d-Prolyl-2-(trifluoromethylsulfonamidopropyl)pyrrolidine: An Organocatalyst for Asymmetric Michael Addition of Aldehydes to β-Nitroalkenes at Ambient Conditions

Abstract

Four 2-(trifluoromethylsulfonamidoalkyl)pyrrolidines and their D-prolinamides were prepared and screened as organocatalysts for the Michael addition reaction of aldehydes with βnitroalkenes at rt and without the use of additives. D-Prolyl-2-(trifluoromethylsulfonamidopropyl)pyrrolidine was found to be the best among the molecules studied, which yielded γ-nitro aldehydes in very high yields (up to 95%), with high diastereoselectivity (up to >99:1) and with up to 97% ee.

Enantioselective Michael Addition of Aldehydes to β‐Nitrostyrenes Catalyzed by (S)‐N‐(D‐Prolyl)‐1‐triflicamido‐3‐phenylpropan‐2‐amine

“…A direct comparison between D‐Prolyl‐2‐(triflicamidopropyl)pyrrolidine (Figure ), the catalyst that we have recently reported and 3 reveals that the latter is a better catalyst for two different reasons. One, the preparation of 3 is rather straight forward and is thus more easily accessible.…”

“…It was observed that the previously reported catalyst resulted in reduced enantioselectivity with an increasing chain length of linear aldehydes. With β‐nitrostyrene, the reaction of propanal resulted in 95 % ee, while the enantioselectivity reduced to 93 % for n ‐butanal and to 86 % for n ‐pentanal . However, the enantioselectivity achieved for reactions with all the three aldehydes and β‐nitrostyrene were similar when 3 is used as the catalyst (entries 7–9, Table ).…”

“…With -nitrostyrene, the reaction of propanal resulted in 95 % ee, while the enantioselectivity reduced to 93 % for n-butanal and to 86 % for n-pentanal. [10] However, the enantioselectivity achieved for reactions with all the three aldehydes and -nitrostyrene were similar when 3 is used as the catalyst (entries 7-9, Table 2). The high enantioselectivity obtained in all of the reactions studied and especially those using isobutyraldehyde makes catalyst 3 a valuable addition to organocatalysts available for Michael addition reactions.…”

“…The catalyst is effective for reactions between α-branched aldehydes and -nitrostyrenes. D-prolyl-2-(triflicamidopropyl)pyrrolidine [10] as a very efficient catalyst for the Michael addition reaction between -nitrostyrenes and aldehydes ( Figure 1). Apart from Wang's catalyst [3] and the catalyst developed by us recently, [10] those using a triflicamide (-NHTf) group as the H-bond donor for asymmetric Michael addition reactions are rare.…”

“…D-prolyl-2-(triflicamidopropyl)pyrrolidine [10] as a very efficient catalyst for the Michael addition reaction between -nitrostyrenes and aldehydes ( Figure 1). Apart from Wang's catalyst [3] and the catalyst developed by us recently, [10] those using a triflicamide (-NHTf) group as the H-bond donor for asymmetric Michael addition reactions are rare. Miura et al used (S)-1-triflicamido-3-phenylpropan-2-amine (1), derived from L-phenylalanine as an organocatalyst for asymmetric aldol reactions.…”