Keywords

1. Iron-catalyzed cycloaddition
2. 1,3-dienes cyclodimerization
3. Regioselective cycloaddition
4. Cis-trans diastereoselectivity
5. Green chemistry catalysis

In a groundbreaking study published in the “Journal of the American Chemical Society,” scientists from the Department of Chemistry at Princeton University have made a significant breakthrough in the field of catalysis, specifically in the iron-catalyzed [4+4]-cycloaddition of 1,3-dienes, leading to the formation of cyclooctadiene products with unprecedented regioselectivity and diastereoselectivity. This discovery opens the door to efficient and scalable synthesis of cyclooctadienes, compounds which previously posed challenges due to a lack of selectivity and control in the dimerization process. The DOI for this publication is 10.1021/jacs.9b02443, and it represents a significant advancement in the arena of sustainable chemistry and synthesis.

The research team, composed of Dr. C. Rose Kennedy, Hongyu Zhong, Rachel L. Macaulay, and led by Paul J. Chirik, developed a family of single-component iron precatalysts capable of orchestrating the cycloaddition process with remarkable levels of control. This process enables the selective formation of either cis- or trans-diastereomers using 4-substituted diene substrates. Notably, the reactions are compatible with a wide range of functional groups common in organic chemistry and can be performed on a multigram scale, exceeding 100 grams, an attribute that underlines its applicability in industrial contexts.

The significance of this research extends beyond just the synthesis of cyclooctadienes. The methodology could lead to a more efficient production of high-density fuels, various polymers, and fragrance compounds, all of which have cyclooctadienes as key intermediates. The study gains further prominence as it makes use of iron, a metal that is abundant, inexpensive, and environmentally benign compared to other catalysts typically employed in chemical synthesis, such as precious metals like palladium and platinum.

Research Background
The synthesis of eight-membered rings, such as cyclooctadienes, through catalytic methods has long been an area of interest in organic chemistry due to their prevalence in natural products, medicines, and materials. However, established catalytic systems often require complex ligands, harsh reaction conditions, and offer limited control over product selectivity, as detailed in prior studies (Hendrickson JB, Martinez H, Hill AR, and others).

Iron-catalyzed reactions, while offering a sustainable alternative to precious metal catalysts, had previously seen limited application in the formation of medium-sized rings. Initial studies pointed towards the potential of iron catalysts, but faced challenges such as poor regio- and diastereoselectivity, limited functional group compatibility, and reduced scalability (Lee H, Hirano M, and others). In light of these challenges, the Princeton team’s work represents a significant leap forward in catalysis and synthetic chemistry.

Study Outcomes and Implications

The published research reveals that the newly developed iron precatalysts exhibit a remarkable ability to control the cycloaddition process, allowing for the procurement of cyclooctadiene products with high regioselectivity. By adjusting the reaction conditions and the choice of diene substrates, chemists can now achieve catalyst-controlled access to desired cis- or trans-diastereomers with good to excellent yields.

One of the most compelling aspects of this research is the utilization of single-component precatalysts or iron dihalide complexes activated in situ, which simplifies the reaction setup and avoids the necessity for additional ligand systems or activators. The study’s insights into the geometry and electronic structure of the catalytic species further contribute to the understanding of how regio- and diastereoselectivity are attained. This knowledge could lead to the development of new catalytic systems for other types of selective transformations.

The research supports the idea of redox-active ligands as a powerful tool for tuning and controlling the reactivity of iron catalysts, which has been a topic of interest in previous studies (Lyaskovskyy V, Bart SC, Bouwkamp MW, and others). The research emphasizes the importance of ligand design in achieving high selectivity and activity while preserving the environmentally friendly nature of the catalytic system.

References

1. Kennedy C.R., Zhong H., Macaulay R.L., Chirik P.J. Regio- and Diastereoselective Iron-Catalyzed [4+4]-Cycloaddition of 1,3-Dienes. J. Am. Chem. Soc. 2019, 141(21), 8557–8573. doi: 10.1021/jacs.9b02443
2. Hendrickson J.B. Molecular Geometry. IV. The Medium Rings. J. Am. Chem. Soc. 1964, 86, 4854–4866. doi: 10.1021/ja01076a021
3. Martinez H., Ren N., Matta M.E., Hillmyer M.A. Ring-Opening Metathesis Polymerization of 8-Membered Cyclic Olefins. Polym. Chem. 2014, 5, 3507–3532. doi: 10.1039/C4PY00478A
4. Hill A.R., Balogh J., Moncho S., Su H.-L., Tuba R., Brothers E.N., Al-Hashimi M., Bazzi H.S. Ring Opening Metathesis Polymerization (ROMP) of Five- to Eight-Membered Cyclic Olefins: Computational, Thermodynamic, and Experimental Approach. J. Polym. Sci. Part A Polym. Chem. 2017, 55, 3137–3145. doi: 10.1002/pola.28655
5. Meylemans H.A., Quintana R.L., Harvey B.G. Efficient Conversion of Pure and Mixed Terpene Feedstocks to High Density Fuels. Fuel 2012, 97, 560–568. doi: 10.1016/j.fuel.2012.02.003

Conclusions
The Princeton team’s study not only showcases the potential of iron catalysis in the strategic synthesis of complex organic structures but also exemplifies the merging of fundamental chemistry with real-world applications. By providing a scalable and green approach to producing cyclooctadienes, the methodology is set to have broad implications across numerous industries. It serves as a testament to the value of interdisciplinary research in resolving longstanding synthetic challenges.