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Mphenicol, respectively (vide infra). Stereochemical assignments from the remaining aldehyde addition goods from Table 1 were made by analogy. The stereochemistry of those products conforms with all the diastereofacial preferences for PKCδ MedChemExpress alkylation reactions of pseudoephenamine amide enolates, offered that a (Z)-enolate (together with the -amino group and enolate oxygen cis) is invoked, which seems to usNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAngew Chem Int Ed Engl. Author manuscript; accessible in PMC 2015 April 25.Seiple et al.Pagequite reasonable.[2b] Syn stereochemistry presumably arises from conventional Zimmerman raxler-type arguments.[8]NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptIn addition to its common, effective, and stereoselective reactions with aldehyde substrates (linear, branched, and -tetrasubstituted aliphatic, aromatic, -oxygenated, and ,unsaturated), pseudoephenamine glycinamide (1) also serves as an exceptional substrate for aldolization with ketone substrates, delivering aldol adducts with totally substituted -centres, as illustrated by the seven examples 13-19 in Table 1. The stereochemistry of aldol adduct 16 (from methyl isopropyl ketone) was established PPARδ Storage & Stability unambiguously by X-ray analysis of its crystalline hydrate; not surprisingly, it was found to become fully consistent using the stereochemistry on the aldehyde aldol adducts (the methyl group acts as the “small” group). We also rigorously established the stereochemistry from the aldol adduct 18 by X-ray analysis of a crystalline derivative (vide infra), and this also conformed to that with the other aldol goods. This solution seems to represent a case of stereochemical matching, where the diastereofacial preferences of your enolate and also the chiral ketone substrate (the latter constant with a Felkin-Ahn trajectory)[9] are reinforcing, accounting for the extraordinarily higher stereoselectivity and yield of this particular transformation. Product 19 (55 isolated yield), from methyl styryl ketone, was formed least efficiently, we think as a consequence of competitive conjugate addition (est. 15 ). As a seemingly minor point, we note that careful evaluation from the 1H NMR spectra with the majority on the purified aldol adducts from Table 1 reveals that along with the two rotameric types of the expected syn-aldol diastereomers, trace (five ) amounts of an “impurity” corresponding towards the N O-acyl transfer solution, a amino ester, are present.[10] This reveals that the latter constitutional isomer is only slightly higher in energy than the tertiary amide kind, delivering a rationale for the outstanding facility with the subsequent transformations with the direct aldol solutions discussed under, namely their hydrolysis and reduction. In contrast to circumstances common for hydrolysis of tertiary amides, hydrolysis on the aldol adducts of Table 1 proceeds below remarkably mild circumstances, more consistent with saponification of an ester than hydrolysis of a tertiary amide (Table 2). One example is, hydrolysis of aldol adduct 4 was complete within four h at 23 within the presence of 1 equiv of sodium hydroxide in 1:1 THF:methanol. As soon as hydrolysis was comprehensive, pseudoephenamine was recovered by extraction with dichloromethane in quantitative yield (95 purity), and also the alkaline aqueous solution was lyophilized to supply the -hydroxy–amino sodium carboxylate 22 in 92 yield and 98 ee (Table 2). The inclusion of methanol was vital to prevent retroald.