TY - JOUR
T1 - Mechanistic Insights into the B(C6F5)3-Initiated Aldehyde-Aniline-Alkyne Reaction to Form Substituted Quinolines
AU - Fasano, Valerio
AU - Radcliffe, James E.
AU - Ingleson, Michael J.
PY - 2017/4/24
Y1 - 2017/4/24
N2 - A substoichiometric quantity of the Lewis acid B(C6F5)3 is sufficient to initiate the aldehyde-amine-alkyne reaction, in a one-pot methodology that enables the synthesis of a range of functionalized quinolines. Optimization studies revealed that key requirements for the high-yielding tricomponent reaction initiated by B(C6F5)3 at raised temperatures include an excess of the in situ generated imine (which acts as a hydrogen acceptor) and an alkyne substituent able to stabilize positive charge buildup during the cyclization. Mechanistic experiments revealed that under these conditions B(C6F5)3 is acting as a Lewis acid-assisted Brønsted acid, with H2O-B(C6F5)3 being the key species enabling catalytic quinoline formation. This was indicated by deuterium labeling studies and the observation that the cyclization of N-(3-phenylpropargyl)aniline using B(C6F5)3 under anhydrous conditions afforded the zwitterion [(N-H-3-B(C6F5)3-4-Ph-quinolinium], which does not undergo protodeboronation to release B(C6F5)3 and the quinoline product under a range of conditions. Finally, a brief substrate scope exploration demonstrated that this is an operationally simple and effective methodology for the production of functionalized quinolines.
AB - A substoichiometric quantity of the Lewis acid B(C6F5)3 is sufficient to initiate the aldehyde-amine-alkyne reaction, in a one-pot methodology that enables the synthesis of a range of functionalized quinolines. Optimization studies revealed that key requirements for the high-yielding tricomponent reaction initiated by B(C6F5)3 at raised temperatures include an excess of the in situ generated imine (which acts as a hydrogen acceptor) and an alkyne substituent able to stabilize positive charge buildup during the cyclization. Mechanistic experiments revealed that under these conditions B(C6F5)3 is acting as a Lewis acid-assisted Brønsted acid, with H2O-B(C6F5)3 being the key species enabling catalytic quinoline formation. This was indicated by deuterium labeling studies and the observation that the cyclization of N-(3-phenylpropargyl)aniline using B(C6F5)3 under anhydrous conditions afforded the zwitterion [(N-H-3-B(C6F5)3-4-Ph-quinolinium], which does not undergo protodeboronation to release B(C6F5)3 and the quinoline product under a range of conditions. Finally, a brief substrate scope exploration demonstrated that this is an operationally simple and effective methodology for the production of functionalized quinolines.
UR - http://www.scopus.com/inward/record.url?scp=85018550621&partnerID=8YFLogxK
U2 - 10.1021/acs.organomet.7b00174
DO - 10.1021/acs.organomet.7b00174
M3 - Article (Academic Journal)
AN - SCOPUS:85018550621
SN - 0276-7333
VL - 36
SP - 1623
EP - 1629
JO - Organometallics
JF - Organometallics
IS - 8
ER -