Synthesis 2020; 52(07): 1047-1059
DOI: 10.1055/s-0039-1690751
paper
© Georg Thieme Verlag Stuttgart · New York

Enantioselective N-Alkylation of Nitroindoles under Phase-Transfer Catalysis

Dmitri Trubitsõn
a  Department of Chemistry and Biotechnology, Tallinn University of Technology, 12618 Tallinn, Estonia   Email: tonis.kanger@taltech.ee
,
Jevgenija Martõnova
a  Department of Chemistry and Biotechnology, Tallinn University of Technology, 12618 Tallinn, Estonia   Email: tonis.kanger@taltech.ee
,
Kristin Erkman
a  Department of Chemistry and Biotechnology, Tallinn University of Technology, 12618 Tallinn, Estonia   Email: tonis.kanger@taltech.ee
,
Andrus Metsala
a  Department of Chemistry and Biotechnology, Tallinn University of Technology, 12618 Tallinn, Estonia   Email: tonis.kanger@taltech.ee
,
Jaan Saame
b  Institute of Chemistry, University of Tartu, 50411 Tartu, Estonia
,
Kristjan Kõster
b  Institute of Chemistry, University of Tartu, 50411 Tartu, Estonia
,
Ivar Järving
a  Department of Chemistry and Biotechnology, Tallinn University of Technology, 12618 Tallinn, Estonia   Email: tonis.kanger@taltech.ee
,
Ivo Leito
b  Institute of Chemistry, University of Tartu, 50411 Tartu, Estonia
,
a  Department of Chemistry and Biotechnology, Tallinn University of Technology, 12618 Tallinn, Estonia   Email: tonis.kanger@taltech.ee
› Author Affiliations
The authors thank the Estonian Ministry of Education and Research (grant nos. IUT 19-32, IUT 19-9, IUT 20-14, PRG399, and PUT 1468) and the Centre of Excellence in Molecular Cell Engineering (2014-2020.4.01.15-0013) for financial support. This work has been partially supported by ASTRA ‘TUT Institutional Development Programme for 2016-2022’ Graduate School of Functional Materials and Technologies (2014-2020.4.01.16-0032).
Further Information

Publication History

Received: 26 September 2019

Accepted after revision: 04 November 2019

Publication Date:
26 November 2019 (online)


Abstract

An asymmetric phase-transfer-catalyzed N-alkylation of substituted indoles with various Michael acceptors was studied. Acidities of nitroindoles were determined in acetonitrile by UV-Vis spectrophotometric titration. There was essentially no correlation between acidity and reactivity in the aza-Michael reaction. The position of the nitro group on the indole ring was essential to control the stereoselectivity of the reaction. Michael adducts were obtained in high yields and moderate enantioselectivities in the reaction between 4-nitroindole and various Michael acceptors in the presence of cinchona alkaloid based phase-transfer catalysts. In addition to outlining the scope and limitations of the method, the geometries of the transition states of the reaction were calculated.

Supporting Information

 
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