Conjugate additions cascades

Scheme 7 Cross-metathesis and oxidation/conjugation addition cascades leading to (-t)-SCH 351448 [26]...

In addition, Wu and Li recently have developed an efficient rhodium-catalyzed cascade hydrostannation/conjugate addition of terminal alkynes and unsaturated carbonyl compounds in water stereoselectively (Scheme 4.5).88... 

In a collection of insightful pieces of work Enders has incorporated an iminium ion conjugate addition of nitroalkanes to a,P-unsaturated aldehydes into a triple cascade reaction generating up to four contiguous stereocentres in one pot, again indicative of the complexity attainable from superficially simple catalysts and techniques [175-177] (Scheme 46). 

In each of the tandem iminium ion/enamine cascade processes described above, the enamine is trapped in an intramolecular fashion. The ability to perform the trapping seQuence in an intermolecular manner would allow for the one—pot introduction of three points of diversity. IVIacNlillan has realised this goal and described a series of secondary amine catalysed conjugate addition—enamine trapping sequences with oc P Unsaturated aldehydes using tryptophan derived imidazolidinone 115 to give the products in near perfect enantiomeric excess (Scheme 47) [178]. 

A highly enantioselective and diastereoselective addition of trisubstituted carbon donors, such as (166), to 2-chloroacrylonitrile (167), catalysed by bifunctional Cin- chona alkaloid catalysts, e.g. (169), has been reported as the first example of an asymmetric cascade that includes conjugate addition and protonation with efficient (g) catalytic control at two non-adjacent stereocentres (168).218... 

This catalytic cascade was first realized using propanal, nitrostyrene and cinnamaldehyde in the presence of catalytic amounts of (9TMS-protected diphenylprolinol ((.S )-71,20 mol%), which is capable of catalyzing each step of this triple cascade. In the first step, the catalyst (S)-71 activates component A by enamine formation, which then selectively adds to the nitroalkene B in a Michael-type reaction (Hayashi et al. 2005). The following hydrolysis liberates the catalyst, which is now able to form the iminium ion of the a, 3-unsaturated aldehyde C to accomplish in the second step the conjugate addition of the nitroalkane (Prieto et al. 2005). In the subsequent third step, a further enamine reactivity of the proposed intermediate leads to an intramolecular aldol condensation. Hydrolysis returns the catalyst for further cycles and releases the desired tetrasubstituted cyclohexene carbaldehyde 72 (Fig. 8) (Enders and Hiittl 2006). 

A one-pot cascade reductive amination, conjugate addition and lactamisation of keto acrylate 112 afforded fused piperidinodiazepinone 113 in good yield <07T7187> while lactamisation was the final step in the synthesis of tetracyclic diazepinone natural products sclerotigenin and (-)-circumdatin-F <07TL3243>. 

Dihydropyridine derivatives can be formed from a cascade sequence wherein conjugate addition of enaminoesters occur with a,(3-unsaturated carbonyl compounds... 

Zard also used a xanthate-mediated radical cascade sequence to synthesize indolines from vinyl sulfanilides in three steps [54]. The initial peroxide-initiated intermolecular addition of the xanthate to the vinyl sulfanilide was followed by an intramolecular cyclization onto the ortho position of the aromatic ring. Further heating with DBU generated the dihydroindole through a base-induced isomerization of the olefinic bond followed by conjugate addition. 

Radical conjugate additions with participation and formation of heterocycles including stereoselective reactions, cascade reactions, and application of conjugate additions in total synthesis of natural products 05T10377. 

Enantioselective Cascade Reactions Initiated by Conjugate Addition... 

Cascade Processes Initiated by Conjugate Addition via Enamine Activation... 

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