镁-双噁唑啉络合物催化3,5-二甲基-N-α,β-不饱和酰基吡唑的不对称共轭氰化反应研究

doi:10.6023/cjoc202107061

摘要/Abstract

报道了镁-双噁唑啉络合物体系催化的TMSCN与3,5-二甲基-N-α,β-不饱和酰基吡唑的不对称共轭氰化反应. 考察了BOX配体结构、配体与金属比例、温度、溶剂等对反应的影响. 研究结果表明, 使用双苄基取代的双噁唑啉配体与二丁基镁(物质的量比为2∶1)在1,2-二氯乙烷中原位生成手性催化剂, 催化剂用量为10 mol%, 反应温度为–32 ℃, 不对称共轭氰化反应催化效果最佳. 将上述催化方法应用于一系列3,5-二甲基-N-α,β-酰基吡唑衍生物, 绝大部分以90%以上的产率和中等以上的对映选择性获得相应的目标产物.

关键词: 双噁唑啉, 三甲基氰硅烷, 3,5-二甲基-N-α,β-不饱和酰基吡唑, 不对称共轭氰化

The asymmetric conjugate cyanation reaction of TMSCN with 3,5-dimethyl-N-α,β-unsaturated acylpyrazole catalyzed by magnesium-bisoxazoline complex was studied. The effects of BOX ligand structure, ligand to metal ratio, temperature, solvent, etc. on the reaction were investigated. The results showed that when bis-benzyl substituted bisoxazoline ligand and dibutylmagnesium (molar ratio 2∶1) were used to generate chiral catalyst in situ in 1,2-dichloroethane, the amount of catalyst was 10 mol%, and the reaction temperature was –32 ℃, and the catalytic effect of asymmetric conjugate cyanation reaction was the best. The catalytic method above was applied to the conjugate cyanation reaction of a series of 3,5-dimethyl-N-α,β-unsaturated acyl pyrazole derivatives, most of the corresponding target products could be obtained with more than 90% yield and moderate to good enantioselectivities.

Key words: bisoxazoline, TMSCN, 3,5-dimethyl-N-α,β-unsaturated acyl pyrazole, asymmetric conjugate cyanation

引用此文

刘云姝, 赵国栋, 武文菊, 王云泽, 喻艳超, 由君, 刘波. 镁-双噁唑啉络合物催化3,5-二甲基-N-α,β-不饱和酰基吡唑的不对称共轭氰化反应研究[J]. 有机化学, 2022, 42(1): 208-217.

Yunshu Liu, Guodong Zhao, Wenju Wu, Yunze Wang, Yanchao Yu, Jun You, Bo Liu. Study on Asymmetric Conjugate Cyanation of 3,5-Dimethyl-N-α,β-unsaturated Acylpyrazole Catalyzed by Magnesium-Bisoxazoline Complex[J]. Chinese Journal of Organic Chemistry, 2022, 42(1): 208-217.

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Entry	Ligand	Yield^b/%	er^c
1	L₁	99	50∶50
2	L₂	99	50∶50
3	L₃	99	50∶50
4	L₄	65	65∶35
5	L₅	63	71∶29
6	L₆	65	53∶47
7	L₇	85	88∶12
8	L₈	70	74∶26
9	L₉	66	84∶16
10	L₁₀	65	51∶49
11	L₁₁	70	88∶12
12	L₁₂	63	83∶17
13	L₁₃	65	83∶17
14	L₁₄	66	79∶21
15	L₁₅	40	50∶50
16	L₁₆	35	50∶50
17	L₁₇	99	50∶50

Entry	Ligand	Yield^b/%	er^c
1	L₁	99	50∶50
2	L₂	99	50∶50
3	L₃	99	50∶50
4	L₄	65	65∶35
5	L₅	63	71∶29
6	L₆	65	53∶47
7	L₇	85	88∶12
8	L₈	70	74∶26
9	L₉	66	84∶16
10	L₁₀	65	51∶49
11	L₁₁	70	88∶12
12	L₁₂	63	83∶17
13	L₁₃	65	83∶17
14	L₁₄	66	79∶21
15	L₁₅	40	50∶50
16	L₁₆	35	50∶50
17	L₁₇	99	50∶50

Entry	n-Bu₂Mg (x mol%)	L₇ (y mol%)	Solvent	T/℃	Yield^b/%	er^c
1^d	10	20	CH₂Cl₂	–18	88	88∶12
2^e	10	20	CH₂Cl₂	–18	60	80∶20
3^f	10	20	CH₂Cl₂	–18	70	84∶16
4^g	10	20	CH₂Cl₂	–18	87	87∶13
5	10	11	CH₂Cl₂	–18	85	84∶16
6	10	10	CH₂Cl₂	–18	86	87∶13
7	10	8	CH₂Cl₂	–18	84	86∶14
8	10	5	CH₂Cl₂	–18	84	81∶19
9	5	10	CH₂Cl₂	–18	60	63∶37
10	15	30	CH₂Cl₂	–18	90	87∶13
11	10	20	Toluene	–18	25	52∶48
12	10	20	PhCl	–18	35	71∶29
13	10	20	ClCH₂CH₂Cl	–18	92	89∶11
14	10	20	CHCl₃	–18	85	80∶20
15	10	20	THF	–18	—	—
16	10	20	Et₂O	–18	—	—
17	10	20	ClCH₂CH₂Cl	25	96	69∶31
18	10	20	ClCH₂CH₂Cl	0	96	73∶27
19^h	10	20	ClCH₂CH₂Cl	–32	95	93∶7
20ⁱ	10	20	CH₂Cl₂	–42	94	92∶8
21ⁱ	10	20	CH₂Cl₂	–50	66	92∶8
22ⁱ	10	20	CH₂Cl₂	–78	0	—

Entry	n-Bu₂Mg (x mol%)	L₇ (y mol%)	Solvent	T/℃	Yield^b/%	er^c
1^d	10	20	CH₂Cl₂	–18	88	88∶12
2^e	10	20	CH₂Cl₂	–18	60	80∶20
3^f	10	20	CH₂Cl₂	–18	70	84∶16
4^g	10	20	CH₂Cl₂	–18	87	87∶13
5	10	11	CH₂Cl₂	–18	85	84∶16
6	10	10	CH₂Cl₂	–18	86	87∶13
7	10	8	CH₂Cl₂	–18	84	86∶14
8	10	5	CH₂Cl₂	–18	84	81∶19
9	5	10	CH₂Cl₂	–18	60	63∶37
10	15	30	CH₂Cl₂	–18	90	87∶13
11	10	20	Toluene	–18	25	52∶48
12	10	20	PhCl	–18	35	71∶29
13	10	20	ClCH₂CH₂Cl	–18	92	89∶11
14	10	20	CHCl₃	–18	85	80∶20
15	10	20	THF	–18	—	—
16	10	20	Et₂O	–18	—	—
17	10	20	ClCH₂CH₂Cl	25	96	69∶31
18	10	20	ClCH₂CH₂Cl	0	96	73∶27
19^h	10	20	ClCH₂CH₂Cl	–32	95	93∶7
20ⁱ	10	20	CH₂Cl₂	–42	94	92∶8
21ⁱ	10	20	CH₂Cl₂	–50	66	92∶8
22ⁱ	10	20	CH₂Cl₂	–78	0	—