Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series.

Arenes undergo rearrangement of phenyl, alkyl, halogen and other groups through the intermediacy of ipso arenium ions in which a proton is attached at the same carbon as the migrating substituent. Interconversions among the six quaterphenyl isomers have been studied here as a model for rearrangements of linear polyphenyls. All reactions were carried out in 1 M CF3SO3H (TfOH) in dichloroethane at 150 °C in a microwave reactor for 30-60 min, with product formation assessed by high field NMR analysis. Under these reaction conditions, m,p'-quaterphenyl is the equilibrium product. This isomer is unchanged by the reaction conditions and all other quaterphenyl isomers rearrange to m,p' as the dominant or sole product. DFT computations with inclusion of implicit solvation support a complex network of phenyl and biphenyl shifts, with barriers to rearrangement in the range of 10-21 kcal/mol. Consistent with experiments, the lowest energy arenium ion located on this surface is due to protonation of m,p'-quaterphenyl. This supports thermodynamic control based on carbocation energies.

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 10-60% of the product. Phenanthrene is nearly inert to the same superacid conditions. DFT and CCSD(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 AlCl3-catalyzed cyclization of 1,1'-binaphthyl to perylene. We provide evidence that this classic organic name reaction proceeds through sequential and reversible formation of 1,2'- and 2,2'-binaphthyl isomers. Acid-catalyzed isomerization of 1,1'-binaphthyl to 2,2'-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 benzo[k]fluoranthene and benzo[j]fluoranthene. At ambient temperature, the observed equilibrium ratio of 1,1'-binaphthyl, 1,2'-binaphthyl, and 2,2'-binaphthyl is <1:3:97. DFT calculations with the inclusion of solvation support a mechanistic scheme in which ipso-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.

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. CCSD(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 o-benzynes were reported in 1997. Computations on intramolecular versions of this tridehydro (-3H2) Diels-Alder 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.

Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer.

Chiral, dimeric natural products containing complex structures and interesting biological properties have inspired chemists and biologists for decades. A seven-step total synthesis of the axially chiral, dimeric tetrahydroxanthone natural product rugulotrosin A is described. The synthesis employs a one-pot Suzuki coupling/dimerization to generate the requisite 2,2'-biaryl linkage. Highly selective point-to-axial chirality transfer was achieved using palladium catalysis with achiral phosphine ligands. Single X-ray crystal diffraction data were obtained to confirm both the atropisomeric configuration and absolute stereochemistry of rugulotrosin A. Computational studies are described to rationalize the atropselectivity observed in the key dimerization step. Comparison of the crude fungal extract with synthetic rugulotrosin A and its atropisomer verified that nature generates a single atropisomer of the natural product.