BF3•Et2O促进的环丙烯基甲醇衍生物重排反应研究

doi:10.6023/cjoc202405015

摘要/Abstract

γ-亚乙烯基-丁烯酸内酯和苯并富烯结构单元在活性天然产物和药物化学中都具有重要的意义. 环丙烯基甲醇衍生物在BF₃•Et₂O的促进下, 脱除羟基后诱导环丙烯C—C断键反应的发生, 并形成联烯碳正离子中间体, 最后经不同的异构重排路径可以“一锅”实现γ-亚乙烯基-丁烯酸内酯和苯并富烯两类化合物的构建. 该合成方法拓展了两类化合物的合成策略, 二者的总收率可达68%~99%, 探究还发现电子效应和反应温度对二者的比例有着较大影响. 此外, 该反应为环丙烯结构的精准C—C键断裂提供了新方法.

关键词: 环丙烯, BF₃•Et₂O, γ-亚乙烯基-丁烯酸内酯, 苯并富烯, 碳−碳键断裂

γ-Ylidenebutenolides and benzofulvenes are of considerable importance in natural product and medicinal chemistry. Cyclopropenylcarbinols were promoted by BF₃•Et₂O to induce the C—C bond cleavage reaction of cyclopropenes via dehydroxylation to form an allene carbocation intermediate. This leads to the construction of γ-ylidenebutenolide and benzofulvene compounds in one pot via different isomerization rearrangement paths. This synthetic strategy expands the synthesis methods of two types of compounds, achieving a total yield of 68%~99%. In addition, the electronic effect and reaction temperature considerably influence the ratio of the two compounds. Moreover, the reaction provides a new method for precise C—C bond cleavage of cyclopropenes.

Key words: cyclopropene, BF₃•Et₂O, γ-alkylidenebutenolide, benzofulvene, C—C bond cleavage

引用此文

荀苗苗, 郭晶晶, 马文兵, 李宇强, 袁长春, 傅凯. BF₃•Et₂O促进的环丙烯基甲醇衍生物重排反应研究[J]. 有机化学, 2024, 44(9): 2760-2776.

Miaomiao Xun, Jingjing Guo, Wenbing Ma, Yuqiang Li, Changchun Yuan, Kai Fu. Study of BF₃•Et₂O-Promoted Rearrangement of Cyclopropenylcarbinols[J]. Chinese Journal of Organic Chemistry, 2024, 44(9): 2760-2776.

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参考文献 24

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Entry	Acid (equiv.)	Solvent	T/℃	Yield/%			Ratio 2a/3a
Entry	Acid (equiv.)	Solvent	T/℃	2a	3a	Total	Ratio 2a/3a
1	CH₃SO₃H (1.0)	Toluene	r.t.	36	28	64	1.3/1
2	p-TsOH (1.0)	Toluene	r.t. to 100	41	38	79	1.1/1
3	Cu(OTf)₂ (2.0)	Toluene	r.t. to 50	40	28	68	1.4/1
4	Yb(OTf)₃ (2.0)	Toluene	r.t. to 100	45	37	82	1.2/1
5	In(OTf)₃ (1.0)	Toluene	r.t.	49	35	84	1.4/1
6	Hf(OTf)₄ (1.0)	Toluene	r.t.	47	34	82	1.4/1
7	TiCl₄ (1.0)	Toluene	r.t.	35	37	72	0.9/1
8	FeCl₃ (1.0)	Toluene	r.t.	41	38	79	1.1/1
9	AlCl₃ (1.0)	Toluene	r.t.	50	30	80	1.7/1
10	BF₃•OEt₂ (1.0)	Toluene	r.t.	50	37	87	1.4/1
11^b	BF₃•OEt₂ (5.0)	Toluene	－78	—	—	—	—
12	BF₃•OEt₂ (5.0)	Toluene	－60	59	33	92	1.8/1
13	BF₃•OEt₂ (3.0)	Toluene	－40	59	33	92	1.8/1
14	BF₃•OEt₂ (1.5)	Toluene	0	50	33	83	1.5/1
15	BF₃•OEt₂ (1.0)	Toluene	60	51	36	87	1.4/1
16^b	BF₃•OEt₂(3.0)	THF	－40 or r.t.	—	—	—	—
17	BF₃•OEt₂(3.0)	THF	50	21	19	40	1.1/1
18	BF₃•OEt₂(3.0)	DCM	－40	53	34	87	1.6/1
19	BF₃•OEt₂(3.0)	DCE	－35	52	36	88	1.4/1
20	BF₃•OEt₂(3.0)	EA	－40 to r.t.	50	26	76	1.9/1
21	BF₃•OEt₂(3.0)	n-Hexane	r.t.	41	38	79	1.1/1
22^c	BF₃•OEt₂ (3.0)	Toluene	－40	60	33	93	1.8/1

