Synthesis of [n,5]-spiroketals by ring enlargement of donor-acceptor-substituted cyclopropane derivatives.
Exocyclic enol ethers served as starting materials for the synthesis of [n,5]-spiroketals (n = 5, 6). A metal-mediated cyclopropanation using ethyl diazoacetate afforded spiroannelated cyclopropane derivatives bearing an ester group. A reduction of the corresponding ester by LiAlH(4), followed by subsequent oxidation using hypervalent iodine reagents, produced [n,5]-spiroketals in moderate to good yields. The key step within this three-step sequence is the ring enlargement of the three-membered ring with an oxygen donor and a carbonyl acceptor group into the five-membered enol ether system. Catalytic amounts of the Lewis acid Yb(OTf)(3) facilitate the ring enlargement and increase the yield of the corresponding spiroketal in many cases. When Yb(OTf)(3) was used, our experiments revealed an open transition state rather than a concerted mechanism because the stereochemistry of the spirocenter was not conserved during the ring enlargement. As a result, the thermodynamically more favored anomeric [n,5]-spiroketal was observed as the major product. All the structures were established unambiguously by NOESY experiments.
Institut für Organische und Biomolekulare Chemie der Georg-August-Universität Göttingen, Tammannstr. 2, 37077 Göttingen, Germany.
Christian
C
Brand
Gesche
G
Rauch
Michele
M
Zanoni
Birger
B
Dittrich
Daniel B
DB
Werz
D018360:Crystallography, X-Ray; D003500:Cyclization; D003521:Cyclopropanes / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D003521:Cyclopropanes; D013141:Spiro Compounds