Protected amino acid chlorides vs protected amino acid fluorides: Reactivity comparisons.

Although Fmoc amino acid fluorides are excellent reagents for coupling of moderately hindered amino acids (e.g., Aib-to-Aib) they are not suited for significantly more hindered systems (e.g., Aib-to-MeAib). While urethane-protected acid chlorides are inherently more reactive than the fluorides they are also ineffective for hindered systems due to competing oxazolone formation. This limitation is by-passed if urethane protection is replaced by arenesulfonyl protection and the Aib-to-MeAib and even the MeAib-to-MeAib couplings are easily achieved via the appropriate acid chlorides but not the acid fluorides. (C) 1997 Elsevier Science Ltd. All rights reserved.