Chiral Primary Amine Tagged to Ionic Group as Reusable Organocatalyst for Asymmetric Michael Reactions of C‐Nucleophiles with α,β‐Unsaturated Ketones

Abstract

The first primary amine-derived organocatalyst modified with an ionic group for asymmetric Michael reactions of C-nucleophiles with a,b-unsaturated ketones was synthesized. In the presence of this catalyst and an acidic co-catalyst (AcOH), hydroxycoumarin and its sulfur-containing analogue reacted with benzylideneacetone derivatives or cyclohexenone to afford the corresponding Michael adducts in high yields (up to 97%) and with reasonable enantioselectivity (up to 80%). The catalyst could be easily recovered and efficiently reused three times, afterwards, its activity and stereodifferentiating ability gradually declined. The analysis of recovered catalyst samples by ESI-MS allowed us to detect undesirable side reactions that poisoned the catalyst, and propose an approach for its reactivation.

Primary Amine Attached to an N‐(Carboxyalkyl)imidazolium Cation: A Recyclable Organocatalyst for the Asymmetric Michael Reaction

“…To verify our hypothesis we synthesized (1 S ,2 S )‐1,2‐diaminodiphenylethane derivative 3 modified with an N ‐(4‐carboxybutyl)imidazolium cation and a PF 6 – anion through N ‐alkylation of benzyl 5‐(1 H ‐imidazol‐1‐yl)pentanoate with pre‐prepared16 bromoamide 4 followed by metathesis of the anion in alkylation product 5‐Br and catalytic deprotection of resulting hexafluorophosphate 5‐PF 6 to give target catalyst 3 . Each step of this sequence selectively afforded either intermediates or the final product in high yields (Scheme ).…”

“…The reaction ran in various solvents [tetrahydrofuran (THF), CH 2 Cl 2 , i PrOH or H 2 O] in the presence of amine 3 (20 mol‐%) to afford adduct 8a with moderate enantioselectivity (62–67 % ee ), which was similar to the values attained in corresponding reactions catalyzed by carboxyl‐free chiral amine 1 (Table 1, Entries 1–4). However, catalyst 3 appeared more active than catalyst 1 under the studied conditions: the yield of product 8a in THF solution after 24 h was 96 %, whereas the corresponding reaction catalyzed with amine 1 afforded compound 8a in just 73 % yield over 45 h 16. The acidic additive (AcOH) exerted a favorable impact on enantioselectivity (Table 1, Entries 5–10).…”

“… [h] The reaction was carried out in the presence of catalyst 1 (20 mol‐%) and AcOH (10 equiv.) at +5 °C for 70 h 16…”

“…For these reactions we have recently synthesized (1 S ,2 S )‐1,2‐diaminodiphenylethane‐based catalyst 1 modified with the N ‐methylimidazolium cation and the PF 6 – anion 16. The catalyst exhibited reasonable activity and enantioselectivity of the reaction between 4‐hydroxycoumarin and benzylideneacetone in the first 3 cycles; although afterwards catalytic efficacy progressively declined.…”

A Snapshot of Ionic-Liquid-Tagged Proline-Based Organocatalysts

“…Current preliminary results from this field so far are furnishing catalysts which possess ever greater recyclability and the potential to catalyse a growing pool of asymmetric transformations. [34] 14 [35] 15 [36] PF 6 PF 6 ϩ ϩ Ϫ ϩ Ϫ Fig. 3.…”