝7.3 Hz, 1H), 1.45~1.24 (m, 13H), 0.87 (t, J＝7.0 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 184.24, 165.29, 161.10, 146.71, 144.32, 121.90, 113.20, 104.63, 62.45, 33.57, 31.71, 29.14, 29.04, 28.75, 22.26, 14.26, 14.03.

  (Z)-2-重氮-2-[5-(3-甲基-2-亚丁烯基)-4-氧代-4, 5-二氢呋喃基]乙酸乙酯(3j)^[8]:黄色液体, 产率73%, n(3j):n(2j)＝88:12. ¹H NMR (500 MHz, CDCl₃) δ: 6.70 (d, J＝12.0 Hz, 1H), 6.26 (s, 1H), 6.18 (d, J＝12.0 Hz, 1H), 4.36 (q, J＝7.0 Hz, 2H), 1.95 (s, 3H), 1.92 (s, 3H), 1.35 (t, J＝7.0 Hz, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ: 184.39, 164.98, 149.35, 144.57, 130.92, 117.33, 109.80, 104.71, 62.44, 26.96, 19.12, 14.26.

  (Z)-2-[5-(环丙基亚甲基)-4-氧代-4, 5-二氢呋喃-2-基]-2-重氮乙酸乙酯(3k)^[8]:黄色固体, 产率72%, n(3k):n(2k)＝85:15. m.p. 122~123 ℃ (lit.^[8] 122~123 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 6.22 (s, 1H), 5.49 (d, J＝11.0 Hz, 1H), 4.35 (q, J＝7.2 Hz, 2H), 1.80~1.69 (m, 1H), 1.34 (t, J＝7.2 Hz, 3H), 1.08~1.01 (m, 2H), 0.72~0.60 (m, 2H); ¹³C NMR (125.8 MHz, CDCl₃) δ: 183.04, 165.83, 161.10, 147.46, 122.12, 104.37, 62.41, 14.24, 9.55, 9.29.

  (Z)-2-(5-苯亚甲基-4-氧代-4, 5-二氢呋喃-2-基)-2-重氮-N, N-二乙基乙酰胺(3n)^[8]:黄色固体, 产率70%, n(3n):n(2n)＝88:12. m.p. 134~136 ℃ (lit.^[8] 134~136 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.66~7.36 (m, 5H), 6.70 (s, 1H), 6.03 (s, 1H), 3.44 (q J＝7.1 Hz, 4H), 1.22 (t, J＝7.1 Hz, 6H); ¹³C NMR (125.8 MHz, CDCl₃) δ: 184.48, 169.27, 159.61, 145.50, 131.89, 131.14, 129.80, 128.93, 111.42, 103.23, 42.01, 13.22; HRMS (ESI) calcd for C₁₇H₁₈N₃O₃ (M+H) 312.1343, found 312.1343.

  (Z)-2-苯亚甲基-5-(1-重氮-2-氧代-2-苯乙基)呋喃- 3(2H)-酮(3o)^[8]:黄色固体, 产率87%, n(3o):n(2o)＝93:7. m.p. 109~110 ℃ (lit.^[8] 109~110 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.69~7.37 (m, 10H), 6.75 (s, 1H), 6.34 (s, 1H); ¹³C NMR (125 MHz, CDCl₃) δ: 184.97, 184.61, 166.76, 144.63, 136.12, 133.06, 131.65, 131.16, 129.95, 128.99, 128.91, 127.43, 112.17, 105.05, 71.98.

  (Z)-5-(1-重氮-2-氧代-2-苯乙基)-2-(4-正丙基苯亚甲基)呋喃-3(2H)-酮(3p)^[8]:黄色固体, 产率76%, n(3p):n(2p)＝88:12, m.p. 88~89 ℃ (lit.^[8] 88~89 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.69~7.20 (m, 9H), 6.75 (s, 1H), 6.34 (s, 1H), 2.60 (t, J＝7.5 Hz, 2H), 1.68~1.61 (m, 2H), 0.94 (t, J＝7.3 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 185.00, 184.66, 166.38, 145.36, 144.31, 136.15, 133.01, 131.24, 129.12, 129.07, 128.97, 127.42, 112.54, 105.16, 72.00, 37.90, 24.19, 13.71.

