10 research outputs found
Beyond Frontier Molecular Orbital Theory: A Systematic Electron Transfer Model (ETM) for Polar Bimolecular Organic Reactions
Polar bimolecular reactions often begin as charge-transfer
complexes
and may proceed with a high degree of electron transfer character.
Frontier molecular orbital (FMO) theory is predicated in part on this
concept. We have developed an electron transfer model (ETM) in which
we <i>systematically</i> transfer one electron between reactants
and then use density functional methods to model the resultant radical
or radical ion intermediates. Sites of higher reactivity are revealed
by a composite spin density map (SDM) of odd electron character on
the electron density surface, assuming that a new two-electron bond
would occur preferentially at these sites. ETM correctly predicts
regio- and stereoselectivity for a broad array of reactions, including
DielsâAlder, dipolar and ketene cycloadditions, Birch reduction,
many types of nucleophilic additions, and electrophilic addition to
aromatic rings and polyenes. Conformational analysis of radical ions
is often necessary to predict reaction stereochemistry. The electronic
and geometric changes due to one-electron oxidation or reduction parallel
the reaction coordinate for electrophilic or nucleophilic addition,
respectively. The effect is more dramatic for one-electron reduction
A Computational Model for the Dimerization of Allene
Computations at the CCSDÂ(T)/6-311+GÂ(d,p)//B3LYP/6-311+GÂ(d,p)
level of theory support long-held beliefs that allene dimerization
to 1,2-dimethylenecyclobutane proceeds through diradical intermediates
rather than a concerted <sub>Ď</sub>2<sub>s</sub> + <sub>Ď</sub>2<sub>a</sub> mechanism. Two diastereomeric transition states with
orthogonal and skew geometries have been located for C2âC2
dimerization of allene, with predicted barriers of 34.5 and 40.3 kcal/mol,
respectively. In dimerization, the outward-facing ligands rotate in
a sense opposite to the forming CâC bond. Both transition states
lead to nearly orthogonal (D<sub>2</sub>) singlet bisallyl (or tetramethyleneethane)
diradical. This diradical has a barrier to planarization of 3.2 kcal/mol
through a planar D<sub>2h</sub> geometry and a barrier to methylene
rotation of 14.3 kcal/mol. Bisallyl diradical closes through one of
four degenerate paths by a conrotatory motion of the methylene groups
with a predicted barrier of 15.7 kcal/mol. The low barrier to planarization
of bisallyl, and similar barriers for methylene rotation and conrotatory
closure are consistent with a stepwise dimerization process which
can still maintain stereochemical elements of reactants. These computations
support the observation that racemic 1,3-disubstituted allenes, with
access to an orthogonal transition state which minimizes steric strain,
will dimerize more readily than enantiopure materials and by a mechanism
that preferentially bonds M and P enantiomers
Computational Studies on a Carbenoid Mechanism for the DoeringâMooreâSkattebøl Reaction
The
reaction of geminal dihalocyclopropanes with metals or alkyllithiums
affords carbenoids which undergo low-temperature ring opening to allenes;
this is known as the DoeringâMooreâSkattebøl reaction.
DFT and CCSDÂ(T)//DFT computations have been used to model the structure,
coordination state, and ring opening of 1-bromo-1-lithiocyclopropane
as a model for cyclopropylcarbenoid chemistry. Both implicit (PCM)
and explicit solvation models have been applied. Carbenoid ring opening
is similar to the process predicted in earlier studies on cyclopropylidene.
The initial disrotatory stereochemistry becomes conrotatory en route
to the alleneâLiBr complex. Predissociation of the carbenoid
to cyclopropylidene + LiBr is not supported by computations. DFT computations
predict modestly exergonic dimerization of the carbenoid, with or
without solvation, and the dimer appears to be the most likely reactive
species in solution. Predicted barriers to ring opening are only modestly
affected by solvation or by dimer formation, remaining in the range
of 9â12 kcal/mol throughout
Dehydropericyclic Reactions: Symmetry-Controlled Routes to Strained Reactive Intermediates
The
conceptual dehydrogenation of pericyclic reactions yields dehydropericyclic
processes, which usually lead to strained or reactive intermediates.
