Two-Component Domino Reactions

Several other options arise from this approach. Thus, amino-N-heterocycles such as 238 can also be used to form l,3-diaza-l,3-butadiens such as 239 as intermediates which undergo the appropriate hetero-Diels-Alder reaction to give 240 and 241 in a ratio of 11 1 [63]. This approach has so far only been used in a two-component domino reaction (Scheme 5.47). 

Based on a domino Knoevenagel/cne reaction, Tietze and Steinmetz developed a stereoselective solid-phase synthesis of cyclopentane and cyclohexane derivatives of type 326 and 327 using a Merrifield resin modiiled with a propandiol linker 320 as shown in Scheme 4.6.3. Subsequent reaction with monomethyl malonoyl chloride 321 afforded the polymer-bound malonate 322, which, in a two-component domino reaction was treated with unsaturated aldehydes 323 in the presence of a catalytic amount of piperidinium acetate and zinc chloride. Except for a-substituted aldehydes, the initial Knoevenagel condensation occurred without addition of dehydrating agents and the subsequent intramolecular ene reaction gave cyclopentane and cyclohexane derivatives 325 after cleavage firom the resin either by reduction or transesterification. 

Two-Component Domino Reaction under Microwave Heating... 

Sadek and coworkers [29] reported two-component domino reactions of l,l,3-tricyano-2-aminopropionitrile 29 with nitroolefins 30 in 1,4-dioxane under microwave irradiation, efficiently providing poly-substituted diaminobenzonitriles 31 in 70-73% yields (Scheme 12.11). 

In addition to simple two-component domino reactions based on relay enantioselective multiorganocatalysis, a number of multicomponent reactions have recently been successfully developed. As an example, in 2008... 

Tietze, L.F. and Steinmetz, A., Stereoselective solid phase synthesis of cyclopentane and cyclohexane derivatives by two component domino reactions Generation of combinatorial libraries, Angew. Chem. Int. Ed. Engl, 35 (1996) 651-652. 

Scheme 42.21 Two-component domino reactions by means of an iminium ion-iminium ion-enamine activation sequence. The shaded circle represents the catalyst scaffold.

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