Synthesis of enantiopure trans‐N‐Boc‐3‐aminobicyclo[2.2.2]octane‐2‐carboxylic acids and their bicyclic 1,3‐amino alcohol derivatives via the [4+2] cycloaddition of 1,3‐cyclohexadiene to a chiral β‐nitroacrylate

Abstract

The chiral β-nitroacrylate 2 derived from the (R)- or (S)-4-(3-hydroxy-4,4-dimethyl-2-oxopyrrolidin-1-yl) benzoic acid 1 acts as a reactive dienophile in a diastereoselective Diels-Alder reaction with 1,3-cyclohexadiene. The major cycloadducts have been isolated and transformed into enantiopure trans(2S,3S)- or (2R,3R)-N-Boc-3-aminobicyclic[2,2,2]octane-2-carboxylic acids 5. The trans-(2S,3S)- or (2R,3R)-N-Boc 3-(hydoxymethyl)-2-aminobicyclic[2,2,2]octane 6 derivatives were also obtained.

Synthesis and Transformations of di-endo-3-Aminobicyclo-[2.2.2]oct-5-ene-2-carboxylic Acid Derivatives

“…cis - and trans -3-Aminobicyclo[2.2.2]octane-2-carboxylic acid were prepared some years ago [ 20 , 21 , 22 ], but their partially saturated analogs and further functionalized derivatives have not yet been described. Our work was focused on the syntheses of di -endo -3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acid and its hydroxyl-substituted derivatives by stereoselective and regioselective functionalization of the double bond via 1,3-oxazine or γ-lactone intermediates.…”

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

“…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 …”

“…The interest in bicyclic amino acids is highlighted by publications on several investigations in recent years. [29][30][31] The wide-ranging utility of these compounds has led to increased interest in their enantioselective syntheses, which demand analytical methods for checking the enantiopurity of these chemical products. The direct and indirect chiral high-performance liquid chromatography (HPLC) are well-known, frequently used, and reliable applied techniques in the enantioseparation of different analytes.…”

Syntheses of Four Enantiomers of 2,3-Diendo- and 3-Endo-aminobicyclo[2.2.2]oct-5-ene-2-exo-carboxylic Acid and Their Saturated Analogues

“…While a range of stereoselective syntheses of enantiomerically enriched small (three- or four-membered: [11,12,13] and medium (five- to eight-membered) cyclic [14,15,16,17] and sterically hindered bicyclic norbornane and norbornene β-amino acids [18,19] or their derivatives have been reported, relatively few examples cocerning the synthesis and applications of enantiomerically enriched bicyclo[2.2.2]octane β-amino acid derivatives have been described [20,21,22,23,24].…”