  (Z)-5-(1-重氮-2-氧代-2-苯乙基)-2-(4-甲氧基苯亚甲基)呋喃-3(2H)-酮(3q)^[8]:黄色固体, 产率72%, n(3q):n(2q)＝89:11. m.p. 132~133 ℃ (lit.^[8] 132~133 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.69~6.89 (m, 9H), 6.70 (s, 1H), 6.31 (s, 1H), 3.83 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 184.82, 184.69, 165.83, 161.01, 143.66, 136.20, 133.03, 132.97, 128.94, 127.42, 124.27, 114.49, 112.37, 105.24, 71.92, 55.32.

  (Z)-5-(1-重氮-2-氧代-2-苯乙基)-2-(4-氟苯亚甲基)呋喃-3(2H)-酮(3r)^[8]:黄色固体, 产率79%, n(3r):n(2r)＝95:5. m.p. 101~102 ℃ (lit.^[8] 101~102 ℃); ¹H NMR (500 MHz, CDCl₃) δ: 7.68~7.04 (m, 9H), 6.67 (s, 1H), 6.33 (s, 1H); ¹³C NMR (125 MHz, CDCl₃) δ: 184.79, 184.49, 166.77, 164.25, 162.26, 144.26 (d, J＝2.50 Hz), 136.03, 133.06 (d, J＝8.0 Hz), 128.94, 127.89 (d, J＝3.5 Hz), 127.40, 116.21 (d, J＝21.7 Hz), 110.91, 104.93, 71.85.

  3.3   环丙烷化反应的一般过程

  3.3.1   重氮γ-吡喃酮环丙烷化的一般方法

  向具搅拌子的10 mL圆底烧瓶中加入Rh₂(OAc)₄ (1 mg, 0.025 mmol), 充入氮气.在室温和快速搅拌下, 向其中逐滴加入对甲基苯乙烯(59 mg, 0.5 mmol)和2b (149 mg, 0.5 mmol)的无水DCE (2 mL)溶液, 反应3 h.然后, 抽滤, 浓缩, 残渣柱层析分离, 得到1-(4-氧代-6-对甲苯基-4H-吡喃-2-基)-2-对甲苯基环丙烷羧酸乙酯(7), 黄色液体(146 mg, 产率75%). ¹H NMR (500 MHz, CDCl₃) δ: 7.32~6.91 (m, 8H), 6.45 (d, J＝2.0 Hz, 1H), 6.25 (d, J＝2.0 Hz, 1H), 4.25~4.18 (m, 2H), 3.24 (t, J＝8.0 Hz, 1H), 2.37 (s, 3H), 2.14 (s, 3H), 2.07 (dd, J＝9.0, 5.5 Hz, 1H), 2.02 (dd, J＝7.5, 5.5 Hz, 1H), 1.20 (t, J＝7.0 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 180.09, 170.44, 164.18, 162.29, 141.68, 137.19, 131.21, 129.50, 129.02, 128.48, 127.69, 125.69, 118.30, 110.28, 61.99, 35.40, 33.21, 21.44, 20.93, 19.61, 14.15; HRMS (ESI) calcd for C₂₅H₂₅O₄ (M+H) 389.1747, found 389.1751.

