10.1021/ja0033032.s002
Graham B. Jones
Graham B.
Jones
Philip M. Warner
Philip M.
Warner
Electronic Control of the Bergman Cyclization: The Remarkable Role
of Vinyl Substitution
American Chemical Society
2001
h abstraction reactivity
heteroaromatic rings
44 cyclization transition states
Remarkable Role
cycloaromatization
Density Functional Theory
benzyne
cyclization barrier
Bergman cyclization
MR
46 enediynes
Vinyl Substitution
groups decrease
calculation
Electronic Control
triplet p
BLYP version
H abstraction step
π conjugation
rate inhibitions
isodesmic equations
annulated examples
level Brueckner
prodrug candidates
vinyl substitution
ab initio study
heteroaromatic systems
Unexpected behavior
39 singlet p
2001-02-16 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Electronic_Control_of_the_Bergman_Cyclization_The_Remarkable_Role_of_Vinyl_Substitution/3631569
We report an ab initio study of the effect of vinyl substitution on the cycloaromatization of 3-ene-1,5-diynes (the Bergman cyclization). The majority of the calculations were conducted by using the BLYP
version of Density Functional Theory, and higher level Brueckner orbital calculations were used for a few key
compounds. In all, 46 enediynes, 44 cyclization transition states, 39 singlet <i>p</i>-benzynes, and 28 related triplet
<i>p</i>-benzynes were studied, including simple vinyl-substituted and annulated examples. The data indicate that
strongly electron-withdrawing groups increase the cyclization barrier, while σ-donating groups decrease it; π
conjugation, especially donation, has little effect. Most annulations, including those involving heteroaromatic
rings, lower the barrier slightly (6 MR) or raise it slightly (5 MR). Larger effects are seen for smaller rings or
charged rings. Some previously observed apparent rate inhibitions are seen to be due to reversibility or forward
reactivity of the intermediate <i>p</i>-benzynes, which are thereby inhibited from the H abstraction step that completes
cycloaromatization. H abstraction reactivity, as judged from the <i>p</i>-benzyne singlet−triplet energy gap and
from isodesmic equations, is also examined. Unexpected behavior is predicted for some heteroaromatic systems.
Finally, we anticipate how these results may be applied to the design of prodrug candidates for subsequent
biological application.