Entry	Acid (equiv.)	Solvent	T/℃	Yield/%			Ratio 2a/3a
Entry	Acid (equiv.)	Solvent	T/℃	2a	3a	Total	Ratio 2a/3a
1	CH₃SO₃H (1.0)	Toluene	r.t.	36	28	64	1.3/1
2	p-TsOH (1.0)	Toluene	r.t. to 100	41	38	79	1.1/1
3	Cu(OTf)₂ (2.0)	Toluene	r.t. to 50	40	28	68	1.4/1
4	Yb(OTf)₃ (2.0)	Toluene	r.t. to 100	45	37	82	1.2/1
5	In(OTf)₃ (1.0)	Toluene	r.t.	49	35	84	1.4/1
6	Hf(OTf)₄ (1.0)	Toluene	r.t.	47	34	82	1.4/1
7	TiCl₄ (1.0)	Toluene	r.t.	35	37	72	0.9/1
8	FeCl₃ (1.0)	Toluene	r.t.	41	38	79	1.1/1
9	AlCl₃ (1.0)	Toluene	r.t.	50	30	80	1.7/1
10	BF₃•OEt₂ (1.0)	Toluene	r.t.	50	37	87	1.4/1
11^b	BF₃•OEt₂ (5.0)	Toluene	－78	—	—	—	—
12	BF₃•OEt₂ (5.0)	Toluene	－60	59	33	92	1.8/1
13	BF₃•OEt₂ (3.0)	Toluene	－40	59	33	92	1.8/1
14	BF₃•OEt₂ (1.5)	Toluene	0	50	33	83	1.5/1
15	BF₃•OEt₂ (1.0)	Toluene	60	51	36	87	1.4/1
16^b	BF₃•OEt₂(3.0)	THF	－40 or r.t.	—	—	—	—
17	BF₃•OEt₂(3.0)	THF	50	21	19	40	1.1/1
18	BF₃•OEt₂(3.0)	DCM	－40	53	34	87	1.6/1
19	BF₃•OEt₂(3.0)	DCE	－35	52	36	88	1.4/1
20	BF₃•OEt₂(3.0)	EA	－40 to r.t.	50	26	76	1.9/1
21	BF₃•OEt₂(3.0)	n-Hexane	r.t.	41	38	79	1.1/1
22^c	BF₃•OEt₂ (3.0)	Toluene	－40	60	33	93	1.8/1

Entry	Substrate 1							T/℃	Product 2 and yield						Product 3 and yield					Total				Ratio 2/3
1								－40												93%				1.8/1
1	1a							－40	2a, 60%						3a, 33%					93%				1.8/1
2								－40												85%				1.9/1
2	1b							－40	2a, 56%						3b, 29%					85%				1.9/1
3								－40												89%				1.5/1
3	1c							－40	2a, 54%						3c, 35%					89%				1.5/1
4								－40												86%				1.9/1
4	1d							－40	2d, 56%						3d, 30%					86%				1.9/1
5^b								－40												86%				1/1.5
5^b	1e							－40	2e, 34%						3e, 52%					86%				1/1.5
6								－40												86%				1.9/1
6	1f							－40	2f, 56%						3f, 30%					86%				1.9/1
Entry			Substrate 1		T/℃					Product 2 and yield						Product 3 and yield		Total					Ratio 2/3
7^b					－40													78%					1/2.9
7^b			1g		－40					2g, 20%						3g, 58%		78%					1/2.9
8					－40													90%					1.6/1
8			1h		－40					2h, 56%						3h, 34%		90%					1.6/1
9^b					－40													75%					1/2.9
9^b			1i		－40					2i, 19%						3i, 56%		75%					1/2.9
10					－40													88%					2.8/1
10			1j		－40					2j, 65%						3j, 23%		88%					2.8/1
11					－40													95%					1/2.1
11			1k		－40					2k, 31%						3k, 64%		95%					1/2.1
12					－40													90%					1/1.8
12			1l		－40					2l, 32%						3l, 58%		90%					1/1.8
13^b					－20													72%					1/1.4
13^b			1m		－20					2m, 30%						3m, 42%		72%					1/1.4
Entry		Substrate 1					T/℃				Product 2 and yield			Product 3 and yield			Total					Ratio 2/3
14							－40										68%					1.1/1
14		1n					－40				2n, 36%			3n, 32%			68%					1.1/1
15^b^,^c							－40										74%					1/2.9
15^b^,^c		1o					－40				2o, 19%			3o, 55%			74%					1/2.9
16							－40										89%					1/6.4
16		1p					－40				2p, 12%			3p, 77%			89%					1/6.4
17							r.t.										94%					3.7/1
17		1q					r.t.				2q, 74%			3q, 20%			94%					3.7/1
18							－40										83%					2.8/1
18		1r					－40				2r, 61%			3r, 22%			83%					2.8/1
19							－40										85%					1/1
19		1s					－40				2s, 42%			3s, 43%			85%					1/1
20							－40										94%					1/1.2
20		1t					－40				2t, 43%			3t, 51%			94%					1/1.2
Entry				Substrate 1		T/℃						Product 2 and yield	Product 3 and yield						Total		Ratio 2/3
21						－40													90%		2.6/1
21				1u		－40						2u, 65%	3u, 25%						90%		2.6/1
22						0													93%		2.3/1
22				1v		0						2v, 65%	3v, 28%						93%		2.3/1
23						0													94%		4.5/1
23				1w		0						2w, 77%	3w, 17%						94%		4.5/1
24						－20													99%		2.9/1
24				1x		－20						2x, 74%	3x, 25%						99%		2.9/1
25						－40													90%		1/1.4
25				1y		－40						2y, 37%	3y, 53%						90%		1/1.4

