叔丁醇钠催化的δ-腈基-δ-芳基-双取代的对亚甲基苯醌和二芳基氧磷的磷氢化反应研究

doi:10.6023/cjoc202104003

摘要/Abstract

报道了一种高效的δ-腈基-δ-芳基-双取代的对亚甲基苯醌和二芳基氧磷的1,6-共轭加成反应, 合成了含有氰基取代的季碳中心的二芳基甲烷膦氧化合物. 在温和的反应条件下此磷氢化反应能够顺利进行, 以74%~92%的收率得到目标产物. 另外, 该反应具有优秀的官能团兼容性, 展示出了很好的底物范围. 所合成的含有氰基取代季碳中心的二芳基(多取代甲基)膦氧化合物在发展新的配体方面具有潜在的应用价值.

关键词: 对亚甲基苯醌, 二芳基甲烷膦氧化合物, 磷氢化, 季碳中心, 1,6-共轭加成反应

An effective method for the construction of diarylmethyl phosphorus oxides containing CN-substituted quaternary stereocenters via 1,6-conjugated addition has been developed. Under mild condition, the hydrophosphonylation process of δ-CN-δ-aryl-disubstituted para-quinone methides (p-QMs) with diarylphosphine oxides underwent smoothly, affording the desired products in 74%~92% yields. In addition, this protocol features great functional group tolerance and displays a broad substrate scope. Diaryl (multi-substituted methyl) phosphorus oxides bearing CN-substituted quaternary stereocenters synthesized by this efficient method has the potential application in the discovery of new ligands.

Key words: para-quinone methide, diarylmethyl phosphorus oxide, hydrophosphonylation, quaternary stereocenter, 1,6- conjugate addition

引用此文

王东琳, 阚玲珑, 马玉道, 刘磊. 叔丁醇钠催化的δ-腈基-δ-芳基-双取代的对亚甲基苯醌和二芳基氧磷的磷氢化反应研究[J]. 有机化学, 2021, 41(8): 3192-3203.

Donglin Wang, Linglong Kan, Yudao Ma, Lei Liu. NaO^tBu-Catalyzed Hydrophosphonylation of δ-CN-δ-aryl-disubstituted para-Quinone Methides with Phosphine Oxides[J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 3192-3203.

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图/表 7

图式1. p-QMs和氧化磷的1,6-磷氢化反应

Scheme 1. 1,6-Hydrophosphonylation of p-QMs with phosphorus oxides

Entry^a	Base	Base/equiv.	Solvent	Time/h	Yield^b/%
1	NaO^tBu	1	ClCH₂CH₂Cl	0.1	86
2	Cs₂CO₃	1	ClCH₂CH₂Cl	2	N.R.
3	NaOH	1	ClCH₂CH₂Cl	2	53
4	K₂CO₃	1	ClCH₂CH₂Cl	0.5	27
5	Et₃N	1	ClCH₂CH₂Cl	0.5	82
6	DBU	1	ClCH₂CH₂Cl	0.5	81
7	NaO^tBu	1	CH₂Cl₂	0.1	77
8	NaO^tBu	1	CH₃CN	0.5	90
9	NaO^tBu	1	THF	0.2	82
10	NaO^tBu	1	CHCl₃	24	35
11	NaO^tBu	1	H₂O	4	80
12	LiO^tBu	1	CH₃CN	0.5	23
13	KO^tBu	1	CH₃CN	0.1	75
14	—	—	CH₃CN	24	12
15	NaO^tBu	0.1	CH₃CN	3	83
16	NaO^tBu	0.2	CH₃CN	1	87

表1. 反应条件的优化

Table 1. Reaction condition optimization

表2. 对亚甲基苯醌的拓展

Table 2. Scope of para-quinone methides

表3. 二芳基氧化磷的拓展

Table 3. Scope of diarylphosphine oxides

图式2. 亚磷酸酯的拓展

Scheme 2. Scope of phosphites

图式3. 机理实验

Scheme 3. Mechanistic experiments

图式4. 可能的反应机理

Scheme 4. A plausible mechanism

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