Catalytic Regioselective Isomerization of 2,2‐Disubstituted Oxetanes to Homoallylic Alcohols

Abstract

The selective isomerization of strained heterocyclic compounds is an important tool in organic synthesis.A n unprecedented regioselective isomerization of 2,2-disubstituted oxetanes into homoallylic alcohols is described. The use of tris(pentafluorophenyl)borane (B(C 6 F 5 ) 3 ) , ac ommercially available Lewis acid was key to obtaining good yields and selectivities since other Lewis acids afforded mixtures of isomers and substantial polymerization. The reaction took place under exceptionally mild reaction conditions and very low catalyst loading (0.5 mol %). DFT calculations disclose the mechanistic features of the isomerization and account for the high selectivity displayed by the B(C 6 F 5 ) 3 catalyst. The synthetic applicability of the new reaction is demonstrated by the preparation of g-chiral alcohols using iridium-catalyzed asymmetric hydrogenation. Dr.A .C abrØ,S.R afael, Prof. X. Verdaguer,P rof. A. Riera Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Regioselective Ring‐Opening of Oxetanes Catalyzed by Lewis Superacid Al(C6F5)3

“… Computed mechanism for the formation of homoallylic and allylic products (E=B, ref. [29]; E=Al, present work).…”

“…Computed mechanism for the formation of homoallylic and allylic products (E=B, ref. [29]; E=Al, present work). extended basis set (def2-TZVP) (see extended computational details in the Supporting Information).…”

“…In a previous study we analyzed, by means of DFT calculations, the mechanism of formation of the homoallylic and allylic products mediated by B(C 6 F 5 ) 3 (Scheme 6, Ar=Ph; E=B). [29] In the present work we have computed the mechanisms from oxetane 2 a, using B(C 6 F 5 ) 3 and Al(C 6 F 5 ) 3 (Scheme 6, Ar = p-MeOPh-, E=B or Al). Moreover, in addition to these two already known pathways, for both B(C 6 F 5 ) 3 and Al(C 6 F 5 ) 3 catalysts and 2 a substrate (Ar = p-MeOPhÀ ), we have investigated the mechanism for the formation of the dimer by-product 5 a, to disclose the origin of the selectivity and rationalize the reduced formation of this by-product with aluminum catalyst.…”

“…Given that we had already tested several LAs, [29] here we focused on Al‐based LAs (Table 1). The previous conditions, using B(C 6 F 5 ) 3 afforded a 67:12:21 ratio of products (entry 1, Table 1).…”

“…To expand the reactivity of this strained heterocycle, our group reported the regioselective ring‐opening of 2,2‐disubstituted oxetanes to homoallylic alcohols using the bulky Lewis superacid B(C 6 F 5 ) 3 (Scheme 1). [29] We found that this commercially available LA, could be employed to control the regioselectivity between the homoallylic and the ( E / Z )‐allylic products that were formed (Scheme 1). The regioselectivities to the homoallylic alcohol ranged from 88% to 99%.…”