Utilizing the drive to synthesize (un)symmetric DPPE derivatives

1,2-Bis(diphenylphosphino)ethane (DPPE) and its derivatives are generally used as bidentate ligands, as these have a big entropic benefit in comparison with monodentate ligands when forming inflexible transition-metal complexes that always exhibit excessive catalytic exercise in a variety of reactions.¹ Furthermore, unsymmetric DPPE derivatives (Ar¹₂P−CH₂−CH₂−PAr²₂; Ar¹ ≠ Ar²) are extra seemingly to enhance the catalytic exercise of such transition-metal complexes in comparison with their symmetric analogues (Ar₂P−CH₂−CH₂−PAr₂), provided that the reactivity of the steel heart might be managed extra precisely by judiciously selecting substituents with a selected digital and steric profile for each phosphorous atoms of unsymmetric ligands. As DPPEs and associated unsymmetric ligands play such an necessary function in natural synthesis, a facile and strong artificial path to DPPE derivatives can be extremely fascinating. The commonest strategies for the synthesis of DPPE derivatives are S_N2 reactions of 1,2-dihaloethanes with alkali-metal diphenylphosphides^2-4, and base-catalyzed hydrophosphination reactions of vinylphosphines⁵. Then again, hitherto reported methods for the synthesis of unsymmetric DPPE derivatives have primarily been restricted to hydrophosphination reactions utilizing vinylphosphines with diarylphosphines that possess totally different substituents on the aryl rings^6-11. Nevertheless, vinylphosphines and diarylphosphines for unsymmetric DPPEs normally should be synthesized upfront, which frequently entails a number of artificial steps. If the 2 carbon-atom spine of DPPE may very well be derived from ethylene fuel, which is a generally encountered versatile two-carbon synthon in trade and tutorial analysis, and if the 2 phosphorous atoms on DPPE may very well be derived from two totally different simply obtainable phosphorus precursors, one might develop a sturdy and on-demand one-step synthesis to offer symmetric and unsymmetric DPPEs (Fig. 1).

To substantiate our speculation for the synthesis of DPPE derivatives from ethylene, we employed quantum-chemical calculations by utilizing the substitute drive induced response (AFIR) technique within the world response route mapping (GRRM) program¹², which has been developed by Prof. Satoshi Maeda (Director of the Institute for Chemical Response Design and Discovery at Hokkaido College). The AFIR technique theoretically induces ‘chemical reactions’ by including a digital synthetic drive between the fragments of compounds to acquire the response pathways that comprise the constructions of substrates, merchandise, intermediates, and even transition states. On this case, we calculated the retrosynthetic route of DPPE by including a man-made drive on one phosphorous atom and its neighboring carbon atom to cleave a C–P bond. Consequently, DPPE was efficiently retrosynthesized, which instructed that DPPE may very well be ready from ethylene and 1,1,2,2-tetraphenyldiphosphine through a radical response.

Based mostly on these theoretical outcomes, we carried out the novel response of ethylene and diphosphine within the presence of an Ir-based photocatalyst underneath irradiation from blue LEDs (Fig. 2). The response easily proceeded to afford DPPE in excessive yield. Nevertheless, diphosphine is unstable underneath atmospheric circumstances and glovebox strategies are required to arrange and deal with it. To understand a extra handy synthesis of DPPE with out the usage of inert-gas strategies, we explored the response circumstances, and we lastly developed a facile and sensible photo-induced synthesis of symmetric DPPE derivatives through a three-component response (3CR) of ethylene, a phosphine oxide, and a chlorophosphine within the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Numerous aryl rings containing electron-donating, electron-withdrawing, and different cumbersome substituents on the phosphorous atoms have been tolerated on this response to afford symmetric DPPE derivatives. Importantly, this 3CR for symmetric DPPEs may be extrapolated to the synthesis of unsymmetric DPPEs. When phosphine oxides and chlorophosphines, every of which possess totally different substituents on their aryl rings, have been used, the corresponding unsymmetric DPPEs have been obtained in excessive yield. Quite a lot of aryl substituents with totally different digital and steric character might be put in on each phosphine moieties. Moreover, the thus obtained (un)symmetric DPPEs may very well be transformed into (un)symmetric bidentate ligands upon discount. A few of these ligands subsequently reacted with Ni, Pd, Pt, or Au salts to kind the corresponding transition-metal complexes. Apparently, a Pd complicated possessing an unsymmetric DPPE spinoff exhibited totally different photophysical properties in comparison with the analogous Pd-dppe complicated.

