Ruthenium catalyzed decarbonylative arylation at sp3 carbon centers in pyrrolidine and piperidine heterocycles.
This paper describes the development of a new catalytic transformation, the ruthenium-catalyzed decarbonylative arylation of cyclic 2-amino esters, which replaces the ester group with an aryl ring at the sp3 carbon center. For example, proline ester amidine 1 is converted to 2-arylpyrrolidine 3 in the presence of arylboronic acids or esters as arene donors and Ru(3)(CO)(12) as the catalyst. This process provides a rapid access to a variety of 2-arylpyrrolidines and piperidines from commercially available proline, hydroxyproline, and pipecolinate esters. The examination of the substrate scope also showed that many arene boronic acids and boronate esters serve as coupling partners. The high chemoselectivity of this process was demonstrated and ascribed to the significant rate difference between the decarbonylative arylation and the C-H arylation. The decarbonylative arylation complements the C-H arylation, since the latter process lacks control over the extent of functionalization, affording a mixture of mono- and bis-arylpyrrolidines. When applied in tandem, these two processes provide 2,5-diarylpyrrolidines in two steps from the corresponding proline esters. It was also demonstrated that the required amidine or iminocarbamate directing group fulfills two major functions: first, it is essential for the ester activation step, which occurs via the coordination-assisted metal insertion into the acyl C-O bond; second, it facilitates the decarbonylation, via the stabilization of a metallacycle intermediate, assuring the formation of the 2-arylated products instead of the corresponding ketones observed before by others.
Gribkov
Denis V
DV
Department of Chemistry, Columbia University, New York, New York 10027, USA.
Pastine
Stefan J
SJ
Schnürch
Michael
M
Sames
Dalibor
D
D001897:Boronic Acids / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D006909:Hydroxyproline / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D008956:Models, Chemical; D010880:Piperidines / Q000138:chemical synthesis*; D011392:Proline / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis*; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism