Directing Group Enhanced Carbonylative Ring Expansions of Amino Substituted Cyclopropanes

Directing Group Enhanced Carbonylative Ring Expansions of Amino Substituted Cyclopropanes

Bower, John F.

Abstract:

Our research programme is focussed upon the development of new catalysis platforms that enable direct access to medicinally valuable chiral scaffolds. Recently, we outlined a metal-catalysed (3+2+1) carbonylative cycloaddition strategy for the synthesis of complex nitrogen containing scaffolds (Scheme 1A). The key metallacyclic intermediates 1 are generated by Rh-catalysed carbonylative ring expansion of readily available amino-substituted cyclopropanes. To control the regioselectivity of this process we have developed a directing group based strategy, which takes advantage of the N-protecting group (Scheme 1B). This approach controls (a) the regioselectivity of oxidative addition (into the more hindered cyclopropane C-C bond) and (b) the regioselectivity of CO insertion. Mechanistic aspects of this process will be discussed. We will also outline a prototypical catalytic process that involves trapping of the metallacyclic intermediate with a tethered alkyne (Scheme 1C). Finally, a brief overview of current directions will be given.

Our research programme is focussed upon the development of new catalysis platforms that enable direct access to medicinally valuable chiral scaffolds. Recently, we outlined a metal-catalysed (3+2+1) carbonylative cycloaddition strategy for the synthesis of complex nitrogen containing scaffolds (Scheme 1A). The key metallacyclic intermediates 1 are generated by Rh-catalysed carbonylative ring expansion of readily available amino-substituted cyclopropanes. To control the regioselectivity of this process we have developed a directing group based strategy, which takes advantage of the N-protecting group (Scheme 1B). This approach controls (a) the regioselectivity of oxidative addition (into the more hindered cyclopropane C-C bond) and (b) the regioselectivity of CO insertion. Mechanistic aspects of this process will be discussed. We will also outline a prototypical catalytic process that involves trapping of the metallacyclic intermediate with a tethered alkyne (Scheme 1C). Finally, a brief overview of current directions will be given.

Palavras-chave:

DOI: 10.5151/chempro-15bmos-4-template_Speech_15th_BMOS-boweredited2

Referências bibliográficas

• [1] 1 A. Nadin, C. Hattotuwagama, I. Churcher, Angew. Chem. Int. Ed. 2012, 51, 1114.
• [2] 2 M. H. Shaw, E. Y. Melikhova, D. P. Kloer, W. G. Whittingham, J. F. Bower, J. Am. Chem. Soc. 2013, 135, 4992.

Como citar:

Bower, John F.; "Directing Group Enhanced Carbonylative Ring Expansions of Amino Substituted Cyclopropanes", p-314-314. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-4-template_Speech_15th_BMOS-boweredited2