Enol Ethers as Substrates for Efficient Z- and Enantioselective Ring-Opening/Cross-Metathesis Reactions Promoted by Stereogenic-at-Mo Complexes: Utility in Chemical Synthesis and Mechanistic Attributes

Abstract

The first examples of catalytic enantioselective ring-opening/cross-metathesis (EROCM) reactions that involve enol ethers are reported. Specifically, we demonstrate that catalytic EROCM of several oxa- and azabicycles, cyclobutenes and a cyclopropene with an alkyl- or aryl-substituted enol ether proceed readily in the presence of a stereogenic-at-Mo monopyrrolide-monoaryloxide. In some instances, as little as 0.15 mol % of the catalytically active alkylidene is sufficient to promote complete conversion within 10 minutes. The desired products are formed in up to 90% yield and >99:1 enantiomeric ratio (er) with the disubstituted enol ether generated in >90% Z selectivity. The enol ether of the enantiomerically enriched products can be easily differentiated from the terminal alkene through a number of functionalization procedures that lead to the formation of useful intermediates for chemical synthesis (e.g., efficient acid hydrolysis to afford the enantiomerically enriched carboxaldehyde). In certain cases, enantioselectivity is strongly dependent on enol ether concentration: larger equivalents of the cross partner leads to the formation of products of high enantiomeric purity (versus near racemic products with one equivalent). The length of reaction time can be critical to product enantiomeric purity; high enantioselectivity in reactions that proceed to >98% conversion in as brief a reaction time as 30 seconds can be nearly entirely eroded within 30 minutes. Mechanistic rationale that accounts for the above characteristics of the catalytic process is provided.

5.26 Cross Metathesis

“…Further comparison of the catalytic abilities of different catalysts was conducted in metathesis reactions of enol ethers presented in Scheme 61. 97 The only examined ruthenium complex (Hov-II) gave poor results despite acceptable conversions, which might be due to a competing oligomerization pathway in this case. This is further proven by an even lower yield in case of metathesis with a more sterically demanding substrate 208.…”

Stereoretentive Olefin Metathesis: An Avenue to Kinetic Selectivity

“…[84,85] Since, many breakthroughs in olefin metathesis have been made using molybdenum catalysts. Recent advancements have built on the catalytic structure of Z-selective systems [16][17][18][19][20][21][22] and have provided access to valuable products through stereoretentive olefin metathesis.…”

“…Catalysts 16 and 17 provided minimal desired product (Table 7, entries 1 and 2), showing preference for the cross metathesis of the terminal olefin. Catalyst 18, a well characterized Z-selective catalyst, [16,19,22] furnished the desired product in low yield but with high Z-selectivity (Table 7, entry 3). Further modification to the imido and aryloxy groups delivered catalysts (19)(20)(21), which performed the cross metathesis much more efficiently (Table 7, entries 4-6).…”

“…Catalyst 18, a well characterized Z-selective catalyst, [16,19,22] furnished the desired product in low yield but with high Z-selectivity (Table 7, entry 3). Further modification to the imido and aryloxy groups delivered catalysts (19)(20)(21), which performed the cross metathesis much more efficiently (Table 7, entries 4-6). It is believed that the mterphenyl-based aryloxy group provides the necessary steric demands for catalytic robustness, reactivity, and selectivity.…”

“…The first examples of kinetically Z-selective processes were reported by Schrock, Hoveyda, and coworkers, identifying both molybdenum-and tungsten-based systems to perform this transformation, which generated the desired Zolefins in high selectivity. [16][17][18][19][20][21][22][23][24][25][26] A large aryloxy-moiety shields one side of the catalyst, forcing the substituents on the generated metallacyclobutane to be all syn (Figure 1 (a)). Later, Grubbs and coworkers introduced a highly efficient, Z-selective olefin metathesis catalyst that utilized a cyclometalated rutheniumcarbene species.…”