Benzannulated cyclooctanol derivatives by ssamarium diiodide induced intramolecular carbonyl-alkene coupling-scope, limitations, stereoselectivity

Abstract

A series of γ-oxo esters 27-34 was prepared from methyl 2-silyloxycyclopropanecarboxylates 1-9 as key building blocks in a flexible modular synthesis. Their samarium diiodide promoted cyclization to benzannulated cyclooctanol derivatives was systematically investigated. Samarium ketyl compounds derived from aldehydes 27 and 28 mainly provided tricyclic γ-lactones 38 and 39 as a result of a cis-selective ring-closure process, whilst the related ketones 29-31 underwent trans-selective reductive cyclization to furnish the expected benzannulated cyclooctanol derivatives 43-45 in moderate to excellent yields. With cyclohexanones 33 and 34 an interesting stereochemical matched/mismatched situation was observed. Whereas diastereomers 33a and 34a smoothly afforded tricyclic products 47 and 48 in good yields, compound 33b with apparently mismatched configuration did not undergo the samarium diiodide promoted ring-closure process. An explanation for this intriguing behaviour is presented, together with an explanation for the cis/trans selectivity. Tricyclic γ-lactone 38 could be smoothly deprotonated at one bridgehead and the generated lithium enolate was trapped with suitable alkyl halides. Remarkably, a clean α-hydroxylation of 38 and 39 by direct employment of molecular oxygen was possible, providing high yields of the corresponding tertiary alcohols 54 and 55. These results demonstrate that the cyclization products prepared can easily be converted into higher functionalized benzannulated cyclooctane derivatives.