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,...

The MARDi cascade is a recently invented three-component Michael-initiated condensation involving 1,3-dicarbonyl derivatives. It allows regio- and stereocontrolled access to a variety of functionalised and substituted seven-membered rings. The substitution array can be diastereoselectively modulated by appropriate choice of the reaction partners, and the reaction allows the control of up to five newly created stereocentres and a complete chiral induction in the case of an optically active ketone precursor. The high level of diastereoselectivity observed has been attributed to total thermodynamic control of the reaction. The attractiveness of the present domino three-component approach to seven-membered rings resides in the diversity of carbo- and heterocyclic structures that can be accessed with total regiocontrol and high stereocontrol by starting from simple substrates, under user and environmentally friendly conditions, as now required in modern organic chemistry.

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[reaction: see text] A versatile stereoselective synthesis of substituted and functionalized heterocyclic seven-membered rings is described. The approach involves a formal two-carbon ring expansion of heterocyclic cyclopentanones through a base-induced anionic domino three-component transformation named the MARDi cascade leading either to oxa-, aza-, or thiacycloheptanes bearing up to five contiguous stereogenic centers.