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metal-free mechanism. Using the previously reported electrophilic boraindene 1 (ref. 13; Fig. 1), Piers, Tuononen and co-workers demonstrate its ability to form an adduct with triethylsilane. While the adduct is not observed spectroscopically in solution at room temperature, variable-temperature nuclear magnetic resonance experiments following a fluorine in the boraindene reagent and a proton in the silane clearly indicate the formation of an adduct, 2, on cooling to 195 K. The thermodynamic parameters governing the equilibrium were found to be consistent with a thermoneutral situation at room temperature. The boraindene–silane adduct 2 was also isolated in the solid state and a crystallographic study affirmed its formulation and revealed the metric details of the Si–H–B contact (Si–H: 1.51(2) Å, B–H: 1.46(2) Å, Si–H–B angle: 157°).

Computational studies were used to compare the stability of 2 to the silane adducts of tris(pentafluorophenyl)borane and a perfluoroarylborole (C6F5)4C4B(C6F5). Based on an analysis of the geometries of these adducts and the computed change in Gibbs free energy and enthalpy for bond

formation, it appears that the Lewis acidity of 1 lies between that of the other two boron species considered, and it is a subtle balance of steric and electronic features that accounts for the stability of 2.

Piers, Tuononen and co-workers go on to show that addition of the nucleophile (Ph3PNPPh3)Cl to mixtures of 1 and silane results in the formation of silyl chloride and (Ph3PNPPh3)((C6F4)C2(C6F5)2BH(C6F5)) 3 (Fig. 1). A direct analogy can be drawn between this reaction and the immediate reaction of silane–boron species with ketones that leads to hydrosilylation via this FLP-type mechanism.

In summary, exploiting the high Lewis acidity and tempered steric environment about the boron centre in 1 has enabled interception of 2 — a species that illuminates the intimate details of the first step in boron–Lewis acid-mediated hydrosilylation of ketones. This finding has significant implications for the role of other Lewis acids in hydrosilylation catalysis and more generally for the mechanism of activation of a range of small molecules by FLPs. Understanding the molecular details

of the mechanism of action is essential to the design and discovery of new and more efficient metal-free catalysts. ❐

Douglas W. Stephan is in the Department of Chemistry, University of Toronto, 80 St George Street, Toronto, Ontario M5S 3H6, Canada. e-mail: dstephan@chem.utoronto.ca

References1. Sabatier, P. Ind. Eng. Chem. 18, 1005–1008 (1926).2. Hudlický, M. Reductions in Organic Chemistry Vol. 2 (American

Chemical Society, 1996).3. Bullock, R. M. (ed.) Catalysis without Precious Metals (Wiley-

VCH, 2010).4. Stephan, D. W. & Erker, G. Angew. Chem. Int. Ed.

49, 46–76 (2010).5. Stephan, D. W. & Erker, G. Top. Curr. Chem. 332, 85–110 (2013).6. Welch, G. C., Juan, R. R. S., Masuda, J. D. & Stephan, D. W.

Science 314, 1124–1126 (2006).7. Brown, H. C., Schlesinger, H. I. & Cardon, S. Z. J. Am. Chem. Soc.

64, 325–329 (1942).8. Wittig, G. & Benz, E. Chem. Ber. 92, 1999–2013 (1959).9. Tochtermann, W. Angew. Chem. Int. Ed. Engl. 5, 351–371 (1966).10. Parks, D. J. & Piers, W. E. J. Am. Chem. Soc.

118, 9440–9441 (1996).11. Rendler, S. & Oestreich, M. Angew. Chem. Int. Ed.

47, 5997–6000 (2008).12. Houghton, A. Y., Hurmalainen, J., Mansikkamäki, A., Piers, W. E.

& Tuononen, H. M. Nature Chem. 6, 983–988 (2014).13. Houghton, A. Y., Karttunen, V. A., Piers, W. E. &

Tuononen, H. M. Chem. Commun. 50, 1295–1298 (2014).