This is a simple scheme for inventing new chemical reactions. Computational
results on two novel dehydropericyclic reactions are presented here.
Conjugated enynes undergo a singlet-state photoisomerization that
transposes the methylene carbon. We previously suggested excited-state
closure to 1,2-cyclobutadiene followed by thermal ring opening. CCSDÂ(T)//DFT
computations show two minima of similar energy corresponding to 1,2-cyclobutadiene,
one chiral and closed shell and the second a planar diradical. The
chiral structure has a low barrier to ring opening and may best explain
results on enyne photoisomerization. The first examples of 1,3-diyne
+ yne cycloadditions to give <i>o</i>-benzynes were reported
in 1997. Computations on intramolecular versions of this tridehydro
(â3H<sub>2</sub>) DielsâAlder reaction support a concerted
mechanism for the parent triyne (1,3,8-nonatriyne); however, a slight
electronic advantage in the concerted path may be outweighed by the
difference in entropy of activation for sequential vs simultaneous
formation of two new ring bonds
Phenyl Shifts in Substituted Arenes via <i>Ipso</i> Arenium Ions
The isomerization of substituted arenes through <i>ipso</i> arenium ions is an important and general molecular
rearrangement that leads to interconversions of constitutional isomers.
We show here that the superacid trifluoromethanesulfonic acid (TfOH),
ca. 1 M in dichloroethane (DCE), provides reliable catalytic reaction
conditions for these rearrangements, easily applied at ambient temperature,
reflux (84 °C), or in a microwave reactor for higher temperatures.
Interconversion of terphenyl isomers in TfOH/DCE at 84 °C gives
an <i>ortho</i>/<i>meta</i>/<i>para</i> equilibrium ratio of 0:65:35, nearly identical to values reported
earlier by Olah with catalysis by AlCl<sub>3</sub>. For the three
triphenylbenzenes, TfOH-catalyzed equilibration strongly (>95%)
favors the 1,3,5-triphenyl isomer. Equilibration of the three possible
tetraphenylbenzenes gives a 61:39 mixture of the 1,2,3,5- and 1,2,4,5-substituted
isomers. Under the reaction conditions explored, none of these structures
undergoes significant Scholl cyclization. DFT calculations with inclusion
of solvation support a mechanistic scheme in which all of the phenyl
migrations occur among a series of <i>ipso</i> arenium ions.
In every case studied, the preferred isomers at equilibrium are those
that yield highly stable cations by the most exothermic, hence least
reversible 1,2-H shift
Acid-Catalyzed Skeletal Rearrangements in Arenes: Aryl versus Alkyl Ring Pirouettes in Anthracene and Phenanthrene
In
1 M triflic acid/dichloroethane, anthracene is protonated at
C9, and the resulting 9-anthracenium ion is easily observed by NMR
at ambient temperature. When heated as a dilute solution in triflic
acid/dichloroethane, anthracene undergoes conversion to phenanthrene
as the major volatile product. Minor dihydro and tetrahydro products
are also observed. MALDI analysis supports the simultaneous formation
of oligomers, which represent 10â60% of the product. Phenanthrene
is nearly inert to the same superacid conditions. DFT and CCSDÂ(T)//DFT
computational models were constructed for isomerization and automerization
mechanisms. These reactions are believed to occur by cationic ring
pirouettes which pass through spirocyclic intermediates. The direct
aryl pirouette mechanism for anthracene has a predicted DFT barrier
of 33.6 kcal/mol; this is too high to be consistent with experiment.
