Albertina G. Moglioni

On the stereoselective hydrogenation of chiral cyclobutyl dehydro-amino acid derivatives: influence of the catalyst in the π-facial diastereoselection

Abstract Several optically active cyclobutyl dehydro-amino acid derivatives have been hydrogenated employing Wilkinson, ( S , S )-chiraphos-Rh and Et-duphos-Rh (both enantiomers) as catalysts. The use of a chiral catalyst has been revealed to be crucial for the production of saturated amino acids with high stereoselectivity from substrates in which the chiral cyclobutyl unit is separated from the double bond by a methylene group.

Stereoselective synthesis of cyclobutyl α-aminocyclopropyl carboxylic acid derivatives

Abstract The highly stereoselective cyclopropanation of chiral cyclobutyl dehydro amino acids, synthesized from (−)-α-pinene or (−)-verbenone, has been achieved by means of a 1,3-dipolar cycloaddition with diazomethane. The proximity of the double bond to the neighbouring stereogenic center of the cyclobutyl moiety is crucial to obtain cyclopropanes as single diastereomers whose configuration has been determined by X-ray structural analysis. DFT theoretical calculations of the more stable conformations allow us to understand the π-facial diastereoselection as the result of steric hindrance by the gem -dimethyl substitutuents and the side chain of the cyclobutane-ring. Chiroptical properties of these products have been studied by ORD and CD techniques and their behavior in CSA-NMR experiments has been ascertained.

Enantiodivergent synthesis of cyclobutyl-(Z)-α, β-dehydro-α-amino acid derivatives from (-)-cis-pinononic acid

Abstract The two enantiomers of the title dehydroamino acids (DHAAs) have been synthesized through respective Wadsworth–Emmons condensations of a suitable phosphonate with enantiomeric cyclobutyl aldehydes. These compounds, in turn, were prepared by selective manipulation of the functional groups starting from (−)- cis -pinononic acid as the common chiral precursor. The CD spectra of the prepared DHAAs are described. These products are suitable for the stereocontrolled synthesis of diferent types of saturated cyclobutyl amino acids and their derivatives.

Stereoselective synthesis of novel cyclobutane dehydro amino acids from (+)-α-pinene

Abstract Several title compounds have been synthesized in good overall yields through highly stereoselective Wittig-Horner condensations of suitable phosphonates with enantiopure aldehydes easily obtained from α-pinene as chiral precursor. These products, presenting two asymmetric carbons, two or four prochiral centers, and appropriate chemical functions, are versatile precursors to a variety of cyclobutane amino acid derivatives.

Stereodivergent syntheses of the first bis(cyclobutane) β-dipeptides

The efficient synthesis of methyl 2-benzyloxycarbonylamino-(1S,2R)-cyclobutane-1-carboxylate starting from 2-methoxycarbonyl-(1R,2S)-cyclobutane-1-carboxylic acid is described. This β-amino acid derivative is antipodal with respect to the (1R,2S)-compound that was previously synthesized in our laboratory from the same chiral hemi ester. In turn, these enantiomeric β-amino acids have been self-condensed and coupled with one another to provide, respectively, enantiomeric and diastereomeric bis(cyclobutane) β-dipeptides. These products are the first reported β-amino acid oligomers containing two directly linked cyclobutane residues.

A comparative study on the 1,3-dipolar cycloadditions of diazomethane and bis(diisopropylamino)phosphinodiazomethane to chiral electron-deficient olefins: reactivity and diastereoselectivity

Abstract The 1,3-dipolar cycloadditions of bis(diisopropylamino)phosphinodiazomethane, 10, to chiral electron-deficient olefins have been investigated for the first time. The results have been compared with those corresponding to the reactions of diazomethane and the same or similar substrates. The experimental observations have been rationalized by DFT theoretical calculations. Diazomethane has been shown to be more reactive than 10 in all cases. The dipolarophiles include compounds synthesized from d -glyceraldehyde acetonide and (−)-verbenone. The latter compounds, bearing a gem-dimethylcyclobutane moiety, are less reactive than those derived from d -glyceraldehyde bearing a dioxolane ring. The influence of the Z/E geometry of the double bond on the reactivity and the π-facial diastereoselectivity has been investigated. Thus, in the reactions of diazomethane, the diastereoselectivity is not dependent on the Z/E stereochemistry but the reactivity is lower for (E)-cyclobutyl derivatives than for their Z isomers. In the reactions between 10 and the glyceraldehyde derivatives, the E isomers are less reactive than the Z ones and afford adducts with poor facial diastereoselectivity due to unfavorable interactions between the reactants in the corresponding transition states.

Synthesis and diastereoselective catalytic hydrogenation of optically active cyclobutyl α, β-dehydro-α-dipeptides

Abstract Optically active cyclobutyl (Z)-α,β-dehydro-α-dipeptides have been efficiently synthesized through the coupling of conveniently protected glycine or (S)-phenylalanine residues with a (Z)-dehydro-α-amino acid derivative prepared, in turn, from (−)-verbenone as a chiral precursor. The alternative use of (R,R)- and (S,S)-Et–duphos–Rh as the hydrogenation catalyst led to the stereoselective production of both diastereomeric saturated dipeptides in each case. Thus, the chirality of the catalyst employed has been shown to be the factor governing the configuration of the newly created stereogenic centre. Regarding structural features, both NMR and CD data establish a marked conformational bias for both the unsaturated and the saturated peptides synthesized herein.