Polyketide building blocks via diastereoselective nitrile oxide cycloadditions with homoallylic alcohols and monoprotected homoallylic diols.
A modular approach to Delta(2)-isoxazolines, latent aldol adducts and polyketide building blocks, is reported. The magnesium-mediated, hydroxyl-directed method allows for the diastereoselective access to a wide variety of masked beta-hydroxy ketones, starting from readily available aliphatic and aromatic oximes, homoallylic alcohols and monoprotected homoallylic diols. The utility of the prepared Delta(2)-isoxazolines as polyketide building blocks is demonstrated by their ready conversion into the corresponding beta-hydroxy ketones. The anti-diastereoselectivity of the reaction was established by derivatization, NOE studies and comparison of known compounds. A rationale for the observed diastereoselectivity is proposed.
Laboratorium für Organische Chemie, ETH Zürich, HCI H335, 8093 Zürich, Switzerland.
Nina
N
Lohse-Fraefel
Erick M
EM
Carreira
D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry*; D020005:Propanols / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D001688:Biological Products; D018942:Macrolides; D009570:Nitriles; D010087:Oxides; D020005:Propanols; C006463:allyl alcohol; D008274:Magnesium