Directed aldol reaction vinylogous

Very recently, a similar primary-tertiary diamine 33-DNBS conjugate was identified to catalyze the first direct aldol reactions of acetoacetal. The reactions afforded vinylogous-type aldol adducts with good yields and excellent enantiose-lectivity (Scheme 5.10). In cases of substituted acetoacetals, good 5yn-diastereose-lectivity was obtained again [20]. 

As practiced in the preceding syntheses by Evans and Nishiyama and Yamamura, the A-ring fragment 43 is formed through substrate-directed vinylogous aldol reaction of the Brassard-type diene 19 and the chiral aldehyde 42, which is prepared using Brown s protocols for enantioselective allylation [53], followed by hydroxy-directed nnn-diastereoselective reduction of the C3 ketone (Me4NB(OAc)3H) [41],... 

Scheme 19.55 Direct vinylogous aldol reaction promoted by a chiral bifunctional primary amine-thiourea.

Later, Melchiorre and coworkers accomplished a challenging direct vinylogous aldol reaction of 3-methyl-2-(yclohexen-l-one with a-keto esters utilising a bifunctional primary amine-thiourea. Catalyst 48 based on the (l/ ,2/ )Kiiphenylethylene-l,2-diamine backbone combined with benzoic acid as cocatalyst promoted the reaction by means of a concomitant activation of both reacting partners (see TS in Scheme 19.55), the ketone via dienamine catalysis and the ester via hydrogen-bonding interactions (Scheme 19.55). 

Table 23.4 Direct vinylogous aldol reaction by Terada and coworkers.

Bifunctional organocatalysts - aminothioureas and aminosquaramides - have been tested in direct asymmetric direct vinylogous aldol reactions of y-crotonolactone (66) with aromatic aldehydes to give 5-substituted 2(5//)fiiranones (y-butenolides, 67) Best yield/r/e/ee performance was 98/90/99%, and the method is an alternative to the vinylogous aldol of silyloxy furans. 

A bifunctional amine/thiourea catalyst gives high ee in a direct vinylogous aldol reaction of allyl ketones with isatins, giving biologically important 3-hydroxy-2-oxindoles. ... 

Moreover, the stereoselective, direct vinylogous aldol reaction of halogenated or a-thio-substituted furanones with aldehydes was achieved by using appropriately tuned 22c as an optimal catalyst (Scheme 7.37) [61]. On the basis of analyses of the absolute configurations of the products as well as the relationship between the catalyst structure and the stereochemical outcomes, a transition state model was proposed. In this model, furanone-derived enolate would be located close to the... 

Scheme 10.29 Direct vinylogous aldol reaction of y-crotonolactone with aldehydes.

Terada and coworkers reported, in 2010, an enantioselective, direct vinylogous aldol reaction of furanone derivatives with aromatic aldehydes catalyzed by axiaUy chiral guanidines (Scheme 10.49) [142]. Initial catalyst screening revealed that both the buUdness and the electronic nature of the G substituent on the guanidine had a large influence on catalytic activity as well as enantio- and diastereoselectivity. 

Recently, direct vinylogous aldol reactions of furanones 150 with aldehydes or ketones have been investigated intensively. These reactions are simple alternatives to the vinylogous Mukaiyama aldol reaction of silyloxy furans discussed in Section... 

Br0nsted Base Catalysis Including Bijunctional Catalysis 819 Table 28.7 Direct vinylogous aldol reactions in Bronsted base catalysis. 

Highly enantioselective direct vinylogous aldol reactions of dihalogenated furanones (150, R = = Cl) with aldehydes (151, R = H) are catalyzed by the... 

Reviews cover organocatalytic vinylogous reactions (both direct and Mukaiyama), recent contributions to regio-, enantio-, and diastereo-control in vinylogous aldol additions, and a 10-year survey of progress in the area (369... 

The direct vinylogous aldol additions of a,j0-dichloro-y-butenolides and -butyro-lactams have been examined computationally, seeking to identify the origin of the observed diastereoselectivities and especially the reversal observed between the two systems.In addition, reactions with ort/io-substituted benzaldehydes have been 0 compared with those with benzaldehyde itself. 

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