Photocatalysis

Introduction

The application of radical chemistry towards organic synthesis is well-developed and wide-reaching, though often hampered by a dependence on toxic radical initiators. These initiators are often used in sub- and even fully stoichiometric amounts and can require the use of short-wave light sources. Alternatively, the burgeoning field of photocatalysis has provided a number of transition-metal complexes and organocatalysts capable of initiating radical formation in the presence of visible light. The application of visible-light mediated photocatalysis has now been demonstrated in scores of noteworthy chemical transformations, and progress in the field continues unabated.

Representative Applications

Late-Stage Incorporation of Small Alkyl Groups into Small Molecules of Biological Interest

Late-Stage Functionalization (LSF) of small, pharmaceutically active molecules can provide modified potency, toxicity and pharmacokinetic profiles with altogether less effort than the ground-up syntheses of analogs. Though LSF with fluorine (and fluorinated alkyl groups) is now readily achieved through use of, amongst other technologies, the zinc sulfinates developed by the Baran Group at Scripps, the incorporation of small, non-fluorous alkyl groups like methyl and ethyl groups has remained an unmet challenge. This is especially relevant as the incorporation of small alkyl groups is likely to yield molecules with more advantageous physiochemical and safety profiles vis à vis their fluorinated brethren.

Ultimately, the late-stage incorporation of methyl, ethyl and cyclopropyl groups to pharmaceutically active small molecules was achieved through a visible light photoredox strategy. Indeed, in the presence of blue light and peroxide alkyl radical precursors, newly available [Ir{dF(CF3)ppy}2(dtbpy)]PF6 catalyst (747793) mediates the formation of the required alkyl radicals (and thus, alkyl group incorporation) typically achieved by methods not amenable to LSF1.

 

Strategy for Room Temperature Lignin Degradation

Lignin represents over 30% of non-fossil fuel based organic carbon, and as such this biomass could be made, with the advent of chemoselective degradation processes, into a primary source of carbon-based feedstock material. The Stephenson Group has recently combined two innovative Sigma-Aldrich products to achieve the selective degradation of lignin-type model compounds in one pot. Indeed, Bobbitt’s salt was used to selectively oxidize benzyl alcohols, followed by photocatalytic reductive C-O bond cleavage to the ketone and alcohol degradation products. This last transformation was achieved without degassing and in the presence of visible light2.

Crossed Intermolecular [2+2] Cycloaddition of Styrenes

The crossed [2 + 2] cycloaddition of styrenes was achieved in high chemoselectivity through use of an appropriately tuned Ru-based visible light photocatalyst. As demonstrated by Prof. Tehshik Yoon, unsymmetrically substituted butanes can thus be prepared on gram scale with Ru(bpm)3.

 

Diversity of Application

The visible light photocatalysts currently available from Sigma-Aldrich have been used in applications that truly span organic chemistry (and beyond). Other reactivities that have been explored include:

  • Reduction of unactivated alkyl, alkenyl and aryl iodides
  • Co-mediated water oxidation for H2 gas production
  • Atom-transfer radical addition of haloalkanes to alkenes
  • Formal hydroaminoalkylation of alkenes

 References

  1. DiRocco, D. A.;  Dykstra, K.; Krska, S.; Vachal, P.; Conway, D. V.; Tudge, M. Angew. Chem. Int. Ed. 2014, 53, 4802. Abstract
  2. Nguyen, J.; Matsuura, B.; Stephenson, C. J. Am. Chem. Soc. 2014, 136, 1218. Abstract
  3. Ischay, M. A.; Ament, M. S.; Yoon, T.P. Chem. Sci. 2012, 3, 2807. Abstract

 

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