Nitrophenylacetonitriles as Versatile Nucleophiles in Enantioselective Organocatalytic Conjugate Additions

Abstract

Arylacetonitriles are able to participate in organocatalytic Michael additions to alpha,beta-unsaturated aldehydes by incorporating a nitro group at the phenyl ring, which acts as a temporary activating group in a remote position and allows further transformations. The sequential protocol Michael addition/NaBH(4) reduction/lactonization allows the synthesis of diastereomerically pure disubstituted lactones in high yield and optical purity.

Chiral‐Zn(NTf2)2‐Complex‐Catalyzed Diastereo‐ and Enantioselective Direct Conjugate Addition of Arylacetonitriles to Alkylidene Malonates

“…[10] Up to 90 % ee values and moderate diastereoselectivities were achieved. Subsequently, the Kim group achieved the corresponding reactions between a,b-unsaturated ketones and cinnamaldehyde in moderate diastereo-and enantioselectivities.…”

Cyanoalkylierung: Alkylnitrile in katalytischen C‐C‐Kupplungen

“…Im Vergleich zu Alkylnitrilen weisen Benzylnitrile eine geringfügig hçhere Azidität auf (pK a 21.9 in DMSO), wenngleich diese immer noch unzureichend für eine katalytische Erzeugung dieser Spezies ist. [13] Die Cyclisierung zu dem entsprechenden Lacton ergab im Wesentlichen das stabilste Diastereomer. [12] Das erste Beispiel für diese Strategie beschrieben Cid, Ruano und Mitarbeiter,die Nitroarylacetonitrilemithilfe von Iminium-Katalyse unter Verwendung des sekundären Amins 2 in Gegenwart einer milden Base (LiOAc) mit a,b-ungesättigten Aldehyden umsetzten (Schema 3).…”

Recent Advances in Organocatalytic Methods for Asymmetric CC Bond Formation

“…By subsequent reduction and hydrolysis the corresponding δ‐lactones are formed in good yields and moderate to very good enantioselectivity. In the last acidic hydrolisation step the previously low diastereoselectivity is overcome by simultaneous epimerization resulting in a nearly exclusive formation of the thermodynamical product (Scheme ) 62…”