Preparation of amino acids and amino acid derivatives

A process for synthesizing an amino acid or an amino acid derivative represented by the structure of Formula 1,

• comprising the steps of:
• (a) subjecting an olefinic substrate represented by the structure of Formula 2
• to a cross metathesis reaction with a cross metathesis substrate represented by the structure of formula
• in the presence of at least one metal carbene olefin metathesis catalyst, to form an unsaturated protected alcohol intermediate represented by the structure of Formula 2a
• (b) subjecting the unsaturated protected alcohol intermediate represented by the structure of Formula 2a to hydrolysis in basic conditions to yield an unsaturated alcohol represented by the structure of Formula 3
• and;
• (c) converting the unsaturated alcohol represented by the structure of Formula 3, to an amino acid or an amino acid derivative represented by the structure of Formula 1, by subjecting the unsaturated alcohol represented by the structure of Formula 3 to a tandem amination-reduction, wherein the tandem amination-reduction is carried out in the presence of a Ruthenium pincer complex represented by the structure of Formula 4:
• wherein:
• R is H, optionally substituted C1-C12 alkyl, optionally substituted C6-C10 aryl, optionally substituted heterocycle or optionally substituted C5-C10 cycloalkyl;
• R1 is —H, —CH3 or —COOR;
• R2 is —OR3;
• R3 is optionally substituted CO(C1-C12 alkyl), optionally substituted CO(C5-C10 cycloalkyl), optionally substituted CO(C6-C10 aryl), or optionally substituted CO(C5-C10 heterocycle);
• R4 is —H or —(CH2)m1OR3;
• R5 is —(CH2)m1OR3;
• a is 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22;
• m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19;
• m1 is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19;
• p is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19;
• L4 and L5 are each independently selected from the group consisting of phosphine (PRaRb), amine (NRaRb), imine, sulfide (SRd), thiol (SH), sulfoxide (S(═O)Rd), heteroaryl containing at least one heteroatom selected from nitrogen and sulfur;
• arsine (AsRaRb), stibine (SbRaRb) and an N-heterocyclic carbene represented by the structures:
• L6 is a mono-dentate two-electron donor selected from the group consisting of CO, PRaRbRc, NO+, AsRaRbRc, SbRaRbRc, SRaRb, nitrile (RdCN), isonitrile (RdNC), N2, PF3, CS, heteroaryl, tetrahydrothiophene and N-heterocyclic carbene;
• R6 and R7 are either each hydrogen or together with the carbons to which they are attached represent a phenyl ring which is fused to the quinolinyl moiety represented by the structure of Formula 4 so as to form an acridinyl moiety;
• Ra, Rb, Rc, Rd, R8, R9 and R10 are each independently alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl or alkylheteroaryl;
• Ya is a monoanionic ligand selected from the group consisting of halogen, OCORd, OCOCF3, OSO2Rd, OSO2CF3, CN, OH, ORd, NRd2;
• a neutral solvent molecule NH3, NR3 and Rd2NSO2Rd, and when Ya is neutral, the whole molecule carries a positive charge;
• Xa represents one, two, three, four, five, six or seven substituents positioned at any carbon atom on the acridinyl moiety, or in the case where R6 and R7 together with the carbons to which they are attached represent a phenyl ring which is fused to the quinolinyl moiety represented by the structure of Formula 4;
• or one, two, three, four or five substituents positioned on any carbon atom on the quinolinyl moiety, or in the case where R6 and R7 are each hydrogen, and is selected from the group consisting of hydrogen, alkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, alkylheteroaryl, halogen, nitro, amide, ester, cyano, alkoxy, alkylamino, arylamino, an inorganic support and a polymeric moiety;
• and with the proviso that the sum of any combination of m1 and p is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.