Organocatalysis in Conjugate Amine Additions. Synthesis of β‐Amino Acid Derivatives.

Abstract

Pyrazole derivatives R 0180Organocatalysis in Conjugate Amine Additions. Synthesis of β-Amino Acid Derivatives.-O-Substituted hydroxylamines are added to pyrazole-derived enoates in the presence of a stoichiometric amount of chiral thiourea THU to give the aminated products with high enantioselectivity. It is influenced by the substitution at the pyrazole moiety, the O-substituent at the hydroxylamine and the configuration at the indanol subunit of the thiourea. Product (VIII) is obtained in high yield and enantioselectivity even with a catalytic amount of THU. -(SIBI*, M. P.; ITOH, K.; J. Am. Chem. Soc. 129 (2007) 26, 8064-8065; Dep. Chem., N. Dak. State Univ., Fargo, ND 58105, USA; Eng.) -Klein 46-103

Direct asymmetric Michael addition of thioether‐based aryl sulfanyl‐propan‐2‐one to nitroalkenes catalyzed by a chiral amine‐thiourea bifunctional organocatalyst

“…Surprisingly, no reactions occurred after 72 h in toluene (entries 1–3, Table 1). Hence, the amine‐thiourea based organocatalysts54–83 2d–2f (see Fig. 1) was examined.…”

Enantioselective Synthesis of ?-amino acids: A Review

“…They are also used in the treatment of many diseases and health issues.Therefore, enantioselective β-amino acids have potential therapeutic values and are a great challenge for chiral synthesis.Therefore, β-amino acids with various substitution patterns are now available. Each approach has itsown advantages and limitations while more than 80 numbers of different approaches have been discussed here but the organo-Rh based and heterogeneous catalyzed approach is found to be more effective ( Scheme 1,2,4,11,12,13,28,29) and (Scheme 8,9,33,34,35,36,37,45,54,63). Other approaches can also be considered to synthesize enantioselective amino acids ( Scheme 11,13,15,40,45,50,61,62,68,70,74).…”

“…Thiourea was used as a catalyst for the conjugate addition of O-substituted hydroxylamines to pyrazolecrotonates by Sibi et al (Scheme 22). The yield of adducts is higher with aliphatic α, β-unsaturated compounds as compared to the phenyl substituted substrates [36].…”

Highly enantioselective Michael addition of α‐nitroacetate to α,β‐unsaturated pyrazolamide catalyzed by a bifunctional squaramide

“…On the other hand, in contrast with those well‐documented acceptors (especially α,β‐unsaturated enones/enals and nitroalkenes), α,β‐unsaturated acid derivative remains a type of less‐explored electrophilic partner presumably due to their relatively lower reactivity in the case of organocatalytic conjugate addition reactions . In this regard, the initial breakthrough has been independently achieved by Takemoto and Soós using the well‐designed bifunctional thiourea.…”

“…Despite these impressive efforts, significant challenges remain, especially with respect to α,β‐unsaturated pyrazolamides . A stoichiometric amount of promoter was required for the conjugate amine addition, and only α,β‐unsaturated pyrazolamides possessing intensively electron‐withdrawing trifluoromethyl motifs provided satisfactory reactivity and enantioselectivity in the conjugate thiol addition . Therefore, whereas the corresponding Michael addition catalyzed by transition metal complexes constitutes a solved problem, the efficient and general organocatalytic process involving α,β‐unsaturated pyrazolamides urgently awaits further attention.…”