Old tricks, new dogs: organocatalytic dienamine activation of α,β-unsaturated aldehydes

Abstract

Here we outline and discuss the state-of-the-art in organocatalytic dienamine activation of enals, classifying examples according to different reactive activation pathways.

From Immobilization to Catalyst Use: A Complete Continuous‐Flow Approach Towards the Use of Immobilized Organocatalysts

“…Before the solutions of the reagents were pumped, the silica-supported organocatalyst was treated with 0.4 M HCl solution in acetonitrile at room temperature for activation of the organocatalyst. Then cyclopentadiene (7) and aldehyde 8 in acetonitrile were pumped through the packed-bed reactor containing the supported organocatalyst 6 a and the collected reaction mixture was recirculated through the loop system. After 48 hours, the cycloadducts 9 a and 9 b were obtained in 50 % yield and 77 % ee and 78 % ee, with productivity of 0.50 mmol(product) h À 1 mmol À 1 (catalyst).…”

“…[1][2][3][4] Combined with ease of handling, chiral organocatalysts are also inexpensive to prepare and versatile, providing different modes of substrate activation and asymmetric induction, being employed in various types of reactions. [5][6][7][8] However, there are still some inherent problems with these reactions, such as the low turnover and the impossibility of recovering the catalyst. [9] To overcome these difficulties, some efforts have been made to support the organocatalysts in a range of solid materials, such as polymers or silica, affording heterogeneous reactions.…”

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

“…In principle, a vinylogous extension of recently reported enantioselective α‐alkylations of aldehydes with N‐acyl quinolinium ions poses several reactivity and selectivity issues . In fact, there are several regioselectivity issues about the nucleophilic addition (α‐selectivity vs γ‐selectivity) of the in situ formed dienamine to the reactive positions of the N‐acylquinolinium ion (α′‐selectivity vs γ′‐ selectivity) (Figure ) . Moreover, the influence and sense of the asymmetric induction imposed by the chiral secondary amine catalyst in S N ‐type γ‐functionalizations are particularly intriguing given the distance of the chiral centres of the organocatalyst from the reactive remote γ‐position.…”

Direct Noncovalent Activation of α,β‐Unsaturated Aldehydes for the Stereodivergent Synthesis of Substituted Cyclohexenes

“…[1] Among aminocatalysis, dienamine catalysis represents af undamental protocol enabling the remote functionalization of the carbonyl functionality throughc atalytically generated dienamine species from a,b-unsaturated aldehydes and chiral amines; [2] numerous novel catalytic asymmetric transformations were implemented based on this catalytic concept (Scheme 1a,r ight). [1] Among aminocatalysis, dienamine catalysis represents af undamental protocol enabling the remote functionalization of the carbonyl functionality throughc atalytically generated dienamine species from a,b-unsaturated aldehydes and chiral amines; [2] numerous novel catalytic asymmetric transformations were implemented based on this catalytic concept (Scheme 1a,r ight).…”

“…To further demonstrate the stereochemical versatility of this cyclization of a,b-unsaturated aldehydes and nitroolefins, the collective synthesis of 4o ut of 16 possible isomersw ere performed using the enantiomers and pseudo-enantiomers of catalysts VII and IX,r espectively (Scheme 2). As showni nS cheme 3, the reduction of the nitro functionality of the product 3aa led to the 1,2-amino alcohol derivatives 5 and 6 andi ns atisfactory resultsw ith respectt ob otht he yield and stereoselectivity;t hese products could serve as chiral building blocks for the synthesis of chiral catalysts/ligands [Scheme 3, (1)].F urthermore, the products could be converted into an axially chiral biaryl 7 through ap alladium-mediated hydroxyl eliminationa nd oxidation with excellent central-to-axial chiral transfer efficiency,w hicho ffered ac onvenienta nd practical methodf or the synthesiso fa xially chiral molecules from acyclic precursors [Scheme 3, (2)]. [15] Derivatization of the products was also conducted to demonstrate the synthetic potentials of the current reaction.…”