A Computational Study on the Addition of HONO to Alkynes toward the Synthesis of Isoxazoles; a Bifurcation, Pseudopericyclic Pathways and a Barrierless Reaction on the Potential Energy Surface

Homopropargyl alcohols react with <i>t-</i>BuONO to form acyloximes which can be oxidatively cyclized to yield ioxazoles. The mechanism for the initial reaction of HONO with alkynes to form acyloximes (e.g., <b>13c</b>) has been explored at the B3LYP/6-31G­(d,p) + ZPVE level of theory. The observed chemoselectivity and regioselectivity are explained via an acid-catalyzed mechanism. Furthermore, the potential energy surface revealed numerous surprising features. The addition of HONO (<b>8</b>) to protonated 1-phenylpropyne (<b>18</b>) is calculated to follow a reaction pathway involving sequential transition states (<b>TS6</b> and <b>TS8</b>), for which reaction dynamics likely play a role. This reaction pathway can bypass the expected addition product <b>21</b> as well as transition state <b>TS8</b>, directly forming the rearranged product <b>23</b>. Nevertheless, <b>TS8</b> is key to understanding the potential energy surface; there is a low barrier for the pseudopericylic [1,3]-NO shift, calculated to be only 8.4 kcal/mol above <b>21</b>. This places <b>TS8</b> well below <b>TS6</b>, making the valley-ridge inflection point (VRI or bifurcation) and direct formation of <b>23</b> possible. The final tautomerization step to the acyloxime can be considered to be a [1,5]-proton shift. However, the rearrangement in the case of <b>17h</b> to <b>13c</b> is calculated to be barrierless, arguably because the pathway is pseudopericyclic and exothermic

Competitive Pseudopericyclic [3,3]- and [3,5]-Sigmatropic Rearrangements of Trichloroacetimidates

The Woodward–Hoffmann rules predict whether concerted pericyclic reactions are allowed or forbidden based on the number of electrons involved and whether the cyclic orbital overlap involves suprafacial or antarafacial orbital overlap. Pseudopericyclic reactions constitute a third class of reactions in which orthogonal orbitals make them orbital symmetry allowed, regardless of the number of electrons involved in the reaction. Based on the recent report of eight-centered ester rearrangements, it is predicted that the isoelectronic eight-centered rearrangements of imidates would also be allowed. We now report that these rearrangements occur, and indeed, an eight-centered rearrangement is slightly favored in at least one case over the well-known six-centered Overman rearrangements, in a trichloroacetimidoylcyclohexadienone, a molecular system where both rearrangements are possible

Competitive Pseudopericyclic [3,3]- and [3,5]-Sigmatropic Rearrangements of Trichloroacetimidates

The Woodward–Hoffmann rules predict whether concerted pericyclic reactions are allowed or forbidden based on the number of electrons involved and whether the cyclic orbital overlap involves suprafacial or antarafacial orbital overlap. Pseudopericyclic reactions constitute a third class of reactions in which orthogonal orbitals make them orbital symmetry allowed, regardless of the number of electrons involved in the reaction. Based on the recent report of eight-centered ester rearrangements, it is predicted that the isoelectronic eight-centered rearrangements of imidates would also be allowed. We now report that these rearrangements occur, and indeed, an eight-centered rearrangement is slightly favored in at least one case over the well-known six-centered Overman rearrangements, in a trichloroacetimidoylcyclohexadienone, a molecular system where both rearrangements are possible

Experimental and Computational Studies on the [3,3]- and [3,5]-Sigmatropic Rearrangements of Acetoxycyclohexadienones: A Non-ionic Mechanism for Acyl Migration

Flash vacuum pyrolysis studies of substituted 6-acetoxy-2,4-cyclohexadienones (<b>3</b> and <b>10</b>) from 300 to 500 °C provide strong experimental evidence that direct [3,5]-sigmatropic rearrangements in these molecules are favored over the more familiar [3,3]-sigmatropic rearrangements. The preference holds when the results are extrapolated to 0.0% conversion, indicating that this is a concerted process. Pyrolysis of 6,6-diacetoxy-2-methyl-2,4-cyclohexadienone (<b>9</b>) at 350 °C gives a modest yield of the initial [3,5]-sigmatropic rearrangement product, 2,6-diacetoxy-6-methyl-2,4-cyclohexadienone (<b>11</b>). Qualitative arguments and electronic structure theory calculations are in agreement that the lowest energy pathway for each [3,5]-sigmatropic rearrangement is via an allowed, concerted pseudopericyclic transition state. The crystal structures of compounds <b>3</b>, <b>9</b>, and <b>10</b> prefigure these transition states. The selectivity for the [3,5] products increases with an increasing temperature. This unexpected selectivity is explained by a concerted, intramolecular, and pseudopericyclic transition state (<b>TS-5</b>) that forms a tetrahedral interemediate (<i>ortho</i>-acid ester <b>4′</b>), followed by similar ring openings to isomeric phenols, which shifts the equilibrium toward the phenols from the [3,5] (but not the [3,3]) products

Experimental and Computational Studies on the [3,3]- and [3,5]-Sigmatropic Rearrangements of Acetoxycyclohexadienones: A Non-ionic Mechanism for Acyl Migration

Flash vacuum pyrolysis studies of substituted 6-acetoxy-2,4-cyclohexadienones (<b>3</b> and <b>10</b>) from 300 to 500 °C provide strong experimental evidence that direct [3,5]-sigmatropic rearrangements in these molecules are favored over the more familiar [3,3]-sigmatropic rearrangements. The preference holds when the results are extrapolated to 0.0% conversion, indicating that this is a concerted process. Pyrolysis of 6,6-diacetoxy-2-methyl-2,4-cyclohexadienone (<b>9</b>) at 350 °C gives a modest yield of the initial [3,5]-sigmatropic rearrangement product, 2,6-diacetoxy-6-methyl-2,4-cyclohexadienone (<b>11</b>). Qualitative arguments and electronic structure theory calculations are in agreement that the lowest energy pathway for each [3,5]-sigmatropic rearrangement is via an allowed, concerted pseudopericyclic transition state. The crystal structures of compounds <b>3</b>, <b>9</b>, and <b>10</b> prefigure these transition states. The selectivity for the [3,5] products increases with an increasing temperature. This unexpected selectivity is explained by a concerted, intramolecular, and pseudopericyclic transition state (<b>TS-5</b>) that forms a tetrahedral interemediate (<i>ortho</i>-acid ester <b>4′</b>), followed by similar ring openings to isomeric phenols, which shifts the equilibrium toward the phenols from the [3,5] (but not the [3,3]) products