Mechanistic study of the tandem intramolecular (4 + 2)/intermolecular (3 + 2) cycloaddition reactions for the formation of polyaza‐ and polyisoxazolidine‐steroids. (24th January 2020)
- Record Type:
- Journal Article
- Title:
- Mechanistic study of the tandem intramolecular (4 + 2)/intermolecular (3 + 2) cycloaddition reactions for the formation of polyaza‐ and polyisoxazolidine‐steroids. (24th January 2020)
- Main Title:
- Mechanistic study of the tandem intramolecular (4 + 2)/intermolecular (3 + 2) cycloaddition reactions for the formation of polyaza‐ and polyisoxazolidine‐steroids
- Authors:
- Opoku, Ernest
Baffour Pipim, George
Tia, Richard
Adei, Evans - Abstract:
- Abstract: The ability to construct molecules with potential applications in biomedicine via efficient and selective molecular design and syntheses hinges on a thorough understanding of underlying reaction mechanisms. The biological importance of steroids and related heterocyclic compounds are well known but theoretical studies aimed at delineating reaction mechanisms to complement efforts of experimentalists are lacking. Herein, we report an extensive theoretical study on the regio‐, stereo‐, and enantio‐selectivity of the tandem sequential intramolecular (4 + 2)/intermolecular (3 + 2) cycloaddition reaction of (E)‐3‐(2‐[furan‐2‐ylmethoxy]phenyl)acrylate derivatives (R1 ) and azides (R3 and R3′ ) as well as nitrones (R2 ) for the formation of steroids. In the reaction of R1 and the azide derivatives R3 and R3′, the intramolecular (4 + 2) cycloaddition of R1 is the rate‐determining step (rds). The reaction is also found to be very selective. Reaction of electron‐withdrawing groups‐substituted R1 with R3 is found to generally increase the barrier of the rds except bromine whiles electron‐donating groups are found to generally decrease the activation energies of the rds. Subsequently, we report a novel reaction of R1 with cyclic nitrone (R2 ), which compares favorably with the azide reaction. Results from the global reactivity descriptors are in good agreement with the activation barrier trends. All the considered reactions in this study are found to be kinetically driven.Abstract: The ability to construct molecules with potential applications in biomedicine via efficient and selective molecular design and syntheses hinges on a thorough understanding of underlying reaction mechanisms. The biological importance of steroids and related heterocyclic compounds are well known but theoretical studies aimed at delineating reaction mechanisms to complement efforts of experimentalists are lacking. Herein, we report an extensive theoretical study on the regio‐, stereo‐, and enantio‐selectivity of the tandem sequential intramolecular (4 + 2)/intermolecular (3 + 2) cycloaddition reaction of (E)‐3‐(2‐[furan‐2‐ylmethoxy]phenyl)acrylate derivatives (R1 ) and azides (R3 and R3′ ) as well as nitrones (R2 ) for the formation of steroids. In the reaction of R1 and the azide derivatives R3 and R3′, the intramolecular (4 + 2) cycloaddition of R1 is the rate‐determining step (rds). The reaction is also found to be very selective. Reaction of electron‐withdrawing groups‐substituted R1 with R3 is found to generally increase the barrier of the rds except bromine whiles electron‐donating groups are found to generally decrease the activation energies of the rds. Subsequently, we report a novel reaction of R1 with cyclic nitrone (R2 ), which compares favorably with the azide reaction. Results from the global reactivity descriptors are in good agreement with the activation barrier trends. All the considered reactions in this study are found to be kinetically driven. Abstract : … (more)
- Is Part Of:
- Journal of heterocyclic chemistry. Volume 57:Number 4(2020)
- Journal:
- Journal of heterocyclic chemistry
- Issue:
- Volume 57:Number 4(2020)
- Issue Display:
- Volume 57, Issue 4 (2020)
- Year:
- 2020
- Volume:
- 57
- Issue:
- 4
- Issue Sort Value:
- 2020-0057-0004-0000
- Page Start:
- 1748
- Page End:
- 1758
- Publication Date:
- 2020-01-24
- Subjects:
- Heterocyclic compounds -- Periodicals
547.59 - Journal URLs:
- http://onlinelibrary.wiley.com/ ↗
- DOI:
- 10.1002/jhet.3900 ↗
- Languages:
- English
- ISSNs:
- 0022-152X
- Deposit Type:
- Legaldeposit
- View Content:
- Available online (eLD content is only available in our Reading Rooms) ↗
- Physical Locations:
- British Library DSC - 4998.200000
British Library DSC - BLDSS-3PM
British Library STI - ELD Digital store - Ingest File:
- 26782.xml