基于原位形成的氮杂邻亚甲基苯醌和卤代萘酚的分子间[4＋1]螺环化/去芳香化反应

doi:10.6023/cjoc202303029

摘要/Abstract

报道了一种碱促进的卤代萘酚与N-(邻氯甲基)芳基酰胺[4＋1]螺环化/去芳构化策略, 以此来直接有效地合成氮杂螺环化合物. 在温和条件下以中等至优秀的收率、高非对映选择性地合成了一系列氮杂螺环化合物. 该反应可以兼容各种官能团, 如醛基、游离羟基和不同的N保护基, 如Bz和Ts等. 对产物进行了转化, 并提出了可能的反应机理.

关键词: 氮杂螺环, [4＋1]环加成反应, 脱芳构化, 螺环化

A base promoted dearomatization strategy for [4＋1] spiroannulation of halonaphthols with N-(o-chloromethyl) aryl amides is reported, which is used to efficiently synthesize azaspirocycles. A range of azaspirocycles were obtained in satisfactory to excellent yield with high diastereoselectivity under mild conditions. Variety functional groups including aldehyde and free hydroxyl group, and different N-protecting groups, such as Bz and Ts are compatibility. The transformation of the product and a possible mechanism were also provided.

Key words: azaspirocyclic compound, [4＋1] cycloaddition reaction, dearomatization, spiroannulation

引用此文

梁俊秀, 刘亚洲, 王阿木, 吴彦超, 马小锋, 李惠静. 基于原位形成的氮杂邻亚甲基苯醌和卤代萘酚的分子间[4＋1]螺环化/去芳香化反应[J]. 有机化学, 2023, 43(11): 3888-3899.

Junxiu Liang, Yazhou Liu, Amu Wang, Yanchao Wu, Xiaofeng Ma, Huijing Li. Dearomatization of Halonaphthols via an Intermolecular [4＋1] Spiroannulation with in situ Formed Aza-ortho-quinone Methides[J]. Chinese Journal of Organic Chemistry, 2023, 43(11): 3888-3899.

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图/表 9

Figure 1. Representative molecules containing azaspirocycles

Figure 2. Construction of azaspirocycles by dearomatization

Entry	Base	Solvent	T/℃	Yield^b/%
1	Cs₂CO₃	DCE	25	83
2	MeONa	DCE	25	60
3	K₂CO₃	DCE	25	93 (92)
4	DBU	DCE	25	0
5	DIPEA	DCE	25	0
6	K₂CO₃	DCM	25	85
7	K₂CO₃	THF	25	82
8	K₂CO₃	DMF	25	0
9	K₂CO₃	Toluene	25	90
10	K₂CO₃	DCE	40	92
11	K₂CO₃	DCE	50	92
12	K₂CO₃	DCE	10	90

Table 1. Optimization of the reaction conditionsa

Scheme 1. Scope of o-chloromethylanilines

Scheme 2. Scope of 1-halo-2-naphthols

Scheme 3. Gram-scale reaction and synthetic applications

Scheme 4. Control experiments and proposed mechanism

Scheme 5. Synthesis of compound 1

Scheme 6. Synthesis of compound 2

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