TY - JOUR
T1 - Kinetics of the Strain-Promoted Oxidation-Controlled Cycloalkyne-1,2-quinone Cycloaddition
T2 - Experimental and Theoretical Studies
AU - Escorihuela, Jorge
AU - Das, Anita
AU - Looijen, Wilhelmus J.E.
AU - Van Delft, Floris L.
AU - Aquino, Adelia J.A.
AU - Lischka, Hans
AU - Zuilhof, Han
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2018/1/5
Y1 - 2018/1/5
N2 - Stimulated by its success in both bioconjugation and surface modification, we studied the strain-promoted oxidation-controlled cycloalkyne-1,2-quinone cycloaddition (SPOCQ) in three ways. First, the second-order rate constants and activation parameters (δH‡) were determined of various cyclooctynes reacting with 4-tert-butyl-1,2-quinone in a SPOCQ reaction, yielding values for δH‡ of 4.5, 7.3, and 12.1 kcal/mol, for bicyclo[6.1.0]non-4-yne (BCN), cyclooctyne (OCT), and dibenzoazacyclooctyne (DIBAC), respectively. Second, their reaction paths were investigated in detail by a range of quantum mechanical calculations. Single-configuration theoretical methods, like various DFT and a range of MP2-based methods, typically overestimate this barrier by 3-8 kcal/mol (after inclusion of zero-point energy, thermal, and solvation corrections), whereas MP2 itself underestimates the barrier significantly. Only dispersion-corrected DFT methods like B97D (yielding 4.9, 6.4, and 12.1 kcal/mol for these three reactions) and high-level CCSD(T) and multireference multiconfiguration AQCC ab initio approaches (both yielding 8.2 kcal/mol for BCN) give good approximations of experimental data. Finally, the multireference methods show that the radical character in the TS is rather small, thus rationalizing the use of single-reference methods like B97D and SCS-MP2 as intrinsically valid approaches.
AB - Stimulated by its success in both bioconjugation and surface modification, we studied the strain-promoted oxidation-controlled cycloalkyne-1,2-quinone cycloaddition (SPOCQ) in three ways. First, the second-order rate constants and activation parameters (δH‡) were determined of various cyclooctynes reacting with 4-tert-butyl-1,2-quinone in a SPOCQ reaction, yielding values for δH‡ of 4.5, 7.3, and 12.1 kcal/mol, for bicyclo[6.1.0]non-4-yne (BCN), cyclooctyne (OCT), and dibenzoazacyclooctyne (DIBAC), respectively. Second, their reaction paths were investigated in detail by a range of quantum mechanical calculations. Single-configuration theoretical methods, like various DFT and a range of MP2-based methods, typically overestimate this barrier by 3-8 kcal/mol (after inclusion of zero-point energy, thermal, and solvation corrections), whereas MP2 itself underestimates the barrier significantly. Only dispersion-corrected DFT methods like B97D (yielding 4.9, 6.4, and 12.1 kcal/mol for these three reactions) and high-level CCSD(T) and multireference multiconfiguration AQCC ab initio approaches (both yielding 8.2 kcal/mol for BCN) give good approximations of experimental data. Finally, the multireference methods show that the radical character in the TS is rather small, thus rationalizing the use of single-reference methods like B97D and SCS-MP2 as intrinsically valid approaches.
UR - http://www.scopus.com/inward/record.url?scp=85042059788&partnerID=8YFLogxK
U2 - 10.1021/acs.joc.7b02614
DO - 10.1021/acs.joc.7b02614
M3 - Article
C2 - 29260879
AN - SCOPUS:85042059788
SN - 0022-3263
VL - 83
SP - 244
EP - 252
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 1
ER -