Ferrocenoyl Amino Acids: A Synthetic and Structural Study.

A series of ester-protected amino acids were coupled to ferrocenecarboxylic acid (1) using the DCC/HOBt protocol to give ferrocenoyl N-amino acids (amino acid = Glu(OBz)(2) (2a), Gly(OEt) (2b), Pro(OBz) (2c), Cys(SBz)OMe (2d), Ala(OBz) (2e), Tyr(OBz) (2f), Phe(OBz) (2g)). All products were fully characterized. The intermediate hydroxybenzotriazole active ester FcCOOBt (3) was isolated and fully characterized. The solid state structures of 2a, 2d, and 3 were determined by single-crystal X-ray diffraction. 2a: monoclinic P2(1) with a = 11.8142(5) Å, b = 9.7560(5) Å, c = 22.9456(10) Å, beta = 90.246(5) degrees, V = 2644.7(2) Å(3), Z = 2, R = 0.046. 2d: orthorhombic P2(1)2(1)2(1) with a = 9.957(2) Å, b = 11.680(2) Å, c = 36.452(2) Å, V = 4239.5(13) Å(3), Z = 4, R = 0.065. The solid state structures of 2a and 2d show extensive C=O.H-N hydrogen bonding. 3: triclinic P&onemacr; with a = 7.0391(5) Å, b = 10.7922(7) Å, c = 11.1690(7) Å, alpha = 108.071(5) degrees, beta = 107.957(5) degrees, gamma = 103.896(5) degrees, V = 712.5(2) Å(3), Z = 2, R = 0.030. The long ester bond distance of 1.427(2) Å provides a rationale for its inherent reactivity toward primary and secondary amines.