Amino Amide Organocatalysts for Asymmetric Michael Addition of β-Keto Esters with β-Nitroolefins

Abstract

Asymmetric Michael addition of β-keto esters with trans-β-nitroolefins using chiral amino amide organocatalyst was tried and afforded synthetically useful chiral Michael adducts in both excellent chemical yields (up to 99%) and stereoselectivities (up to dr. 99:1, up to 98% ee).

New Sugar Based γ-Amino Silyl Ether Organocatalysts for Asymmetric Michael Addition of β-Keto Esters with Nitroolefins

“…Asymmetric Michael addition of various β-keto esters 3a-g with nitroolefins 4a-f using catalyst 2d On the other hand, the reaction with 7-membered 2-oxocycloheptanecarboxylate 3e brought about the large decrease of enantioselectivity, although chiral 5e was obtained in good chemical yield and moderate diastereoselectivity (71%, dr. 63:37, 27% ee) (entry 4). 7 Furthermore, the use of aromatic ring fused indanone based β-keto ester 3f gave the corresponding 5f with moderate chemical yield, diastereoselectivity and enantioselectivity (55%, dr. 60:40, 49% ee) (entry 5). 7 Next, the reactions of β-keto ester 3a with various nitroolefins 4b-f using catalyst 2d were tried under same reaction condition (entries 6-10).…”

“…7 Furthermore, the use of aromatic ring fused indanone based β-keto ester 3f gave the corresponding 5f with moderate chemical yield, diastereoselectivity and enantioselectivity (55%, dr. 60:40, 49% ee) (entry 5). 7 Next, the reactions of β-keto ester 3a with various nitroolefins 4b-f using catalyst 2d were tried under same reaction condition (entries 6-10). The reaction with bromine substituted nitroolefin 4b afforded the adduct 5g in good chemical yield, diastereoselectivity and with moderate enantioselectivity (85%, dr. 82:18, 45% ee) (entry 6).…”

“…8 Furthermore, the use of fluorine substituted nitroolefin 4c afforded 5h in good chemical yield, diastereoselectivity and low enantioselectivity (81%, dr. 66:34, 34% ee) (entry 7). 7 When the reaction using methyl substituted nitroolefin 4d was carried out, the corresponding 5i was furnished in good chemical yield and moderate diastereoselectivity, but enantioselectivity was low (78%, dr. 65:35, 21% ee) (entry 8). 7 Nitroolefin 4e with bulky naphthyl group afforded 5j in moderate chemical yield, diastereoselectivity and with low enantioselectivity (47%, dr. 59:41, 20% ee) (entry 9).…”

“…7 When the reaction using methyl substituted nitroolefin 4d was carried out, the corresponding 5i was furnished in good chemical yield and moderate diastereoselectivity, but enantioselectivity was low (78%, dr. 65:35, 21% ee) (entry 8). 7 Nitroolefin 4e with bulky naphthyl group afforded 5j in moderate chemical yield, diastereoselectivity and with low enantioselectivity (47%, dr. 59:41, 20% ee) (entry 9). 9 Moreover, the reaction using heterocyclic furanyl nitroolefin 4f afforded adduct 5k in moderate chemical yield and stereoselectivities (58%, dr. 60:40, 51% ee) (entry 10).…”

“…9 Moreover, the reaction using heterocyclic furanyl nitroolefin 4f afforded adduct 5k in moderate chemical yield and stereoselectivities (58%, dr. 60:40, 51% ee) (entry 10). 7 To expand the generality and scope of the keto ester, the reaction of dimethyl malonate 3g with 4a was also examined in the same reaction condition, but only trace of the corresponding Michael adduct was observed (entry 11).…”