Rearrangement Reactions of Lithiated Oxiranes

Abstract

The first computational study of the rearrangement reactions of oxiranes initiated by lithium dialkylamides is presented. Aside from the well-known carbenoid insertion pathways, both β-elimination and α-lithiation have been suggested as the exclusive mechanism by which oxiranes react in the presence of organolithium bases. The products of the former are allyl alcohols (and, in some cases, dienes) and are ketones in the case of the latter. The computational studies reported in this work indicate that both mechanisms could be simultaneously operational. In particular, our work shows that the allyl alcohols from β-elimination are unlikely to undergo 1,3-hydrogen transfer to the vinyl alcohols and thus to the ketones, suggesting that ketones are formed through the opening of the oxirane ring after α-substitution. Elimination of LiOH from the lithiated allyl alcohol is found to result in the diene product. Low activation barriers for β-elimination are offered as the explanation for the few special cases where the allyl alcohol is the dominant or exclusive product. These findings are consistent with the product distributions observed in several experiments.

C–H and C–O bond activation with a rhodium(i) β-diiminate complex

“…In this context, it should be noted that ring-lithiated oxiranes are known to rearrange to enolates. 24,25 This reaction has been studied computationally 26,27 and has a relatively high activation energy (≈ 30 kcal mol −1 ). In view of the much lower oxophilicity of Rh compared to Li, it is perhaps not surprising that oxiranylrhodium species would not readily rearrange to enolates.…”

Correction to Rearrangement Reactions of Lithiated Oxiranes

“…The last statement of the first paragraph of the Introduction of ref states that the reaction of 1,2-epoxy-5-hexene with lithium 2,2,6,6-tetramethylpiperidide (LTMP) leads to the aldehyde, presumably by the keto–enol isomerization of the vinyl alcohol. However, in 2004, Hodgson et al reported that terminal epoxides in the presence of hindered lithium amides like LTMP formed the enamine almost exclusively by trapping of the lithiated epoxide by the lithium amide .…”

“…In contrast to the ring-opening considered in Scheme 2 of ref , which was at the β-carbon with respect to the deprotonated center, the α-ring-opening mechanism is also known. This latter pathway involves the formation of carbenes or carbenoids, leading to vinyl alcohols (and ketones) directly in certain cases , and allyl alcohols if the α-deprotonation is followed or accompanied by a 1,2 H-transfer .…”

“…This latter pathway involves the formation of carbenes or carbenoids, leading to vinyl alcohols (and ketones) directly in certain cases , and allyl alcohols if the α-deprotonation is followed or accompanied by a 1,2 H-transfer . Because our focus in ref was on noncarbenoid rearrangements, we did not consider these reactions in our computations. At the same time, we regret that our Introduction failed to mention these possibilities and, therefore, conveyed an incomplete picture of the richness of oxirane rearrangement chemistry.…”