Cross-cyclization, epoxides

Cross-Cyclization of Epoxides with Homoallylic Alcohols. 232... 

Cross-cyclization of epoxides with homoallylic amines is an easy way to access tetrahydropyran moieties, which form the core structure of many biologically important natural products such as avermectins, aplysiatoxin, oscillatoxins, latrunculins, talaromycins, acutiphycins, and apicularens. Even though many methods are available for the synthesis of this moiety [14—24], its importance and wide applicability demands further methods. 

Table 1 Cross-cyclization of epoxides with homoallylic alcohols...

Epoxides undergo cross-cyclization with homoallylic alcohols in the presence of zirconium tetrachloride under mild conditions to give the corresponding tetrahydropyran derivatives (Scheme 45).75... 

The synthesis of 2-benzyl-4-chloro-tetrahydropyran derivatives has been reported using Bids as a reagent in the cross-cyclization between epoxides and homoallylic alcohols (Equation 41) [84]. Since the rearrangement of epoxides is known to be catalyzed by bismuth(III) salts, it is possible that a similar mechanism operates in this reaction [74]. 

Once this process is explored with the model system to assess the level of enantioselectivity, we will then prepare alkyl zinc reagent 48 from 44 using standard methods - - and cross couple 48 to aryl bromide 18 using the appropriate chiral catalysts (Scheme 7). Although the acetonide stereocenter in 48 is somewhat remote from the coupling site, the stereocenter may serve to enhance the stereoselectivity of the cross-coupling process because the two possible products are diastereomers, not simply enantiomers. This reaction will produce 49 from (S)-48 and 30 from (R)-48 that can then be converted to epoxides 31 and 32 using standard methods. Epoxide 31 leads to heliannuol D 4 after base-promoted epoxide cyclization and deprotonation. Similarly, epoxide 32 leads to heliannuol A 1 after acid-promoted cyclization. 

---