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This paper describes an intermolecular cross-selective [2 + 2] photocycloaddition reaction of exocyclic arylidene oxetanes, azetidines, and cyclobutanes with simple electron-deficient alkenes. The reaction takes place under mild conditions using a commercially available Ir(III) photosensitizer upon blue light irradiation. This transformation provides access to a range of polysubstituted 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, and spiro[3.3]heptane motifs, which are of prime interest in medicinal chemistry as gem -dimethyl and carbonyl bioisosteres. A variety of further transformations of the initial cycloadducts are demonstrated to highlight the versatility of the products and enable selective access to either of a syn - or an anti -diastereoisomer through kinetic or thermodynamic epimerization, respectively. Mechanistic experiments and DFT calculations suggest that this reaction proceeds through a sensitized energy transfer pathway.

The design of stereodivergent transformations is of great interest to the synthetic community as it allows funneling of a given reaction pathway toward one stereochemical outcome or another by only minor adjustments of the reaction setup. Herein, we present a physical organic approach to invert the sense of induction in diastereoselective cyclopropanation of alkenes with N-enoxyphthalimides through rhodium(III) catalysis. Careful parametrization of catalyst-substrate molecular determinants allowed us to interrogate linear-free energy relationships and establish an intuitive and robust statistical model that correlates an extensive number of data points in high accuracy. Our multivariate correlations-steered mechanistic investigation culminated with a robust and general diastereodivergent cyclopropanation tool where the switch from trans- to cis-diastereoinduction is attributed to a mechanistic dichotomy. Selectivity might be determined by the flexibility of rhodacyclic intermediates derived from ring-opened versus -unopened phthalimides, induced by both their respective ring size and the Sterimol B 1 parameter of the Cp X ligand on rhodium.

A novel, electron-deficient cyclopentadienyl iridium(III) catalyst enables sequential cleavage of arene C(sp 2 )-H and methoxy C(sp 3 )-H bonds of anisoles, generating reactive metalacycles that insert difluoroalkynes to afford chromenes under mild reaction conditions. This transformation is an arylalkylation of an alkyne-a carbocarbation-via a nonchelate-assisted cleavage of two C-H bonds.

Cp X Rh(III)-catalyzed C-H functionalization reactions are a proven method for the efficient assembly of small molecules. However, rationalization of the effects of cyclopentadienyl (Cp X ) ligand structure on reaction rate and selectivity has been viewed as a black box, and a truly systematic study is lacking. Consequently, predicting the outcomes of these reactions is challenging because subtle variations in ligand structure can cause notable changes in reaction behavior. A predictive tool is, nonetheless, of considerable value to the community as it would greatly accelerate reaction development. Designing a data set in which the steric and electronic properties of the Cp X Rh(III) catalysts were systematically varied allowed us to apply multivariate linear regression algorithms to establish correlations between these catalyst-based descriptors and the regio-, diastereoselectivity, and rate of model reactions. This, in turn, led to the development of quantitative predictive models that describe catalyst performance. Our newly described cone angles and Sterimol parameters for Cp X ligands served as highly correlative steric descriptors in the regression models. Through rational design of training and validation sets, key diastereoselectivity outliers were identified. Computations reveal the origins of the outstanding stereoinduction displayed by these outliers. The results are consistent with partial η 5 -η 3 ligand slippage that occurs in the transition state of the selectivity-determining step. In addition to the instructive value of our study, we believe that the insights gained are transposable to other group 9 transition metals and pave the way toward rational design of C-H functionalization catalysts.

α,β-Unsaturated oxime pivalates are proposed to undergo reversible C(sp(2))-H insertion with cationic Rh(III) complexes to furnish five-membered metallacycles. In the presence of 1,1-disubstituted olefins, these species participate in irreversible migratory insertion to give, after reductive elimination, 2,3-dihydropyridine products in good yields. Catalytic hydrogenation can then be used to convert these molecules into piperidines, which are important structural components of numerous pharmaceuticals.