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Mono endo-6- And bis endo,endo-12-N,N-diethylcarbamoyl derivatives of Tröger’s Base. Synthesis and exo-endo isomerization study

Dawaigher, Sami LU ; Lindbäck, Emil LU ; Strand, Daniel LU ; Cederbalk, Anna ; Winikoff, Stuart ; Harmata, Michael ; Snieckus, Victor and Wärnmark, Kenneth LU (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
; ; ; ; ; ; and
organization
publishing date
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
2020-09-25 01:59:22
@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 (&gt; 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},
  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},
}