无过渡金属参与的偕二氟环丙烷双脱氟烷氧基化合成环丙酮缩酮

doi:10.6023/cjoc202406020

有机化学 ›› 2025, Vol. 45 ›› Issue (6): 2222-2230.DOI: 10.6023/cjoc202406020 上一篇下一篇

研究论文

无过渡金属参与的偕二氟环丙烷双脱氟烷氧基化合成环丙酮缩酮

车琳^a, 江忠涛^b, 杨慧^b, 胡芳东^a^,^*(), 夏莹^b^,^*()

^a 临沂大学化学化工学院山东临沂 276000
^b 四川大学华西公共卫生学院/华西第四医院生物治疗全国重点实验室成都 610041

收稿日期:2024-06-14 修回日期:2024-07-28 发布日期:2024-09-10
通讯作者: 胡芳东, 夏莹
基金资助:
国家自然科学基金(22371189); 国家自然科学基金(22001180); 国家自然科学基金(21801109); 青年千人计划(15-YINGXIA); 山东省自然科学基金(ZR2024MB154)

Transition-Metal Free Synthesis of Cyclopropanone Ketals via Double Defluorinative Alkoxylation of gem-Difluorinated Cyclopropanes

Lin Che^a, Zhong-Tao Jiang^b, Hui Yang^b, Fangdong Hu^a^,^*(), Ying Xia^b^,^*()

^a School of Chemistry and Chemical Engineering, Linyi University, Linyi, Shandong 276000
^b West China School of Public Health and West China Fourth Hospital, and State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041

Received:2024-06-14 Revised:2024-07-28 Published:2024-09-10
Contact: Fangdong Hu, Ying Xia
Supported by:
National Natural Science Foundation of China(22371189); National Natural Science Foundation of China(22001180); National Natural Science Foundation of China(21801109); Thousand Young Talents Program(15-YINGXIA); Natural Science Foundation of Shandong Province(ZR2024MB154)

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摘要/Abstract

在不发生高张力C—C键断裂的情况下实现偕二氟环丙烷中C—F键的转化是一个棘手的挑战. 在无过渡金属参与的碱性条件下, 发展了通过偕二氟环丙烷的双脱氟化合成环丙酮缩酮的实例. 多种偕二氟环丙烷与醇可以用于目前的反应, 以高收率合成相应的产物. 在机理研究的基础上说明该反应是通过消除加成而不是直接取代进行的. 这不仅为环丙酮缩酮的合成提供了一种新的策略, 而且为偕二氟环丙烷的非开环C—F键转化提供了一种新的范例.

关键词: 偕二氟环丙烷, 脱氟化, 烷氧基化, 环丙酮缩酮, 消除与加成

The C—F bond transformation of gem-difluorinated cyclopropanes without cleavage of the highly strained C—C bond is an intractable challenge. The synthesis of cyclopropanone ketals via double defluorination of gem-difluorinated cyclopropanes under transition-metal free and basic conditions has been developed. A broad range of gem-difluorinated cyclopropanes and alcohols are amenable in present reaction to permit the synthesis of corresponding products in high yields. The reaction is elucidated to proceed via elimination and addition other than direct substitution based on the mechanistic studies. This transformation not only provides a new strategy for the construction of cyclopropanone ketals, but also reveals a new paradigm on C—F bond transformation without ring-opening of gem-difluorinated cyclopropanes.

Key words: gem-difluorinated cyclopropanes, defluorination, alkoxylation, cyclopropanone ketals, elimination and addition

引用此文

车琳, 江忠涛, 杨慧, 胡芳东, 夏莹. 无过渡金属参与的偕二氟环丙烷双脱氟烷氧基化合成环丙酮缩酮[J]. 有机化学, 2025, 45(6): 2222-2230.

Lin Che, Zhong-Tao Jiang, Hui Yang, Fangdong Hu, Ying Xia. Transition-Metal Free Synthesis of Cyclopropanone Ketals via Double Defluorinative Alkoxylation of gem-Difluorinated Cyclopropanes[J]. Chinese Journal of Organic Chemistry, 2025, 45(6): 2222-2230.

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Entry	Variation from the standard conditions	Yield^b/%
1	None	90
2	LiO^tBu instead of NaO^tBu	21
3	KO^tBu instead of NaO^tBu	31
4	Cs₂CO₃ instead of NaO^tBu	Not detected
5	THF instead of DMF	81
6	DCE instead of DMF	Not detected
7	60 ℃ instead of 70 ℃	88
8	80 ℃ instead of 70 ℃	77
9	2 equiv. MeOH instead of 3 equiv. MeOH	80
10	4 equiv. NaO^tBu instead of 5 equiv. NaO^tBu	82

Entry	Variation from the standard conditions	Yield^b/%
1	None	90
2	LiO^tBu instead of NaO^tBu	21
3	KO^tBu instead of NaO^tBu	31
4	Cs₂CO₃ instead of NaO^tBu	Not detected
5	THF instead of DMF	81
6	DCE instead of DMF	Not detected
7	60 ℃ instead of 70 ℃	88
8	80 ℃ instead of 70 ℃	77
9	2 equiv. MeOH instead of 3 equiv. MeOH	80
10	4 equiv. NaO^tBu instead of 5 equiv. NaO^tBu	82

无过渡金属参与的偕二氟环丙烷双脱氟烷氧基化合成环丙酮缩酮

Transition-Metal Free Synthesis of Cyclopropanone Ketals via Double Defluorinative Alkoxylation of gem-Difluorinated Cyclopropanes

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