利用微波辅助[3+3]环化反应合成稠合吡啶衍生物

doi:10.6023/cjoc202102018

摘要/Abstract

报道了一类新型的微波辅助对甲基苯磺酸促进的[3+3]环化反应. 利用烯胺酮或烯胺内酯可作为1,3-双亲核试剂及炔丙醇可作为1,3-双亲电试剂的特性, 使其在微波辐射及对甲苯磺酸促进条件下于冰醋酸中在70 ℃反应, 实现了[3+3]环化反应, 分别区域选择性地合成了2,2-二芳基取代四氢喹啉-5(1H)-酮衍生物和2,2-二芳基取代二氢呋喃并[3,4-b]吡啶-5-酮衍生物, 产率良好. 该反应利用微波合成技术促使反应, 在短时间内完成(30 min), 唯一副产物为水. 此外, 该方法具有原料简单易得、操作简单及底物普适性广等优点, 从而为具有潜在应用价值的稠合吡啶骨架的构建提供了一种绿色、经济且高效的合成策略, 符合绿色化学理念.

关键词: 微波合成, [3+3]环化, 喹啉-5(1H)-酮衍生物, 呋喃并[3,4-b]吡啶-5-酮衍生物, 绿色化学

A new microwave-assisted p-TsOH-promoted [3+3] cyclization was developed. By using the characteristics of enaminones or enamino lactones as 1,3-dinucleaphilic reagents and propargyl alcohols as 1,3-electrophilic reagents, p-TsOH- promoted [3+3] cyclization of these substrates at 70 ℃ was carried out in acetic acid under microwave irradiation, regioselectively affording 2,2-diaryl-substituted tetrahydroquinoline-5(1H)-ones and 2,2-diaryl-substituted dihydrofuro[3,4-b]pyridin- 5-ones in good yields. The reaction can be completed within a short period (30 min) by microwave synthetic technology, in which water was the sole by-product. This method features simple and available starting materials, simple operation and wide substrate scope, and provides a green, economic, and efficient synthetic strategy for the construction of fused pyridine skeleton with potential application, which is consistent with the concept of green chemistry.

Key words: microwave synthesis, [3+3] cyclization, quinoline-5(1H)-one, furo[3,4-b]pyridin-5-one, green chemistry

引用此文

吴亚男, 杜建宇, 郝文娟, 姜波. 利用微波辅助[3+3]环化反应合成稠合吡啶衍生物[J]. 有机化学, 2021, 41(4): 1563-1571.

Yanan Wu, Jianyu Du, Wenjuan Hao, Bo Jiang. Synthesis of Fused Pyridines via Microwave-Assisted [3+3] Cyclization[J]. Chinese Journal of Organic Chemistry, 2021, 41(4): 1563-1571.

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图/表 7

. 图示1 稠合吡啶衍生物的微波合成

Scheme 1. Microwave-assisted synthesis of fused pyridines

Entry	Promotor (equiv.)	Solvent	Temp./℃	Yield^b/%
1	p-TsOH (1.0)	Acetone	100	N.R.
2	p-TsOH (1.0)	DCE	100	N.R.
3	p-TsOH (1.0)	DCM	100	Trace
4	p-TsOH (1.0)	MeCN	100	30
5	p-TsOH (1.0)	Toluene	100	Trace
6	p-TsOH (1.0)	EtOH	100	Trace
7	p-TsOH (1.0)	HOAc	100	58
8	p-TsOH (0.5)	HOAc	100	45
9	p-TsOH (2.0)	HOAc	100	55
10	BF₃?Et₂O (1.0)	HOAc	100	37
11	TFA (1.0)	HOAc	100	21
12	TfOH (1.0)	HOAc	100	Trace
13	p-TsOH (1.0)	HOAc	90	61
14	p-TsOH (1.0)	HOAc	80	65
15	p-TsOH (1.0)	HOAc	70	70
16	p-TsOH (1.0)	HOAc	60	60

表1. 化合物3a反应条件的优化a

Table 1. Optimization of reaction conditions for the synthesis of 3a

. 图示2 四氢喹啉-5(1H)-酮衍生物3的合成

Scheme 2. Synthesis of tetrahydroquinoline-5(1H)-ones 3

图1. 含有喹啉骨架的生物活性分子

Figure 1. Bioactive molecules containing pyridine skeletons

图示3. 二氢呋喃并[3,4-b]吡啶-5-酮衍生物5的合成

Scheme 3. Synthesis of dihydrofuro[3,4-b]pyridin-5-ones 5

图2. 化合物5a的晶体结构

Figure 2. Crystal structure of compound 5a

图示4. 可能的反应机理

Scheme 4. Possible reaction mechanism

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