CarbonCarbon Bond Formation by the Photoelimination of Small Molecules in Solution and in Crystals

Abstract

The formation of CÀC bonds is arguably the most important reaction in organic synthesis. While many strategies have been developed to link organic fragments with a wide range of thermal processes, photochemical syntheses based on the elimination of a small molecule, X (Scheme 2.1), offer significant advantages when the desired structures are highly strained or hindered. In this chapter, we will describe examples of the generation of CÀC bonds through the photoinduced extrusion of small molecules such as N 2 , CO 2 , CO, and SO 2 , as well as the formal extrusion of S atoms. After describing the most general mechanistic aspects covering these reactions and the current scope and limitations, we will illustrate examples involving these reactions in solution. Following that, we will describe a strategy based on the use of crystalline solids that helps to control the fate of the reaction intermediates. Finally, we will illustrate the use of crystalline ketones (X¼CO) as one of the most promising general methods for the synthesis of compounds with all-carbon adjacent stereogenic quaternary centers.The photoelimination of a small stable molecule X accompanied by the formation of a new CÀC bond could, in principle, take place in a concerted manner through cyclic transition states with simultaneous bond-breaking and bond-making steps that follow trajectories determined by orbital symmetry considerations. However, as it pertains to photodecarbonylation reactions, theoretical analysis on the formation of hydrogen and CO from formaldehyde suggests that the concerted process is significantly less likely than the stepwise cleavage of the HÀC(O)ÀH bonds [1]. Similar conclusions have been made for the elimination of N 2 and H 2 from simple diazene (HN¼NH) [2]. In fact, evidence for concerted reactions is available only in a handful of cases (vide infra). Most examples involve a four-step process that starts with electronic excitation (step 1) and is followed by an a-cleavage reaction (step 2) to give a primary biradical or radical pair (BR-1). Subsequent dissociation of the small molecule X (step 3) results in the formation of the secondary biradical or radical pair (BR-2), which is followed by radical-radical combination to give the desired product (step 4).Handbook of Synthetic Photochemistry. Edited

Transient Kinetics and Quantum Yield Studies of Nanocrystalline α-Phenyl-Substituted Ketones: Sorting Out Reactions from Singlet and Triplet Excited States

“…Considering that the radical stabilizing energy that results from two α-phenyl groups (RSE ≥ 20.5 kcal/mol) is significantly larger than the values known to enable the reaction (RSE ≥ 11 kcal/mol), one may expect the α-cleavage reaction in ketones 1a – 1c to be very fast and quantum efficiency for the solid state reactions to be high, especially if the reaction were to proceed exclusively from the triplet excited state. However, an increase in the radical stabilization of the α-substituents also increases the rate of α-cleavage from the singlet excited state, so that formation of 1 RP-1 (step 3′ in Scheme ) may compete with intersystem crossing (step 2).…”

“…On the other hand, nanocrystals with sizes smaller than the wavelength of light can be seen as a state in transition between supramolecular entities and bulk crystals, with strongly reduced scattering, dichroism, and birefringence that enable their measurement by transmission spectroscopy methods, including laser flash photolysis . With that in mind, it is now possible to address subtle mechanistic aspects of several solid-state photoreactions, including the photoinduced decarbonylation of crystalline ketones with radical stabilizing substituents at the two α-positions, such as aryl-susbtituted ketones 1a – 1c in Scheme and Scheme . , The reaction is expected to proceed by an initial α-cleavage of the weakest C–C bond and ultimately results in the formation of product 2 , which maintains the stereochemical information on the reactant by the stereospecific formation of a sterically congested C–C bond. , As indicated in Scheme , the reaction starts by electronic excitation (step 1, Scheme ), which results in the sequential cleavage of the two α-bonds (steps 3 and 6) to generate, respectively, radical pairs RP-1 and RP-2 , which can exist either in a singlet or a triple state . It has been reported that reactions in crystals require the two bond-cleavage steps to be exothermic, and with α-substituents that provide radical stabilization energies (RSEs) greater than 11 kcal/mol, this requirement is easily met in ketones with aryl groups on both α-carbons (the RSE of an α-phenyl group is 16.5 kcal/mol) .…”

Mechanistic Insights into Dissolved Organic Sulfur Photomineralization through the Study of Cysteine Sulfinic Acid

“…For example, sulfonamide antibiotics, a class of pollutants ubiquitous in the environment, are known to undergo SO 2 extrusion via direct and indirect photolysis, − sulfate radical-mediated oxidation, − and other oxidation processes. − In particular, SO 2 extrusion was proposed to be the primary photodegradation route for five six-membered sulfonamides, and sulfate was reported among the photoproducts . Photoinduced extrusion of SO 2 from organic sulfones is also exploited in synthetic organic chemistry as a mild route to form new C–C bonds, both via direct (requiring a chromophore β to the sulfone) and triplet-induced photolysis. , Unfortunately, the organic chemistry literature is limited to reactions performed in organic solvents and with the specific aim of obtaining highly unstable ring structures for further synthetic transformations . Further research is needed to assess whether natural sulfones and other DOS components can liberate SO 2 upon photolysis under environmentally relevant conditions.…”

Taming Radical Pairs in Nanocrystalline Ketones: Photochemical Synthesis of Compounds with Vicinal Stereogenic All-Carbon Quaternary Centers

“…We have shown that energetic profiles, such as the one represented in Scheme , are helpful for reactions to occur in the crystalline state . In the absence of collisions, rotations, and conformational motions, reactions in crystals must be nearly barrierless.…”