Computational and Experimental Confirmation of the Diradical Character of para-Quinonedimethide.

The ground-state structure of the parent para-quinonedimethide (p-QDM) molecule is generally represented in its closed shell form, i.e., as a cyclic, nonaromatic, through-conjugated/cross-conjugated hybrid comprising four C═C bonds. Nonetheless, p-QDM has been theorized to contain a contribution from its open-shell aromatic singlet diradical form. VBSCF calculations identify an open-shell contribution of 29% to the structure, while CASPT2(16,16)/def2-TZVP and ωB97XD/aug-cc-pVTZ calculations predict that dimerization proceeds along an open-shell singlet diradical pathway with a low (77 kJ/mol) barrier toward dimerization, which occurs by way of C-C bond formation between the exocyclic methylene carbons. A similar low (98 kJ/mol) barrier exists toward the reaction between a p-QDM molecule and the radical trap TEMPO. These predictions are verified experimentally through the isolation of bis-TEMPO-trapped p-QDM, its C-C coupled dimer, and by demonstrating that a mixture of p-QDM and TEMPO can initiate the radical polymerization of n-butyl acrylate at ambient temperature. In contrast to p-QDM, tetracyanoquinone (TCNQ) neither dimerizes nor reacts with TEMPO, despite having a similar diradical character to p-QDM. This lack of reactivity is consistent with both a higher kinetic barrier and a thermodynamically unfavorable process, which is ascribed to destabilizing steric clashes and polar effects.

Total Synthesis of Matrine Alkaloids.

The total synthesis of three diastereomeric matrine natural products is reported. The 8-step synthesis commences with simple acyclic precursors, forms all 4 rings of the tetracyclic natural product framework, and forges 10 of the 20 covalent bonds of the target structure. A cross-conjugated triene is positioned at the core of an acyclic branched structure. This precursor collapses to the tetracyclic natural product framework through an orchestrated sequence of two separate intramolecular cycloadditions. A subsequent, late-stage hydrogenation is accompanied by strain-release redox epimerizations to deliver the three natural products. An unprecedented carba-analogue is prepared in the same way. Semisynthetic manipulations of matrine provide access to 10 additional natural products.

A General Stereoselective Synthesis of [4]Dendralenes.

The first general synthesis of branched tetraenes ([4]dendralenes) involves two or three steps from inexpensive, commodity chemicals. It involves an unprecedented variation on Suzuki-Miyaura cross-coupling, generating two new C-C bonds in a one-flask operation with control of diastereoselectivity. The broad scope of the method is established through the synthesis of more than 60 diversely substituted [4]dendralene molecules, along with substituted buta-1,3-dienes and other [n]dendralenes. [4]Dendralenes are demonstrated to be significantly more kinetically stable than their well-known [3]dendralene counterparts. The first stereoselective synthesis of these compounds is also reported, through the catalyst-controlled generation of both E- and Z-diastereomeric products from the same precursor. Novel, through-conjugated/cross-conjugated hybrid molecules are introduced. The first selective dienophile cycloadditions to substituted [4]dendralenes are reported, thus paving the way for applications in target-oriented synthesis.

Substituted Tetraethynylethylene-Tetravinylethylene Hybrids.

A general synthetic approach to molecular structures that are hybrids of tetraethynylethylene (TEE) and tetravinylethylene (TVE) is reported. The synthesis permits the controlled preparation of many previously inaccessible structures, including examples with different substituents on each of the four branching arms. Most substituted TVE-TEE hybrids are found to be significantly more robust compounds than their unsubstituted counterparts, enhancing the prospects of their deployment in conducting materials and devices. Their participation in pericyclic reaction cascades, leading to sp3-rich polycycles, is demonstrated. The utilization of TEE-TVE hybrids as building blocks for larger acyclic, through/cross-conjugated hydrocarbon frameworks is also established. Aryl-substituted TEEs, TVEs, and their hybrids are fluorescent, with some exhibiting aggregation-induced emission enhancement. The structural requirements are defined and explained, setting the scene for applications as fluorescent probes and organic light-emitting diodes.

Five Step Total Synthesis of Lythranidine.

A concise synthesis of the alkaloid lythranidine is reported. The strategy exploits the target's local C2 symmetry by adopting a two directional synthetic approach, first in an acyclic environment, then in a cyclic system and finally in a bridged macrocyclic domain. The latter phase of the synthesis, which installs all four stereocenters, involves a thermodynamically controlled, twofold intermolecular/transannular aza-Michael addition and a twofold hydride reduction. The synthesis is one third of the length of the most step-economic previous approach, providing access to gram quantities of the natural product. The broad-spectrum nature of the synthesis is demonstrated through the preparation of three diastereomeric analogues of the natural product.

Unlocking Acyclic π-Bond Rich Structure Space with Tetraethynylethylene-Tetravinylethylene Hybrids.

Literature reports describe tetraethynylethylene (TEE) as unstable but tetravinylethylene (TVE) as stable. The stabilities of these two known compounds are reinvestigated, along with those of five unprecedented TEE-TVE hybrid compounds. The five new C10 hydrocarbons possess a core, tetrasubstituted C═C bond carrying all possible combinations of vinyl and ethynyl groups. A unified strategy is described for their synthesis, whereupon cross-conjugated ketones are dibromo-olefinated then cross-coupled. Due to an incorrect but nonetheless widely held belief that acyclic π-bond rich hydrocarbons are inherently unstable, a standardized set of robustness tests is introduced. Whereas only TVE survives storage in neat form, all seven hydrocarbons are remarkably robust in dilute solution, generally surviving exposure to moderate heat, light, air, and acid. The first X-ray crystal structure of TEE is reported. Subgroups of hybrids based upon conformational preferences are identified through electronic absorption spectra and associated computational studies. These new acyclic π-bond rich systems have extensive, untapped potential for the production of stable, conjugated carbon-rich materials.