Abstract
Selenium-containing amino acids are valuable targets but methods for the stereoselective α-selenation of simple amino acid precursors are rare. We herein report the enantioselective electrophilic α-selenation of azlactones (masked α-amino acid derivatives) and isoxazolidin-5-ones (masked β-amino acids) using Cinchona alkaloids as easily accessible organocatalysts. A variety of differently substituted derivatives was accessed with reasonable levels of enantioselectivities and further studies concerning the stability and suitability of these compounds for further manipulations have been carried out as well.
Highlights
Non-natural a- and b-amino acids (AA) are compounds of high significance and value.1-3 the introduction of efficient and reliable strategies to access novel AA-derivatives in an enantioselective fashion has been a heavily investigated topic within the synthesis- and catalysis-oriented community.26 Hereby, the development of methods that allow for direct stereoselective functionalizations of simple a- or b-AA derivatives and precursors became an especially thoroughly explored field of research
Considering the high value of organoselenium compounds for medical applications,8-10 as well as their use in stereoselective syntheses and catalysis approaches,11 and the importance of Se-containing AA in particular,9 the lack in generally applicable methods to access novel a-selenated a-AA (a-Se-a-AA) or b-AA derivatives (a-Se-b-AA) comes as a surprise
Based on our own recent experience in the field of asymmetric organocatalysis, we opted for the use of chiral quaternary ammonium salts18 and chiral organobases (i.e. Cinchona alkaloids19 and Takemoto’s bifunctional thioureacontaining amine D20; Fig. 1) as catalysts for the investigated electrophilic a-selenation reactions
Summary
Non-natural a- and b-amino acids (AA) are compounds of high significance and value. the introduction of efficient and reliable strategies to access novel AA-derivatives in an enantioselective fashion has been a heavily investigated topic within the synthesis- and catalysis-oriented community. Hereby, the development of methods that allow for direct stereoselective functionalizations of simple (masked) a- or b-AA derivatives and precursors became an especially thoroughly explored field of research. The development of methods that allow for direct stereoselective functionalizations of simple (masked) a- or b-AA derivatives and precursors became an especially thoroughly explored field of research. Considering the high value of (chiral) organoselenium compounds for medical applications, as well as their use in (or for) stereoselective syntheses and catalysis approaches, and the importance of Se-containing AA in particular, the lack in generally applicable methods to access novel a-selenated a-AA (a-Se-a-AA) or b-AA derivatives (a-Se-b-AA) comes as a surprise. Inspired by the value of organoselenium compounds and considering the availability of established electrophilic Se-transfer reagents, we became interested in developing organocatalytic protocols to control the asymmetric a-selenation of accessible azlactones 1 (as aAA precursors) and isoxazolidin-5-ones 2 (as b-AA building blocks) (Scheme 1).. Targeted organocatalytic electrophilic a-selenation of masked a- and b-AA derivatives 1 and 2
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
