Synthesis of 1,2-diaminoadamantane and chiral ligands derived from it

Synthesis of 1,2-Disubstituted Adamantane Derivatives by Construction of the Adamantane Framework

“…The adamantane skeleton is often used as a building block when steric bulk, lipophilicity, or rigidity is required [28]. Formally replacing one hydrogen atom at carbon 1 and one hydrogen atom at carbon 2 in the adamantane molecule with two substituents (the same or different) leads to the formation of compounds that are chiral [29]. To date, mostly 1,3-disubstituted achiral adamantane derivatives, utilized as rigid spacers, have been reported.…”

“…The final racemic product was resolved into individual enantiomers and used for the synthesis of various chiral ligands. The power of the approach is that all steps were carried out without the necessity of column chromatography purification as the crystalline products were easily precipitated/recrystallized [29]. The di-carboxylic acid 91 from adamantan-2-one (88) was also prepared through a Lewis acid-promoted Demjanov reaction with ethyl diazoacetate (96) and subsequent cleavage with alkaline hydrogen peroxide (Scheme 21) [71].…”

“…The final racemic product was resolved into individual enantiomers and used for the synthesis of various chiral ligands. The power of the approach is that all steps were carried out without the necessity of column chromatography purification as the crystalline products were easily precipitated/recrystallized [29]. Primary alcohol 101 (Scheme 22) was subjected to an acid-catalyzed sigmatropic rearrangement when refluxed in formic acid to form the adamantane derivative 102, which was further oxidized without purification using Jones reagent to ketone 103 in a 56% yield [72].…”