We envisaged that a nickel metallaphotoredox mechanism could be initiated by photoexcitation of 2,4,5,6-tetra(9H-carbazol-9yl)isophthalonitrile (4CzIPN, PC) with blue LEDs to generate a long-lived excited state (lifetime τ = 5.1 µs, PC*) (Figure ). The Ni(0) complex 1 is generated in situ through two discrete SET events (E1/2,red [PC/ The proposal in Figure requires 1-carboxylic acid isochroman, THIQ, and isothiochroman substrates, and we found a trifluoroacetic acid (TFA) mediated cyclisation that efficiently produces a range of such starting materials. The process is desirable because it can be performed at multi-gram scale and does not require chromatography for purification. In addition, all acids were bench-stable under air and visible light for at least one year without visible degradation or reduction in reaction performance. Adaptation of reaction conditions previously reported for radical decarboxylation resulted in surprisingly low yields (0-10%) due to formation of dimeric side products through radical homocoupling. Subsequent optimization revealed that the highest yields were attained using a combination of 2-methyltetrahydrofuran (a green, renewable solvent derived from corn cob waste) and K3PO4 solid. In addition, the inclusion of water (up to 20 equiv.) helped suppress ester formation from C-O coupling in certain substrates. With these optimized conditions (Figure ), we probed the generality of this method for the synthesis of 1-alkyl isochromans. Initially, substituted benzyl bromides were tested, and these underwent efficient cross-coupling with excellent functional group tolerance: the reaction proceeds in the presence of ethers (11), thioethers (12), halogens (8, 9, 15), nitriles (17), trifluoromethyl- (10), and trifluoromethoxy-( ) groups. Only nitro compounds are poorly tolerated in this reaction, consistent with known incompatibility of nickel catalysis and nitro groups. The broad scope of the new reaction system was demonstrated through the use of further substituted isochroman derivatives, other heteroatoms (i.e., N in THIQ substrates and S in isothiochromans) and alternative alkyl bromides (Figure ). Of particular note is the successful inclusion of electron withdrawing groups such as halogens on the isochroman aromatic ring, reaction partners that are unlikely to cooperate in traditional OPS, TPS, and PS reactions. Gratifyingly, reactions involving S and N derivatives to produce isothiochromans and THIQ compounds respectively were generally more successful than the isochroman series. This improved reactivity is likely due to the increased stability of the carbon-centered radical intermediate. Notably, alkyl bromide 32 containing bromosubstituted heterocycle was well tolerated, enabling the possibility of sequential cross-coupling reactions for increased molecular complexity; this result is surprising since nickel metallaphotoredox catalysis is known to couple sp 3 -carbons with aryl halides under similar conditions. While coupling of secondary carboxylic acids with secondary bromides is often difficult and a known issue in nickel catalysis, Interestingly, when using propargyl bromide (Table ), a mixture was obtained of the desired propargyl product and the allene isomer in a ratio that depended on the substrate. In most cases, the propargylated product was preferred, and in only one case was the allene was slightly favored (entry 1, Table ). Longer chains at the R2 position (entry 4-5, Table ) resulted in larger proportions of propargylic products, likely owing to steric factors that prevent generation of the Ni-allene intermediate required for the side reaction. Further studies on the synthesis of allenes via metallaphotoredox catalysis are ongoing in our laboratory. Compound numbers in the first column refer to products in the order alkyne, allene.