Highly Efficient Phosphazene Base-Catalyzed Michael Addition of β-Ketoesters in Water

Abstract

Michael addition of various b-ketoesters with severalMichael acceptors in water containing 10 mol% of N-phenyltris(dimethylamino)iminophosphorane results in high yield conversion to the corresponding adducts.Water mediated reactions 1 offer useful and more environmentally friendly alternatives to their harmful organic solvent versions and have received increasing interest in recent years. Moreover, the use of reagents in catalytic amounts is a target of major interest with the increasing attention of green chemistry 2 and atom economy. 3 Recently, the attention was focused on catalytic Michael addition in water using water-tolerant Lewis acids. For example, although quite slow, the reaction of bketoesters 4a and a-nitroesters 4b catalyzed by ytterbium triflate Yb(OTf) 3 was found effective but only with vinyl ketones and acroleins. More recently, utilization of a scandium-containing Lewis acid-surfactant catalyst system 5 proved to be more efficient in terms of catalytic activity, and shorter reaction times were reported in the case of a,b-unsaturated ketones. Contemporaneously, amphiphilic resin-supported quaternary ammonium hydroxide 6 was shown to catalyze the Michael addition of cyclic b-ketoesters in the presence of a large excess of several acceptors. These recent results together with our own involvement in the development of synthetic methodologies using Michael addition, 7 prompted us to disclose our preliminary results in this field. Our synthetic approach rests upon the base-catalyzed Michael reaction of b-ketoesters in water. To our surprise, this reaction has not been the center of much interest and has only been reported occasionally in the case of 1,3-cycloalkanediones 8 and nitroalkanes 9 which are known to react with acroleins or vinyl ketones in water even without a basic catalyst. 10 The lack of generality of this approach is probably due to the difficulty in controlling side reactions or subsequent transformations of the adducts such as intramolecular aldolization 11 and retro-Michael reaction. To circumvent this drawback, non-ionic bases 12 have emerged as powerful alternatives to commonly used alkali metal alkoxides and hydroxide reagents. 13 Our recent interest in the development of new chiral iminodiazaphospholidines 14 and their synthetic applications in asymmetric catalysis led us to investigate the use of phosphazene bases in the catalytic Michael addition of b-ketoesters towards a,b-unsaturated compounds in water as solvent. These new strong non-ionic bases are even more water-stable and basic than other well-known nitrogen nonionic bases 15 and surprisingly, no example of such Michael addition is reported to date. 16 In this communication we now report the highly efficient and mild catalytic Michael addition of b-ketoesters 1a-f in water towards a series of acceptors 2a-e using 10 mol% of N-phenyl-tris(dimethylamino)iminophosphorane 17 leading to synthetically valuable adducts 3a-l in high yields (Scheme). SchemeThe overall transformation proved to be general and although unoptimized,...

Michael Additions in Aqueous Media: “On‐Water” and “In‐Water” Processes from α‐Nitro Ketones and Their Anions

“…To give an example, the Michael addition reaction is one of the most important methods for creating carbon-carbon bonds [5] and is of interest to green chemistry because it proceeds with complete atom economy. [12] For the specific case of the reaction between α-nitro ketones and liquid-conjugated enones, which also act as the reaction media, a solvent-free protocol for Michael additions in the presence of silica gel has been described. Some watertolerant compounds that catalyse the Michael reaction include ytterbium(III) triflate on its own [6] or in the presence of a variety of ligands, [7] scandium tris(dodecylsulfate), [8] vanadate species in an apatite framework, [9] water-soluble calixarenes as inverse phase-transfer catalysts, [10] amphiphilic resin-supported quaternary ammonium hydroxides [11] and phosphazene bases.…”

Porous Organic Polymers Constructed from Tröger's Base as Efficient Carbon Dioxide Adsorbents and Heterogeneous Catalysts

“…Recently, our group has reported a series of porous organic ligands (POLs) synthesized through solvothermal radical polymerization methods from the corresponding vinyl‐functionalized ligand monomers themselves, for which the concentration of organic ligands was maximized because of the composition of the porous polymers with pure organic ligands. For example, if we used vinyl‐functionalized diphosphine monomers (v‐dppe), a POP called POL‐dppe was synthesized . As a result of the high ligand concentration, the supported Rh catalyst shows extraordinary catalytic properties in the heterogeneous hydroformylation of olefins.…”

Phosphazene: Preparation, Reaction and Catalytic Role

“…The organic base methodology has also been applied to the synthesis of (R)-a-methyl a-amino acids starting from (R)-alanine. When dihalides are used as electrophiles in the presence of BEMP, a spontaneous N-alkylation also takes place giving bicyclic oxazinones, which can be hydrolyzed to an enantiomerically pure heterocyclic compound [25] Michael addition reaction of various b-ketoesters with several Michael acceptors in water containing 10 mol% of N-phenyl-tris(dimethylamino)iminophosphorane results in high yield conversion to the corresponding adducts [26] (Scheme 5.11).…”