The barrier to rotation around the N-alkenyl bond of 38 N-alkenyl-N-alkylacetamide derivatives was measured (ΔG∞ rotation varied between <8.0 and 31.0 kcal mol-1). The most important factor in controlling the rate of rotation was the level of alkene substitution, followed by the size of the nitrogen substituent and, finally, the size of the acyl substituent. Tertiary enamides with four alkenyl substituents exhibited half-lives for rotation between 5.5 days and 99 years at 298 K, sufficient to isolate enantiomerically enriched atropisomers. The radical cyclizations of a subset of N-alkenyl-N-benzyl-α-haloacetamides exhibiting relatively high barriers to rotation round the N-alkenyl bond (ΔG∞ rotation >20 kcal mol-1) were studied to determine the regiochemistry of cyclization. Those with high barriers (>27 kcal mol-1) did not lead to cyclization, but those with lower values produced highly functionalized γ-lactams via a 5-endo-trig radical-polar crossover process that was terminated by reduction, an unusual cyclopropanation sequence, or trapping with H2O, depending upon the reaction conditions. Because elevated temperatures were necessary for cyclization, this precluded study of the asymmetric transfer in the reaction of individual atropisomers. However, enantiomerically enriched atropsiomeric enamides should be regarded as potential asymmetric building blocks for reactions that can be accomplished at room temperature.

Axially Chiral Enamides: Substituent Effects, Rotation Barriers, and Implications for their Cyclization Reactions / Clark, Andrew J; Curran, Dennis P.; Fox, David J.; Ghelfi, Franco; Guy, Collette S.; Hay, Benjamin; James, Natalie; Phillips, Jessica M.; Roncaglia, Fabrizio; Sellars, Philip B.; Wilson, Paul; Zhang, Hanmo. - In: JOURNAL OF ORGANIC CHEMISTRY. - ISSN 0022-3263. - 81:13(2016), pp. 5547-5565. [10.1021/acs.joc.6b00889]

Axially Chiral Enamides: Substituent Effects, Rotation Barriers, and Implications for their Cyclization Reactions

GHELFI, Franco;RONCAGLIA, Fabrizio;
2016

Abstract

The barrier to rotation around the N-alkenyl bond of 38 N-alkenyl-N-alkylacetamide derivatives was measured (ΔG∞ rotation varied between <8.0 and 31.0 kcal mol-1). The most important factor in controlling the rate of rotation was the level of alkene substitution, followed by the size of the nitrogen substituent and, finally, the size of the acyl substituent. Tertiary enamides with four alkenyl substituents exhibited half-lives for rotation between 5.5 days and 99 years at 298 K, sufficient to isolate enantiomerically enriched atropisomers. The radical cyclizations of a subset of N-alkenyl-N-benzyl-α-haloacetamides exhibiting relatively high barriers to rotation round the N-alkenyl bond (ΔG∞ rotation >20 kcal mol-1) were studied to determine the regiochemistry of cyclization. Those with high barriers (>27 kcal mol-1) did not lead to cyclization, but those with lower values produced highly functionalized γ-lactams via a 5-endo-trig radical-polar crossover process that was terminated by reduction, an unusual cyclopropanation sequence, or trapping with H2O, depending upon the reaction conditions. Because elevated temperatures were necessary for cyclization, this precluded study of the asymmetric transfer in the reaction of individual atropisomers. However, enantiomerically enriched atropsiomeric enamides should be regarded as potential asymmetric building blocks for reactions that can be accomplished at room temperature.
2016
21-giu-2016
81
13
5547
5565
Axially Chiral Enamides: Substituent Effects, Rotation Barriers, and Implications for their Cyclization Reactions / Clark, Andrew J; Curran, Dennis P.; Fox, David J.; Ghelfi, Franco; Guy, Collette S.; Hay, Benjamin; James, Natalie; Phillips, Jessica M.; Roncaglia, Fabrizio; Sellars, Philip B.; Wilson, Paul; Zhang, Hanmo. - In: JOURNAL OF ORGANIC CHEMISTRY. - ISSN 0022-3263. - 81:13(2016), pp. 5547-5565. [10.1021/acs.joc.6b00889]
Clark, Andrew J; Curran, Dennis P.; Fox, David J.; Ghelfi, Franco; Guy, Collette S.; Hay, Benjamin; James, Natalie; Phillips, Jessica M.; Roncaglia, F...espandi
File in questo prodotto:
File Dimensione Formato  
acs.joc.6b00889.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 1.91 MB
Formato Adobe PDF
1.91 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1138230
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 34
  • ???jsp.display-item.citation.isi??? 34
social impact