Siloxyallyl cations cycloaddition

Enolsilane derivatives provide siloxyallyl cations for [4+3] cycloaddition having a known and robust M. The stereospecific transfer of preformed enolsilane geometry to cycloadducts also enable the stereochemistry of cycloadducts to be controlled when the enolsilanes are prepared. These factors contribute to afford cleaner cycloadditions. 

Siloxyallyl cations are comparatively reactive and electrophilic, and their cycloadditions proceed under mild reaction conditions and at low temperatures, being sufficiently reactive to be trapped by dienes. These conditions can accommodate various preexisting functionalities in the substrate molecule and thus exhibit a good potential and compatibility to be adapted to building cycloheptane substructures in complex natural product syntheses. These advantages merit the arguable extra step to prepare the enolsilanes for [4+3] cycloaddition reactions. 

Both Hosomi and Shimizu subjected a-haloketones to deprotonation and silylation, whereupon a-halo enolsilanes were obtained [17] and then used in [4+3] cycloadditions (Scheme 18.8) [9,10,14]. Both methods then employed Lewis acids to generate a similar siloxyallyl cation dieno-phile that underwent cycloaddition with dienes in moderate to excellent yields. 

Hosomi used a-bromo enolsilane 4a as substrate, from which was generated the siloxyallyl cation 5 through debro-mination facilitated by ZnCl2 (Scheme 18.8) [9]. This species underwent cycloaddition with furan and cyclopentadiene to afford 6 and 8, respectively. The reactions proceeded at low temperatures and were complete in a short reaction time. 

Shimizu and Tsuno employed the less reactive chloro analogue 4b, which was converted to the siloxyallyl cation by the silver salt method [14] (Scheme 18.8), used previously in the dehalogenation of other allyl halides to generate allyl cations [18]. Excellent cycloaddition yields of 6 and 8 were obtained, again in a relatively short reaction time. 

Shimizu et al. also demonstrated that, although the [4+3] cycloaddition proceeded through the same 2-siloxyallyl cation as intermediate, the reaction mechanism and outcome could still be strongly influenced by solvent (Scheme 18.10). While the reactions performed in nitromethane were concerted, in the less polar solvent system of THF/ether, the reaction of (Z)-39 was more stepwise, class B/C-like, resulting in the formation of alkylated furan 43 as the major reaction product. The reaction of 44 in THF/ether yielded cycloadducts 46 and 47 in a ratio that did not correspond to the geometry of the enol ether, in addition to yielding alkylated furans 49 and 50 as the major products. 

More effective stabilization of the siloxyallyl cation was provided by a sulfur donor substituent and resulted in the generation of dienophUes, which could undergo [4+3] cycloadditions with pyrrole derivatives in high yields [19]. Enolsilane 56 in the presence of triflimide generated the corresponding sulfur-stabilized siloxyallyl cation 57, which reacted with A-nosyl pyrrole (R = = H) to afford cyclo-... 

Enolsilanes with additional alkyl substituents such as 63 and 66 are expected to form even more stabilized substituted siloxyallyl cations 64 and 67, but they underwent reaction with A -nosyl pyrrole affording diminished cycloaddition yields, presumably due to the steric hindrance imposed by the methyl groups (Scheme 18.13). 

Aungst and Funk reported studies on the related a-siloxy- 3-substituted acroleins such as 84 almost contemporaneously (Scheme 18.17) [23]. Siloxyacrolein 84 was prepared by a retro-hetero-Diels-Alder reaction of dioxin derivative 83. Compared with 79, compound 84 bears an additional carbon substituent that would further stabilize siloxyallyl cation 85 and favored its formation, with the result that even acyclic dienes like butadiene underwent [4+3] cycloaddition effectively. 

Hoffmann and coworkers optimized the chiral auxiliary to further improve the diastereomeric excess. Increasing the steric buUdness of R had no effect on the product yield nor the diastereoselectivity (Scheme 18.26), but a change of Ar from phenyl to naphthyl resulted in an amplification of the diastereoselectivity of the cycloaddition, an outcome that was assumed to be due to more effective shielding of one 7i-face of the siloxyallyl cation by the naphthyl than by the phenyl substiment [31]. 

Computational studies by Krenske et al., however, revealed a different explanation for this observed diastereo-selectivity [33]. Using the Lewis acid activated enolsilane 105 and furan as the model for calculations, it was found that the lowest energy pathway was a stepwise cycloaddition, where a W-form of the siloxyallyl cation reacted with the diene in the endo mode. The methoxy group of the siloxyallyl cation was coplanar and in conjugation with the allyl group. 

Vinylogous a-Siloxyacroleins Eguchi and coworkers reported the first eur(o-selective cycloaddition of furan and cyclopentadiene with siloxyallyl cation 156 generated from vinylogous siloxyacrolein 155 in the presence of a stoichiometric amount of SnCU as shown in Scheme 18.35 [38]. Significantly, this reaction provided functionalized cycloadducts 157-159. 

These results clearly implied that while the [4+3] cycloaddition of 174 was a stepwise, class B-type of reaction, it did not proceed through the intermediacy of the putative classical siloxyallyl cation 169 (R = Et) (Figure 18.5), which would necessitate racemic cycloadducts. The reactive species... 

The species undergoing [4-1-3] cycloaddition in the aziridinyl enolsilane reaction is not the typical siloxyallyl cation, but is probably similar to the intermediate in the analogous reaction of epoxy enolsilanes, because the cycloaddition of enantiomerically enriched aziridinyl enolsilane 217 in nitro-ethane afforded cycloadducts with largely retention of enantiomeric purity (Scheme 18.51). The same reaction mediated by TfOH in dichloromethane gave cycloadducts with higher... 

Cyclopropyl Enolsilanes Eguchi and coworkers reported a [4-f3] cycloaddition from enolsilane 232 bearing an activated cyclopropane (Scheme 18.52) [38]. Using a stoichiometric amount of TiCU in the presence of dienes, the cycloaddition proceeded in moderate yields to give directiy alkylated cycloadducts 234, 235 and 237, 238, which were presumed to form via the intermediacy of the siloxyallyl cation 233. The concomitant formation of alkylated product 236 showed that this was a Class B/C cycloaddition. To date, there have been no other reports of this type of cyclopropyl enolsilane undergoing [4- -3] cycloaddition. 

Colchicine is the principal alkaloid constituent of Colchi-cum autumnale, a compound capable of binding to tubulin and arresting mitosis. Cha and coworkers completed the asymmetric total synthesis of colchicine [45], in which the seven-membered ring was constructed by the diastereoselective cycloaddition of enolsilane 105 with a chiral and sterically congested 2,3-substituted fiiran 243 (Scheme 18.54), via the procedure of Murray and Albizati. This cycloaddition proceeded very successfully via an endo transition state C4 with the siloxyallyl cation approaching from the sterically less... 

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