Entry	Substrate 1							T/℃	Product 2 and yield						Product 3 and yield					Total				Ratio 2/3
1								－40												93%				1.8/1
1	1a							－40	2a, 60%						3a, 33%					93%				1.8/1
2								－40												85%				1.9/1
2	1b							－40	2a, 56%						3b, 29%					85%				1.9/1
3								－40												89%				1.5/1
3	1c							－40	2a, 54%						3c, 35%					89%				1.5/1
4								－40												86%				1.9/1
4	1d							－40	2d, 56%						3d, 30%					86%				1.9/1
5^b								－40												86%				1/1.5
5^b	1e							－40	2e, 34%						3e, 52%					86%				1/1.5
6								－40												86%				1.9/1
6	1f							－40	2f, 56%						3f, 30%					86%				1.9/1
Entry			Substrate 1		T/℃					Product 2 and yield						Product 3 and yield		Total					Ratio 2/3
7^b					－40													78%					1/2.9
7^b			1g		－40					2g, 20%						3g, 58%		78%					1/2.9
8					－40													90%					1.6/1
8			1h		－40					2h, 56%						3h, 34%		90%					1.6/1
9^b					－40													75%					1/2.9
9^b			1i		－40					2i, 19%						3i, 56%		75%					1/2.9
10					－40													88%					2.8/1
10			1j		－40					2j, 65%						3j, 23%		88%					2.8/1
11					－40													95%					1/2.1
11			1k		－40					2k, 31%						3k, 64%		95%					1/2.1
12					－40													90%					1/1.8
12			1l		－40					2l, 32%						3l, 58%		90%					1/1.8
13^b					－20													72%					1/1.4
13^b			1m		－20					2m, 30%						3m, 42%		72%					1/1.4
Entry		Substrate 1					T/℃				Product 2 and yield			Product 3 and yield			Total					Ratio 2/3
14							－40										68%					1.1/1
14		1n					－40				2n, 36%			3n, 32%			68%					1.1/1
15^b^,^c							－40										74%					1/2.9
15^b^,^c		1o					－40				2o, 19%			3o, 55%			74%					1/2.9
16							－40										89%					1/6.4
16		1p					－40				2p, 12%			3p, 77%			89%					1/6.4
17							r.t.										94%					3.7/1
17		1q					r.t.				2q, 74%			3q, 20%			94%					3.7/1
18							－40										83%					2.8/1
18		1r					－40				2r, 61%			3r, 22%			83%					2.8/1
19							－40										85%					1/1
19		1s					－40				2s, 42%			3s, 43%			85%					1/1
20							－40										94%					1/1.2
20		1t					－40				2t, 43%			3t, 51%			94%					1/1.2
Entry				Substrate 1		T/℃						Product 2 and yield	Product 3 and yield						Total		Ratio 2/3
21						－40													90%		2.6/1
21				1u		－40						2u, 65%	3u, 25%						90%		2.6/1
22						0													93%		2.3/1
22				1v		0						2v, 65%	3v, 28%						93%		2.3/1
23						0													94%		4.5/1
23				1w		0						2w, 77%	3w, 17%						94%		4.5/1
24						－20													99%		2.9/1
24				1x		－20						2x, 74%	3x, 25%						99%		2.9/1
25						－40													90%		1/1.4
25				1y		－40						2y, 37%	3y, 53%						90%		1/1.4

BF₃•Et₂O促进的环丙烯基甲醇衍生物重排反应研究

Study of BF₃•Et₂O-Promoted Rearrangement of Cyclopropenylcarbinols

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