Computation‐Guided Scope Exploration of a Conjugate Addition/Truce‐Smiles Cascade Reaction for Scaffold Diversification DOI Creative Commons
Brendan Horst,

Leopoldo J. Gabella Carena,

Michael T. Doppert

et al.

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Abstract Based on the successful application of a nitroaryl transfer cascade reaction in total synthesis various monoterpene indole alkaloids proceeding via fused bicyclic intermediate, we investigated analogous reactions involving spiro, bridged, and alternatively intermediates. Unfortunately, none these was found to afford desired product. DFT studies original process revealed that Truce‐Smiles rearrangement is rate‐determining step. In addition, subsequent SO 2 extrusion accompanied by retro‐Mannich ring opening, resulting stabilized enolate only recyclizes after activation cyclic imine moiety. Computation profiles proposed alternative showed barrier for unreasonably high bridged systems, but moderately higher five‐membered spiro system. Reasoning even more electron‐deficient arenesulfonamides should have lower rearrangement, synthesized corresponding 2,4‐dinitrobenzenesulfonamide precursor it indeed smoothly undergoes at room temperature. this case, however, produces product, as intermediate 2,4‐dinitrophenyl‐substituted insufficiently nucleophilic undergo Mannich cyclization.

Language: Английский

Computation‐Guided Scope Exploration of a Conjugate Addition/Truce‐Smiles Cascade Reaction for Scaffold Diversification DOI Creative Commons
Brendan Horst,

Leopoldo J. Gabella Carena,

Michael T. Doppert

et al.

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Abstract Based on the successful application of a nitroaryl transfer cascade reaction in total synthesis various monoterpene indole alkaloids proceeding via fused bicyclic intermediate, we investigated analogous reactions involving spiro, bridged, and alternatively intermediates. Unfortunately, none these was found to afford desired product. DFT studies original process revealed that Truce‐Smiles rearrangement is rate‐determining step. In addition, subsequent SO 2 extrusion accompanied by retro‐Mannich ring opening, resulting stabilized enolate only recyclizes after activation cyclic imine moiety. Computation profiles proposed alternative showed barrier for unreasonably high bridged systems, but moderately higher five‐membered spiro system. Reasoning even more electron‐deficient arenesulfonamides should have lower rearrangement, synthesized corresponding 2,4‐dinitrobenzenesulfonamide precursor it indeed smoothly undergoes at room temperature. this case, however, produces product, as intermediate 2,4‐dinitrophenyl‐substituted insufficiently nucleophilic undergo Mannich cyclization.

Language: Английский

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