Mild Iridium‐Catalysed Isomerization of Epoxides. Computational Insights and Application to the Synthesis of β‐Alkyl Amines

Abstract

The isomerization of epoxides to aldehydes using the readily available Crabtree's reagent is described. The aldehydes were transformed into synthetically useful amines by a one-pot reductive amination using pyrrolidine as imine-formation catalyst. The reactions worked with low catalyst loadings in very mild conditions. The procedure is operationally simple and tolerates a wide range of functional groups. A DFT study of its mechanism is presented showing that the isomerization takes place via an iridium hydride mechanism with a low energy barrier, in agreement with the mild reaction conditions.

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

“…First, we tested Crabtreesc atalyst (1)a si tg ave satisfactory results when using N-sulfonyl aziridines [18] and epoxides. [19] However, we observed that, without any external activation, conversion was very low (entry 1) with the homoallylic alcohol 3a being the only product that could be quantified. Activation of the catalyst with H 2 to form an Ir-H,H complex as the catalytically active species led to polymerization (entry 2).…”

“…Then ovelty of the transformation led us to perform amechanistic study.Our previous studies of iridium-catalyzed isomerization of N-sulfonyl aziridines and epoxides ( Figure 2) disclosed at wo-step mechanism in which the initial ringopening step is followed by metal-assisted tautomerization. [18,19] Thes electivity of the process depends on the CÀH hydrogen involved in the tautomerization. However,t he metal-free nature of the oxetane isomerization raises new questions regarding the hydrogen migration step,i np articular, the identity of the agent assisting the Hm igration and how the homoallylic alcohol (3)/allylic alcohol (4)s electivity is defined.…”

“…[18] Similarly,t he conversion of epoxides into aldehydes was achieved by hydrogen activation of reagent 1. [19] Inspired by these selective transformations,w ew ondered if 2,2-disubstituted oxetanes would be selectively isomerized when using the appropriate catalyst. In contrast to the regioselective isomerization of epoxides [20] (also called Meinwald rearrangement) the regioselective isomerization of oxetanes still remains achallenge,and to the best of our knowledge,n os ynthetic protocols have been described to date.Most probably,the easy polymerization of 2-substituted oxetanes under acidic conditions has hampered their synthetic use.…”

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

“…With 2 a in hand, the isomerization reaction was performed using several catalysts at a 5 mol % loading at room temperature, as shown in Table . First, we tested Crabtree's catalyst ( 1 ) as it gave satisfactory results when using N ‐sulfonyl aziridines and epoxides . However, we observed that, without any external activation, conversion was very low (entry 1) with the homoallylic alcohol 3 a being the only product that could be quantified.…”

“…Particularly, we reported the selective iridium‐catalyzed isomerization of N ‐sulfonyl aziridines into allylic amines using Crabtree's catalyst ( 1 ) under very mild reaction conditions and without external activation . Similarly, the conversion of epoxides into aldehydes was achieved by hydrogen activation of reagent 1 . Inspired by these selective transformations, we wondered if 2,2‐disubstituted oxetanes would be selectively isomerized when using the appropriate catalyst.…”