Unsaturated ketones fragmentation

Numerous pyridines have been synthesized using cyanoacetamide (or cyanothioacetamide), malononitrile, malonamide and closely related compounds, which provide the N-C(2)-C(3) fragment for reviews see (86H(24)2023,87H(26)205,93CR1991). Principal co-reagents are a,(3-unsaturated ketones, arylidene malononitriles (review (83H(20)519)), and (3-diketones or (3-ketoaldehydes. 

Peptidomimetics in which one amide bond is replaced by a phosphinic acid (R-P(0H)(=0)-R phosphinic peptides ) are of interest as potential protease inhibitors [17-19]. These compounds have been prepared either from orthogonally protected phosphorus-containing monomers [17,18,20], or by forming the phosphorus-containing fragments on solid phase, as sketched in Figure 11.4 [19,21], Phosphinic acids have been prepared on solid phase mainly by reaction of carbon electrophiles with monoalkylphosphinates. As carbon electrophiles, acrylates, aldehydes, reactive alkyl halides, or a, 3-unsaturated ketones can be used. 

Fragmentation of homoallylic aikoxides.3 Thermolysis of homoallylic alcohols requires temperatures >200°. However, fragmentation of bicyclo[2.2.2]-5-octene-2-alkoxides (1) prepared as shown in equation (I), occurs at 90-120° and results mainly in unsaturated ketones (2) formed by cleavage of the allylic (C -C2) bond. Although the exo-alkoxide is cleaved noticeably faster than the endo-cpimer, both aikoxides give the same product. 

Thus, the alternative direction of the reaction of or o-hydroxychalcone 5 is not associated only with a specific influence of hydroxyl group, but most likely is due to several other reasons. Indeed, the presence of a hydroxyl group in other fragments of an unsaturated ketone does not change the reaction direction. 

Figure 13-2 Gaschromatogram (a) and SlM-speclrum (b) of two isomers of an unsaturated ketone after selective enrichment, m/e = relative molecular or fragmental mass t = time.

Scheme VIII/13. Conversion of a,/ -unsaturated ketones to alkynones by fragmentation.

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