Diphenylprolinol Silyl Ethers as Efficient Organocatalysts for the Asymmetric Michael Reaction of Aldehydes and Nitroalkenes

Abstract

A subtle change in catalyst structure can sometimes improve catalytic activity dramatically, as we found in our recent study on a-aminoxylation, tandem O-nitroso aldol/Michael reactions, and Mannich reactions catalyzed by the siloxyproline 4, a highly active proline surrogate (Scheme 1).[1] The simple introduction of a siloxy group into the proline structure leads to an increase in the catalytic activity, thus allowing a decrease in catalyst loading and shorter reaction times, without compromising the enantioselectivity, and is accompanied by broadening of the substrate scope. This higher activity can be attributed to the increased solubility of 4 in organic solvents. The fact that the substitution of a hydroxy group for a siloxy group can dramatically affect catalytic activity prompted us to investigate other catalytic systems, and these investigations led us to the diphenylprolinol silyl ether 2. The parent diphenyl-2-pyrrolidinemethanol (1, diphenylprolinol), a commercially available amino alcohol developed by Corey and co-workers, has proved to be a very useful ligand for asymmetric synthesis: B-alkylated oxazaborodine is a useful catalyst for the CBS reduction, [2] while an effective, asymmetric Lewis acid catalyst prepared from B-aryl oxazaborodine and a Brønsted acid promotes the Diels-Alder reaction of a broad range of substrates with excellent enantioselectiv-

Organocatalytic enantioselective β-functionalization of aldehydes by oxidation of enamines and their application in cascade reactions

“…As a result, the process would serve as a valuable method for asymmetric synthesis of chiral fluorinated compounds 18 . A model reaction between 3-phenylpropionaldehyde (1a, R = Ph) and FBSM was carried out in the presence of diphenylprolinol trimethylsilyl (TMS) ether (I) ( Table 1) [19][20][21] , a widely used organocatalyst in aminocatalysis, in CH 2 Cl 2 at room temperature (RT; Table 1, entry 1). Screening of several oxidants (entries 1-6) showed that the use of IBX was encouraging.…”

A Greener, Efficient Approach to Michael Addition of Barbituric Acid to Nitroalkene in Aqueous Diethylamine Medium

“…Interestingly, the Michael product was separated in enol form and not in keto form in very good to excellent yields ( Table 2, entries [13][14][15][16][17][18][19][20]. Finally, to show the generality of the procedure, we tested ferrocene nitroalkene as Michael acceptor and the products were obtained in very good yields (Table 2, entries 9, 19).…”

“…[10][11][12][13]. Extensive studies have been devoted to the development of catalytic systems for Michael additions of various active methines such as pronucleophiles to nitroalkenes including cinchona organocatalysts [14], enzymes [15], various chiral amines [16,17], transition metal-free organocatalysts [18][19][20] and chiral metal complexes [21][22][23][24][25].…”

Die asymmetrische Aminokatalyse – Goldrausch in der organischen Chemie

“…[90] Im Anschluss daran kamen die Katalysatoren XIXa-e bei einer Reihe asymmetrischer nucleophiler Additionen zum Einsatz, z. B. bei enantioselektiven konjugierten Additionen, [87,91] Arylierungen, [92] Mannich-Reaktionen [87] und Aminomethylierungen.…”