Summary o-Benzynes (arynes) are among the most versatile of all reactive (short-lived) intermediates in organic chemistry. These species can be trapped to give products that are valuable from the perspective of both fine (pharmaceuticals) and commodity (agrochemicals, dyes, polymers, etc.) chemicals. Here we show a fundamentally new strategy that unites a de novo generation of benzynes, through the title hexadehydro-Diels–Alder (HDDA) reaction, with their in situ elaboration into structurally complex benzenoid products. In the HDDA reaction a 1,3-diyne is engaged in a [4+2] cycloisomerization with a third (pendant) alkyne–the diynophile–to produce the highly reactive benzyne intermediate. The metal- and reagent-free reaction conditions for this simple, thermal transformation are notable. The subsequent and highly efficient trapping reactions increase the power of the overall process. Finally, we provide examples of how this de novo benzyne generation approach allows new modes of intrinsic reactivity to be revealed.

A Ni-catalyzed reductive cross-coupling of styrenyl aziridines with aryl iodides is reported. This reaction proceeds by a stereoconvergent mechanism and is thus amenable to asymmetric catalysis using a chiral bioxazoline ligand for Ni. The process allows facile access to highly enantioenriched 2-arylphenethylamines from racemic aziridines. Multivariate analysis revealed that ligand polarizability, among other features, influences the observed enantioselectivity, shedding light on the success of this emerging ligand class for enantioselective Ni catalysis.

No abstract

The rates of the hexadehydro-Diels–Alder (HDDA) reaction of substrates containing, minimally, a 1,3,8-triyne subunit are reported. Several series of related substrates, differing in the nature of the three-atom tether that links the 1,3-diyne and diynophile, were examined. Seemingly small changes in substrate structure result in large differences in cyclization rate, spanning more than 8 orders of magnitude. The reactivity trends revealed by these studies should prove useful in guiding substrate design and choice of reaction conditions in future applications.

The hexadehydro-Diels–Alder (HDDA) cascade enables the synthesis of complex benzenoid products with various substitution patterns via aryne intermediates. The first stage of this cascade involves generation of a highly reactive ortho-benzyne intermediate by a net [4+2] cycloisomerization of a triyne substrate. The benzyne can be rapidly ‘trapped’ either intra- or intermolecularly with a myriad of nucleophilic or π-bond-donating reactants. As a representative example of a general procedure to synthesize highly substituted benzenoids, this protocol describes the synthesis of a typical triyne substrate and its use as the reactant in an HDDA cascade to form a phthalide. The synthetic procedure detailed herein (four chemical reactions) takes 16–20 h of active effort over a several day period for preparation of the triyne precursor and ~2 h of active effort over a 3-day period for generation and trapping of the benzyne and isolation of the phthalide product.