  3.3.2   重氮3(2H)-呋喃酮环丙烷化的一般方法

  向具搅拌子的10 mL圆底烧瓶中加入Rh₂(OAc)₄ (1 mg, 0.025 mmol), 充入氮气.然后, 向其中逐滴加入对甲基苯乙烯(59 mg, 0.5 mmol)和3b (149 mg, 0.5 mmol)的无水DCE (2 mL)溶液, TLC监测反应进程.搅拌1 h后, 抽滤, 浓缩, 然后柱层析分离, 得到(Z)-1-[5-(4-甲基苯亚甲基)-4-氧代-4, 5-二氢呋喃-2-基]-2-对甲苯基环丙烷羧酸乙酯(8), 黄色液体(150 mg, 产率77%). ¹H NMR (500 MHz, CDCl₃) δ: 7.46~6.92 (m, 8H), 6.50 (s, 1H), 5.85 (s, 1H), 4.30~4.25 (m, 2H), 3.38 (t, J＝8.5 Hz, 1H), 2.38 (s, 3H), 2.24 (dd, J＝8.0, 5.0 Hz, 1H), 2.15 (dd, J＝9.0, 4.5 Hz, 1H), 2.15 (s, 3H), 1.29 (t, J＝7.0 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃) δ: 187.76, 176.90, 169.60, 145.27, 140.36, 137.39, 131.43, 130.92, 129.54, 129.19, 129.03, 128.37, 128.37, 112.62, 109.68, 62.09, 36.30, 32.02, 21.58, 20.98, 14.16; HRMS (ESI) calcd for C₂₅H₂₅O₄ (M+H) 389.1747, found 389.1750.

  辅助材料(Supporting Information) 化合物2a~2l, 2n~2s, 3a~3k, 3n~3r, 4s, 7和8的NMR谱图.这些材料可以免费从本刊网站(http://sioc-journal.cn/)下载.

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• 

  图式 1  1, 3-二羰基前体环化的可能方式

  Scheme 1  Possible mode of the cyclization of 1, 3-dicarbonyl precursors

  下载: 全尺寸图片 幻灯片
  

  图式 2  重氮γ-吡喃酮2形成的合理机理

  Scheme 2  Possible mechanism for the formation of diazo γ-pyrone 2

  下载: 全尺寸图片 幻灯片
  

  图式 3  重氮3(2H)-呋喃酮3形成的合理机理及Et₃N的促进环化作用

  Scheme 3  Proposed mechanism for the formation of diazo 3(2H)-furanone 3 and Et₃N-promoted cyclization

  下载: 全尺寸图片 幻灯片
  

  图式 4  重氮γ-吡喃酮和重氮3(2H)-呋喃酮的环丙烷化

  Scheme 4  Cyclopropanation of diazo γ-pyrone and diazo 3(2H)-furanone

  下载: 全尺寸图片 幻灯片

  表 1  环化反应的条件优化^a

  Table 1.  Optimization of the cyclization

  Entry	Catalyst	Base	Solvent	T/℃	t/h	Yieldb/%	n(2b):n(3b):n(4b)c
  1	HSbF6	—	MeOH	60	22	95	100:0:0
  2	TsOH	—	MeOH	60	34	90	100:0:0
  3	H2SO4	—	MeOH	60	35	84	100:0:0
  4	HCl	—	MeOH	60	24	90	100:0:0
  5	TFA	—	MeOH	60	34	87	100:0:0
  6	H3PO4	—	MeOH	60	26	85	100:0:0
  7	TfOH	—	MeOH	60	34	93	100:0:0
  8	HOAc	—	MeOH	60	37	89	100:0:0
  9	HSbF6	—	THF	60	0.5	NRd	—
  10	HSbF6	—	MeCN	60	9.5	NRd	—
  11	HSbF6	—	EtOAc	60	9.5	NRd	—
  12	HSbF6	—	EtOH	60	9	95	100:0:0
  13	HSbF6	—	EtOH	80	6	95	100:0:0
  14	HOAc	—	DCE	25	144	94	7:93:0[8]
  15	HOAc	DBU (1 equiv.)	DCE	25	1	80	0:0:100
  16	HOAc	DIPAE (1 equiv.)	DCE	25	7	72	11:89:0
  17	HOAc	Et3N (1 equiv.)	DCE	25	1	96	2:98:0
  18	HOAc	Et3N (1 equiv.)	DCM	25	1.5	88	4:96:0
  19	HOAc	Et3N (1 equiv.)	DMF	25	8	63	0:0:100
  20	HOAc	Et3N (1 equiv.)	THF	25	24	NRd	—
  21	HOAc	Et3N (1 equiv.)	MeCN	25	0.5	NRd	—
  22	HOAc	Et3N (0.5 equiv.)	DCE	25	16	80	15:85:0
  23	HOAc	Et3N (0.1 equiv.)	DCE	25	34	75	21:79:0
  a Reaction conditions: ethyl 2-diazo-3, 5-dioxo-7-p-tolylhept-6-ynoate (1b, 0.2 mmol), catalyst (10 mol%), solvent (4 mL). b Total yield of isolated products (2b+ 3b+4b). c The ratio was determined by 1H NMR spectroscopic analysis (500 MHz) and was confirmed by separation by column chromatography. d Starting material was recovered.

