2-Pyridones are known to undergo a facile [4+4] photocycloaddition with themselves and other conjugated molecules. These transformations provide an access to complex molecular structures such as highly substituted cyclooctanoid derivatives, which normally represent a significant synthetic challenge. Moreover, the 2-pyridone photoadducts can be further elaborated into various biologically relevant products. The work presented here broadens the horizons of the [4+4] photocycloaddition in two distinct directions: 1) by utilizing [4+4] photocycloaddition in a total synthesis of crinipellin natural products possessing antibiotic and antitumor activity and 2) by developing a novel type of [4+4] photocycloaddition that employs a conjugated enyne as a partner of 2- pyridone. Our approach to the tetraquinane core of the crinipellins features intramolecular [4+4] photocycloaddition of a tethered furan-pyridone molecule followed by a four-step transannular ring closure. The sequence allows for a rapid assembly of a molecular framework by installing 19 of the 20 required carbon atoms and all but two stereogenic centers. The described synthesis represents an interesting new approach to these polycyclic molecules and a way to access crinipellin analogues. The enyne-pyridone [4+4] photocycloaddition led to formation of intriguing 1,2,5-cyclooctatriene-based products. Presence of the allene functionality was used as a lever in exploring the possibilities for derivatization of these photoadducts. Our investigations of enyne-pyridone photocycloaddition have come a long way: from the first proof-of-concept intermolecular trials producing complex mixtures, through the initial investigations of the intramolecular variant that taught us how to direct the reaction to the necessary mode ([2+2] vs. [4+4] photocycloaddition), and eventually to the controlled formation of stable allenic photoadducts and their further transformation into a diverse set of functionalized molecular scaffolds. We found that the inherent kinetic instability of 1,2,5-cyclooctatrienes facilitates several pathways of strain relief: allene-allene [2+2] dimerization, photooxidative decarbonylation when the irradiation is conducted in presence of air, isomerization of the 1,2-diene fragment into a 1,3-diene and the acid-promoted Cope rearrangement. Additionally, enyne-pyridone photoadducts can undergo transannular ring closure when treated with bromine and also be transformed into valuable bicyclo [5.1.0] octane structures that incorporate a rare example of a stable cyclopropanone by a fast and selective epoxidation-rearrangement process. Several important goals were achieved in the described research study. First, strategic incorporation of [4+4] photocycloaddition as one of the key steps in targeted synthesis of natural products has demonstrated the potential of this powerful reaction. Second, an efficient new approach to a tetraquinane skeleton was developed and successfully executed. Third, the fundamental basis for the novel photochemical transformation (enyne-pyridone cycloaddition) was set and major trends for this reaction were established resulting in obtaining stable allenic photoadducts. Finally, chemical properties and reactivity of stabilized amide-bridged 1,2,5-cyclooctatriene photoproducts were investigated breaking the ground for future involvement of these intermediates in synthetic strategies towards biologically active natural products and their analogues. / Chemistry

Chemists have always been fascinated by the cumulated diene system of allenes with its extraordinary properties such as the axial chirality of the elongated tetrahedron and a higher reactivity than non-cumulated C-C double bonds. The equilibrium geometry for an allene is linear with orthogonal pairs of substituents. An allene incorporated into a carbocyclic ring of nine or more carbon atoms is relatively unstrained. However, if the ring size is decreased, the linear perpendicular allene will be twisted and bent until, at some point, the energy gained by pi bonding in the two double bonds will be insufficient to offset the increased strain. Furthermore, ring constraints will exert torsion toward a planar arrangement of ligands. Therefore, one of the fundemantal questions is the influence of ring size on the barrier to pi bond rotation. Herein we wish to unveil a review of our research related to desperately seeking for five membered ring allenes such as, cyclopenta-1,2-diene (1) and some of its derivatives, e.g. 2, and 3. Furthermore, we will address a simple, mild and efficient method for the reduction of 1,4-benzoquinones 4 to corresponding hydroquinones 5.