Aryl ether formation by reaction of phenoxide nucleophiles with chloroarene-Mn(C0)3 cationic complexes, followed by reaction of the aryloxyarene-Mn(C0)3 complex with chiral glycine enolate equivalents, provides methodology for the synthesis of protected ristomycinic acid derivatives in a state of high optical purity.
Ristocetin A (l), a member of the group of glycopeptide antibiotics related to vancomycin (2),l presents a considerable challenge for the synthetic organic chemist, not least because the aryl ether linkages characteristic of this molecule must be constructed in the presence of arylglycine derivatives.
Such compounds are prone to racemization under mildly basic conditions,2 so that the usual methods for aryl ether construction, such as the Ullman coupling procedure,3 may not be used, although this method has been applied to the preparation of aryl ethers of the isodityrosine type. 4 Evans et al.5 and Suzuki et al.6 have developed elegant approaches to the vancomycin skeleton based on a thallium (III)-promoted intramolecular oxidative coupling procedure to furnish the requisite aryl ethers. Our own work in this area aims at using a transition metal moiety to activate arenes toward nucleophilic addition, allowing the use of very mild reaction conditions to effect the construction of aryl ethers from arylglycine derivatives. 7 The present paper describes our expansion of these studies to the preparation of an F/G diary1 ether subunit for ristocetin A, which corresponds to a protected form of ristomycinic acid (3).
We anticipate that such building blocks will ultimately find application in a projected total synthesis of ristocetin A. Cl OR Cl (1) RISTOCETIN A (R. R' and I?" E sugar units) (2) VANCOHYCIN (R' -sugar unit)
$ Dedicated to Professor Charles Rees on the occasion of his retirement.