Asymmetric Diels–Alder Cycloaddition of 1‐Aminocyclohexadiene to Chiral Acrylate: Synthesis of Enantiopure Bridgehead‐Aminobicyclo[2.2.2]octane‐2‐carboxylic Acid Derivatives

Abstract

The acrylate derivative of the (R)-4-(3-hydroxy-4,4-dimethyl-2-oxopyrrolidin-1-yl)benzoic acid benzyl ester (R)-2 reacted with 1-(benzyloxycarbonylamino)cyclohexadiene 3 under microwave irradation in solvent-free conditions to yield [4+2] cycloadducts in good yields (91 %). The reaction proceeded with moderate endo selectivity (67 %) and good facial selectivity (90 %). The major cycloadducts were isolated and transformed to afford three enantiopure bicyclic β-amino acids: (1S,2R,4R)-1-(benzyloxycarbonylamino)bicyclo[2.2.2]oct-

New 1,3-amino alcohols derived from enantiopure bridgehead β-aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acids

“…Solvents were dried and purified by conventional methods prior to use. The enantiopure compounds (1S,2R,4R)-5, (1R,2R,4S)-6 and (2R)-7 were prepared as previously described (Songis et al 2007(Songis et al , 2008a.…”

“…2), resulting from an endo and an exo selectivity on the same Ca Si face of the chiral dienophile (R)-1 respectively, were isolated in pure form after column chromatography on silica gel. Stereochemistry of the endo adduct 3, that crystallized from diethyl ether/petroleum ether, has been confirmed unambigously by X-ray diffraction analysis (Songis et al 2007). …”

“…This prompted us to synthesize new constrained 1,3-amino alcohols from some enantiopure bicyclic b-amino acids recently developed in our group (Songis et al 2007(Songis et al , 2008a. These bicyclic b-amino acids were obtained by using the asymmetric Diels-Alder cycloaddition between the chiral acrylate (R)-1 (Akkari et al 2004;Calmès et al 2005) and the 1-(benzyloxycarbonylamino)cyclohexadiene 2 (Fig.…”

12/10‐Helix in Mixed β‐Peptides Alternating Bicyclic and Acyclic β‐Amino Acids: Probing the Relationship between Bicyclic Side Chain and Helix Stability

“…Over the last few years, we investigated the ability of peptide sequences incorporating the ( S )‐1‐aminobicyclo[2.2.2]octane‐2‐carboxylic acid [( S )‐ABOC] residue, a constrained β 2, 3, 3 ‐trisubstituted bicyclic amino acid, to adopt well‐defined structures. We previously showed the high propensity of the ABOC residue to drive helical architectures in both oligoureas and hybrid‐oligoamides in alternation with α‐amino acids –.…”

Enantiomeric Separation of Bicyclo[2.2.2]octane‐Based 2‐Amino‐3‐Carboxylic Acids on Macrocyclic Glycopeptide Chiral Stationary Phases

“…22 Conformationally constrained bicyclo[2.2.2]octane β-amino acids are also of great interest, owing to their role in both synthetic and medicinal chemistry. [23][24][25][26][27][28] These compounds simultaneously combine the particular structural properties of constrained cyclic amino acids and those of β-amino acids that are more resistant than α-amino acids to enzymatic degradations. The interest in bicyclic amino acids is highlighted by publications on several investigations in recent years.…”