Asymmetric Mannich Reaction of α‐Keto Imines Catalyzed by Diarylprolinol Silyl Ether

Abstract

Synthetic methods: An asymmetric catalytic, desulfonylative Mannich reaction of α-keto imines with aldehydes, as catalyzed by diarylprolinol silyl ether 1, was developed. It gave the Mannich product in good yield with excellent anti and enantioselectivity (see scheme; Boc = tert-butoxycarbonyl, TMS = trimethylsilyl).

Organocatalysis: Key Trends in Green Synthetic Chemistry, Challenges, Scope towards Heterogenization, and Importance from Research and Industrial Point of View

“…An asymmetric catalytic, desulfonylative Mannich reaction of keto imines with aldehydes, as catalyzed by diarylprolinol silyl ether, was developed. It gave the Mannich product in good yield with excellent anti-and enantioselectivity [292]. New chiral bis(betaine)s, containing two catalytically active centers, have been designed and have proven to be promising organocatalysts for the direct Mannich type reaction of azlactones with a broad spectrum of aliphatic imines [293].…”

α-Amido sulphones as useful intermediates in the preparation ofC-chiral α-aminophosphonates and α-aminophosphonic acids

“…Next, we turned our attention towards the modification of the reaction conditions, and more specifically the reaction temperature, and we decided to lower the temperature as much as possible in order to favour the diastereoselective formation of one of the diastereoisomers (Table 3, entries [16][17][18][19]. The preliminary attempts that we have performed required the generation of the imine from α-amido sulphone 1a (K 2 CO 3 [2 equiv.…”

“…[1][2][3] Their utility stems from two aspects: the first one is their high stability and ease of preparation via simple acid-promoted three-component reactions of various aldehydes, sulfinates and carbamates, 2 and the second one is their very simple transformation into reactive N-acylimine derivatives under either acidic or basic conditions (Scheme 1a). Selected protocols where α-amido sulfones have been used as substrates include reactions with organometallic reagents leading to the generation the N-acylimines required for the subsequent nucleophilic addition, [4][5][6][7] reactions with allylating reagents leading to the synthesis of homoallylamino derivatives, 8,9 reactions with cyanide ions providing α-amido nitriles, [10][11][12] reactions with malonates and related derivatives, [13][14][15] reactions with enolates from simple carbonyl derivatives, [16][17][18] and finally reactions with nitronate anions leading to 2-nitroamine derivatives. [19][20][21] Surprisingly, despite the extensive utility of α-amido sulfones in the preparation of structurally diverse compounds, their utility as imine precursors in the preparation of α-substituted aminophosphonates and aminophosphonic acids, important classes of compounds endowed with very interesting biological activities, [22][23][24][25][26] including excellent enzyme inhibitors, 27,28 drug candidates for antibiotics, 29,30 and antibacterial and antifungal agents, 31 is scarcely described in the literature.…”

Imine and iminium precursors as versatile intermediates in enantioselective organocatalysis

“…They later explored a MannicheWittig sequence in more detail with a-keto imine precursors. 52 Due to partial racemization of the Mannich product after isolation, they decided to carry out an immediate Wittig reaction with 26 after a short SiO 2 chromatography, thus synthesizing chiral a-aminoketones carrying an a,b-unsaturated ester functionality.…”