氮杂环卡宾催化乙酸酯和β-硅基烯酮的[4+2]环合反应:高立体选择性合成β-硅基δ-内酯

doi:10.6023/cjoc202105002

摘要/Abstract

在氮杂环卡宾催化下, 乙酸酯和β-硅基烯酮发生[4+2]环合反应, 可高立体选择性地合成具有潜在应用价值的β-硅基δ-内酯类化合物. 该方法具有底物简单易得、反应条件温和、底物普适性好和操作简单等优点, 且反应规模放大10倍后也得到了优异的产率和对映体选择性. 该反应产物在氢化还原反应中均呈现出优良的实验结果, 可转化为降血脂药Ezetimibe.

关键词: 氮杂环卡宾, 手性有机硅烷化合物, 不对称催化, β-硅基烯酮, 乙酸酯

Asymmetric synthesis of chiral organosilanes with a potential application was realized by N-heterocyclic carbene- catalyzed [4+2] annulation of acetates and β-silyl enones. This strategy exhibits easy to obtain raw materials, mild reaction conditions, good substrate tolerance, simple operation and so on. Notably, excellent yield and enantioselectivity were also observed with expanding the reaction scale by 10 times. The target product showed excellent results in hydrogenation reduction. Moreover, the hypolipidemic drug ezetimibe was obtained through the synthetic transformation of the resulting products.

Key words: N-heterocyclic carbene, chiral organosilanes, asymmetric catalysis, β-silyl enone, acetate

引用此文

张雨霞, 郭京程, 黄杰, 付振乾. 氮杂环卡宾催化乙酸酯和β-硅基烯酮的[4+2]环合反应:高立体选择性合成β-硅基δ-内酯[J]. 有机化学, 2021, 41(11): 4467-4475.

Yuxia Zhang, Jingcheng Guo, Jie Huang, Zhenqian Fu. N-Heterocyclic Carbene-Catalyzed [4+2] Annulation of Acetates and β-Silyl Enones: Highly Enantioselective Synthesis of β-Silyl δ-Lactones[J]. Chinese Journal of Organic Chemistry, 2021, 41(11): 4467-4475.

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图/表 6

图1. 四氢吡喃-2-酮类结构中具有代表性的生物活性天然产物和药物

Figure 1. Representative bioactive natural products and pharmaceuticals based on a tetrahydro-2H-pyran-2-one

Entry	NHC	1	Base	Solvent	Yield^b/%	ee^c/%
1	A	1a	DBU	THF	44	—
2	B	1a	DBU	THF	17	99
3	B	1b	DBU	THF	88	99
3	B	1b	DBU	1,4-Dioxane	55	99
4	B	1b	DBU	CH₃CN	54	99
5	B	1b	DBU	TOL	66	99
6	B	1b	DBU	DCM	66	99
7	B	1b	DBU	CHCl₃	57	99
8	B	1b	Et₃N	THF	50	99
9	B	1b	DIPEA	THF	49	99
10	B	1b	K₂CO₃	THF	40	99
11	B	1b	DMAP	THF	51	99
12	B	1b	DBN	THF	85	99
13^d	B	1b	DBU	THF	86	99
14^e	B	1b	DBU	THF	74	99
15^f	B	1b	DBU	THF	69	99
16^d^,^g	B	1b	DBU	THF	80	99

表1. 反应条件的优化a

Table 1. Optimization of reaction conditions

图式1. 化合物6的合成

Scheme 1. Synthesis of compound 6

表2. 底物的适用范围a

Table 2. Substrate scope of the reaction

表3. 氢化还原反应的适用范围a

Table 3. Substrate scope of the hydrogenation reduction reaction

图式2. 合成转化

Scheme 2. Synthetic transformations

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