Understanding the Origin of the Regioselectivity in Cyclopolymerizations of Diynes and How to Completely Switch It

Grubbs-type olefin metathesis catalysts are known to cyclopolymerize 1,6-heptadiynes to afford conjugated polyenes containing five- or six-membered carbocycles. Although high levels of regioselectivity up to >99:1 were observed previously for the formation of five-membered rings, it was neither possible to deliberately obtain six-membered rings at similar levels of selectivity nor understood why certain catalysts showed this selectively. Combining experimental and computational methods, a novel and general theory for what controls the regiochemistry of these cyclopolymerizations is presented. The electronic demands of the ruthenium-based Fischer carbenes are found to innately prefer to form five-membered rings. Reducing the electrophilicity of the carbene by enforcing a trigonal-bipyramidal structure for the ruthenium, where stronger π-backdonation increases the electron density on the carbene, is predicted to invert the regioselectivity. Subsequent experiments provide strong support for the new concept, and it is possible to completely switch the regioselectivity to a ratio of <1:99

Room-Temperature Ring-Opening of Quinoline, Isoquinoline, and Pyridine with Low-Valent Titanium

The complex (PNP)­TiCH^<i>t</i>Bu­(CH₂^<i>t</i>Bu) (PNP = N­[2-P^<i>i</i>Pr₂-4-methyl­phenyl]₂^–) dehydrogenates cyclo­hexane to cyclo­hexene by forming a transient low-valent titanium-alkyl species, [(PNP)­Ti­(CH₂^<i>t</i>Bu)], which reacts with 2 equiv of quinoline (<b>Q</b>) at room temperature to form H₃C^<i>t</i>Bu and a Ti­(IV) species where the less hindered C₂N₁ bond of <b>Q</b> is ruptured and coupled to another equivalent of <b>Q</b>. The product isolated from this reaction is an imide with a tethered cyclo­amide group, (PNP)­TiN­[C₁₈H₁₃N] (<b>1</b>). Under photolytic conditions, intra­molecular CH bond activation across the imide moiety in <b>1</b> occurs to form <b>2</b>, and thermolysis reverses this process. The reaction of 2 equiv of isoquinoline (<b>Iq</b>) with intermediate [(PNP)­Ti­(CH₂^<i>t</i>Bu)] results in regio­selective cleavage of the C₁N₂ and C₁H bonds, which eventually couple to form complex <b>3</b>, a constitutional isomer of <b>1</b>. Akin to <b>1</b>, the transient [(PNP)­Ti­(CH₂^<i>t</i>Bu)] complex can ring-open and couple two pyridine molecules, to produce a close analogue of <b>1</b>, complex (PNP)­TiN­[C₁₀H₉N] (<b>4</b>). Multi­nuclear and multi­dimensional NMR spectra confirm structures for complexes <b>1</b>–<b>4</b>, whereas solid-state structural analysis reveals the structures of <b>2</b>, <b>3</b>, and <b>4</b>. DFT calculations suggest an unprecedented mechanism for ring-opening of <b>Q</b> where the reactive intermediate in the low-spin manifold crosses over to the high-spin surface to access a low-energy transition state but returns to the low-spin surface immediately. This double spin-crossover constitutes a rare example of a two-state reactivity, which is key for enabling the reaction at room temperature. The regio­selective behavior of <b>Iq</b> ring-opening is found to be due to electronic effects, where the aromatic resonance of the bicycle is maintained during the key CC coupling event