Ring-Opening Metathesis/Oxy-Cope Rearrangement:  A New Strategy for the Synthesis of Bicyclic Medium Ring-Containing Compounds

Abstract

Ring-opening/ring-closing metathesis on cyclobutene-containing substrates with angular oxygen functionality provides a stereospecific introduction of 1,5-bis-dienes required for an anion-accelerated oxy-Cope rearrangement. The reaction sequence offers generally a stereocontrolled preparation of a variety of medium ring-containing bicyclic ring systems, while rearrangement to the bicyclo[7,3,0]dodecane (9-5) system leads to a mixture of olefin isomers.

A symmetry-driven approach to the putative spiroketal core of the didemnaketals

“…Considering carefully the transition state models for anionic oxy-Cope reactions developed by Snapper, 22 and supported by our previous work on a different system, 23 we recognized that for a prototypical hydroxydiene (30, Scheme 3), four possible transition states (30ae30d) could lead to a cyclononenone product. Each of these products would bear a different stereochemical signature of the transition state that led to its formation.…”

“…Literature precedent 21,22 indicated that the two transition states (30c and 30d) in which the oxygen atom was placed in a pseudoequatorial orientation should be favoured. Conveniently, these both lead to the same diastereomeric outcome at the two carbons b to the carbonyl function (i.e., the sterochemical labels R anti and R trans are syn in both expected products).…”

“…We therefore conceived of a different route to this key intermediate, passing this time through ester 20b (Scheme 5). 32,33 Beginning with racemic 4-methylcyclopentenone (40), 34 we performed a hydrosilation to selectively access enol silyl ether 41, which was then subjected to a zirconium-mediated [2þ2] reaction 22 to provide bicycle 42 as a single diastereomer. Once again, the olefinic partner for ring-opening/cross-metathesis reaction was tethered to the structure by means of the free alcohol, and Grubbs second generation catalyst was used to access the desired spirocycle (44).…”

A resourceful new strategy in organic synthesis: Tandem and stepwise metathesis/non-metathesis catalytic processes

“…A tandem ring-opening metathesis/ring-closing metathesis/oxy-Cope rearrangement, developed by White and Snapper, enables flexible access to building blocks and various polycyclic units useful in synthesis of natural compounds (Scheme 36) [83]. The strategy benefits from the recognized high activity and selectivity displayed in metathesis reactions by the second generation Grubbs and Hoveyda-Grubbs catalysts.…”

"Ring Closing Metathesis of Substrates Containing more than two C-Cdouble Bonds: Rapid Access to Functionalized Heterocycles"

“…This has for instance recently been exploited by White and Snapper for a synthetic approach to bicyclic medium sized ring systems: cyclobutene 150 (obtained in three steps via Lewis-acid mediated [2+2]-cycloaddition) rearranges cleanly in the presence of [Ru-IV] to 151, which undergoes -after desilylation and deprotonation of the tertiary alcohol -a Cope-rearrangement to the bicyclic product 152 (Scheme 44) [109].…”