Roduct stereochemically homologous with L-threonine. Moreover, the absolute and relative
Roduct stereochemically homologous with L-threonine. Additionally, the absolute and relative stereochemistries of syn aldol adducts 8 and 9 (from para-nitrobenzaldehyde and para-methanesulfonylbenzaldehyde, respectively) were rigorously established to type a homochiral series with 4 on the basis of their prosperous conversion to active antibiotics identical with chloramphenicol and thiamphenicol, respectively (vide infra). Stereochemical assignments in the remaining aldehyde addition solutions from Table 1 had been produced by analogy. The stereochemistry of these merchandise conforms with all the diastereofacial preferences for alkylation reactions of pseudoephenamine amide enolates, supplied that a (Z)-enolate (with all the -amino group and enolate oxygen cis) is invoked, which appears to usNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAngew Chem Int Ed Engl. Author manuscript; obtainable 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 basic, efficient, 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, giving aldol adducts with fully 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 unambiguously by X-ray analysis of its GLUT3 review crystalline hydrate; not surprisingly, it was found to be fully consistent with all the stereochemistry in 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 evaluation of a crystalline derivative (vide infra), and this also conformed to that on the other aldol products. This item seems to represent a case of stereochemical matching, where the diastereofacial preferences of your enolate and also the chiral ketone substrate (the latter consistent having a Felkin-Ahn trajectory)[9] are ALK3 review 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 believe as a consequence of competitive conjugate addition (est. 15 ). As a seemingly minor point, we note that cautious analysis on the 1H NMR spectra of your majority from the purified aldol adducts from Table 1 reveals that in addition to the two rotameric types on the anticipated syn-aldol diastereomers, trace (five ) amounts of an “impurity” corresponding for the N O-acyl transfer solution, a amino ester, are present.[10] This reveals that the latter constitutional isomer is only slightly greater in energy than the tertiary amide type, providing a rationale for the outstanding facility in the subsequent transformations on the direct aldol merchandise discussed under, namely their hydrolysis and reduction. In contrast to circumstances typical for hydrolysis of tertiary amides, hydrolysis in the aldol adducts of Table 1 proceeds under remarkably mild situations, far more constant with saponification of an ester than hydrolysis of a tertiary amide (Table 2). As an example, hydrolysis of aldol adduct four was comprehensive within four h at 23 inside the.