title: Tandem catalysis in domino olefin cross-metathesis/intramolecular oxa-conjugate cyclization: concise synthesis of 2,6-cis-substituted tetrahydropyran derivatives.
abstract: Herein, we describe the concise synthesis of 2,6-cis-substituted tetrahydropyran derivatives based on a domino olefin cross-metathesis/intramolecular oxa-conjugate cyclization (CM/IOCC) reaction. We have found that the domino CM/IOCC of δ-hydroxy olefins with α,β-unsaturated carbonyl compounds (e.g., trans-crotonaldehyde or N-acryloyl-2,5-dimethylpyrrole) could be efficiently achieved in the presence of the second-generation Hoveyda-Grubbs catalyst under elevated temperature conditions, directly affording 2,6-cis-substituted tetrahydropyrans in excellent yields with synthetically useful diastereoselectivity ("auto-tandem catalysis"). In addition, we have found that the domino CM/IOCC of δ-hydroxy olefins with α,β-unsaturated carbonyl compounds could be achieved simply by performing CM in the presence of a Brønsted acid in CH(2)Cl(2) at 25-35 °C, which delivered 2,6-cis-substituted tetrahydropyrans in good yields with excellent diastereoselectivity ("orthogonal-tandem catalysis"). To understand the mechanism of auto-tandem catalysis in the domino CM/IOCC reaction, we have investigated the role of ruthenium hydride complexes in the IOCC of a ζ-hydroxy α,β-unsaturated ketone as a model case.
authors.affiliation: Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan. hfuwa@bios.tohoku.ac.jp
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fuwa
authors.forename: Takuma
authors.initials: T
authors.lastname: Noguchi
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Noto
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D015394:Molecular Structure; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D011714:Pyrans