Synthetic studies on thyrsiferol. Elaboration of the bromotetrahydropyran ring

• Published in: Journal of organic chemistry Vol. 53; no. 25; pp. 5876 - 5885
• Main Authors: Broka, Chris A, Lin, Yi Tsong
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.12.1988; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Stereoselectivity; Cyclization; Model compound; Six membered ring; Bicyclic compound; Bromine Organic compounds; Electrophilic reaction; Oxygen heterocycle; Triol
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo00260a016

A synthesis of the tricyclic bromo ether 2, a model for the left halves of thyrsiferol (1) and venustatriol, has been developed. This approach employs a series of three electrophilic cyclizations to deliver the target compound with good stereochemical control. The first of these, the mercuricyclization that stereoselectively furnishes the rightmost ring of 2, was found to be a thermodynamically controlled process. Construction of the chair-twist-boat pyranopyran moiety characteristic of these natural products also utilizes a mercuricyclization protocol. For the elaboration of the bromotetrahydropyran ring, a novel tactic was introduced that relies on the use of a trifluoroacetyl hemithioacetal (15), derived via a Pummerer rearrangement, as a surrogate for a strongly hydrated by poorly reactive aldehyde. For the final bromoetherification leading to 2, NBS was found to be the reagent of choice. A route to enantiomerically pure alcohol 24, the precursor necessary for construction of 1 itself, is also outlined.