Direct enantioselective vinylogous Mannich‐type reactions of acyclic enals: New experimental insights into the E/Z‐dilemma

Abstract

The direct heterofunctionalization of acyclic α,β‐unsaturated aldehydes with N‐acylquinolinium ions contemplating the formation of two stereocentres is studied using dienamine catalysis. This work gives some new experimental insights on the remote stereocontrol in dienamine catalysis using unbiased aliphatic systems and large electrophiles, pointing to a (Z)‐preference of the reactive configuration of the second double bond.

DyKAT by DiCat: Stereoconvergent Dienamine-Catalyzed Claisen Rearrangements

“…This is consistent with the reactivity of cycloalkylidenals 1h – i (Scheme ), which can form only dienamines with ( Z )-β,γ-olefins. Notably, while similar chiral dienamine intermediates have been observed in situ by 1 H NMR , and similar dienamine substrates (i.e., dienes for Diels-Alder cycloadditions) have been isolated, to the best of our knowledge, this is the first time a chiral dienamine reactive intermediate has been isolated from a catalytic asymmetric reaction. Collectively, these data suggest that the E , Z -dienamine required for the Claisen rearrangement can be accessed from both enantiomers of the starting material, confirming the plausibility of DyKAT in dienamine-catalyzed reactions and the mechanism in Scheme .…”

“…The root of this is the multiple reactive centers on vinylogous intermediates, leading to multiple reaction outcomes and a lack of comprehensive understanding of catalyst control over outcomes, which together have precluded rational design of broadly useful synthetic transformations. Stereochemical outcomes of reactions of dienamine intermediates are rationalized by invoking dienamine conformation, alkene geometry, and/or specific interactions between catalysts and electrophiles . There exists, however, no robust general model for asymmetric induction at remote centers of dienamine intermediates.…”

Experimental and Computational Studies Unraveling the Peculiarity of Enolizable Oxoesters in the Organocatalyzed Mannich-Type Addition to Cyclic N-Acyl Iminium Ions

“…Acyl Mannich-type reactions, by the combination of simple aminocatalysts and metal catalysts, have been recently developed with aliphatic and α,β-unsaturated aldehydes by our research group [20,27,28]. Since our experience in this field, we have always noticed that MacMillan catalyst L1 and Hayashi-Jørgensen catalyst L2 showed the To the best of our knowledge, we are aware of only one example featuring a Mannich reaction of oxoesters 1a,b, in which these compounds behave as nucleophilic donor.…”