Solid-state photodecarbonylation is an attractive but underutilized methodology to forge hindered C–C bonds in complex molecules. This study discloses the use of this reaction to assemble the vicinal quaternary stereocenter motif present in bis­(cyclotryptamine) alkaloids. Our strategy was enabled by experimental and computational investigations of the role of substrate conformation on the success or failure of the solid-state photodecarbonylation reaction. This informed a crystal engineering strategy to optimize the key step of the total synthesis. Ultimately, this endeavor culminated in the successful synthesis of the bis­(cyclotryptamine) alkaloid “psychotriadine,” which features the elusive piperidinoindoline framework. Psychotriadine, a previously unknown compound, was identified in the extracts of the flower Psychotria colorata, suggesting it is a naturally occurring metabolite.

Recent work has shown that diarylmethyl radicals generated by pulsed laser excitation in nanocrystalline (NC) suspensions of tetraarylacetones constitute a valuable probe for the detailed mechanistic analysis of the solid-state photodecarbonylation reaction. Using a combination of reaction quantum yields and laser flash photolysis in nanocrystalline suspensions of ketones with different substituents on one of the α-carbons, we are able to suggest with confidence that a significant fraction of the initial α-cleavage reaction takes place from the ketone singlet excited state, that the originally formed diarylmethyl-acyl radical pair loses CO in the crystal with time constants in the sub-nanosecond regime, and that the secondary bis(diarylmethyl) triplet radical pair has a lifetime limited by the rate of intersystem crossing of ca. 70 ns.

Radical pairs generated in crystalline solids by bond cleavage reactions of triplet ketones offer the unique opportunity to explore a frontier of spin dynamics where rigid radicals are highly entangled as the result of short interradical distances, large singlet−triplet energy gaps (ΔE ST ), and limited spin−lattice relaxation mechanisms. Here we report the pulsed laser generation and detection of strongly entangled triplet acyl−alkyl radical pairs generated in nanocrystalline suspensions of 1,1-diphenylmethyl 2-ketones with various 3-admantyl substituents. The sought-after triplet acyl−alkyl radical pairs could be studied for the first time in the solid state by taking advantage of the efficient triplet excited state α-cleavage reactions of 1,1-diphenylmethyl ketones and the slow rate of CO loss from the acyl radicals, which would have to generate highly unstable phenyl and primary alkyl radicals or relatively unstable secondary and tertiary alkyl radicals. With the loss of CO prevented, the lifetime of the triplet acyl−alkyl radical pair intermediates is determined by intersystem crossing to the singlet radical pair state, which is followed by immediate bond formation to the ground state starting ketone. Experimental results revealed biexponential kinetics with long-lived components that account for ca. 87−92% of the transient population and lifetimes that extend to the range of 53−63 μs, the longest reported so far for this type of radical pair. Structural information inferred from the starting ketone will make it possible to analyze the affects of proximity and orientation of the singly occupied orbitals and potentially help set a path for the use of triplet radical pairs as qubits in quantum information technologies.

Photochemical reactions in crystals occur under conditions of highly restricted molecular mobility such that only one product is generally obtained, even when there are many others that can be observed in the gas phase or in solution. A series of 2-(1-adamantyl)-o-alkyl-acetophenones with γ-hydrogen atoms on both the adamantyl and ortho aromatic groups was selected to determine whether one can engineer and observe competing Norrish type II reaction pathways in the crystalline state. It was shown that excited state competition for hydrogen abstraction between secondary adamantyl and benzylic hydrogens is affected not only by the relative bond dissociation energies but also by the molecular conformation in the crystal. The subsequent fate of the resulting biradical species is determined by competition between radical recombination to form the photoproduct and reverse hydrogen atom transfer to regenerate the starting ketone. Crystallographic information, photoproduct distributions in solution and in the solid state, and the results of multiple mechanistic experiments, including transient absorption spectroscopy in acetonitrile and with nanocrystals suspended in water, are reported. The results demonstrate that it is possible to engineer competing reactions in crystals and that consideration of all of the aforementioned factors is necessary to account for the observed photoproduct selectivity.

The macroscopic motion of crystals induced by a solid-state photochemical reaction, also known as photosalience, is of interest for the development of micromechanical actuators and crystalline molecular machines. Using microcrystal electron diffraction, we report evidence for a minimum crystal size threshold below which photosalience is not observed for benzylidenebutyrolactone. We confirm our observations by solving the crystal structure of micron-scale specimens before and after their topotactic single crystal-to-single crystal reaction and by collecting transmission electron microscopy images that reveal the absence of photosalient effects for crystals that are below ca. 10 μm in size. These results indicate that photosalience depends not only on the ability of crystals to support a photochemical reaction but also on a size threshold where the accumulated product phase can form a layer that is separate from that of the reactant, such that their different packing dimensions are able to transduce the collective strain accumulated at the molecular-level boundaries into the macroscopic motion that propels the entire crystal specimen.