Amine-Salt-Controlled, Catalytic Asymmetric Conjugate Addition of Various Amines and Asymmetric Protonation

Abstract

The combined use of chiral Pd complex 2 and amine salt enabled completely regulated release of free nucleophilic amine. Under these conditions, an efficient catalytic asymmetric conjugate addition of various amines was achieved to afford beta-amino acid derivatives in high chemical yields with up to 98% ee. Furthermore, a highly enantioselective protonation in 1,4-addition of amine was also developed. [reaction: see text]

Recent advances and applications in asymmetric aza-Michael addition chemistry

“…The same authors have exemplified the utility of the 1,4 adducts, and converted them into acylaziridines, syn-1,3-amino alcohols, and anti-1,3-amino alcohols. Hamashima et al 49 employed a combination of a chiral Pd complex 116 and an amine salt, enabling a completely regulated release of free nucleophilic amine (Scheme 30). This combination suppressed both the decomposition of the catalyst by the amine and the uncontrolled spontaneous reaction thus ensuring an efficient catalytic asymmetric conjugate addition of various amines on alkenoyl 1,3-oxazolan-2-ones 118 to afford b-amino acid derivatives 119 in high chemical yields with ees up to 98%.…”

Acid-Base Catalysis of Chiral Pd Complexes: Development of Novel Catalytic Asymmetric Reactions and Their Application to Synthesis of Drug Candidates

“…Finally, we would like to describe an interesting example where acid-base catalysis of the Pd complexes was the key to success, thereby the reactivity of the free amine was properly controlled to solve problems found in aza-Michael reaction catalyzed by Lewis acids. 68) Catalytic asymmetric conjugate addition of nitrogen nucleophiles is a useful reaction because the products are recognized as key compounds for the synthesis of not only chiral natural and unnatural b-amino acids.…”

Palladium‐Catalysed Enantioselective Conjugate Addition of Aromatic Amines to α,β‐Unsaturated N‐Imides. Effect of the Chelating Moiety

“…[8] The authors reasoned that this suppresses uncatalysed addition of the aromatic amine, and prevents catalyst deactivation by amine coordination. Thus, the reaction between 4a and the trifluoromethanesulfonate salt of p-anisidine was carried out.…”