Michael Reactions of Pseudoephedrine Amide Enolates:  Effect of LiCl on Syn/Anti Selectivity

Abstract

The stereochemical outcome of the asymmetric Michael reaction of pseudoephedrine amide enolates changes dramatically in the presence of LiCl. Reaction of the enolate in the absence of LiCl results in formation of the anti Michael adduct with high selectivity, whereas in the presence of lithium chloride the syn adduct is favored. This method provides access to enantiomerically enriched trans-3,4-disubstituted delta-lactones from the anti Michael adducts by a two step reduction/lactonization sequence. Information obtained from NMR studies indicates that, under both enolization conditions, the (Z)-enolate is formed. A model to explain the turnover in selectivity based on NMR evidence is presented.

Electrospray[+] tandem quadrupole mass spectrometry in the elucidation of ergot alkaloids chromatographed by HPLC: screening of grass or forage samples for novel toxic compounds

“…Peptide bond carbonyl oxygens have recently been studied as recipients for H atoms in rearrangements of peptide radicals and radical cations in which electron transfer through a pi‐orbital system occurs in either the same or the opposite direction to proton migration, depending on the electronic properties of the protein chain, and leading to peptide N–C bond dissociation or side‐chain loss and generation of iminolic products 33, 34. Rearrangement of the amide to an enol rather than iminol has precedents in the synthetic lab, as revealed in certain lithium complexes and, as with amide‐iminol tautomerism, affected by the nature of adjacent functionalities 35–38. It appears likely that amide conversion to iminol is energetically favored over amide conversion to enol owing to anticipated superior acidity of the amide versus C–H and stability of the transient polar iminol;39 this may explain the relatively gradual appearance of diastereomeric peaks in Figs 2(B), (E), (F), (H), (I) and (J) by acid‐ or alkali‐induced epimerization involving an intermediate potentially stabilized by conjugation of bonds 1 and 2 in intermediate X (Scheme ).…”

A multigram-scale lower E-factor procedure for MIBA-catalyzed direct amidation and its application to the coupling of alpha and beta aminoacids

“…Characterization data of the product matched that found in the literature. 21 Preparation and characterization data of N-benzyl-2-phenylacetamide (11). The title compound was prepared using the general procedure for the multigram organocatalytic amid-ations, affording 6.693 g of 11 and 89% yield, 5.415 g of 11 and 72% yield, in toluene and CH 2 Cl 2 respectively.…”

Direct asymmetric syntheses of chiral aldehydes and ketones via N-acyl chiral auxiliary derivatives including chiral Weinreb amide equivalents

“…The use of the pseudoephedrine 50 as a chiral auxiliary has been extended to aldol reactions, 65,66 Mannich reactions, 67,68 conjugate addition reactions, 69 aza-Michael reactions 70 and enolate amination reactions. 67,71,72 Direct conversion to enantiomerically enriched aldehydes or ketones has also been successfully demonstrated by treatment with hydride reducing agents such as Li(EtO) 3 AlH or organometallic reagents (typically alkyl lithiums or Grignard reagents) followed by an aqueous workup.…”