  下载: 导出CSV

  表 2  重氮γ-吡喃酮2和重氮3(2H)-呋喃酮3的区域选择性合成^a

  Table 2.  Regioselective synthesis of diazo γ-pyrones 2 and diazo 3(2H)-furanones 3

  Entry	R/R1 (1)	Method A				Method B
  		t/h	Yieldb/%	n(2):n(3):n(4)c		t//h	Yieldb/%	n(2):n(3):n(4)c
  1	Ph/OEt (1a)	9.0	88	100:0:0		1.5	92	5:95:0
  2	p-MeC6H4/OEt (1b)	6.0	95	100:0:0		1.0	96	2:98:0
  3	p-nPrC6H4/OEt (1c)	4.0	95	100:0:0		6.0	92	6:94:0
  4	3, 5-tBu2C6H3/OEt (1d)	6.5	95	100:0:0		7.5	89	8:92:0
  5	p-MeOC6H4/OEt (1e)	2.0	93	100:0:0		7.0	88	11:89:0
  6	p-ClC6H4/OEt (1f)	4.0	91	100:0:0		3.0	89	10:90:0
  7	p-FC6H4/OEt (1g)	2.0	90	100:0:0		2.5	92	9:91:0
  8	3-Thienyl//OEt (1h)	2.5	90	100:0:0		6.0	94	10:90:0
  9	(E)-Me(CH2)6CH＝CH/OEt (1i)	3.5	88	100:0:0		3.5	88	10:90:0
  10	Me2C＝CH/OEt (1j)	10	85	100:0:0		5.0	83	12:88:0
  11	Cyclopropyl/OEt (1k)	2.0	86	100:0:0		7.5	85	15:85:0
  12	n-Bu/OEt (1l)	6.0	96	100:0:0		8.0	92	98:2:0
  13	Et3Si/OEt (1m)	—d				—d
  14	Ph/NEt2 (1n)	1.5	60	100:0:0		4.0	80	12:88:0
  15	Ph/Ph (1o)	1.5	88	100:0:0		1.5	94	7:93:0
  16	p-nPrC6H4/Ph (1p)	3.0	90	100:0:0		5.5	87	12:88:0
  17	p-MeOC6H4/Ph (1q)	4.5	89	100:0:0		6.0	85	11:89:0
  18	p-FC6H4/Ph (1r)	2.0	85	100:0:0		2.0	83	5:95:0
  19	n-Bu/Ph (1s)	3.0	94	0:0:100		4.0	93	0:0:100
  a Method A: The reaction was carried out by using 1 (0.2 mmol) and HSbF6 (10 mol%) in EtOH (4 mL) at 80 ℃. Method B: The reaction was carried out by using 1 (0.2 mmol), Et3N (0.2 mmol) and HOAc (10 mol%) in DCE (4 mL) at 25 ℃. b Isolated total yield (2+3+4). c The ratio was determined by 1H NMR spectroscopic analysis (500 MHz) and was confirmed by separation by column chromatography. d No anticipated product was observed.

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