Cu(II)-Mediated One-Pot Alkoxide Conjugate Addition/Radical Cyclizations as a Versatile Method to Highly Functionalized Tetrahydrofuran Derivatives

Abstract

The synthesis of highly functionalized 3-nitrotetrahydrofurans starting from allylic alcohols and nitroalkenes through an efficient CuCl 2 -mediated tandem anionic/radical process is reported. The one-pot reaction consists of oxa-Michael addition/SET/radical 5-exo-cyclization-ligand transfer. Functionalization of the THF ring is facile and provides diverse substituted derivatives.

Synthesis of 3,4‐Fused Bicyclic β‐Lactams and Their Transformation into Methyl cis‐3‐Aminotetrahydrofuran‐2‐carboxylates

“…Due to the high stereoselectivity in the Staudinger synthesis of cis ‐β‐lactams 4 and transfer of this relative configuration through the reaction sequence, cis ‐3‐aminotetrahydrofuran‐2‐carboxylates 7 were deduced as the final reaction products. Moreover, the experimental coupling constants between the protons at C‐2 and C‐3 in tetrahydrofurans 7 (6.2–8.3 Hz, CDCl 3 ) are in accordance with coupling constants of similar compounds described in the literature 36,37. Nonetheless, coupling constants of 4.6–4.8 Hz between the protons at C‐2 and C‐3 have also been reported for cis ‐3‐azidotetrahydrofuran‐2‐carboxylates, making a conclusive stereochemical assignment solely based on coupling constants precarious 38…”

ChemInform Abstract: Synthesis of 3,4‐Fused Bicyclic β‐Lactams and Their Transformation into Methyl cis‐3‐Aminotetrahydrofuran‐2‐carboxylates.

“…Thus, the synthesis of the desired 3-aminotetrahydrofuran-2-carboxylates 7a-e was accomplished through ring opening of bicyclic cis-βlactams 6a-e by means of HCl in methanol. [36,37] Nonetheless, coupling constants of 4.6- 4.8 Hz between the protons at C-2 and C-3 have also been reported for cis-3-azidotetrahydrofuran-2-carboxylates, making a conclusive stereochemical assignment solely based on coupling constants precarious. Treatment of β-lactam 6d with 4 or 8 equiv.…”

“…Moreover, the experimental coupling constants between the protons at C-2 and C-3 in tetrahydrofurans 7 (6.2-8.3 Hz, CDCl 3 ) are in accordance with coupling constants of similar compounds described in the literature. [36,37] Nonetheless, coupling constants of 4.6- 4.8 Hz between the protons at C-2 and C-3 have also been reported for cis-3-azidotetrahydrofuran-2-carboxylates, making a conclusive stereochemical assignment solely based on coupling constants precarious. [38] Subsequently, NOESY experiments were performed on 3-aminotetrahydrofuran-2-carboxylates 7.…”

Nitroalkenes as Amination Tools

“…The oxy -Michael products 40 obtained through reactions between nitroalkenes and allylic alcohols can be cyclized to the corresponding tetrahydrofuran derivatives in the presence of CuCl 2 (Scheme 3.21 ) [46] . The ring -closure occurs with modest diastereoselectivity by a mechanism in which the radical generated α to the nitro group attacks the unsaturated system and the formed resulting exocyclic radical is trapped by CuCl 2 .…”