Roman A. Valiulin

Rapid Photoassisted Access to N,O,S‐Polyheterocycles with Benzoazocine and Hydroquinoline Cores: Intramolecular Cycloadditions of Photogenerated Azaxylylenes

o-Azaxylylenes have been known for half a century,[1] but remained in relative synthetic obscurity until a decade ago, when in this journal Corey reported their first preparation under simple mild conditions via base-induced elimination of hydrogen chloride from derivatives of o-chloromethylaniline,[2] noting that “Surprisingly, simplest method possible for o-azaxylylene production [...] has never been reported.”

Harvesting the strain installed by a Paternò-Büchi step in a synthetically useful way: high-yielding photoprotolytic oxametathesis in polycyclic systems.

High-yielding one-pot photoinduced transformation of readily available endoaroyl and heteroaroyl Diels-Alder adducts into novel polycyclic aldehydes or their hemiacetals, decorated by carbo- and heterocyclic pendants, is described.

Direct screening of solution phase combinatorial libraries encoded with externally sensitized photolabile tags

Solution phase combinatorial chemistry holds an enormous promise for modern drug discovery. Much needed are direct methods to assay such libraries for binding of biological targets. An approach to encoding and screening of solution phase libraries has been developed based on the conditional photorelease of externally sensitized photolabile tags. The encoding tags are released into solution only when a sought-for binding event occurs between the ligand and the receptor, outfitted with an electron-transfer sensitizer. The released tags are analyzed in solution revealing the identity of the lead ligand or narrowing the range of potential leads.

Taming chlorine azide: access to 1,2-azidochlorides from alkenes.

The in situ preparation and trapping of chlorine azide provided a versatile one-pot method for the azidochlorination of alkenes. Gaseous ClN3 generated from sodium azide, hypochlorite, and acetic acid can be explosive if isolation is attempted. Instead, we generated the reagent in biphasic media in the presence of olefinic compounds dissolved in the organic layer or evenly emulsified throughout the solution in the absence of organic solvent. Under these conditions, ClN3 is created slowly and trapped immediately at the aqueous-organic interface. The resulting safe and reliable procedure provided 1,2-azidochloride derivatives of a variety of substrates, with evidence for both polar and radical mechanisms. Minor impurities characterized in the product mixtures indicated the presence of alternative reaction pathways deriving primarily from radical intermediates.

Double-Tandem [4π+2π]·[2π+2π]·[4π+2π]·[2π+2π] Synthetic Sequence with Photoprotolytic Oxametathesis and Photoepoxidation in the Chromone Series

Chromones are introduced into a double-tandem [4(π)+2(π)]·[2(π)+2(π)]·[4(π)+2(π)]·[2(π)+2(π)] synthetic sequence, culminating in photoprotolytic oxametathesis, which leads to an expeditious growth of molecular complexity over a few experimentally simple steps. The overall reaction can potentially be utilized in diversity-oriented synthesis, as it allows for three or more diversity inputs furnishing novel unique polycyclic scaffolds decorated with a variety of functionalities and aromatic/heterocyclic pendants. The polycyclic alkenes, resulting from the oxametathesis step, were found to undergo efficient and clean photoinduced epoxidation when irradiated in the presence of molecular oxygen.

Photoinduced intramolecular cyclopentanation vs photoprotolytic oxametathesis in polycyclic alkenes outfitted with conformationally constrained aroylmethyl chromophores.

Intramolecular photoinduced cyclizations are investigated in photoprecursors assembled in a modular fashion via a Diels-Alder reaction of acetylenic dienophiles with subsequent Michael additions of aromatic ketones to install a chromophore capable of initiating Paternò-Büchi cycloadditions or radical cyclization cascades. The protolytic oxametathesis in these systems allows for rapid access to novel polycyclic scaffolds decorated by formyl groups and carboxylates suitable for subsequent modifications. In conformationally constrained photoprecursors, a radical rearrangement takes place resulting in intramolecular 1,3-diradical cyclopentanation of the double bond.

Strained to the Limit: When a Cyclobutyl Moiety Becomes a Thermodynamic Sink in a Protolytic Ring Opening of Photogenerated Oxetanes

Strained polycyclic oxetanes generated photochemically from the Diels-Alder adducts of cyclic dienes and enones undergo deep skeletal rearrangements under protolytic ring-opening conditions offering expeditious access to chlorohydrins and other products of unique skeletal topology.

Effect of Intramolecular Paternò−Büchi Reaction on the Thermodynamics and Kinetics of Nearly Degenerate [3,3]-Sigmatropic Shift in Fluxional Polycycles

In reactions with weak dienophiles, cyclooctatetraene (COT) often yields 2:1 adducts possessing the fluxional bicyclo[5.1.0]octadiene moiety. They undergo fast, nearly degenerate Cope rearrangement with an activation barrier similar to that of the parent dihydrobullvalene. Irradiation to excite the carbonyl moiety induces an intramolecular Paterno-Buchi cyclization yielding endo-oxetanes and significantly changing the Cope-averaged NMR spectra. In this paper we examine the effect of skeletal distortion caused by intramolecular [2 + 2]-photoaddition on thermodynamics and the activation barrier of the [3,3]-sigmatropic tautomerism. Our finding is that such a distortion lifts the energetic degeneracy of the two valence tautomers, while not affecting the activation barrier.

Cascade transformations involving thiocarbonyls: photoassisted access to bicyclic thiiranes and oxapentalenes

Phenyl(thio)glyoxal, generated via the Norrish type II fragmentation of phenacyl sulfide, undergoes known [4+2] cycloaddition with dienes and the photoactive product is further converted via the interrupted Paternò–Büchi reaction channel into a dihydrofuran derivative possessing the oxapentalene core. The reaction can be carried out in one step as the chromophores are nearly identical and the extended cascade is initiated with the same UV LED source.