TY - JOUR
T1 - Mono endo-6- And bis endo,endo-12-N,N-diethylcarbamoyl derivatives of Tröger’s Base. Synthesis and exo-endo isomerization study
AU - Dawaigher, Sami
AU - Lindbäck, Emil
AU - Strand, Daniel
AU - Cederbalk, Anna
AU - Winikoff, Stuart
AU - Harmata, Michael
AU - Snieckus, Victor
AU - Wärnmark, Kenneth
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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.
AB - 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.
KW - Amides
KW - Deuterium Quench
KW - Diastereoselectivity
KW - Enolates
KW - Tröger’s Base
UR - http://www.scopus.com/inward/record.url?scp=85090137012&partnerID=8YFLogxK
U2 - 10.24820/ARK.5550190.P011.183
DO - 10.24820/ARK.5550190.P011.183
M3 - Article
AN - SCOPUS:85090137012
SN - 1551-7004
VL - 2020
JO - Arkivoc
JF - Arkivoc
IS - 7
M1 - A41
ER -