Efficient Addition of Acid Enediolates to Epoxides

Abstract

We report new conditions to facilitate the addition of dianions of carboxylic acids to epoxides as an alternative method to the use of aluminum enolates. These conditions require the use of a sub-stoichiometric (10%) amount of amine for dianion generation and the previous activation of the epoxide with LiCl. Other Lewis acids have been shown to be less ef-

Unexplored Nucleophilic Ring Opening of Aziridines

“…In this case, sub-stoichiometric amount of the amide did not led to any improvement ( Table 1 , entry 6). The last two entries in Table 1 reproduce the best conditions that we obtained in the addition of dianions of carboxylic acids to epoxides [ 21 , 22 ] by using LiCl as a disaggregating agent in the enolate solution (entry 8) or as a Lewis acid activating the epoxide (entry 9) where the dianion solution was added (inverse addition) to a mixture of the electrophile with LiCl in THF.…”

Unusual Regioselectivity in the Opening of Epoxides by Carboxylic Acid Enediolates

“…LiCl play a double role: it can be acting as a disaggregating agent of the dienediolate and secondly as an activating agent in the opening of the epoxide througt its coordination to the oxygen atom. It is well known that different halides can be responsible to the stereoselectivity in enolate reactions [ 6 , 7 ], but in this case its influence in the diastereoselectivity is low.…”

“…Carboxylic acid (2.25 mmol) in THF (2 mL) was slowly added at -78 ºC to stirred lithium amide [for sub-stoichiometric conditions: cyclohexylisopropyl amine (0.45 mmol) and BuLi (4.5 mmol)] in THF (2 mL), according to the method already described. [ 6 ] The solution was stirred for 30 min at 0 ºC and cooled again to -78 ºC. The dianion mixture was added at -78 °C through the needle to a flask containing epoxide (2.25 mmol) and LiCl (94.4 mg, 2.25 mmol) in THF (2 mL) and then the solution was stirred for 16 hours at room temperature.…”

“…The use of a sub-stoichiometric amount of amine for the dianion generation permits minimization of other nucleophiles present in the reaction medium, thus avoiding the generation of amino alcohols. This, along with an activation of the epoxide with LiCl, allows obtaining good yields for the additions to primary and secondary epoxides [ 6 ]. For primary epoxides, γ-lactones are directly obtained, thus avoiding a further cyclization step.…”

The ring opening and oligomerisation reactions of an epoxide and an episulfide on aluminosilicates in the liquid phase

“…Their versatility lies in the fact that they can be easily prepared [3,4], they are stable under normal circumstances (room temperature, atmospheric pressure) yet the rings are reactive enough: they can be opened by acids [5] or bases [6] in catalytic reactions and by electrophiles (very rare) [7] or nucleophiles (significantly more abundant) [8] in stoichiometric transformations. The epoxide ring can be opened in the solid state and for this purpose various oxides [9], molecular sieves [10], clays [11], acidic membranes [11,12] and even metals in the homogeneous [13] or the heterogeneous phase (supported transition metals) [14] may be used.…”