In MOF (metal–organic framework) chemistry, solvothermal synthesis methods are widely applied1. Often crystallization

at elevated temperatures is the only means of generating robust frameworks from a given metal and ligand system. Traditionally, solvothermal synthesis is carried out, on scales of tens of milligrams to a few grams, in Teflon cups. These are then inserted into stainless steel pressure vessels. Soon after the field of MOF synthesis emerged around two decades ago, it was quickly realized that variation of reaction conditions — stoichiometry, solvent, concentration, temperature, time and pH — can lead to numerous different product phases.

The application of high-throughput screening of conditions for MOF synthesis was advocated by Cheetham and others around a decade ago2. However, the cost of individual steel pressure vessels (about $500 each) is not insubstantial, especially when numerous conditions need to be used

for such a screen. Construction of reactor arrays for the purpose has already been demonstrated to be effective, but these bespoke systems are even more costly.

A recent report in Angewandte Chemie International Edition by Leroy Cronin, Ross Forgan and colleagues3 is a potentially exciting development for many researchers, including those working on high-temperature crystallizations of MOFs. The paper describes how an inexpensive array of hydrothermal reaction chambers can be 3D printed in polypropylene (reactor R3 in Fig. 1a). Loading these chambers with reagents allows a number of individual reactions to be set up simultaneously for exploration of crystallization conditions. The Cronin group has previously championed 3D printing for use in custom labware4,5, and for these reactors, the economics of production seem attractive after an initial outlay on the 3D printer itself. Polypropylene is a cheap thermoplastic ($25 per kg) and each

individual reactor uses only around 20 g of material, making the cost of production much more economically reasonable than traditional steel pressure vessels.

Choosing a thermoplastic with suitable characteristics for solvothermal reaction vessels, but that can still be 3D printed, presents an engineering challenge. Many contemporary 3D printers use either hydrolytically biodegradable polylactic acid, or acrylonitrile-butadiene — which is soluble in many common organic solvents — both of which would be unsuitable for solvothermal crystallizations. The team behind the research has shown that the polypropylene vessels can, perhaps surprisingly, withstand the rigors of conditions such as aqueous dimethylformamide up to 140 °C for several days, as well as the presence of acids and bases.

Synthesis of MOFs using the reactors described by Cronin, Forgan and co-workers

METAL–ORGANIC FRAMEWORKS

3D frameworks from 3D printersHigh-throughput screening of solvothermal crystallization conditions for MOFs and other solids may receive a boost from the application of 3D printing techniques to low-cost, disposable pressure vessels.

Ian D. Williams

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seems ideally suited to a two-step approach: the first being an initial screening of crystallization conditions on a small scale. Using 5 × 5 arrays of 1-ml-capacity cylindrical vessels, they explored the synthetic parameter space for MOFs derived from a series of diacid and bipyridine linkers (Fig. 1b). Once optimal crystallization conditions were identified, traditional pressure vessels could then be employed to synthesize the desired products on a preparative scale. As an alternative to a stainless steel vessel, a scaled up reactor with 20 ml capacity was also 3D printed, and used to prepare well-known MOFs such as MIL-96 and HKUST-1 on a larger scale.

Two limitations of this approach may be noted, which will undoubtedly be overcome or minimized with some effort. First, the 3D printing must be interrupted at some point before completion to load reagents into the vessels. For high-throughput screening, coupling this to some form of automated reagent dispensing would be desirable, but the logistics of this would need to be worked out. Second, the recovery and analysis

of samples seems slightly cumbersome. Because the plastic vessels are sealed, access to the products is carried out by drilling holes into the reaction chambers and extracting crystalline powders. In contrast, using traditional reactors, the vessels can be cooled, the contents inspected and, if necessary, re-heated to continue the crystallization process. The idea of disposable one-reaction vessels may seem to be a drawback, but the waste is certainly no worse than many multi-well screens used in protein crystallization. Furthermore, as screening numerous synthesis conditions for MOFs creates much waste — including heavy or toxic metals — the proposed method could minimize this ‘synthetic waste’ and thus mitigate the use of disposable labware.

