Synthesis 2022; 54(17): 3823-3830
DOI: 10.1055/s-0040-1719886
special topic
Special Issue in memory of Prof. Ferenc Fülöp

Application of Proline-Derived (Thio)squaramide Organocatalysts in Asymmetric Diels–Alder and Conjugate Addition Reactions

a   Department of Organic Chemistry & Technology, Budapest University of Technology & Economics, Szent Gellért tér 4, 1111 Budapest, Hungary
,
Sándor Nagy
a   Department of Organic Chemistry & Technology, Budapest University of Technology & Economics, Szent Gellért tér 4, 1111 Budapest, Hungary
,
Dávid Kis
a   Department of Organic Chemistry & Technology, Budapest University of Technology & Economics, Szent Gellért tér 4, 1111 Budapest, Hungary
,
Péter Bagi
a   Department of Organic Chemistry & Technology, Budapest University of Technology & Economics, Szent Gellért tér 4, 1111 Budapest, Hungary
,
Béla Mátravölgyi
a   Department of Organic Chemistry & Technology, Budapest University of Technology & Economics, Szent Gellért tér 4, 1111 Budapest, Hungary
,
Blanka Tóth
b   Department of Inorganic & Analytical Chemistry, Budapest University of Technology & Economics, Szent Gellért tér 4, 1111 Budapest, Hungary
,
Péter Huszthy
a   Department of Organic Chemistry & Technology, Budapest University of Technology & Economics, Szent Gellért tér 4, 1111 Budapest, Hungary
,
László Drahos
c   MS Proteomics Research Group, Research Centre for Natural Sciences, Magyar Tudósok körútja 2, 1117 Budapest, Hungary
,
József Kupai
a   Department of Organic Chemistry & Technology, Budapest University of Technology & Economics, Szent Gellért tér 4, 1111 Budapest, Hungary
› Author Affiliations
This research was funded by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (J.K.). It was also supported by the National Research, Development and Innovation Office (grant numbers FK138037 and K128473), and the Richter Gedeon Excellence PhD Scholarship of Richter Gedeon Talentum Foundation, Richter Gedeon Plc. (G.D.).


Dedicated to the memory of Prof. Ferenc Fülöp

Abstract

The synthesis of chiral proline-derived squaramide and thiosquaramide organocatalysts, which are capable of the dual activation in asymmetric reactions is reported. The (thio)squaramide moiety can form hydrogen bonds to activate the substrates and to stereocontrol the reaction, while the pyrrolidine unit can form enamines to activate carbonyl compounds via aminocatalysis. Comparing the performance of thiosquaramide to squaramide, the Diels–Alder reaction of (anthracen-9-yl)acetaldehyde and trans-β-nitrostyrene was examined, which has been investigated in the literature using quantum chemical calculations. Both squaramide and thiosquaramide gave excellent yields (up to 99%) and enantiomeric excess values (up to 98%). Moreover, their catalytic performance was compared in conjugate addition of lawsone to β,γ-unsaturated α-keto ester.

Supporting Information



Publication History

Received: 14 October 2021

Accepted after revision: 17 December 2021

Article published online:
09 February 2022

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