Primary water Michael reactions

All Michael reactions are performed in water at a concentration of up to 50 wt% of amine, to which 2.5-4 moles of acrylonitrile per mole of primary amine are added. In the double cyanoethylation, the first acrylonitrile molecule reacts at room temperature, while the reaction temperature has to be raised to 80°C to accomplish the double Michael adduct. The reaction time required to achieve complete conversion increases with generation from 1 h for DAB-JenAfter completion of the reaction the excess acrylonitrile is removed by distillation, making use of the water-acrylonitrile azeotrope. 

The hetero Michael reaction between primary or secondary amines and a,p-unsaturated compounds in water for the synthesis of P-amino derivatives was investigated by Loh et al [60]. Addition of 20mol% of InCl3 was found to improve yields but had no influence on diastereoselectivities (Figure 8.33). 

Gordon and Danishefsky [112] used the reaction of a chromium Fischer car-bene complex 164 with a cycloalkine 163 to build the naphthoquinone core 165 (Dotz reaction, review [113]), a procedure often used for synthesis of the linearly condensed anthracyclinones (e.g., [114]). The quinone ketone 165 has nucleophilic and electrophilic centers correctly positioned to furnish a ben-zo[fl]anthraquinone. However, treatment with NaH or Triton B gave the spiro-compounds 166 as a mixture of two stereoisomers. These products evidently arose from Michael addition of the ketone enolate to the naphthoquinone double bond. But the weaker base DBU induced cyclization at ambient temperature to the benzo[a]anthraquinone 167 in 65% yield (Scheme 42). The primary aldol adduct apparently eliminated water and the resulting dihydrobenzo[a]anthraquinone aromatized under basic conditions in the presence of air. This is an instructive example of the influence of the base on the cyclization mode. 

Li and coworkers reported the conjugate addition of alkyl groups to enamides mediated by zinc in aq. NH4CI to generate a -amino acid derivatives (Eq. 4.73). No reaction was observed in the absence of water. Both secondary and tertiary alkyl groups such as linear (2-butyl, 2-propyl, 2-pentyl), cyclic (cyclohexyl, cyclopentyl, cycloheptyl), and bulky ones (tert-butyl) were all transferred to the substrate successfully. Even simple primary iodides and methyl iodide provided the desired products in good yields. Miyabe et al. as well as Jang and Cho reported the addition of alkyl radicals from alkyl iodide to a,p unsaturated ketones, esters, and nitriles mediated by indium in aqueous media. Indium-mediated Michael addition of allyl bromide to l,l-dicyano-2-arylethenes also proceeded well in aqueous medium. ... 

A recent study revealed that the rate of aza-Michael-initiated ring-closure reaction between vinyl selenone 8 and primary amines 9 forming aziridines 10 (Scheme 2) was accelerated significantly in water [25]. The reactions in case of many substrates were accomplished in 3-7h as against over 24h when carried out in toluene. An asymmetric aziridination under the reaction conditions in the presence of either catalyhc or stoichiometric amounts of (R)-BINOL gave excellent yields of aziridines, but very poor enantioselectivity (ee 18% and 10% in two reactions investigated) was observed. 

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