P-Ketoacetals

MeONa/HCOOEt) and ketalisation (H2SO4/CH3OH), produced the p-ketoacetal (9EIZ 80/20). A Wittig reaction with methyltriphenyl phosphorane (tBuOK/Ph3p+CH3, Br ) followed by hydrolysis of the p-methyleneketal, produced the 13-methylene isomer of retinal, as a 9E and 9Z mixture (80/20), Fig. (40). 

Keto-piperidine from cyclic imine and P-ketoacetate. 

It is worthwhile emphasising here that the observed chemoselectivity is due to the fact that enolethers are better electrophiles than the free carbonyl groups. In fact, the ketoacetal 15, obtained by chromatography, is an equilibrium 60 40 mixture of methyl epimers at C(4) in which the desired a-epimer 5 is the predominant isomer. However, the pure compound 5. could be obtained in good yields by recrystallisation from hexane (m.p. 117-118 °C) and re-equilibration-crystallisation recycling of the remaining mixmre 15 in the mother liquor. 

An early structural modification of FA and AP involved alkylation at C-9 and/or N-10. 10-MethylFA (447) [197] was prepared by reaction of 2,4,5-triamino-6-hydroxypyrimidine, 2,3-dibromopropionaldehyde and diethyl p-methylaminobenzoylglutamate (35), followed by alkaline hydrolysis (the Waller condensation). Analogous utilization of 2,2,3-trichlorobutyraldehyde and the requisite p-(JV-substituted amino)benzoylglutamate furnished (448a-c) (Scheme 3.88) [198]. The preparation of (450) by condensation of 2,4,5,6-tetraaminopyrimidine and the a-ketoacetal (449) was reported without details (Scheme 3.89) [199],... 

The first report concerning the synthesis of 10-deaza-10-oxafolates described the preparation of 10-deaza-10-oxaFA (498) and 10-deaza-10oxaAP (499) by condensation of the ketoacetal (497) with the appropriate pyrimidine, followed by ester hydrolysis (Scheme 3.99) [51]. An improved, unambiguous synthesis [ 174] of (498) and (499) is outlined in Scheme 3.100 and is a modification of the Boon-Leigh procedure. Reaction of (500) with methyl p-hydroxy-... 

Ketoacetals are available from the Lewis acid catalysed Michael addition of hemiacetal vinylogues to 3,4-dihydropyrans. The products are a source of hydroxy- and amino- acetals and hence give access to annulated tetrahydropyrans (95JCS(P 1)2103). 

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