Synthesis of diketopiperazines

A method of preparing a compound of formula I:

• comprising reacting an acid catalyst with a compound of formula II in such a manner so as to produce the compound of formula I with an enantiomeric excess greater than about 50%:
• wherein:
• R1, R2, and R3 are separately selected from the group consisting of hydrogen;
• halogen;
• mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
• C1-C24 alkyl, C2-C24 alkenyl, C2-C24 alkynyl, alkoxy, acyl, arylalkyl, heteroarylalkyl, alkyloxycarbonyloxy, ester, arylalkoxy, and alkylthio;
• and mono-substituted, poly-substituted or unsubstituted variants of the following residues:
• acyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, cycloalkoxy, aryl, heteroaryl, heterocycloalkyl, carbonyl, carbonylacyl, amino, aminocarbonyl, amide, aminocarbonyloxy, nitro, azido, phenyl, hydroxyl, arylthio, oxysulfonyl, carboxy, and cyano;
• R4 and R5 are separately selected from the group consisting of hydrogen;
• mono -substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
• C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-6 heteroalkyl, C2-6 aminoalkyl, C2-6 haloalkyl, C1-6 alkoxycarbonyl, aryl-C1-6-alkyl, and C2-6 hydroxyalkyl;
• and mono-substituted, poly-substituted and unsubstituted variants of the following residues:
• C3-8 cycloalkyl, —C(O)—C5-6 aryl substituted with C1-3 alkyl or halo, C5-6 aryl, C5-6 heteroaryl, C5-6 cycloalkyl, and C5-6 heterocycloalkyl;
• any bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond;
• and
• any carbon-carbon double bond has a configuration selected from the group consisting of cis and trans.