Diastereoselective Isomerization of (E)‐β‐Nitroenones into β‐Nitro‐β,γ‐Unsaturated Ketones under Microwave Conditions

Abstract

We report herein an unprecedented conversion of β-nitroenones into β-nitro-β,γ-unsaturated ketones. The reaction proceeds under microwave irradiation, furnishing products in good yields and excellent diastereoselectivity. The mechanism of the reaction has been rationalized by means of DFT modelling, which showed that sequential enolization/isomerization steps allowed to break the conjugation of the reagent. The E isomer is preferentially formed thanks to the solvent, which acts catalytically and dictates the regiochemical outcome. Moreover, the obtained β-nitro-β,γ-unsaturated ketones have been efficiently converted into 1,2,5trisubstituted pyrroles by a one-pot approach.

Visible‐Light‐Driven Competitive Stereo‐ and Regioisomerization of (E)‐β‐Nitroenones

“…In striking contrast to the thermal deconjugation of 1 a , [9] present photochemical approach allows to form both (Z) isomer 1 b and ( E/Z )‐ 1 c (Figure 1). This is due to the inherent easiness of the intramolecular 1,5‐HAT involved in this case.…”

“…Nitroalkenes are a class of versatile building blocks in organic synthesis [1] due to both the markedly electron‐deficient character of olefin moiety (that act as an efficient Michael acceptors [2] as well as coupling partner in cycloadditions [3] ) and the versatility of the nitro functional group, that can be smoothly converted into a wide range of functionalities including amines and hydroxylamines, [4] nitrile oxides [5] and carbonyls derivatives such as imines [6] . Among compounds bearing a nitroalkene moiety, β‐nitroenones ( I , Scheme 1) have received only few attention in literature, being employed rarely in conjugate addition reactions, [7] as precursors of furans and pyrroles under reductive heterogeneous conditions [8] and in the preparation of β‐Nitro‐β,γ‐enones III [9] . In the latter case, a microwave intramolecular 1,5‐sigmatropic rearrangement and subsequent formation of enol II from the starting β‐nitroenones was suggested to play a key role in the process [9] …”

“…Among compounds bearing a nitroalkene moiety, β‐nitroenones ( I , Scheme 1) have received only few attention in literature, being employed rarely in conjugate addition reactions, [7] as precursors of furans and pyrroles under reductive heterogeneous conditions [8] and in the preparation of β‐Nitro‐β,γ‐enones III [9] . In the latter case, a microwave intramolecular 1,5‐sigmatropic rearrangement and subsequent formation of enol II from the starting β‐nitroenones was suggested to play a key role in the process [9] …”

Diastereoselective Conversion of β‐Nitro‐β,γ‐Unsaturated Ketones into Conjugated (E,E)‐Dienones

“…In conclusion, we developed a new protocol for synthesizing conjugated dienones starting from easily accessible starting materials [6a] . These products were obtained in good yields (61–73%) and in a E , E stereoselectivity.…”

A New and Effective One‐Pot Synthesis of Polysubstituted Carbazoles Starting from β‐Nitro‐β,γ‐Unsaturated‐Ketones and Indoles

“…Stimulated by these structures, we have recently focused our attention on exploring the reactivity of β‐nitro‐β,γ‐unsaturated ketones 1 , and we found the latter to be precious precursors of the polysubstituted pyrroles 3 (Scheme 1). [7] The synthetic importance of 1 is due to the presence of two electrophilic centers in relative 1,4‐positions and the opportunity to aromatize the intermediate 2 by the elimination of HNO 2 and H 2 O. This peculiarity allows to use and consider 1 as useful source of 1,3‐diene synthons.…”