ADDP and PS-PPh₃: an efficient Mitsunobu protocol for the preparation of pyridine ether PPAR agonists

• Paul S. Humphries,
• Quyen-Quyen T. Do and
• David M. Wilhite

Beilstein J. Org. Chem. 2006, 2, No. 21, doi:10.1186/1860-5397-2-21

• Paul S. Humphries Quyen-Quyen T. Do David M. Wilhite Pfizer Global R&D, Department of Medicinal Chemistry, 10614 Science Center Drive, San Diego, CA 92121, USA 10.1186/1860-5397-2-21 Abstract A series of pyridine ether PPAR agonists were synthesized through an ADDP and PS-PPh3 modified Mitsunobu

• (Figure 1). Aromatic ethers are structural motifs found in many naturally occurring molecules and compounds of medicinal interest.[13] We envisaged the pyridyl ether moiety of 1 to be efficiently formed via Mitsunobu coupling of the requisite pyridinol and alkyl alcohols.[14][15][16][17] Our first attempt

• at the Mitsunobu reaction between pyridinol 2 and alcohol 3, utilizing a modification of the conditions originally reported by Mitsunobu,[18] afforded pyridyl ether 4 in 54% yield (Scheme 1). Interestingly, the reaction did not reach completion and pyridinol 2 was recovered, despite the fact that it

Methods for the synthesis of polyhydroxylated piperidines by diastereoselective dihydroxylation: Exploitation in the two-directional synthesis of aza-C-linked disaccharide derivatives

• Andrew Kennedy,
• Adam Nelson and
• Alexis Perry

Beilstein J. Org. Chem. 2005, 1, No. 2, doi:10.1186/1860-5397-1-2

• and 18 were epimerised by Mitsunobu[43][44] inversion to yield the anti allylic alcohols 16 and 19. Diastereoselective dihydroxylation of a model system The diastereoselectivity of the dihydroxylation of the model compounds 15 and 17-19 was studied under both Upjohn[45] (cat. OsO4, NMO, acetone-water

• ] although the reducing agent still approaches the ketone from a pseudo-axial direction, the net stereochemical outcome is different (see Figure 6). The configuration of both alcohols in the bis-allylic alcohols trans-27 and cis-27 was cleanly inverted using a Mitsunobu reaction, and the resulting diesters