The ensemble of experimental and computational models supports a multistep
isomerization process, which proceeds by reduction to 1,2,3,4-tetrahydroanthracene,
acid-catalyzed isomerization to 1,2,3,4-tetrahydrophenanthrene with
a predicted DFT barrier of 19.7 kcal/mol, and then reoxidation to
phenanthrene. By contrast, DFT computations support a direct pirouette
mechanism for automerization of outer ring carbons in phenanthrene,
a reaction demonstrated previously by Balaban through isotopic labeling
Scholl Cyclizations of Aryl Naphthalenes: Rearrangement Precedes Cyclization
In
1910, Scholl, Seer, and Weitzenbock reported the AlCl<sub>3</sub>-catalyzed
cyclization of 1,1â˛-binaphthyl to perylene. We provide evidence
that this classic organic name reaction proceeds through sequential
and reversible formation of 1,2â˛- and 2,2â˛-binaphthyl
isomers. Acid-catalyzed isomerization of 1,1â˛-binaphthyl to
2,2â˛-binaphthyl has been noted previously. The superacid trifluoromethanesulfonic
acid (TfOH), 1 M in dichloroethane, catalyzes these rearrangements,
with slower cyclization to perylene. Minor cyclization products are
benzoÂ[<i>k</i>]Âfluoranthene and benzoÂ[<i>j</i>]Âfluoranthene. At ambient temperature, the observed equilibrium ratio
of 1,1â˛-binaphthyl, 1,2â˛-binaphthyl, and 2,2â˛-binaphthyl
is <1:3:97. DFT calculations with the inclusion of solvation support
a mechanistic scheme in which <i>ipso</i>-arenium ions are
responsible for rearrangements; however, we cannot distinguish between
arenium ion and radical cation mechanisms for the cyclization steps.
Under similar reaction conditions, 1-phenylnaphthalene interconverts
with 2-phenylnaphthalene, with the latter favored at equilibrium (5:95
ratio), and also converts slowly to fluoranthene. Computations again
support an arenium ion mechanism for rearrangements
Biomimetic Total Synthesis of (Âą)-Griffipavixanthone via a Cationic CycloadditionâCyclization Cascade
We
report the concise, biomimetic total synthesis of the dimeric,
DielsâAlder natural product griffiÂpaviÂxanthone
from a readily accessible prenylated xanthone monomer. The key step
utilizes a novel interÂmolecular [4+2] cycloadditionâcyclization
cascade between a vinyl <i>p-</i>quinone methide and an <i>in situ</i> generated isomeric diene promoted by either Lewis
or Brønsted acids. Experimental and computational studies of
the reaction pathway suggest that a stepwise, cationic DielsâAlder
cycloaddition is operative
Concerted vs Stepwise Mechanisms in Dehydro-DielsâAlder Reactions
The DielsâAlder reaction is not limited to 1,3-dienes.
Many cycloadditions of enynes and a smaller number of examples with
1,3-diynes have been reported. These âdehydroâ-DielsâAlder
cycloadditions are one class of dehydropericyclic reactions which
have long been used to generate strained cyclic allenes and other
novel structures. CCSDÂ(T)//M05-2X computational results are reported
for the cycloadditions of vinylacetylene and butadiyne with ethylene
and acetylene. Both concerted and stepwise diradical routes have been
explored for each reaction, with location of relevant stationary points.
Relative to 1,3-dienes, replacement of one double bond by a triple
bond adds 6â6.5 kcal/mol to the activation barrier; a second
triple bond adds 4.3â4.5 kcal/mol to the barrier. Product strain
decreases the predicted exothermicity. In every case, a concerted
reaction is favored energetically. The difference between concerted
and stepwise reactions is 5.2â6.6 kcal/mol for enynes but diminishes
to 0.5â2 kcal/mol for diynes. Experimental studies on intramolecular
diyne + ene cycloadditions show two distinct reaction pathways, providing
evidence for competing concerted and stepwise mechanisms. Diyne +
yne cycloadditions connect with arynes and ethynyl-1,3-cyclobutadiene.
This potential energy surface appears to be flat, with only a minute
advantage for a concerted process; many diyne cycloadditions or aryne
cycloreversions will proceed by a stepwise mechanism
Microwave-Based Reaction Screening: Tandem Retro-DielsâAlder/DielsâAlder Cycloadditions of <i>o</i>-Quinol Dimers
We have accomplished a parallel screen of cycloaddition
partners
for <i>o</i>-quinols utilizing a plate-based microwave system.
Microwave irradiation improves the efficiency of retro-DielsâAlder/DielsâAlder
cascades of <i>o-</i>quinol dimers which generally proceed
in a diastereoselective fashion. Computational studies indicate that
asynchronous transition states are favored in DielsâAlder cycloadditions
of <i>o</i>-quinols. Subsequent biological evaluation of
a collection of cycloadducts has identified an inhibitor of activator
protein-1 (AP-1), an oncogenic transcription factor