UVM Theses and Dissertations
Format:
Print
Author:
Yang, Yanbo
Dept./Program:
Chemistry
Year:
2014
Degree:
Ph. D.
Abstract:
The dissertation describes Pd⁰-catalyzed formal 1,3-diaza-Claisen rearrangement and the design and development of cationic 1,3-diaza-Claisen rearrangement.
Our previous work has shown that isocyanates react with azanorbornenes and azabicyclo[2.2.2]octeries under thermal conditions to afford zwitterionic intermediates that undergo a thermal 1,3-diaza-Claisen rearrangement to give both ureas and isoureas. However, some azanorbomenes and azabicyclooctenes failed to rearrange or proceeded in low yields. To address these challenging substrates for the thermal 1,3-diaza-Claisen rearrangement, we have developed a Pd⁰-catalyed formal 1,3-diaza-Claisen rearrangement. Interestingly, under Pd⁰-catalyzed condition, both isocyanates with electron-withdrawing groups and isocyanates without electron-withdrawing groups react with azanorbomenes and azabicyclo[2.2.2]octenes to provide ureas as the only products in high yields. More importantly, the reactions that failed under thermal conditions were all successful under Pd⁰-catalysis. In addition to azanorbomenes and azabicyclo[2.2.2]octenes, other ring systems were also investigated. Pd⁰ catalysis has broadened the scope of tertiary allylic amines that react with isocyanates to afford 1,3-diaza-Claisen rearrangement products.
In the presence of p-TsCI and NEt₃, aIlylaminopropyl benzyl ureas were initially dehydrated to form protonated carbodiimides whose presence was confirmed by the infrared absorption frequency at 2100 cm⁻¹ which is the characteristic band of -N=C=N-; then the in situ generated protonated carbodiimides were poised for further cationic 1,3-diaza-Claisen rearrangement to afford synthetically challenging guanidines. The effect of acid on the rearrangement was ascertained by the fact that no rearrangement product was observed by simply heating free base carbodiimide 3.10 in benzene at reflux. Other dehydration reagents, such as Tf₂O, Ts₂O, MsCI were also investigated, and none ofthem provide satisfactory results. A selection of allyamino benzyl ureas with different tether length, substituents, or in varied ring systems, were synthesized to explore the scope ofthis methodology. This methodology works best at allylaminopropyl benzyl ureas, and the substituents on the benzyl group does not seem to affect the reaction rate in a significant way.
Our previous work has shown that isocyanates react with azanorbornenes and azabicyclo[2.2.2]octeries under thermal conditions to afford zwitterionic intermediates that undergo a thermal 1,3-diaza-Claisen rearrangement to give both ureas and isoureas. However, some azanorbomenes and azabicyclooctenes failed to rearrange or proceeded in low yields. To address these challenging substrates for the thermal 1,3-diaza-Claisen rearrangement, we have developed a Pd⁰-catalyed formal 1,3-diaza-Claisen rearrangement. Interestingly, under Pd⁰-catalyzed condition, both isocyanates with electron-withdrawing groups and isocyanates without electron-withdrawing groups react with azanorbomenes and azabicyclo[2.2.2]octenes to provide ureas as the only products in high yields. More importantly, the reactions that failed under thermal conditions were all successful under Pd⁰-catalysis. In addition to azanorbomenes and azabicyclo[2.2.2]octenes, other ring systems were also investigated. Pd⁰ catalysis has broadened the scope of tertiary allylic amines that react with isocyanates to afford 1,3-diaza-Claisen rearrangement products.
In the presence of p-TsCI and NEt₃, aIlylaminopropyl benzyl ureas were initially dehydrated to form protonated carbodiimides whose presence was confirmed by the infrared absorption frequency at 2100 cm⁻¹ which is the characteristic band of -N=C=N-; then the in situ generated protonated carbodiimides were poised for further cationic 1,3-diaza-Claisen rearrangement to afford synthetically challenging guanidines. The effect of acid on the rearrangement was ascertained by the fact that no rearrangement product was observed by simply heating free base carbodiimide 3.10 in benzene at reflux. Other dehydration reagents, such as Tf₂O, Ts₂O, MsCI were also investigated, and none ofthem provide satisfactory results. A selection of allyamino benzyl ureas with different tether length, substituents, or in varied ring systems, were synthesized to explore the scope ofthis methodology. This methodology works best at allylaminopropyl benzyl ureas, and the substituents on the benzyl group does not seem to affect the reaction rate in a significant way.