Highly enantioselective access to cyclic beta-amino acids

A method of forming a compound of formula I:

• where:
• R1 and R2 each independently represent R6aOC(O)—, C1 to C10 alkyl, a carbocyclic ring system, and a heterocyclic ring system, where the C1 to C10 alkyl, carbocyclic ring system and heterocyclic ring system are unsubstituted or substituted by one or more substituents selected from the group consisting of halo, OR7a, aryl, Heta, and C1 to C6 alkyl, which C1 to C6 alkyl and aryl are unsubstituted or substituted by one or more halo groups;
• R3 represents C1 to C10 alkyl, C2 to C10 alkenyl, a carbocyclic ring system, and a heterocyclic ring system, where the C1 to C10 alkyl, C2 to C10 alkenyl, carbocyclic ring system and heterocyclic ring system are unsubstituted or substituted by one or more substituents selected from the group consisting of halo, OR7b, aryl, Hetb, and C1 to C6 alkyl, which C1 to C6 alkyl and aryl are unsubstituted or substituted by one or more halo groups;
• R4 represents a nitrogen protecting group;
• R5 represents H, R6bOC(O)—, C1 to C10 alkyl, a carbocyclic ring system, and a heterocyclic ring system, where the C1 to C10 alkyl, carbocyclic ring system and heterocyclic ring system are unsubstituted or substituted by one or more substituents selected from the group consisting of halo, OR7c, aryl, Hetc, and C1 to C6 alkyl, which C1 to C6 alkyl and aryl are unsubstituted or substituted by one or more halo groups;
• Heta to Hetc are each independently a 4- to 14-membered heterocyclic ring system that is unsubstituted or substituted with one or more substituents selected from halo and C1 to C6 alkyl, which is unsubstituted or substituted by one or more halo groups;
• R6a and R6b and R7a to R7c are each independently C1 to C10 alkyl that is unsubstituted or substituted by one or more halo groups;
• comprising the steps of reacting a compound of formula II:
• where R1, R2, R4 and R5 are as defined above, with a compound of formula III:
• where R3 is as defined above, in the presence of a solvent, a base comprising KH2PO4, and a catalyst of formula IV:
• where:
• the * represents a chiral centre;
• R8 is a protecting group for OH;
• and
• R9 and R9′ each independently represent an aryl group that is unsubstituted or substituted by one or more groups selected from halo, C1 to C6 alkyl, phenyl, and naphthyl, where the C1 to C6 alkyl, phenyl and naphthyl are unsubstituted or substituted by one or more halo groups, optionally wherein R9 and R9′ are identical.