The photochemical dynamics of three classes of organic photoredox catalysts employed in organocatalyzed atom-transfer radical polymerization (O-ATRP) are studied using time-resolved optical transient absorption and fluorescence spectroscopies. The nine catalysts selected for study are examples of N-aryl and core-substituted dihydrophenazine, phenoxazine and phenothiazine compounds with varying propensities for control of polymerization outcomes. Excited singlet state lifetimes extracted from the spectroscopic measurements are reported in N,Ndimethylformamide (DMF), dichloromethane (DCM) and toluene. Ultrafast (< 200 fs to 3 ps) electronic relaxation of the photocatalysts after photoexcitation at near-UV wavelengths (318-390 nm) populates the first singlet excited state (S1). The S1-state lifetimes range from 130 ps to 40 ns with considerable dependence on the photocatalyst structure and the solvent. Competition between ground-electronic state recovery and intersystem crossing controls triplet state populations and is a minor pathway in the dihydrophenazine derivatives, but is of greater importance for phenoxazine and phenothiazine catalysts. Comparison of our results with previously reported O-ATRP performances of the various photoredox catalysis shows that high triplet-state quantum yields are not a pre-requisite for controlling polymer dispersity. For example, the 5,10-di(4-cyanophenyl)-5,10-dihydrophenazine photocatalyst, shown previously to exert good polymerization control, possesses the shortest S1-state lifetime (135 ps in DMF and 180 ps in N,N-dimethylacetamide) among the nine examples reported here, and a negligible triplet state quantum yield. The results call for a re-evaluation of the excited state properties of most significance in governing the photocatalytic behaviour of organic photoredox catalysts in O-ATRP reactions.

AbstractOrganic substitutes for ruthenium and iridium complexes are increasingly finding applications in chemical syntheses involving photoredox catalysis. However, the performance of these organic compounds as electron-transfer photocatalysts depends on their accessible photochemical pathways and excited state lifetimes. Here, the UV-induced dynamics of N-phenyl phenoxazine, chosen as a prototypical N-aryl phenoxazine organic photoredox catalyst, are explored in three solvents, N,N-dimethyl formamide, dichloromethane and toluene, using ultrafast transient absorption spectroscopy. Quantum chemistry calculations reveal the locally excited or charge-transfer electronic character of the excited states, and are used to assign the transient electronic and vibrational bands observed. In toluene-d8, complete ground-state recovery is (31 ± 3) % by internal conversion (IC) from the photo-excited state (or from S1 after IC but before complete vibrational relaxation), (13 ± 2) % via direct decay from vibrationally relaxed S1 (most likely radiative decay, with an estimated radiative lifetime of 13 ns) and (56 ± 3) % via the T1 state (with intersystem crossing (ISC) rate coefficient kISC = (3.3 ± 0.2) × 108 s−1). In dichloromethane, we find evidence for excited state N-phenyl phenoxazine reaction with the solvent. Excited state lifetimes, ISC rates, and ground-state recovery show only modest variation with changes to the solvent environment because of the locally excited character of the S1 and T1 states.

Scheme 32. Anderson's study into the synthesis and reactivity of bridge lithiated bicyclo[1.1.0]butane. a) Bridge deprotonation and functionalization of bicyclo[1.1.0]butyl amide 128. b) Attempted enantioselective deprotonation of bicyclo[1.1.0]butane bridging methylenes. a The identity of the major stereoisomer was not determined. c) Sequential bridge deprotonation and functionalization. d) Application of deuterated bicyclo[1.1.0]butane 131 in the mechanistic study of difluorocarbene insertion.

Despite the favorable properties that azetidine rings can engender on drug-compounds, methods for the diversity-oriented synthesis of azetidine-based structures are significantly underdeveloped. Herein, we report the successful realization of a multicomponent [1,2]-Brook rearrangement/strain-release-driven anion relay sequence and its application to the modular synthesis of substituted azetidines. The rapidity of the reaction, as confirmed by in situ infra-red spectroscopy, leverages the strain-release ring-opening of azabicyclo-[1.1.0]butane to drive the equilibrium of the Brook rearrangement. The three electrophilic coupling partners, added sequentially to azabicyclo[1.1.0]butyl-lithium, could be individually varied to access a diverse compound library. The utility of this methodology was demonstrated in a 4-step synthesis of the EP2 receptor antagonist PF-04418948.

Due to their intrinsic rigidity, three‐dimensionality and structural novelty, spirocyclic molecules have become increasingly sought‐after moieties in drug discovery. Herein, we report a strain‐release driven synthesis of azetidine‐containing spirocycles by harnessing the inherent ring strain of the azabicyclo[1.1.0]butane (ABB) fragment. Novel ABB‐ketone precursors bearing silyl‐protected alcohols were synthesized in a single step and shown to engage in electrophile‐induced spirocyclization‐desilylation reactions. Primary, secondary and tertiary silyl ethers were effectively transformed into a library of new spiro‐azetidines, with a range of substituents and ring sizes. In addition, the products are generated with synthetically useful ketone and protected‐amine functional groups, which provides the potential for further elaboration and for this chemistry to be utilized in the rapid assembly of medicinally relevant compounds.