Powerful Kinetic Diastereoselection in Ruthenium-Catalysed Ring-Closing Metathesis of (Homoallyl)vinylcyclopropanes

Abstract

Homoallyl‐substituted vinyl cyclopropanes 1a‐c, which are readily prepared by reaction of allylindium reagents with α,β‐unsaturated ketones and aldehydes, undergo Ru‐catalysed RCM reactions with Grubbs catalyst to give [4.1.0]bicyclooct‐2‐ene (norcarene) type bicyclic products. Noncyclisable ‘trans’ homoallyl‐substituted vinyl cyclopropanes 1b and 1c are separated from their ‘cis’ diastereomers by RCM to 5b and 5c ‐ but only with moderate efficiency due to a competing homo‐cross metathesis (‘dimerisation’) to give 7b and 7c, respectively. However, the four diastereomers of the (homoallyl)distyrylcyclopropane 14a obtained from indium‐mediated reaction of dibenzylideneacetone and crotyl bromide undergo remarkable kinetic diastereoselection in their RCM reactions to give a 4,7‐dimethyl[4.1.0]bicyclohept‐2‐ene‐type product 15a. This process allows recovery of a single diastereomer (> 95%) of 14a without dimerisation being a significant side reaction. Furthermore, the RCM product 15a is obtained rich in one diastereomer (ca. 90%). The kinetic diastereoselection and lack of dimerisation can be rationalised by considering developing transannular interactions and a pseudo‐A1,3 strain model.

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

“…Other examples for diastereoselective RCM by differentiation of diastereotopic vinyl moieties include the formation of carbacycles and have been reported by LloydJones et al [69] and by Shishido et al [70]. Although the RCM-step does not establish a heterocyclic fragment in these cases, we will briefly discuss the work by Shishido et al as they have demonstrated the utility of carbacycles obtained via diastereoselective RCM in the synthesis of indole alkaloids.…”

Equilibrium Ring-Closing Metathesis

“…Dimerization can be viewed as an arrested oligomerization reaction: where catalyst reactivity is insuf- ficient to effect metathesis at the deactivated site, acyclic head-to-head dimers are formed. 133,138,140,[144][145][146][147][148][149][150][151][152] Establishment of equilibrium will depend on whether the catalyst is competent to reinitiate metathesis at the internal olefinic site.…”

“…This strategy has been widely used to induce RCM of acyclic head-to-head dimers formed from unsymmetrically deactivated dienes (section 3.1.4). 133,138,140,[144][145][146][147][148][149][150][151][152] Low catalyst activity inhibits metathesis at the internal, 1,2-disubstituted olefinic site. Hoveyda and co-workers reported that dimer 76 (Figure 30) could not be induced to undergo backbiting with Ru-5, for example.…”

“…Unsymmetrically deactivated α,ω-dienes, in which one olefin is sterically hindered − or conjugated with an electron-withdrawing substituent, − typically undergo preferential dimerization at the other, unperturbed, olefinic site (Figure ). Dimerization can be viewed as an arrested oligomerization reaction: where catalyst reactivity is insufficient to effect metathesis at the deactivated site, acyclic head-to-head dimers are formed. ,,,− Establishment of equilibrium will depend on whether the catalyst is competent to reinitiate metathesis at the internal olefinic site. The low reactivity of Ru-1 toward internal olefins limits its efficacy in RCM of this class of dienes. − , A number of studies have shown conversion of such ADMET dimers into the desired RCM products by treatment with a more reactive catalyst. − Selected examples of this behavior are described in section .…”

“…Oligomeric species formed during RCM have typically been characterized following chromatographic isolation, usually by mass spectrometry (MS), where the molecular ion is observable. Ionization methods range from conventional electron impact ,− ,− (including GC-MS) ,, and FAB ,,− methodsthese limiting observation to suitably volatile species, often cyclic dimers or trimers of complex precursorsto electrospray ionization ,,, (sometimes in conjunction with HPLC separation) ,, and MALDI ,, (matrix-assisted laser desorption−ionization), for less volatile materials. GPC (SEC) characterization of reaction products can give insight into the degree of oligomerization, where appropriate columns are employed. ,, Viscometry measurements, utilized in early ROMP studies (section 2.1) are also of interest in this context, but we are aware of no study exploring their utility in RCM.…”