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First selective direct mono-arylation of piperidines using ruthenium-catalyzed C-H activation.

Schwarz MC, Dastbaravardeh N, Kirchner K, Schnürch M, Mihovilovic MD - Monatsh. Chem. (2013)

Bottom Line: A Ru-catalyzed mono-arylation in α-position of saturated cyclic amines is reported employing a C-H activation protocol.Substitution of the pyridine directing group with a bulky group, e.g., trifluoromethyl in the 3-position, proved to be crucial to avoid bis-arylation.Additionally, the directing group can be cleaved, taking advantage of an unprecedented detrifluoromethylation reaction.

View Article: PubMed Central - PubMed

Affiliation: Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria.

ABSTRACT

Abstract: A Ru-catalyzed mono-arylation in α-position of saturated cyclic amines is reported employing a C-H activation protocol. Substitution of the pyridine directing group with a bulky group, e.g., trifluoromethyl in the 3-position, proved to be crucial to avoid bis-arylation. This highly selective transformation can be performed with different amines and arylboronate esters. Additionally, the directing group can be cleaved, taking advantage of an unprecedented detrifluoromethylation reaction.

No MeSH data available.


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Mentions: Bis-arylation occurs due to a low energy barrier for rotation of the directing group around the C–N bond as observed for pyridine or the cyclic imine. Free rotation therefore allows insertion of the catalyst into both C–H bonds after complexation of the catalyst to the nitrogen of pyridine (Scheme 2). For this reason, it was envisioned to install a bulky group in 3-position of the pyridine directing group to hamper this free rotation, subsequently avoiding a second arylation step. The trifluoromethyl group was chosen for several reasons: (i) similar directing groups have already been successfully applied in direct arylation reactions [37–39]; (ii) it gave better results as compared with the simpler CH3 group (typically ~10 % better conversion); (iii) only mono-arylated product was obtained in the initial screening; and (iv) it is easy to install in good yields.


First selective direct mono-arylation of piperidines using ruthenium-catalyzed C-H activation.

Schwarz MC, Dastbaravardeh N, Kirchner K, Schnürch M, Mihovilovic MD - Monatsh. Chem. (2013)

© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4494768&req=5

Mentions: Bis-arylation occurs due to a low energy barrier for rotation of the directing group around the C–N bond as observed for pyridine or the cyclic imine. Free rotation therefore allows insertion of the catalyst into both C–H bonds after complexation of the catalyst to the nitrogen of pyridine (Scheme 2). For this reason, it was envisioned to install a bulky group in 3-position of the pyridine directing group to hamper this free rotation, subsequently avoiding a second arylation step. The trifluoromethyl group was chosen for several reasons: (i) similar directing groups have already been successfully applied in direct arylation reactions [37–39]; (ii) it gave better results as compared with the simpler CH3 group (typically ~10 % better conversion); (iii) only mono-arylated product was obtained in the initial screening; and (iv) it is easy to install in good yields.

Bottom Line: A Ru-catalyzed mono-arylation in α-position of saturated cyclic amines is reported employing a C-H activation protocol.Substitution of the pyridine directing group with a bulky group, e.g., trifluoromethyl in the 3-position, proved to be crucial to avoid bis-arylation.Additionally, the directing group can be cleaved, taking advantage of an unprecedented detrifluoromethylation reaction.

View Article: PubMed Central - PubMed

Affiliation: Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria.

ABSTRACT

Abstract: A Ru-catalyzed mono-arylation in α-position of saturated cyclic amines is reported employing a C-H activation protocol. Substitution of the pyridine directing group with a bulky group, e.g., trifluoromethyl in the 3-position, proved to be crucial to avoid bis-arylation. This highly selective transformation can be performed with different amines and arylboronate esters. Additionally, the directing group can be cleaved, taking advantage of an unprecedented detrifluoromethylation reaction.

No MeSH data available.


Related in: MedlinePlus