News & Views | Published:

Organic chemistry

Shape control in reactions with light

Nature volume 515, pages 4546 (06 November 2014) | Download Citation

Subjects

The report of a light-activated catalyst that dictates the three-dimensional shape — the stereochemistry — of molecules formed in an organic reaction suggests a new strategy for controlling such reactions using visible light. See Letter p.100

Photochemical reactions can occur when a molecule absorbs light. Such reactions are greatly valued by organic chemists for their ability to promote fascinating changes in molecular structure that cannot be replicated in any other way. However, the application of these reactions for syntheses has long been hindered by several practical limitations. One of the biggest is the dearth of effective strategies for controlling the three-dimensional shape of the organic molecules produced. On page 100 of this issue, Huo et al.1 report an elegant approach to address this long-standing challenge.

The interaction between light and matter constitutes one of the most active areas of scientific research. This year, for instance, the Nobel prizes for physics and chemistry were awarded for the development of efficient light-emitting devices and for the use of fluorescence in ultrahigh-resolution microscopy, respectively. From energy science to biomedicine to materials engineering, photochemistry is a vibrant theme of such research, transecting many fields.

Photochemical reactions have been used to streamline complex syntheses and to build structurally unusual organic frameworks. However, organic molecules are generally transparent to visible light — they cannot absorb its energy for use in chemical reactions. Organic photochemical reactions have typically needed ultraviolet light, which requires specialized equipment and instrumentation capable of handling high-energy ultraviolet photons. This has limited the study of photochemical synthesis to a fairly small community of specialists.

But in the past several years, a variety of exciting photoreactions have been developed that use visible light, and so can be carried out with simple household light sources or even sunlight2. The key insight was that certain transition-metal complexes (typically based on ruthenium or iridium) that absorb relatively low-energy wavelengths of visible light can be used as catalysts to activate a wide range of organic substrates, thereby enabling new reactions to take place. Although this development has fuelled renewed interest in photochemical synthesis, control over the three-dimensional structure of the organic products has remained a problem.

This is an important problem, because the ability to form one mirror-image isomer (stereoisomer) of a molecule in preference to the other has profound ramifications in biological and pharmaceutical contexts: the two mirror-image forms often have drastically different physiological effects. Similarly, the macroscopic physical properties of polymeric organic materials can be strongly affected by the stereochemistry of their monomeric components. Stereoselective synthesis therefore remains one of the central challenges in modern synthetic chemistry.

Since 2009, Eric Meggers' research group has been developing methods for preparing ruthenium and iridium complexes as single stereoisomers3. In studying these complexes as catalysts for several organic reactions, Meggers and co-workers have demonstrated4,5 that the three-dimensional arrangement of the complexes can be transferred with exceptional fidelity to the organic products that they create. The same research group — Huo et al. — now shows that these transition-metal catalysts are also photoactive, and that this property can be exploited to perform highly stereoselective photochemical reactions.

As a model system, the authors chose to study the α-alkylation of carbonyl compounds — a benchmark reaction in stereoselective synthesis (Fig. 1). The iridium catalyst first binds to an acyl imidazole compound, creating a structurally well-defined enolate complex. Photoexcitation of this complex initiates an electron-transfer process that converts a reagent (a benzyl halide) into a highly reactive radical intermediate. The geometry of the catalyst shields one face of the planar enolate from reaction (the bottom face in Fig. 1) and forces the radical to form a bond to it preferentially from the opposite face. The iridium catalyst thus serves two distinct roles: it simultaneously photoactivates one component of the reaction (the benzyl bromide) and controls the facial selectivity of the other (the enolate).

Figure 1: Light-controlled stereoselectivity.
Figure 1

Huo et al.1 report a general reaction in which a light-activated iridium catalyst controls the stereochemistry of the product. In this example, an acyl imidazole forms an enolate (blue), which in turn forms a complex with the catalyst (red). Bonds shown in bold project above the plane of the page, whereas hashed bonds project behind the page. The catalyst also converts α-bromo-2,4-dinitrotoluene (a benzyl halide compound) into a radical intermediate and a bromide ion (Br) by donating an electron (e). The radical reacts only at the top face of the enolate, because part of the catalyst blocks the bottom face. This ensures that the stereochemistry of the product is well defined (the green group in the product projects above the page in most of the formed molecules, rather than below). Me, methyl; Ph, phenyl; t-Bu, tert-butyl (C(CH3)3, a highly bulky group); Ir, iridium; Br, bromine; the dot on the radical indicates a single electron.

These findings will attract considerable attention from synthetic chemists. Photochemical activation typically produces highly reactive intermediates whose stereochemical preferences have historically proved difficult to control6. Some of the most successful approaches have needed two catalysts, with one performing the photochemical activation and the other dictating the stereoselectivity of the reaction7,8. The discovery of a single transition-metal catalyst that fulfils both roles is a crucial conceptual step forward.

Huo and colleagues' reaction design combines the previously reported, precise stereoselective control exerted by their transition-metal complexes with the practicality of using visible light for photochemistry. Future investigations will surely build on this impressive result. Because the products of the reported reaction could also be made by more-conventional methods, the next step will be to show that the new catalytic strategy is applicable to other classes of photoreaction for unmet synthetic applications. More broadly, this work provides inspiration for chemists to further explore how photochemistry might be used to transform organic synthesis.

References

  1. 1.

    et al. Nature 515, 100–103 (2014).

  2. 2.

    & Science 343, 1239176 (2014).

  3. 3.

    , & Acc. Chem. Rev. 46, 2635–2644 (2013).

  4. 4.

    et al. J. Am. Chem. Soc. 135, 10598–10601 (2013).

  5. 5.

    , , & J. Am. Chem. Soc. 136, 2990–2993 (2014).

  6. 6.

    Chem. Rev. 92, 741–770 (1992).

  7. 7.

    & Science 322, 77–80 (2008).

  8. 8.

    , , & Science 344, 392–396 (2014).

Download references

Author information

Affiliations

  1. Kazimer L. Skubi and Tehshik P. Yoon are in the Department of Chemistry, University of Wisconsin–Madison, Madison, Wisconsin 53706, USA.

    • Kazimer L. Skubi
    •  & Tehshik P. Yoon

Authors

  1. Search for Kazimer L. Skubi in:

  2. Search for Tehshik P. Yoon in:

Corresponding author

Correspondence to Tehshik P. Yoon.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/515045a

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Newsletter Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing