Intermolecular reactions aldehyde trapping

Synthesis of furans has been carried out via three-component reactions involving intermolecular carbonyl ylide formation. Johnson and co-workers have revealed [65] the consequence of intermolecular carbonyl ylide generation followed by trapping with a selective dipolarophile to obtain furan ring systems. On the basis of this approach, the diazosulfone 8 underwent intermolecular reaction with aldehydes in the presence of Rh2 (oct)4 to form carbonyl ylide intermediates, which could be trapped by alkynes in an inter-or intramolecular manner to yield substituted dihydrofurans 9 or 11, which were later converted to furans 10 and 12, respectively (Scheme 2). 

In a recent publication, Perumal and coworkers [441] described the condensation of an aldehyde 2-863 with an aniline 2-864 to give an imine which is trapped by a dienophile. However, when using this approach an intermolecular cycloaddition takes place as the reaction is performed as a three-component process using enol ethers or cyclopentadiene as dienophiles (Scheme 2.192). When using enol ether 2-... 

Carbonyl compounds can also act as the nncleophtles in intermolecular processes with 1,6-enynes. Thus, the gold(I)-catalyzed reaction between enynes and aldehydes or acetone gives stereoselectively tricyclic compounds (equation 71). The transformation is mechanistically intriguing, as it proceeds by a rearrangement of the initially formed cyclopropyl gold carbene (the intermediate in the donble-cleavage mechanism), which is then trapped by the carbonyl compound to form the products. 

Addition of alkyl radicals to alkenes is a useful C-C bond formation reaction in which a a-C-C bond is made from a n-C-C bond in a very exothermic reaction. In contrast, n-C-O bonds of ketone and aldehyde are nearly as strong as a-C-C bonds. Therefore, ketones and aldehydes cannot be used as intermolecular traps in synthesis (Scheme 2.7). 

Under strictly anhydrous conditions, the iminophosphorane intermediate that is formed as a result of the Staudinger reaction can react with aldehydes and ketones in an intermolecular fashion (as in the synthesis of imine 36 described above) or intramolecularly with a variety of carbonyl containing functional groups to afford a host of products. Nitrogen containing ring systems such as cyclic imines (44) represent just one of the many products one can prepare and the reaction is particularly well suited for the facile synthesis of five, six, and seven-membered rings. In addition to aldehydes and ketones, carboxylic acids, esters, thio-esters, and amides can also react in an intramolecular fashion to trap an iminophosphorane to afford a variety of heterocycles. Examples from the current literature are described in Section 2.5.5. 

Two homoallylamines (12 and 13) were synthesized and then hydroformy-lated in methanol (Scheme 5). In this solvent, the condensation of the nitrogen atom with the aldehyde does not require the addition of an acid, and the intermediate acyliminium ion was trapped intermolecularly to yield hemiaminals 10 and 11. The formation of the second ring occurred via the incorporation of an allyl chain in the sixth position of the piperidine ring. This processing was performed using allyl-TMS in the presence of BF3 Et20. The low yield of this reaction (56% and 58%) was offset by the high diastereoselectivity, since only the cis stereoisomer was isolated. 

In contrast to the diverse insertion chemistry of vinylpalladium intermediates discussed in Sects. IV.3 and IV.5, the reactions of vinylpalladium complexes with electrophiles had not been reported until recently. Although a single report on the annulation of the o-mer-curio benzaldehyde with diphenylacetylene into the corresponding indenols and inde-nones catalytic in palladium and stoichiometric in copper had been communicated in 1992, the more synthetically useful protocol for the catalytic version of this type of transformation remained unknown until 1999. In this section the intermolecular carbopalladation of alkynes with aryl halides followed by the intramolecular trapping of the formed vinylpalladium species with ketones, aldehydes, and nitriles will be discussed. 

The spirodioxolane 32 was synthesized in moderate to good yield [74] from a similar three-component reaction involving diazo ester, aryl aldehyde and p-benzoquinone. Here, p-benzoquinone acts as the dipolarophile to trap the intermolecular carbonyl ylide generated from 13 and the aldehyde (Scheme 10). 

In 2004, Vignola and List [111] demonstrated the ability of proline-derived catalysts to overcome drawbacks associated with the stoichiometric alkylation of preformed aldehyde enolates when they described an elegant amino acid catalyzed intramolecular a-alkylation reaction of haloaldehydes. The reaction furnished substituted cyclopentanes, cyclopropanes, and pyrrolidines in good yields and good enantio-selectivities (Scheme 8.23), when commercially available (5)-a-methyl proline (LV) as catalyst was used. The presence of a stoichiometric amount of additional base (tertiary amine) was required, not only to trap the hydrogen halide produced in the reaction but also because it has also significant effect on the stereoselectivity of the C—C bond-formation process by stabilizing the ant/ -TS of the /ra 5-enamine intermediate. Nevertheless, an intermolecular version of the reaction remains still elusive, mainly because of the deactivation of the amine catalyst by A -alkylation with the alkyl halide [112]. 

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