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Publication
Light as a powerful tool to create new synthons from aromatic building blocks
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Authors
Abstract(s)
O potencial das aziridinas biciclícas tem sido comprovado nos últimos anos como bloco de construção importante para a síntese em química medicinal. A síntese de aziridinas biciclícas através da transformação fotoquímica por radiação UV de sais de piridínio é conhecida há décadas e poucos desenvolvimentos foram observados desde então, com exceção da fotoquímica em fluxo. Aqui, apresentamos o impacto do efeito do contra-ião do sal de piridina na reatividade relativamente à síntese de aziridinas bicíclicas.
O ião trifluoroacetato proporcionou a síntese de aziridinas biciclícas com incorporação de álcoois mais volumosos. Além disso, também foi possível integrar dióis, que podem fornecer uma estrutura base sinteticamente relevante para o desenvolvimento de novos núcleos moleculares e funcionalização posteriores.
Devido à expansão exponencial da fotoquímica através luz visível, foi testada a viabilidade da síntese de aziridinas biciclícas nessas condições. Infelizmente, o alto estado energético T1 do sal de piridina não permite o evento de “sensitizing” com os fotocatalisadores atuais. Outros esforços na funcionalização via carbeno, formado in situ por LED azul, de aziridinas biciclícas não foram bem-sucedidos.
Vários trabalhos sobre a reatividade catalisada por metais de aziridinas biciclícas têm sido relatados. No entanto, a desejada resolução assimétrica tem sido particularmente desafiante, exigindo uma "ativação" prévia. Aqui, apresentamos a primeira resolução cinética de aziridinas biciclícas não ativadas através de uma reação Tsuji-Trost não convencional com formação de nova ligação C-C. Conclusões sobre possíveis vias mecanísticas foram alcançadas através de reações experimentais com material enantiopuro e cálculos de DFT. Ambos os métodos, revelaram uma forte prevalência para uma resolução cinética standard. Deste modo, novos aminociclopentenos sinteticamente relevantes foram preparados.
The potential of bicyclic aziridines has been proved on recent years as crucial building block for medicinal chemistry synthesis. Their synthesis through UV photochemical transformation of pyridinium salts has been known from decades with some stagnation in development besides application of flow photochemistry. Despite that, two new total synthesis and enzymatic resolution of bicyclic aziridines has been successfully exemplified in our group. Now, here in we highlighted the impact of pyridinium salt counter anion eƯect that unveil diƯerent reactivity. Trifluoroacetate anion aƯorded synthesis of bicyclic aziridines with incorporation of bulkier alcohols. Moreover, diols were also possible of integration and may supply a relevant core for further development and functionalization. Due to visible light photochemistry exponential expansion in chemistry, feasibility of bicyclic aziridine synthesis under these conditions were tested. Unfortunately, the high T1 state of pyridinium does not allow sensitization phenomena with the currently photosensitizers. Other eƯorts on functionalization via blue LED mediated carbene of bicyclic aziridines were not successful. Several works on metal catalysed reactivity of bicyclic aziridines have been reported. Between Pd, La, and Y, a lot of metals have been explored. However, their desired asymmetric resolution has been particularly challenging with the requirement of pre “activation”. Here in, we presented the first kinetic resolution of non-activated bicyclic aziridines through an unconventional Tsuji-Trost reaction with new C-C bond formation. Insights into potential mechanistic pathways were achieved based on key experimental reactions and DFT calculations, revealing a strong prevalence for a standard kinetic resolution. Through this, synthetically relevant new aminocyclopentenes were prepared.
The potential of bicyclic aziridines has been proved on recent years as crucial building block for medicinal chemistry synthesis. Their synthesis through UV photochemical transformation of pyridinium salts has been known from decades with some stagnation in development besides application of flow photochemistry. Despite that, two new total synthesis and enzymatic resolution of bicyclic aziridines has been successfully exemplified in our group. Now, here in we highlighted the impact of pyridinium salt counter anion eƯect that unveil diƯerent reactivity. Trifluoroacetate anion aƯorded synthesis of bicyclic aziridines with incorporation of bulkier alcohols. Moreover, diols were also possible of integration and may supply a relevant core for further development and functionalization. Due to visible light photochemistry exponential expansion in chemistry, feasibility of bicyclic aziridine synthesis under these conditions were tested. Unfortunately, the high T1 state of pyridinium does not allow sensitization phenomena with the currently photosensitizers. Other eƯorts on functionalization via blue LED mediated carbene of bicyclic aziridines were not successful. Several works on metal catalysed reactivity of bicyclic aziridines have been reported. Between Pd, La, and Y, a lot of metals have been explored. However, their desired asymmetric resolution has been particularly challenging with the requirement of pre “activation”. Here in, we presented the first kinetic resolution of non-activated bicyclic aziridines through an unconventional Tsuji-Trost reaction with new C-C bond formation. Insights into potential mechanistic pathways were achieved based on key experimental reactions and DFT calculations, revealing a strong prevalence for a standard kinetic resolution. Through this, synthetically relevant new aminocyclopentenes were prepared.
Description
Keywords
fotoquímica catálise assimétrica paládio aziridina aminociclopentenos photochemistry asymmetric palladium catalysis aziridines aminocyclopentenes