Asymmetric Organocatalytic 1,6-Conjugate Addition of Alkynyl 8-Methylenenaphthalen-2(8H)-one Formed In Situ: Synergistic Construction of Axial and Central Chirality

IF 5 1区化学 Q1 CHEMISTRY, ORGANIC

Organic Letters Pub Date : 2025-01-26 DOI:10.1021/acs.orglett.4c0486410.1021/acs.orglett.4c04864

Meiwen Liu, Yihao Zhang, Xin-Yan Ke, Shao-Fei Ni and Pengfei Li*,

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引用次数: 0

Abstract

Organocatalytic enantioselective formal nucleophilic substitution reactions of α-(2-hydroxynaphthalen-8-yl)propargyl alcohols with 1-(1H-indol-3-yl)naphthalen-2-ols have been established for the first time. With the aid of a suitable chiral phosphoric acid, alkynyl 8-methylenenaphthalen-2(8H)-one was formed in situ from the corresponding α-(2-hydroxynaphthalen-8-yl)propargyl alcohol, followed by enantioselective 1,6-conjugate additions of 1-(1H-indol-3-yl)naphthalen-2-ols to afford a number of enantioenriched (R_a,S_c)-2,3-disubstituted indoles in 50–80% yields with 81–93% ee and (S_a,S_c)-2,3-disubstituted indoles in 18–40% yields with 79–96% ee. Notably, these nucleophilic substitution products were characterized by the presence of functional groups, including indole, naphthol, and alkynyl units, while exhibiting both axial and central chirality.

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原位形成的烷基8-亚甲基萘-2(8H)- 1的不对称有机催化1,6-共轭加成：轴向和中心手性的协同构建

首次建立了α-（2-羟基萘-8-基）丙炔醇与1-（1h -吲哚-3-基）萘-2-醇的有机催化对映选择性亲核取代反应。在合适的手性磷酸的辅助下，由相应的α-（2-羟基萘-8-基）丙炔醇原位生成炔基8-亚甲基萘-2(8H)- 1，然后在1-（1h -吲哚-3-基）萘-2-醇的1,6对映选择性加成后，得到了一些对映丰富的(Ra,Sc)-2,3-二取代吲哚，收率为50-80%，ee为81-93%，(Sa,Sc)-2,3-二取代吲哚，收率为18-40%，ee为79-96%。值得注意的是，这些亲核取代产物的特点是存在官能团，包括吲哚、萘酚和炔基单位，同时表现出轴向和中心手性。

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来源期刊

Organic Letters 化学-有机化学

CiteScore

9.30

自引率

11.50%

发文量

1607

审稿时长

1.5 months

期刊介绍： Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.