Nitroacrylates are pluripotent substrates that have already found interesting applications as electrophiles in anti-Michael additions as well as dienophiles in Diels Alder reactions.(1) Our group has recently reported the possibility of obtaining cyclohexanone derivatives by a stereoselective organocatalyzed one-pot methodology from (E)-beta-subsituteted-beta-nitroacrylates and alfa,beta-unsaturated ketones.(2) The so obtained products are direct precursors of cyclic beta-amino acids and can be seen as advanced intermediates for the synthesis of beta-lactams or natural products. The reaction is promoted by Cinchona alkaloids derived primary amines in the presence of an acidic co-catalyst and afford two diasteroisomers in high yield - typically 80% - and enantiomeric excess up to 98%.(3) Replacing traditional heating with microwave irradiation afforded cleaner reactions in shortened time, passing from 48 hours to 30 minutes, with improved dr (20:80) and high ee (up to 94%). The application of microwave technology to this organocatalytic methodology allowed also employing C1 substituted enones, leading to cyclohexanones with four contiguous stereocenters with enantioselectivity exceeding 93%, although in low yield and diasteromeric ratio. Solvent and temperature effect were investigated, but no substantial changes the reaction outcome were observed. The combination of different substitution patterns on both reaction partners is still under investigation, so to obtain densely functionalized cyclic nitro esters with high selectivity. References: 1 Jensen, K. L.; Dickmeiss, G.; Donslund, B. S.; Poulsen, P. H.; Jorgensen, K. A. Org. Lett., 2011, 13, 14, 36782; Mukherjee, S., Corey, E. J. Org. Lett., 2010, 12, 5, 1024. 2 Massolo, E.; Benaglia, M., Annunziata, R; Palmieri, A; Celentano, G; Forni, A. Adv. Syn. Catal. 2014, 356, 493-500. 3 For a related work see: Wu, L.-Y.; Bencivenni, G.; Mancinelli, M.; Mazzanti, A.; Bartoli, G.; Melchiorre, P. Angew. Chem. Int. Ed., 2009, 48, 7196-7199.

Nitroacrylates reactivity In stereoselective organocatalyzed cascade reactions / E. Massolo, M. Benaglia, D. Parravicini, R. Annunziata. ((Intervento presentato al convegno ORCA-COST meeting tenutosi a Palermo nel 2014.

Nitroacrylates reactivity In stereoselective organocatalyzed cascade reactions

E. Massolo
Primo
;
M. Benaglia
;
R. Annunziata
Ultimo
2014

Abstract

Nitroacrylates are pluripotent substrates that have already found interesting applications as electrophiles in anti-Michael additions as well as dienophiles in Diels Alder reactions.(1) Our group has recently reported the possibility of obtaining cyclohexanone derivatives by a stereoselective organocatalyzed one-pot methodology from (E)-beta-subsituteted-beta-nitroacrylates and alfa,beta-unsaturated ketones.(2) The so obtained products are direct precursors of cyclic beta-amino acids and can be seen as advanced intermediates for the synthesis of beta-lactams or natural products. The reaction is promoted by Cinchona alkaloids derived primary amines in the presence of an acidic co-catalyst and afford two diasteroisomers in high yield - typically 80% - and enantiomeric excess up to 98%.(3) Replacing traditional heating with microwave irradiation afforded cleaner reactions in shortened time, passing from 48 hours to 30 minutes, with improved dr (20:80) and high ee (up to 94%). The application of microwave technology to this organocatalytic methodology allowed also employing C1 substituted enones, leading to cyclohexanones with four contiguous stereocenters with enantioselectivity exceeding 93%, although in low yield and diasteromeric ratio. Solvent and temperature effect were investigated, but no substantial changes the reaction outcome were observed. The combination of different substitution patterns on both reaction partners is still under investigation, so to obtain densely functionalized cyclic nitro esters with high selectivity. References: 1 Jensen, K. L.; Dickmeiss, G.; Donslund, B. S.; Poulsen, P. H.; Jorgensen, K. A. Org. Lett., 2011, 13, 14, 36782; Mukherjee, S., Corey, E. J. Org. Lett., 2010, 12, 5, 1024. 2 Massolo, E.; Benaglia, M., Annunziata, R; Palmieri, A; Celentano, G; Forni, A. Adv. Syn. Catal. 2014, 356, 493-500. 3 For a related work see: Wu, L.-Y.; Bencivenni, G.; Mancinelli, M.; Mazzanti, A.; Bartoli, G.; Melchiorre, P. Angew. Chem. Int. Ed., 2009, 48, 7196-7199.
organocatalysis; nitroacrylates; cascade reactions
Settore CHIM/06 - Chimica Organica
Nitroacrylates reactivity In stereoselective organocatalyzed cascade reactions / E. Massolo, M. Benaglia, D. Parravicini, R. Annunziata. ((Intervento presentato al convegno ORCA-COST meeting tenutosi a Palermo nel 2014.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/251980
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