Condensation-rearrangement cascade

The first route to 2H-azaphosphirene complexes XIII, published by Streubel et al. in 1994 [22], used a triethylamine-induced condensation-rearrangement cascade starting from amino(aryl)carbene metal complexes VIII and [bis-(trimethylsilyl)methylene]halophosphanes IX (X=Cl,Br) (Schemes) the yields are generally good (50 - 85%) [19,23]. Experimental details and scope of this method as well as progress in this field were summarized quite recently [24]. 

Blechert et developed a multicomponent cascade reaction for the synthesis of indole derivatives as depicted in Scheme 1.8.5.17. The first step of the sequence involves formation of a nitrone derivative starting from phenylhydroxylamines and aldehydes. The resulting nitrones were not isolated but captured by a cyanoallene in a 1,3-dipolar cycloaddition reaction followed by hetero-Cope rearrangement, ring-opening and condensation to yield an indole derivative. 

The Overman pyrrolidine synthesis is a tandem reaction, or cascade, used to generate acylpyrrolidine derivatives. This process begins with condensation of an allylic alcohol/ether-containing secondary homoallylic amine with an aldehyde, followed by an aza-Cope rearrangement and subsequent Mannich reaction. Commonly, this reaction is run in refluxing benzene with an acidic additive, such as c/-10-camphorsulfonic acid (CSA). 

In a convenient one-pot process, easily accessed propargyl vinyl ethers and aromatic amines are effectively converted into tetra- and pentasubstituted 5-methylpyrroles, which can fnrther be transformed into 5-formylpyrroles via 2-iodoxybenzoic acid (IBX)-mediated oxidation (Binder and Kirsch 2006). The cascade reaction proceeds through a silver(l)-catalyzed propargyl Claisen rearrangement, an amine condensation, and a gold(l)-catalyzed 5-exo-dig heterocyclization, as shown in Schane 11.4. 

Murugavel and Punniyamurthy developed a Cul-catalyzed one-pot synthesis of iminocoumarin aryl methyl ethers from ynal, phenol, and sulfonyl azide via a cascade [3-1-2]-cycloaddition, 1,3-pseudopericyclic ketenimine rearrangement, 1,4-conjugate addition, and aldol-type condensation at room temperature under air [195] (Scheme 8.120). 

With a similar strategy of combined diarylprolinol silyl ether and N-heterocyclic carbene catalysts, j0rgensen and coworkers [21] examined the cascade reaction of easily accessible i-keto heteroaryl-sulfones as nucleophiles with a,P-unsaturated aldehydes (Scheme 43.11). In this cascade reaction, following the initial iminium ion-catalyzed Michael reaction of nucleophiles to a,(i-unsaturated aldehydes, the subsequent step was then promoted by carbene catalyst 57 to afford 2,4-disubstituted cyclopentenones 55 via an intramolecular benzoin condensation initiated Smiles rearrangement. The superiority of combinational use of two catalysts in the similar Michael/benzoin cascade reaction was also independently demonstrated by Enders et al. (Scheme 43.12) [22]. 

SCHEME 5.9 Ru-catalyzed cascade Meyer-Schuster rearrangement/aldol condensation. 

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