This analysis technique, through which computational calculations are used to find the seeds of recent reactions that may be realized and expanded by experimental investigations, will most definitely substitute typical trial-and-error approaches in experimental natural chemistry. We hope that our work will lay the muse for the essentially new growth of helpful new reactions past such trial-and-error approaches.

For extra particulars, together with mechanistic investigations on such 3CR reactions, please seek advice from our manuscript “A theory-driven synthesis of symmetric and unsymmetric 1,2-bis(diphenylphosphino)ethane analogues through radical difunctionalization of ethylene” in Nature Communications.

References

1. van Leeuwen, P. W. N. M., Kamer, P. C. J., Reek, J. N. H. & Dierkes, P. Ligand chew angle results in metal-catalyzed C−C bond formation. Rev. 100, 2741–2770 (2000).
2. Honaker, M. T., Sandefur, B. J., Hargett, J. L., McDaniel, A. L. & Salvatore, R. N. CsOH-promoted P-alkylation: A handy and extremely environment friendly synthesis of tertiary phosphines. Tetrahedron Lett. 44, 8373−8377 (2003).
3. Yang, Z. et al. Artificial technique of bis(diphenylphosphine)alkane. CN102633836 (2012).
4. Xuan, X., Liang, R., Li, Y., Zhao, P. & Cui, Y. A way for getting ready bis(diphenylphosphino)alkane. CN104558030 (2015).
5. Bunlaksananusorn, T. & Knochel, P. t-BuOK-catalyzed addition phosphines to functionalized alkenes: A handy synthesis of polyfunctional phosphine derivatives. Tetrahedron Lett. 43, 5817−5819 (2002).
6. Sadanani, N. D., Walia, A., Kapoor, P. N. & Kapoor, R. N. Some transition steel complexes of novel ditertiary phosphine: [2-{Di(p-tolyl)phosphino}-ethyl] diphenylphosphine. Coord. Chem. 11, 39−44 (1981).
7. Cotton, F. A. & Kitagawa, S. Direct proof favouring an inside flip of dimetal models in cubiodal ligand cages. Polyhedron 7, 463−470 (1988).
8. Brunner, H. & Stumpf, A. Optisch aktive Übergangsmetall-Komplexe CV. Faciale und meridionale Chromcarbonylphosphin-Komplexe. Organomet. Chem. 459, 139−144 (1993).
9. Casey, C. P. et al. Electronically dissymmetric DIPHOS derivatives give increased n:i regioselectivity in rhodium-catalyzed hydroformylation than both of their symmetric counterparts. Am. Chem. Soc. 121, 63–70 (1999).
10. Carraz, C.-A. et al. Rhodium(I) complexes of unsymmetrical diphosphines: Environment friendly and steady methanol carbonylation catalysts. Commun. 1277−1278 (2000).
11. Yue, W.–J., Xiao, J.-Z., Zhang, S. & Yin, L. Speedy synthesis of chiral 1,2-bisphosphine derivatives by means of copper(I)-catalyzed uneven conjugate hydrophosphination. Chem. Int. Ed. 59, 7057−7062 (2020).
12. Maeda, S., Ohno, Okay. & Morokuma, Okay. Systematic exploration of the mechanism of chemical reactions: The worldwide response route mapping (GRRM) technique utilizing the ADDF and AFIR strategies. Chem. Chem. Phys. 15, 3683−3701 (2013).