HERON reactions of anomeric amides: understanding the driving force

Title
HERON reactions of anomeric amides: understanding the driving force
Publication Date
2015
Author(s)
Glover, Stephen
( author )
OrcID: https://orcid.org/0000-0002-9344-8669
Email: sglover@une.edu.au
UNE Id une-id:sglover
Rosser, Adam A
( author )
OrcID: https://orcid.org/0000-0002-4123-7704
Email: arosser3@une.edu.au
UNE Id une-id:arosser3
Type of document
Journal Article
Language
en
Entity Type
Publication
Publisher
John Wiley & Sons Ltd
Place of publication
United Kingdom
DOI
10.1002/poc.3322
UNE publication id
une:17136
Abstract
Calculations show that anomeric amides, amides bearing two electronegative atoms at the amide nitrogen, are unusual in structure and reactivity. They have much reduced amide resonance and also undergo the HERON reaction where anomeric destabilisation results in migration of one substituent from nitrogen to the carbonyl and formation of a resonancestabilised nitrene. B3LYP/6-31G(d) calculations demonstrate how resonance and HERON reactivity are affected by bisalkoxyl substitution and aminoalkoxyl substitution at nitrogen. Because transition state structures for model reactions of N,Ndimethoxyacetamide and N-methoxy-N-dimethylaminoacetamide demonstrate complete loss of amide resonance, the overall barriers to their HERON reactions can be partitioned into a resonance (RE) and a rearrangement component (Erearr). REs for both amides have been calculated by isodesmic methods (carbonyl substitution nitrogen atom replacement and a calibrated trans amidation method), and the reduction in total electronegativity at the amide nitrogen in N-methoxy-Ndimethylaminoacetamide results in an increase in amide resonance of about 4 kcal mol⁻¹ relative to N,N-dimethoxyacetamide (RE of 8.6 kcal mol⁻¹). However, there is a large decrease in Erearr by some 20 kcal mol⁻¹ to 10 kcal mol⁻¹. Changes in these energies are rationalised on the basis of an increase in amide nitrogen lone pair energy, which increases resonance, and a higher energy substituent nitrogen lone pair enhancing the nN-σ*NO anomeric effect and the ease of rearrangement. Intramolecular HERON reactions in twisted 1-aza-2-adamantanones, with no amide resonance, support the above variations in the rearrangement components to the activation barriers. On the strength of these findings, hydroxamic esters with only one oxygen at nitrogen will not undergo HERON reactions.
Link
Citation
Journal of Physical Organic Chemistry, 28(3), p. 215-222
ISSN
1099-1395
0894-3230
Start page
215
End page
222

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