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. An unprecedented regioselective isomerization of 2,2‐disubstituted oxetanes into homoallylic alcohols is described. The use of tris(pentafluorophenyl)borane (B(C6F5)3), a commercially 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(C6F5)3 catalyst. The synthetic applicability of the new reaction is demonstrated by the preparation of γ‐chiral alcohols using iridium‐catalyzed asymmetric hydrogenation.

Access to α,α-difluoro(arylthio)methyl oxetanes from α,α-difluoro(arylthio)methyl ketones and trimethylsulfoxonium halides: scope, mechanism and applications

“…In pathway I , the oxetane ring of 3a opened first under acidic conditions to afford alcohol intermediate 3-C . 13 The subsequent hydrolysis of the fluoride in intermediate 3-C provided intermediate thioester 3-D . 14 In pathway II , the hydrolysis of the fluoride of 3a occurred first to deliver intermediate 3-E .…”

Computational Organometallic Catalysis: Where We Are, Where We Are Going

“…This allows the definition of a system of differential equations, which can be solved numerically by using the initial concentrations of all the compounds as starting conditions [43,44] . The outcome of the microkinetic modeling is the evolution of the concentration of each species with time (Figure 4), [45] which is precisely what most experiments measure. The computational cost of this procedure, which can also be used as additional testing of a proposed reaction mechanism, is very low.…”

“…Figure 4. Microkinetic modeling of the isomerization of 2-phenyl-2-methyloxetane 2 a to allylic alcohol catalyzed by BF 3 • Et 2 O [45]. II: zwitterionic intermediate; 3 a: homoallylic alcohol product; 4 a: E/Z-allylic alcohol products.…”

Enantioselective Ir-Catalyzed Hydrogenation of Terminal Homoallyl Sulfones: Total Synthesis of (−)-Curcumene

“…16 With the aim to expand the substrate scope to terminal olefins, the group developed a new methodology to synthesize homoallylic alcohols through a highly selective Lewis acid catalyzed isomerization of 2,2-oxetanes (Scheme 1). 17 Although the reaction was highly diastereoselective, some homoallylic alcohols were difficult to purify from their corresponding E/Z-allylic isomer, whose presence resulted in a substantial decrease of the enantioselectivity of the hydrogenated products. To overcome this, we envisioned a new strategy on the basis of the replacement of the OH group by a sulfonyl group, as this approach might increase the enantioselectivity, ease the separation of the regioisomers, and facilitate a wide range of reactivity.…”