Copper-Catalyzed Skeletal Rearrangement of O-Propargylic Aryloximes into Four-Membered Cyclic Nitrones - Chirality Transfer and Mechanistic Insight

Abstract

Copper-catalyzed skeletal rearrangement of O-propargylic aryloximes (E)-1 were carried out to afford the corresponding four-membered cyclic nitrones 2 in good to excellent yields. The optimal reactions conditions of the highly regioselective reactions involved the use of [CuCl(cod)] 2 in acetonitrile at 70°C. In the case of (Z)-1, however, the reaction proceeded in the absence of the copper catalysts to afford the identical compound 2 in good yields. Furthermore, the reactions were also carried out using chiral substrates (R)-1 in the presence of Cu catalysts to afford (R)-2 with good levels of chirality transfer.

Facile Synthesis of Azetidine Nitrones and Diastereoselective Conversion into Densely Substituted Azetidines

“…Thep reparation of related exomethylene azetidine nitrones from N-allenylnitrone intermediates has been reported by Nakamura and co-workers.These compounds are prone to thermal isomerization reactions through C À Nb ond cleavage and rearrangement (Scheme 1B). [14,15] Our discovery of amodular method to access thermally stable azetidine nitrones with an embedded stereocenter to direct further functionalization prompted our investigation of the reactivity of these compounds (Scheme 1C). [16] Herein, we report the optimization and scope of the facile synthesis of azetidine nitrones 4 from oxime 1 and alkenylboronic acids 2 through N-alkenylnitrone 4p-electrocyclization, as well as functionalization of these compounds by diastereoselective cycloaddition, reduction, and alkylation to access novel highly substituted azetidines.…”

Divergent Functionalizations of Azetidines and Unsaturated Azetidines

“…Using a different approach to the cycloaddition reactions discussed above, Nakamura and coworkers have recently developed electrocyclizations of N ‐allenylnitrones 142 to access 3‐benzylidene azetidine nitrones 143 (Scheme A) . The electrocyclization precursors can be generated from O ‐propargylic oximes 141 via a copper‐catalyzed [2,3]‐sigmatropic rearrangement and spontaneously undergo a subsequent 4π‐electrocyclization under the reaction conditions .…”

“…A variety of 143 can be formed from 141 using this approach. Oximes with equivalent Ar 1 and Ar 2 substituents give single products such as 143 a – 143 d when treated with a CuBr catalyst in toluene at 100 °C . In contrast, oximes with different groups in these positions give a mixture of regioisomeric products such as 143 e : 143 e′ and 143 f : 143 f′ , when treated with a [CuCl(COD)] 2 catalyst in MeCN at 70 °C (Scheme A) .…”

“…An investigation into the origin of these regioisomeric mixtures determined that while E ‐143 e shows no change when heated in MeCN in the absence of a copper catalyst, minor product Z ‐143 e undergoes E / Z ‐isomerization and rearrangement to give regioisomeric E ‐143 e′ (Scheme B). This rearrangement is proposed to occur through zwitterionic intermediate 144 and the authors suggest that increased 1,2‐allylic strain release may facilitate this pathway for Z ‐143 e . Initial investigations into the reactivity of 3‐benzylidene azetidine nitrones 143 have focused on their use as precursors to pyridines via ring‐expansion processes .…”

Novel achievements with an old metal: copper-promoted synthesis of four-membered azacycles

“…The group of Terada has described the utility of (E)-Opropargyl arylaldoximes for the preparation of four-membered 55 cyclic nitrones. 54 In a preliminary communication 55 and subsequently in a full paper later, 56 Terada and co-workers reported the copper-catalyzed skeletal rearrangement of Opropargyl aryloximes 126 in the presence of Cu(I) in order to afford the corresponding products 127 and 128. The optimal reaction conditions of the highly regioselective reactions involve the use of [CuCl(cod)] 2 in MeCN at 70 ºC (Scheme 44).…”