Unsaturated aldehydes cyclic, synthesis

The synthetic utility of the carbonylation of zirconacycles was further enhanced by the development of a pair of selective procedures producing either ketones or alcohols [30] and has been extensively applied to the synthesis of cyclic ketones and alcohols, most extensively by Negishi [22—27,29—33,65,87,131—134], as detailed below in Section I.4.3.3.4. The preparation of unsaturated aldehydes by carbonylation with CO is not very satisfactory. The use of isonitriles in place of CO, however, has provided a useful alternative [135], and this has been applied to the synthesis of curacin A [125]. Another interesting variation is the cyanation of alkenes [136]. Further developments and a critical comparison with carbonylation using CO will be necessary before the isonitrile reaction can become widely useful. The relevant results are shown in Scheme 1.35. 

Thiosalicylaldehydes afford chiral thiochromene-3-carbaldehydes 39 on reaction with a,P-unsaturated aldehydes catalysed by a chiral pyrrolidine silyl ether. Initial activation of the enal triggers sequential Michael and aldol reactions and dehydration completes the highly enantioselective synthesis <06JA10354, 06TL8547>. In a similar manner, cyclic enones afford cycloalkanone[ ]thiochromenes <06TL8679>. 

Lee and coworkers presented a facile synthesis of fused pyrans 116 in 65-90% yields in water by reacting a variety of cyclic 1,3-dicarbonyls 33 with a,fi-unsaturated aldehydes 115 (Scheme 12.45). The key step is a formal [3+3] cycloaddition though a domino Knoevenagel/6 [i-electrocyclization. This methodology has been applied to the synthesis of biologically interesting pyranocoumarin, pyranoquinolinone, and pyranonaphthoquinone derivatives [69]. 

Unsaturated Aldehydes and Ketones. - A five-step procedure for the synthesis of cyclic 3-nitroalkenones from the... 

The stereoselective conjugate addition of /3-keto-ester anions to substituted cyclopentenones has been reported. Similar anions also add in conjugate fashion to a,/3-unsaturated aldehydes in the presence of a phase-transfer catalyst. Asymmetric induction in the conjugate addition of cyclic /3-keto-esters to enones is achieved by the use of cinchona alkaloids as bases. A further 1,5-dicarbonyl synthesis is achieved by a seven-stage sequence involving two conjugate additions the yields reported in each step are excellent (Scheme 80). ... 

A somewhat related two-step method for the synthesis of areno[a]quinolizines involves the preparation of a cyclic hemiacetal from a p-dicarbonyl compound and an a,p-unsaturated aldehyde. The subsequent reaction of this hemiacetal with tryptamine in the presence of a Brpnsted acid affords the target product, probably through a Pictet-Spengler reaction, and the use of chiral Brpnsted acids has been investigated and found to lead to good enantioselections in some cases [74]. The reaction between P-amidoesters derived from tryptamine and a,p-unsaturated aldehydes affords lactams derived from the indolo[2,3-fl]quinolizin-4-one system [75]. 

As an extension of this work, the same authors explored such methodology for the synthesis of 2,6-disubstituted dihydropyrans using secondary homopropargylic alcohols (Scheme 10, route E). Surprisingly, the treatment of pent-4-yn-2-ol and 3-methylbutanal in the presence of FeCls led to unsaturated ( )-(3-hydroxyketone and ( )-a,p-unsaturated ketone in 2.5 1 ratio and 65% yield, without any trace of the expected Prins-type cyclic product (Scheme 22) [36]. To test the anion influence in this coupling, FeCE and FeBrs were used in a comparative study for the reaction of pent-4-yn-2-ol (R = R" = H, = Me) and several aldehydes. A range of aldehydes except for benzaldehyde was transformed into unsaturated (3-hydroxy-ketones in moderate to good yields. 

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