吲哚发散性氢化及其在(±)-α-和γ-Lycoranes的全合成中的应用

doi:10.6023/cjoc202501010

摘要/Abstract

氢化吲哚结构广泛存在于药物、天然产物、材料和农药分子中, 然而高效构建氢化吲哚的合成方法较少. 此文报道了一种通过在温和条件下氢化取代吲哚构建氢化吲哚结构的方法. 该方法用廉价钯/碳作为催化剂, 在氢气(101 kPa)条件下, 室温或60 ℃即可实现. 通过调节反应溶剂、反应温度和催化剂用量, 化学选择性地实现了取代吲哚发散性地氢化为不同饱和程度的含氮杂环结构, 如二氢吲哚、四氢吲哚、六氢吲哚和全氢化吲哚等. 使用该方法实现了(±)-α-和γ-lycoranes的3步发散性全合成, 证明了该方法在含有氢化吲哚结构的天然产物全合成中的高效性.

关键词: 全合成, α-lycorane, γ-lycorane, 氢化吲哚, 氢化

Hydroindoles are highly enriched in a variety of medicines, natural products, materials, and agrochemicals, however rapid and efficient access of this type of structure is still formidable. Herein, the construction of hydroindoles via hydrogenation of substituted indoles under atmospheric pressure of H₂ at relatively low temperatures utilizing Pd/C as the catalyst is reported. And the controlled divergent hydrogenation of substituted indoles to dihydroindoles, tetrahydroindoles, hexahydroindoles, or octahydroindoles could be achieved by careful manipulation of reaction parameters, including reaction solvents, catalyst loading, and temperature. The efficiency of this method was demonstrated by the divergent syntheses of (±)-α- and γ-lycoranes in a three-step synthetic route.

Key words: total synthesis, α-lycorane, γ-lycorane, hydroindole, hydrogenation

引用此文

韩守乐, 娄明亮, 刘晓磊, 李根, 王馨, 吴青翠, 齐湘兵. 吲哚发散性氢化及其在(±)-α-和γ-Lycoranes的全合成中的应用[J]. 有机化学, 2025, 45(3): 913-924.

Shoule Han, Mingliang Lou, Xiaolei Liu, Gen Li, Xin Wang, Qingcui Wu, Xiangbing Qi. Divergent Hydrogenation of Indoles and Its Applications in Total Syntheses of (±)-α- and γ-Lycoranes[J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 913-924.

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参考文献 15

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Entry	Solvent	Pd/C (mol%)	T/℃	t/h	9-1∶9-2∶9-3∶9-4^b
1	HFIP	1.3	25	20	1.0∶0.2∶1.0∶0
2	HFIP	2.5	25	23	0∶0∶1.0∶0.4
3	HFIP	2.5	60	24	0∶0∶0.9∶1.0
4^c	HFIP/TFA, V∶V=3∶1	6.3	25	27	0∶0∶0∶1.0
5^c	HFIP/TFA, V∶V=3∶1	6.3	60	12	0∶0∶0∶1.0
6	HFIP/TFA, V∶V=3∶1	2.5	60	24	0∶0∶0∶1.0
7	HFIP/TFA, V∶V=3∶1	2.5	25	24	0∶1.0∶0∶0.3
8	HFIP/TFA, V∶V=3∶1	1.3	60	16	0∶1.0∶0∶1.0
9	HFIP/TFA, V∶V=1∶1	1.3	25	18	0∶1.0∶0∶0
10	HFIP/TFA, V∶V=3∶1	2.5	25	22	0∶1.0∶0∶0.4
11	HFIP/HOAc, V∶V=3∶1	2.5	60	24	Messy
12	HFIP/HOAc, V∶V=3∶1	2.5	25	24	0∶0.7∶1.0∶0
13	HFIP/HOAc, V∶V=1∶1	2.5	25	22	0.5∶0.4∶1.0∶0
14	MeOH/TFA, V∶V=1∶1	2.5	25	22	0.3∶1.0∶0:0.4

Entry	Solvent	Pd/C (mol%)	T/℃	t/h	9-1∶9-2∶9-3∶9-4^b
1	HFIP	1.3	25	20	1.0∶0.2∶1.0∶0
2	HFIP	2.5	25	23	0∶0∶1.0∶0.4
3	HFIP	2.5	60	24	0∶0∶0.9∶1.0
4^c	HFIP/TFA, V∶V=3∶1	6.3	25	27	0∶0∶0∶1.0
5^c	HFIP/TFA, V∶V=3∶1	6.3	60	12	0∶0∶0∶1.0
6	HFIP/TFA, V∶V=3∶1	2.5	60	24	0∶0∶0∶1.0
7	HFIP/TFA, V∶V=3∶1	2.5	25	24	0∶1.0∶0∶0.3
8	HFIP/TFA, V∶V=3∶1	1.3	60	16	0∶1.0∶0∶1.0
9	HFIP/TFA, V∶V=1∶1	1.3	25	18	0∶1.0∶0∶0
10	HFIP/TFA, V∶V=3∶1	2.5	25	22	0∶1.0∶0∶0.4
11	HFIP/HOAc, V∶V=3∶1	2.5	60	24	Messy
12	HFIP/HOAc, V∶V=3∶1	2.5	25	24	0∶0.7∶1.0∶0
13	HFIP/HOAc, V∶V=1∶1	2.5	25	22	0.5∶0.4∶1.0∶0
14	MeOH/TFA, V∶V=1∶1	2.5	25	22	0.3∶1.0∶0:0.4