Mono endo-6- And bis endo,endo-12-N,N-diethylcarbamoyl derivatives of Tröger’s Base. Synthesis and exo-endo isomerization study
(2020) In Arkivoc 2020(7).- Abstract
An efficient synthetic route to the mono-endo-6- and bis-endo,endo-6,12-N,N-diethylcarbamoyl derivatives of Tröger’s base (TB), endo-7 and endo-8, is reported. Studies of reaction time, proton source, and additive allowed establishment of optimized conditions for the conversion of exo-7 into the corresponding isomer endo-7. With a longer reaction time, the exo,exo-6,12 bis-carbamoyl derivative exo-8 was converted into the corresponding endo,endo-bis-carbamoyl product endo-8. Single crystal X-ray crystallographic analysis confirmed the structural and stereochemical assignments made on the basis of 1H NMR, mechanistic, and calculational studies. Deuterium quench experiments using LDA, CD3ONa/CD3OD and DCl/CD3OD conditions of... (More)
An efficient synthetic route to the mono-endo-6- and bis-endo,endo-6,12-N,N-diethylcarbamoyl derivatives of Tröger’s base (TB), endo-7 and endo-8, is reported. Studies of reaction time, proton source, and additive allowed establishment of optimized conditions for the conversion of exo-7 into the corresponding isomer endo-7. With a longer reaction time, the exo,exo-6,12 bis-carbamoyl derivative exo-8 was converted into the corresponding endo,endo-bis-carbamoyl product endo-8. Single crystal X-ray crystallographic analysis confirmed the structural and stereochemical assignments made on the basis of 1H NMR, mechanistic, and calculational studies. Deuterium quench experiments using LDA, CD3ONa/CD3OD and DCl/CD3OD conditions of both exo-7 and exo-8 afforded exo-7d1 and exo-8d2, respectively (> 95% deuterium incorporation), supporting an enolate mechanism for the isomerization. In contrast, when repeating the experiment with DCl/CD3OD, no deuterium was incorporated, suggesting the traditional ring-opening mechanism involving an iminium ion.
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- author
- Dawaigher, Sami LU ; Lindbäck, Emil LU ; Strand, Daniel LU ; Cederbalk, Anna ; Winikoff, Stuart ; Harmata, Michael ; Snieckus, Victor and Wärnmark, Kenneth LU
- organization
- publishing date
- 2020-02-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amides, Deuterium Quench, Diastereoselectivity, Enolates, Tröger’s Base
- in
- Arkivoc
- volume
- 2020
- issue
- 7
- article number
- A41
- publisher
- Arkat USA Inc
- external identifiers
-
- scopus:85090137012
- ISSN
- 1551-7004
- DOI
- 10.24820/ARK.5550190.P011.183
- language
- English
- LU publication?
- yes
- id
- c7e7eed4-d84d-452d-b462-0a4ff8d25d12
- date added to LUP
- 2020-09-24 15:10:03
- date last changed
- 2022-06-28 23:09:25
@article{c7e7eed4-d84d-452d-b462-0a4ff8d25d12, abstract = {{<p>An efficient synthetic route to the mono-endo-6- and bis-endo,endo-6,12-N,N-diethylcarbamoyl derivatives of Tröger’s base (TB), endo-7 and endo-8, is reported. Studies of reaction time, proton source, and additive allowed establishment of optimized conditions for the conversion of exo-7 into the corresponding isomer endo-7. With a longer reaction time, the exo,exo-6,12 bis-carbamoyl derivative exo-8 was converted into the corresponding endo,endo-bis-carbamoyl product endo-8. Single crystal X-ray crystallographic analysis confirmed the structural and stereochemical assignments made on the basis of <sup>1</sup>H NMR, mechanistic, and calculational studies. Deuterium quench experiments using LDA, CD3ONa/CD3OD and DCl/CD3OD conditions of both exo-7 and exo-8 afforded exo-7d1 and exo-8d2, respectively (> 95% deuterium incorporation), supporting an enolate mechanism for the isomerization. In contrast, when repeating the experiment with DCl/CD3OD, no deuterium was incorporated, suggesting the traditional ring-opening mechanism involving an iminium ion.</p>}}, author = {{Dawaigher, Sami and Lindbäck, Emil and Strand, Daniel and Cederbalk, Anna and Winikoff, Stuart and Harmata, Michael and Snieckus, Victor and Wärnmark, Kenneth}}, issn = {{1551-7004}}, keywords = {{Amides; Deuterium Quench; Diastereoselectivity; Enolates; Tröger’s Base}}, language = {{eng}}, month = {{02}}, number = {{7}}, publisher = {{Arkat USA Inc}}, series = {{Arkivoc}}, title = {{Mono endo-6- And bis endo,endo-12-N,N-diethylcarbamoyl derivatives of Tröger’s Base. Synthesis and exo-endo isomerization study}}, url = {{http://dx.doi.org/10.24820/ARK.5550190.P011.183}}, doi = {{10.24820/ARK.5550190.P011.183}}, volume = {{2020}}, year = {{2020}}, }