Nitrocyclopropanes represent a special class of cyclopropane compounds, which are present in some natural products and used as precursors of pharmacologically relevant targets. In the last few decades, there has been a renewed interest in the stereoselective synthesis of nitrocyclopropanes, which is most frequently achieved through Michael initiated ring closure (MIRC) reactions between electrophilic alkenes and suitable nucleophiles bearing a good leaving group. Recently, it has been reported that racemic 2,5-dihydrothiophene-3-carbaldehydes, obtained by secondary amine-catalyzed domino sulfa-Michael/aldol condensations of 1,4-dithiane-2,5-diol 1 with α,β-unsaturated aldehydes, are convenient substrates for diastereoselective cyclopropanations with bromonitromethane to give bicyclic nitrocyclopropanes via domino Michael/α-alkylation reactions catalyzed by DL-proline. As a logical extension of this work, it has been investigated an asymmetric version of the above process by using a chiral proline surrogate as catalyst, with the aim at combining the two catalytic domino sequences to access the target nitrocyclopropane scaffolds by a challenging four reaction, one-pot process. Our studies led to disclose a one-pot, four-step method wherein chiral dihydrothiophenes, prepared by an organocatalytic domino sulfa-Michael/aldol condensation reaction, are treated in-situ with bromonitromethane anion to provide the target compounds with good diastereo- and enantioselectivies. This process is efficiently carried out by using (S)-diphenylprolinol TMS ether as the only and one organocatalyst triggering both the domino sulfa-Michael/aldol condensation step and the following domino Michael/α-alkylation reaction.

One-pot, four-step organocatalytic asymmetric synthesis of functionalized nitrocyclopropanes

ZAGHI, Anna;BERNARDI, Tatiana;BERTOLASI, Valerio;BORTOLINI, Olga;MASSI, Alessandro;DE RISI, Carmela
2015

Abstract

Nitrocyclopropanes represent a special class of cyclopropane compounds, which are present in some natural products and used as precursors of pharmacologically relevant targets. In the last few decades, there has been a renewed interest in the stereoselective synthesis of nitrocyclopropanes, which is most frequently achieved through Michael initiated ring closure (MIRC) reactions between electrophilic alkenes and suitable nucleophiles bearing a good leaving group. Recently, it has been reported that racemic 2,5-dihydrothiophene-3-carbaldehydes, obtained by secondary amine-catalyzed domino sulfa-Michael/aldol condensations of 1,4-dithiane-2,5-diol 1 with α,β-unsaturated aldehydes, are convenient substrates for diastereoselective cyclopropanations with bromonitromethane to give bicyclic nitrocyclopropanes via domino Michael/α-alkylation reactions catalyzed by DL-proline. As a logical extension of this work, it has been investigated an asymmetric version of the above process by using a chiral proline surrogate as catalyst, with the aim at combining the two catalytic domino sequences to access the target nitrocyclopropane scaffolds by a challenging four reaction, one-pot process. Our studies led to disclose a one-pot, four-step method wherein chiral dihydrothiophenes, prepared by an organocatalytic domino sulfa-Michael/aldol condensation reaction, are treated in-situ with bromonitromethane anion to provide the target compounds with good diastereo- and enantioselectivies. This process is efficiently carried out by using (S)-diphenylprolinol TMS ether as the only and one organocatalyst triggering both the domino sulfa-Michael/aldol condensation step and the following domino Michael/α-alkylation reaction.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2329966
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