Abstract
The cross-metathesis (CM) of methallyl halides catalyzed using four different ruthenium-based complexes—Grubbs catalyst, Grubbs second-generation catalyst, Hoveyda-Grubbs second-generation catalyst, and Stewart–Grubbs catalyst—was investigated. When methallyl chloride or bromide was reacted with a model substrate containing a benzyl ether group, the Grubbs catalyst, and Grubbs second-generation catalyst did not promote the reaction well. However, the Hoveyda–Grubbs second-generation catalyst and Stewart–Grubbs catalyst afforded the corresponding products in moderate to good yield with moderate E/Z selectivity. Accordingly, several functionalized methallyl halides were prepared by CM. Various functional groups were well-tolerated in this system when the Stewart–Grubbs catalyst was used. To demonstrate the practical utility of our method, methallyl halide CM was successfully employed for the formal total synthesis of a natural product (–)-presphaerene, in which the precursor of the key cyclopentanecarboxylate intermediate was efficiently prepared in three steps.
Highlights
Methallyl halide moieties are typically introduced by conversion of a preexisting aldehyde via olefination–reduction–halogenation (Phoenix et al, 2008; Tanabe et al, 2014; Kauhl et al, 2016) or Grignard addition–halogenation sequences (Davies et al, 2010; Ghosh and Li, 2011), especially in natural product synthesis
The CM of methallyl halides could serve as a synthetic shortcut, substituting a single step for the numerous functional-group transformations required for the corresponding conventional sequences, this reaction has not been hitherto successfully applied to natural product synthesis
In contrast to the CM of methallyl chloride, Cross-Metathesis of Methallyl Halides TABLE 1 | Cross-metathesis (CM) of methallyl halides with olefin 2a
Summary
Methallyl halide moieties are typically introduced by conversion of a preexisting aldehyde via olefination–reduction–halogenation (Phoenix et al, 2008; Tanabe et al, 2014; Kauhl et al, 2016) or Grignard addition–halogenation sequences (Davies et al, 2010; Ghosh and Li, 2011), especially in natural product synthesis. The CM of methallyl halides could serve as a synthetic shortcut, substituting a single step for the numerous functional-group transformations required for the corresponding conventional sequences, this reaction has not been hitherto successfully applied to natural product synthesis. An attempt to introduce a methallyl chloride moiety into a complex olefin for the total syntheses of the natural products stephacidins A and B and notoamide B using rutheniumbased catalysts I and II did not afford the corresponding product (Artman III et al, 2007). We investigated the ruthenium-complexcatalyzed CM of methallyl halides with several functionalized olefins and its application to the formal total synthesis of a sphaeroane diterpene, (–)-presphaerene (1) (Figure 2) (Cafieri et al, 1983)
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