Aldehydes cycloaddition

Because ketones are generally less reactive than aldehydes, cycloaddition reaction of ketones should be expected to be more difficult to achieve. This is well reflected in the few reported catalytic enantioselective cycloaddition reactions of ketones compared with the many successful examples on the enantioselective reaction of aldehydes. Before our investigations of catalytic enantioselective cycloaddition reactions of activated ketones [43] there was probably only one example reported of such a reaction by Jankowski et al. using the menthoxyaluminum catalyst 34 and the chiral lanthanide catalyst 16, where the highest enantiomeric excess of the cycloaddition product 33 was 15% for the reaction of ketomalonate 32 with 1-methoxy-l,3-butadiene 5e catalyzed by 34, as outlined in Scheme 4.26 [16]. 

On the other hand, hikosamine (284), obtained by degradation of hikizimy-cin (285), was synthesized by the recently developed diene-aldehyde cycloaddition reaction (85JA7762). Hexoaldose 278 was synthesized starting with the Eu(fod)3 (83JA3716) mediated cyclocondensation of furfural (275) with diene... 

Yamamoto and co-workers have introduced a conceptually interesting series of catalysts that incorporate an acidic proton into the active catalyst. Termed Bronsted acid-assisted chiral Lewis acid (BLA), catalyst 14 selectively catalyzes a number of diene-aldehyde cycloadditions reactions (Scheme 16) [67]. While extremely selective for the substrates shown, no aldehydes lacking an a-substitu-ent were reported to be effective in this reaction. This feature was addressed in... 

Asymmetric ketene-aldehydes cycloaddition leading to the enantiomerically enriched (3-lactones (83) is catalyzed effectively by trifluoromethanesulfonylated aluminum Lewis acid (80), which controls the stereochemistry much more efficiently than the corresponding tosylated catalyst (Scheme 5.22) [7]. The lactones (83) are useful precursors for the enantiomerically enriched (3-amino acids (84). 

Optically active p-lactones are readily prepared by ketene-aldehyde cycloaddition using 72 as the chirality inducer.The products are excellent precursors of p-amino acids. The [2 + 2]cycloaddition of ketenes and imines in the presence of 0-benzoylqui-nine leads to numerous ciT-2,3-disubstituted p-lactams. ... 

Nelson and co-workers reported a cinchona alkaloid-Lewis acid-catalyzed acycl chloride aldehyde reaction, an extension of ketene-aldehyde cycloaddition, providing 3,4-cw-p-lactones 168 with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (>96% de), [69], The methodology was later applied by the group in the enantioselective total synthesis of (-)-pironetin (Scheme 3.53). 

Scheme 3.53 Cinchona alkaloid 145/LiC10,-catalyzed ketene-aldehyde cycloadditions...

Diene-aldehyde cycloadditions in which the carbohydrate contains the formyl group were studied at high pressure by Jurczak and co-workers (55). Cycloaddition of 1-methoxybutadiene to aldehyde 59 at 20 kbar and 53° C occurred to give 60 with complete stereoselectivity. When the reaction was carried out at 11 kbar in the presence of Eu(fod)3 as a catalyst, a 98 2 ratio of the cycloadducts was obtained in which 60 was the major product. The diastereoselectivity of the reaction is consistent with a Felkin-Anh transition state in which the diene approaches the formyl group from the less hindered face, in the endo mode. 

The diene-aldehyde cycloaddition has been further developed in the laboratories of Danishefsky and co-workers, where significant advances in methodology have been demonstrated by many successful applications to the synthesis of natur products (56-55). Two examples in which carbohydrate-derived substrates are utilized in the cycloaddition step are the synthesis of octosyl acid A and the synthesis of spectinomycin. In the synthesis of octosyl acid A (Scheme 9), Danishefsky s diene reacted with aldehyde 61 to give 62 in 85% yield (59). The stereoselectivity of the addition to 61 was that predicted by Cram s rule. For the synthesis of spectinomycin, cycloaddition of diene 64 to acetaldehyde occurred in the presence of Eu(fod)3 to give a 5.7 1 mixture of two products. The major diastereomer was the one desired for the spectinomycin synthesis 40),... 

Other Uses. Reagent 1 has been used for enantioselec-tive enolborination, albeit with poor (1.1 1) selectivity. Similar bis-sulfonamide-derived boron Lewis acids have been used for aldol additions, " ester-Mannich reactions, Diels-Alder reactions,Ireland-Claisen reactions, and [2,3]-Wittig rearrangements. Similar bis-sulfonamide-derived aluminum Lewis acids have been used for aldol additions, Diels-Alder reactions, - [2 + 2] ketene-aldehyde cycloadditions, cy-clopropanation of allylic alcohols, and polymerization. ... 

The exclusive orientation observed in this reaction is unusual and cannot be adequately accounted for on the basis of frontier orbital theory. A similar inconsistency was also found on irradiation of azirine 233. The orientation of the cycloaddition reaction of aldehyde 233 proceeds in an alternate regiochemical sense from that observed with related bimolecular nitrile ylide-aldehyde cycloadditions where one obtains only d-oxazolines 235. In... 

Scheme 4.32 Phosphine catalyzed lactone formation from ketene/aldehyde cycloaddition.

Gold(I)-Catalyzed Reactions of 1, 6-Enynes with Aldehydes Cycloaddition Versus Metathesis-Type Reactions... 

E)-Chalcones 4 were prepared via Claisen-Schmidt condensation of methyl ketones with different aromatic aldehydes. Cycloaddition reaction of 4 with thiourea yielded the eorresponding thioxypyrimidine 5 derivatives. Compounds 5 were condensed with chloroacetic acid to yield thiazolopyrimidine 6. Also thione 5 were also condensed, in one pot reaction, with chloroacetic acid and aromatic aldehyde to yield arylmethylene derivatives 7 which could also be prepared directly by condensation of 5 with aromatic aldehydes (Scheme 2) [14-20]. 

There has been unremitting interest in the development of various reaction systems initiated by Al(III) complexes based on sterically encumbered dianionic ligands bearing various Lewis base moieties at properly designed positions. In this area, a series of optically active Al(III) triamine complexes, such as complex 88 (Fig. 29), have been reported as Lewis acid catalysts for the mediation of various asymmetric transformations, including ketene-aldehyde cycloaddition reactions (Eq. 16 for more detail on these transformations, see Chapter 6 Reactions triggered by Lewis acidic organoaluminum species ) [225, 226]. 

More recently, Karadedian and Kerr have applied the successful cyclopropane/aldehyde cycloaddition reaction in the asymmetric synthesis of (+)-isatisine A starting from the homochiral (5)-vinylcyclopropane diester [40a,b], A close examination of isatisine A revealed that the stereochemistry between and of the tetrahydroftiran could be achieved through a cycloaddition reaction starting from the S cyclopropane. 

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