Syntheses of strained cyclic dienes were accomplished via palladium(II)-catalyzed oxidative cyclizations of terminal bis(vinylboronate esters). The reactions generate strained (E,E)-1,3-dienes that undergo spontaneous 4π-electrocyclizations to form bicyclic cyclobutenes. Formation of the cyclobutenes is driven by the strain in the medium-ring (E,E)-1,3-diene intermediate. Thermal ring openings of the cyclobutenes give (Z,Z)-1,3-diene products, again for thermodynamic reasons. DFT calculations verified the thermodynamic versus kinetic control of the reactions, and kinetic studies are in excellent agreement with the calculated energy changes. An extension of the tandem coupling/4π-electrocyclization pathway was demonstrated by a palladium(II)-catalyzed oxidative homocoupling/8π-electrocyclization cascade.

The Pauson–Khand reaction is a powerful tool for the synthesis of cyclopentenones through the efficient [2 + 2 + 1] cycloaddition of dicobalt alkyne complexes with alkenes. While intermolecular and intramolecular variants are widely known, transannular versions of this reaction are unknown and the basis of this study. Macrocyclic enyne and dienyne complexes were readily synthesized by palladium(II)-catalyzed oxidative macrocyclizations of bis(vinyl boronate esters) or ring-closing metathesis reactions followed by complexation with dicobalt octacarbonyl. Several reaction modalities of these macrocyclic complexes were uncovered. In addition to the first successful transannular Pauson–Khand reactions, other intermolecular and transannular cycloaddition reactions included intermolecular Pauson–Khand reactions, transannular [4 + 2] cycloaddition reactions, intermolecular [2 + 2 + 2] cycloaddition reactions, and intermolecular [2 + 2 + 1 + 1] cycloaddition reactions. The structural and reaction requirements for each process are presented.

The first transannular [4 + 2] cycloaddition reactions of macrocyclic dicobalt hexacarbonyl–dienyne complexes were demonstrated. Complexes were conveniently prepared through palladium(II)-catalyzed intramolecular oxidative cyclization of bis(vinylboronate esters) followed by complexation with dicobalt octacarbonyl. Transannular [4 + 2] cycloaddition reactions of the complexes occurred at lower temperatures and shorter times than transannular Diels–Alder reactions of metal-free dienynes. Intermolecular control reactions confirmed the effect of cobalt complexation on [4 + 2] cycloaddition reactions of unactivated alkynes and dienes.

A new strategy to access macrocyclic enynes was developed. To block undesired ene–yne cyclization pathways, alkynes were protected via bromination and the resultant acyclic vic-(E)-dibromotrienes participated in selective ene–ene ring closing metathesis reactions. Zinc-promoted deprotection of (E)-dibromodienes provided macrocyclic enynes in high yields.

Density functional theory calculations were performed on a set of 13 transannular Diels–Alder (TADA) reactions with 10–18-membered rings. The results were compared with those for bimolecular and intramolecular Diels–Alder reactions in order to investigate the controlling factors of the high TADA reactivities. The effects of tether length, heteroatoms, and alkynyl dienophiles on reactivity were analyzed. We found a correlation between tether length and reactivity, specifically with 12-membered macrocycles undergoing cycloaddition most readily. Furthermore, modifying 12-membered macrocycles by heteroatom substitution and utilizing alkynyl dienophiles enhances the reaction rates up to 105-fold.

Palladium(II)-catalyzed macrocyclizations of bis(vinylboronate ester) compounds are demonstrated to provide a strategically efficient approach to transannular Diels–Alder reaction substrates. In several systems reported, the macrocycle is preorganized such that cycloaddition at room temperature occurs concomitantly with cyclization. Numerous advantages over palladium(0)-catalyzed cross-coupling approaches are demonstrated.

As a complement to Pd(0)-catalyzed cyclizations, seven Pd(II)-catalyzed cyclization strategies are reported. α,ω-Diynes are selectively hydroborated to bis(boronate esters), which cyclize under Pd(II)-catalysis producing a diverse array of small, medium, and macrocyclic polyenes with controlled E,E, Z,Z, or E,Z stereochemistry. Various functional groups are tolerated including aryl bromides, and applications are illustrated.

Copper(II) acetate catalyzes the coupling of pinacol vinylboronates with silanols producing enol silyl ethers. This represents a novel enol silyl ether synthesis via formation of the C–O bond instead of the conventional Si–O bond. This also constitutes the first transition-metal-catalyzed oxidative cross-coupling with silanols.

A copper-promoted coupling of vinyl pinacol boronate esters and alcohols for the synthesis of enol ethers is reported. The reaction occurs in 50−99% yield and is compatible with a variety of functional groups. Cupric acetate is the copper source, and triethylamine buffer is used to prevent protodeboration; the reaction occurs at room temperature. In addition to excellent chemoselectivity, the reaction is stereospecific.

Simple alkenes and alkynes, with 3-hexyne in particular, are found to be important π ligands for oxidative copper-based coupling (modern Ullmann) reactions. This enabled syntheses of various alkoxydienes with removable protecting groups that are valuable substrates for Diels−Alder reactions from alcohols and vinyl boronate esters. In addition to demonstrating that 3-hexyne is a ligand for copper in both stoichiometric and catalytic reactions, the reaction atmosphere was found to play a critical role.