Photochemically Produced Aminocyclobutanes as Masked Dienes in Thermal Electrocyclic Cascade Reactions

Cyclobutane products of a triplet sensitized enamide-alkene intramolecular [2 + 2] photocycloaddition have been shown to undergo fragmentation under acidic conditions. This lability has been exploited by inducing a complexity-generating thermal electrocyclic cascade sequence involving the <i>in situ</i> formation of a cyclobutene, followed by electrocyclic ring opening, Diels–Alder cycloaddition, and subsequent lactamization. This combination of excited state photochemistry and thermal electrocyclic cascade reactions allows simple planar molecules to be rapidly transformed into sp³-rich scaffolds

Unusually Facile Thermal Homodienyl-[1,5]-Hydrogen Shift Reactions in Photochemically-Generated Vinyl Aziridines

A range of photochemically generated tri‐ and tetracyclic vinyl aziridines have been found to undergo a general and surprisingly low temperature ring opening through a [1,5]‐hydrogen shift reaction. The rate of the process was found to be highly dependent on the structure and substitution around the azirdine ring and the alkene terminus, with some substrates being observed to undergo ring opening at temperatures as low as 25 °C. The rigid nature of these polycyclic systems precludes a conformational explanation of these rate differences, and an Eyring study confirmed a negligible entropic barrier to the reaction. However, the Eyring plots for two different aziridines systems showed a significant difference in their enthalpies of activation. It is therefore believed that the levels of aziridine ring strain, as well as electronic effects, are the dominant factors in this sequence

Short Flow-Photochemistry Enabled Synthesis of the Cytotoxic Lactone (+)-Goniofufurone

A photochemical approach to the cytotoxic lactone (+)-goniofufurone (1) is reported. Paterno−̀ Büchi [2 + 2] photo- cycloaddition from known enol ether 4, derived from the readily available sugar D-isosorbide, yielded oxetane 7. This slow, dilute reaction was scaled up by using flow photochemistry to yield &gt;40 g of 7. Installation of the key lactone ring was achieved via a unique Wacker- style oxidation of an enol−ether bond. Acid-catalyzed aqueous ring opening provided 1 in five steps from 4 (11.5% overall)

Pd(II)-Catalyzed [4 + 2] Heterocyclization Sequence for Polyheterocycle Generation

A new Pd­(II)-catalyzed cascade sequence for the formation of polyheterocycles, from simple starting materials, is reported. The sequence is applicable to both indole and pyrrole substrates, and a range of substituents are tolerated. The reaction is thought to proceed by a Pd­(II)-catalyzed C–H activated Heck reaction followed by a second Pd­(II)-catalyzed aza-Wacker reaction with two Cu­(II)-mediated Pd(0) turnovers per sequence. The sequence can be considered a formal [4 + 2] heterocyclization

Short, Gram-Scale Syntheses of β- And γ-Lycorane Using Two Distinct Photochemical Approaches

The synthesis of two diastereomeric members of the lycorane alkaloid family is reported. Although the routes are quite different in their approach, both involve the use of photochemistry as a key step, enabling the synthesis of gram quantities in the case of β-lycorane

Combining photochemistry and catalysis:rapid access to sp³ - rich polyheterocycles from simple pyrroles

Use of FEP flow reactor technology allows access to gram quantities of photochemically-generated tricyclic aziridines. These undergo a range of novel palladium-catalyzed ring-opening and cycloaddition reactions, likely driven by their inherent strain, allowing incorporation of further functionality by fusing additional heterocyclic rings onto these already complex polycyclic cores. This rapid, 2-step access to complex sp3 – rich heterocycles should be of interest to those in the fields of drug discovery and natural product synthesis

Pd-Catalyzed Cascade Reactions of Aziridines: One-step Access to Complex Tetracyclic Amines

The combination of palladium catalysis and thermal cycloaddition is shown to transform tricyclic aziridines into complex, stereodefined tetracyclic products in a single step. This highly unusual cascade process involves a diverted Tsuji–Trost sequence leading to a surprisingly facile intramolecular Diels–Alder reaction. The starting materials are accessible on multigram scales from the photochemical rearrangement of simple pyrroles. The tetracyclic amine products can be further elaborated through routine transformations, highlighting their potential as scaffolds for medicinal chemistry