om7b00042_si_002.xyz (289.17 kB)
Effect of Substituent on the Mechanism and Chemoselectivity of the Gold(I)-Catalyzed Propargyl Ester Tandem Cyclization
dataset
posted on 2017-03-15, 12:53 authored by Yunhe Li, Alexander M. Kirillov, Ran Fang, Lizi YangThis study reports a detailed theoretical
analysis of the mechanisms
and chemoselectivity for the formation of benzo[b]fluorenes or benzofulvenes from propargyl esters catalyzed by an
organometallic Au(I) complex. Three different substitution patterns
within the 1,5-diyne ester substrates were explored to rationalize
the reaction mechanism and chemoselectivity. DFT calculations reveal
that the title reaction proceeds through four main steps: (i) 1,3-acyl-shift,
(ii) 6-endo-dig or 5-exo-dig cyclization, (iii) Friedel–Crafts-type,
and (iv) proton transfer, with step (ii) being rate-determining in
all studied pathways. In the absence of substituents at the aromatic
rings of the substrate (R = H), the 6-endo-dig cyclization is favored. In turn, in the presence of
one strong electron-donating substituent at the backbone (R = OCH3) of the substrate, the 5-exo-dig cyclization is favored. Besides, a modification of the substrate’s
acetyl group by a pivaloyl group leads to an activation barrier difference
between the 6-endo-dig and 5-exo-dig cyclizations, which increases and
suppresses the formation of benzofulvenes. The obtained theoretical
data are in a very good agreement with prior experimental evidence,
suggesting that the substituent plays a crucial role in the outcome
of the final product. High chemoselectivity can be explained by the
hindrance (torsional strain) along the forming C–C bond and
the carbocation stability provided by substituents.