Lewis Acid‐Catalyzed [3+2] Cycloaddition of Donor‐Acceptor Cyclopropanes and Enamines: Enantioselective Synthesis of Nitrogen‐Functionalized Cyclopentane Derivatives

Abstract

As traightforward and efficient method for the synthesiso fn itrogen-functionalized cyclopentane derivatives via [3+ +2] cycloaddition of enamines with donor-acceptor cyclopropanes in the presence of catalytic amounts of various Lewis acids at room temperature has been developed; furthermore,t he corresponding b-amino acid was synthesized by monodecarboxylation and hydrogenolysis.A nenantioenricheds ynthesis of nitrogen-functionalized cyclopentane derivatives throughd ynamic kinetic asymmetric transformation of racemic donor-acceptor cyclopropanes hasa lso been achieved employingac opper complex[ Cu(OTf) 2 -L1] as the catalyst affording an enantiomeric ratio up to 8:1.

Biosynthetically Inspired Syntheses of Secu′amamine A and Fluvirosaones A and B

“…As an alternative approach to assemble the five‐membered E ring, we envisioned a [3+2] cycloaddition between the enamine moiety of 20 and a carbon‐based 1,3‐dipole. Although various synthetic routes toward substituted five‐membered carbocyclic systems are reported, there are only a few reports that utilize enamine and three‐carbon based 1,3‐dipoles as building blocks to access nitrogen‐substituted cyclopentanes . After extensive experimentation, we discovered that the TMS‐functionalized methallyl iodide 48 was the optimal 1,3‐dipole for pairing with 20 towards a one‐ or two‐step cycloadditive transformation (Scheme ).…”

“…Although various synthetic routes toward substituted fivemembered carbocyclic systems are reported, there are only afew reports that utilize enamine and three-carbon based 1,3-dipoles as building blocks to access nitrogen-substituted cyclopentanes. [31][32][33] After extensive experimentation, we discovered that the TMS-functionalized methallyl iodide 48 was the optimal 1,3-dipole for pairing with 20 towards ao ne-or two-step cycloadditive transformation (Scheme 6). When we treated 20 with 48 in the presence of silver carbonate,t he mono-methallylated enamine 50 (66 %) was isolated along with the bis-methallylated pentacycle 49 (8 %).…”

Donor–Acceptor Cyclopropanes as an Expedient Building Block Towards the Construction of Nitrogen‐Containing Molecules: An Update

“…Recently, our group reported a straightforward and efficient method for the synthesis of nitrogen‐functionalized cyclopentane derivatives 177a and 177b via [3+2] cycloaddition of enamines 176 with DACs 3 in the presence of a catalytic amount of a Lewis acid [MgI 2 /Cu(OTf) 2 ] (Scheme ) . The reaction proceeds through the nucleophilic addition of enamine 176 to activated cyclopropane xiv and generation of intermediate xlvii .…”

“…Recently,o ur group reported as traightforward and efficient method for the synthesis of nitrogen-functionalized cyclopentane derivatives 177a and 177b via [3+ +2] cycloaddition of enamines 176 with DACs 3 in the presence of ac atalytic amount of aL ewis acid [MgI 2 /Cu(OTf) 2 ]( Scheme63). [95] Ther eactionp roceeds throught he nucleophilic addition of enamine 176 to activated cyclopropane xiv and generation of intermediate xlvii.I ntermediate xlvii can adopt two possible conformations: xlviii and xlix.I nc onformer xlviii,t he twob ulky groups repel each other, resulting in the formation of the minor isomer 177b.O nt he other hand, conformer xlix featuring less steric hindrance leads to the formation of major isomer 177a (Scheme 64). Electron-withdrawing and electron-releasing substituents present on the aromaticr ings were well tolerated under the reactionc onditions and the respective substrates afforded cyclopentane derivatives with good yields.A na symmetric synthesiso f the desired cyclopentane derivatives has also been achieved throughadynamic kinetic asymmetric transformation (DYKAT) using the copper complex [Cu(OTf) 2 -L 9 ]a sc atalyst.…”

Enantioselective synthesis of compounds containing bis-benzylic quaternary stereocenters through palladium-catalyzed conjugate additions of arylboronic acids

“…3-(3-Pyridyl)-cyclohex-2-enone 1i,23 (E)-4phenylcyclohept-2-enone 1j,22 (E)-4-phenylpent-3-en-2-one 1k24 were synthesized according to reported literature procedures. (4R,4'R)-2,2'-(propane-2,2-diyl)bis(4-phenyl-4,5dihydrooxazole) ((R)-PhBox),25 (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyOx),26 and (S)-4-isopropyl-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-i-PrPyOx)27 were prepared according to previously reported literature procedures. Palladium trifluoroacetate,(4S,4'S)-2,2'-(propane-2,2-diyl)bis(4-(tert-butyl)-4,5-dihydrooxazole) ((S)-t-BuBox),3,5dimethylphenylboronic acid and 2,4-dinitrophenylhydrazine were purchased from Sigma-Aldrich and used without further purification.…”