Tandem Michael-type sequences

Scheme 4.36 Multicatalysed tandem Michael-type sequences between alkynes, DIBAL, and trisubstituted enones.

Scheme 1.12. A tandem sequence of Michael-type addition and [4 + 2] cycloaddition diastere-oselectively affords highly functionalized 1,2,3,4-derivatives of Cgo (type ( )-169) with two adjacent bridges and a noninherently chiral functionalization pattern. Deprotonation of ( )-169 and subsequent alkylation leads to an inherently chiral addition pattern in ( )-170.

Increasing importance has to be attributed to modem tandem (or cascade ) techniques—reaction sequences that can be performed as a one-pot procedure because the first reaction step creates the arrangement of functional groups needed for the second to occur. Schemes 5-7 present some in situ preparations for iminium species, which can then react further with appropriate nucleophiles that are already present (preferably in the same molecule). Most elegantly, in situ generation of iminium ions for tandem processes was performed by a 3,3-sigmatropic (aza-Cope-type) rearrangement (Scheme 5), but also by initial Michael-type addition reactions to vinyl-substituted Atio... 

Other types of multicomponent reactions have also been successfully developed, such as the first practical three-component imino-Reformatsky reaction, and a pseudo-three-component reaction between allenes and isocyanates, providing excellent levels of enantioselectivity. Finally, excellent results were described for several novel enantioselective tandem sequences. For example, very high enantioselectivities were reached in tandem Michael/ intramolecular cyclisation sequences, as well as in a remarkable multicat-alytic Michael sequence occurring between enones, alkynes, and DIBAL, which stereoselectively afforded a range of chiral p-alkenyl ketones bearing an all-carbon-substituted quaternary stereogenic centre in excellent enantioselectivities. 

Huge success of benzodiazepenes as pharmaceutical scaffolds has prompted preparation and evaluation of het-erocyde-annulated benzodiazepine derivatives. A tandem Michael addition-condensation sequence xmder MW irradiation was also proved to be useful for the synthesis of amino-substituted pyrimidine-fused diazepine derivatives of the type 96 from 4,5,6-triaminopyrimidine and chalcones [57]. Similarly, the pyridine-fused derivatives (97) were prepared xmder MW-assisted solvent and catalyst-free condition [58], Condensation of thiadiazole-annulated phen-ylene diamines with appropriate carbonyl compounds using sulfamic acid as organocatalyst led to the formation of corresponding diazepine derivatives 98 in excellent yields [59] (Figure 4). 

Dommo-type reactions involve careful design of a multistep reaction in a one-pot sequence in which the first step creates the functionality to trigger the second reaction and so on, making this approach economical and environmentally friendly. A classical example of a tandem reaction is the Robinson annulation (a Michael reaction followed by aldol condensation and dehydration). 

The cyclization reactions described in this chapter and, occasionally, even the acyclic condensation reactions, can often be prefaced by a different type of process such as a Michael reaction. We shall term such a sequence a tandem reaction and a number of these have already been described. Others will be collected here to illustrate the types of processes that have been observed. The cycloenones (198), when treated with a nucleophile (199) under basic conditions, react in a Michael fashion to give the intermediates (200), which then undergo the Dieckmann reaction to give the bicyclic dione (201). Similarly, methyl cinnamate (202) reacts with the nucleophile (203) in the same tandem sequence to give the cyclopentanone (204) as a diastereomeric mixture (Scheme 89). ... 

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