One other virtue of the traditional steel pressure vessel is that high pressure build-up and potentially explosive situations are avoided by a safety rupture disc. In the case of the 3D-printed vessels, direct catastrophic failure would occur, so users of the method must be aware of such safety issues and studiously avoid vessel overfill. It is also

essential to provide secondary containment of the plastic vessels within the ovens.

The method could prospectively be used by both academic groups researching MOF chemistry6,7, as well as industrial labs for screening and scale-up. Although application to MOF synthesis is an obvious choice, the approach could also be applied to other branches of crystallization, crystal engineering or high-temperature synthesis. This could include polymorph screening for pharmaceuticals from different solvents8, organic co-crystal formation9, as well as classical inorganic zeolite or various organic syntheses.

To develop the reactors further, more rigid and thermally stable vessels might be required, allowing higher temperatures to be probed. Cronin, Forgan and co-workers describe the failure of the polypropylene vessels to occur just above 140 °C, related to the softening temperature of the plastic. It may be notable that 3D printers working with carbon and glass-fibre polymer composites are now available. Owing to the versatility of 3D printing, ultimately the technique could be applied to manufacturing more complex vessel shapes, as well as modification of the vessel material and lining. However for many metal–organic and organic crystallizations, the current design should suffice as described.

The International Year of Crystallography (2014) is celebrating just over a century of X-ray crystallography. However in spite of all advances made, it seems that growing crystals will always pose a permanent challenge. One ‘futuristic’ solution for this, offered tongue-in-cheek at a recent meeting, is direct 3D printing of the crystal! Of course, while the current work doesn’t aim to achieve this directly, for many crystalline solids formed at high temperature it may offer the next best thing — a method that can offer a cheap and effective way of exploring crystallization conditions involving elevated temperatures. We’ll be trying it out soon! ❐

Ian D. Williams is in the Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. e-mail: chwill@ust.hk

References1. Stock, N. & Biswas, S. Chem. Rev. 112, 933–969 (2012).2. Forster, P. M., Stock, N. & Cheetham, A. K. Angew. Chem. Int. Ed.

44, 7608–7611 (2005).3. Kitson, P. J., Marshall, R. J., Long, D., Forgan, R. S. &

Cronin, L. Angew. Chem. Int. Ed. http://dx.doi.org/10.1002/anie.201402654 (2014).

4. Symes, M. D. et al. Nature Chem. 4, 349–354 (2012).5. Johnson, R. D. Nature Chem. 4, 338–339 (2012).6. Thakuria, R. et al. Int. J. Pharm. 453, 101–125 (2013).7. Furukawa, H., Cordova, K. E., O’Keeffe, M. & Yaghi, O. M.

Science 341, 499–504 (2013).8. Aaltonen, J. et al. Eur. J. Pharm. Biopharm. 71, 23–37 (2009).9. Friscic, T. & Jones, W. J. Pharm. Pharmacol. 62, 1547–1559 (2011).

R1a

b

R2 R3 R4

7.2 cm1.6 cm

3.4 cm2.0 cm

Figure 1 | 3D-printed reactionware enables solvothermal synthesis of metal–organic frameworks. a, Different designs for bespoke polypropylene reactors, and their 3D-printed physical manifestations, including a 5 × 5 array for screening of reaction conditions (R3). b, Cu MOF (left) and Cd MOF (right) crystal structures, found by screening different combinations of diacid and dipyridine ligands using the 5 × 5 reactor array. Cu, orange; Cd, yellow; N, blue; O, red; C, grey. Figure reproduced with permission from ref. 3, © 2014 Wiley.

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