Co‐Metal‐Free Enantioselective Conjugate Addition Reactions of Zinc Reagents

Abstract

Asymmetric conjugate addition of diethylzinc to cinnamaldehyde in a co-metal-free fashion by using N,O-ligands with planar and central chirality is described. Different modulations of the ligand structure, including several combinations of the chiral units, indicate that a [2.2]paracyclophane backbone is essential for the activity and the enantioselectivity of the generated active catalyst. By using the optimized ligand, an isolated yield of 90 % was obtained with up to 99 % ee.

Roadmap towards N‐Heterocyclic [2.2]Paracyclophanes and Their Application in Asymmetric Catalysis

“…Further investigations, for example, by Noyori and Soai,9,10 showed that catalysis with [2.2]paracyclophane zinc complexes having a nitrogen–oxygen coordination motif is feasible. In recent years, we combined the rigidity of the [2.2]paracyclophane backbone with novel metal coordinating moieties and described the asymmetric conjugate addition (ACA) of diethylzinc to cinnamaldehyde utilizing different [2.2]paracyclophane ligands 11–13. In this publication we present a series of new [2.2]paracyclophane derivatives bearing N‐heterocycles with various substitution patterns.…”

Catalytic Enantioselective β‐Alkylation of α,β‐Unsaturated Aldehydes by Combination of Transition‐Metal‐ and Aminocatalysis: Total Synthesis of Bisabolane Sesquiterpenes

“…In particular, the enantioselective copper‐catalyzed conjugate addition of organometallic reagents using different types of chiral ligand systems on the metal provides high stereocontrol 3. This research has shown that the direct transition‐metal‐catalyzed enantioselective 1,4‐addition of an organometallic reagent to an α,β‐unsaturated aldehyde 5 in the presence of a chiral ligand is very challenging due to a competing 1,2‐addition reaction, which gives both the β‐aldehyde 6 and alcohol 7 , respectively (Scheme ) 4b–c. 5…”

Theoretical Approach Towards the Understanding of Asymmetric Additions of Dialkylzinc to Enals and Iminals Catalysed by [2.2]Paracyclophane‐Based N,O‐Ligands

“…Aminoalcohols can be used as convenient catalysts for 1,2‐additions 1. To obtain a 1,4‐product, one should either use special Hoveyda‐type catalysts with the addition of a copper salt2 or [2.2]paracyclophane‐based N,O‐ligands 3. The second route has the key advantage that it does not involve any co‐metals and therefore is more convenient.…”

“…Bräse et al. examined a series of paracyclophane‐containing catalysts and proved its utility, especially for addition reactions to enals3 and iminals4 (Scheme ). However, in the case of iminals, the 1,4‐addition product was clearly favoured.…”

“…Moreover, the origin of enantioselectivity in 1,4‐addition reactions is still unclear. When the R p ‐configured paracyclophane N,O‐ligand was used, for example ( R p , R )‐ 4 , the ( S )‐ 2 a product was always obtained when reacted with cinnamaldehyde 1 a , whereas the ( R )‐ 2 b product was observed with N ‐formylbenzylimine 1 b 3. 4 This is because the priority of substituents on the stereogenic centre changes upon substitution of CH with N groups in the 1,4‐addition product.…”