2‐Azanorbornane‐Based Amino Alcohol Organocatalysts for Asymmetric Michael Reaction of β‐Keto Esters with Nitroolefins

Abstract

New optically active 2‐azanorbornane‐based amino alcohol organocatalysts were designed and synthesized, and these catalysts were successfully employed in the asymmetric Michael reaction of β‐keto esters with nitroolefins to obtain the corresponding chiral Michael adducts with both high chemical yields (up to 99 %) and high stereoselectivities (up to dr = 91:9, up to 91 % ee).

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

“…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).…”

Simple primary β-amino alcohols as organocatalysts for the asymmetric Michael addition of β-keto esters to nitroalkenes

“…The determination of absolute configuration and stereoselectivity of 4, 4′ were confirmed on comparision with previous data. 10 …”

“…The compounds are the known compounds and the structures were identified by spectral data which were in good agreement with those reported. 10,11 …”

“… 8 Our group has reported that the cage type 2-azanorbornane-based amino alcohols Y act as an efficient organocatalyst in this addition. 10 However, this catalyst Y has a complex structure and requires a multistep route for the synthesis, although efficient catalytic activity is observed. Based on these backgrounds, we have planned to try the asymmetric Michael addition of β-keto esters A with nitroalkenes B using more simplified β-amino alcohol organocatalyst X ( Scheme 1 ).…”

Amino alcohol‐derived chiral stationary phases

“…However, the chiral amino alcohols are readily available on their own, and many amino alcohols cannot be prepared from the amino acids; thus, the starting materials are classified separately from the amino acids. Amino alcohols are examples of the simple chiral compounds that have been widely used in various fields 41–89 . They have been used as starting materials to prepare the chiral catalysts used in the asymmetric organic synthesis and to prepare chiral NMR chemical shift reagents 41–63 …”