& Shape-Persistent Macrocycles

Cyclotetrabenzoin: Facile Synthesis of a Shape-PersistentMolecular Square and Its Assembly into Hydrogen-BondedNanotubes

Qing Ji,[a] Ha T. M. Le,[a] Xiqu Wang,[a] Yu-Sheng Chen,[b] Tatyana Makarenko,[a]

Allan J. Jacobson,[a] and Ognjen S. Miljanic*[a]

Abstract: Cyanide-catalyzed benzoin condensation of ter-ephthaldehyde produces a cyclic tetramer, which we pro-

pose to name cyclotetrabenzoin. Cyclotetrabenzoin isa square-shaped macrocycle ornamented with four a-hy-droxyketone functionalities pointing away from the cen-tral cavity, the dimensions of which are 6.9 Õ 6.9 æ. In thesolid state, these functional groups extensively hydrogenbond, resulting in a microporous three-dimensional organ-

ic framework with one-dimensional nanotube channels.This material exhibits permanent—albeit low-porosity,with a Langmuir surface area of 52 m2 g¢1. Cyclotetraben-

zoin’s easy and inexpensive synthesis and purification mayinspire the creation of other shape-persistent macrocycles

and porous molecular crystals by benzoin condensation.

Shape-persistent macrocycles and cages[1] have been the sub-

ject of much attention as components of ordered three-(porous materials),[2] two- (assemblies at liquid–solid interfa-

ces),[3] and one-dimensional (organic nanowires and nanofi-brils)[4] functional ensembles. While traditionally syntheses ofshape-persistent large rings were challenging, the use of dy-namic combinatorial chemistry (DCC)[5] allowed error-correctionin the preparation of thermodynamically stabilized species and

opened up faster routes to macrocycles and cages based onimine,[2h–o, 4c, d] boronate ester,[2f, g] alkyne,[6] and boroxine[7] func-tionalities. In this Communication, we report arguably theshortest route to a shape-persistent macrocycle: a one-stepsynthesis of a 24-membered ring through benzoin condensa-tion of terephthaldehyde. This macrocycle self-assembles into

an unusual microporous crystal structure through the forma-tion of hydrogen-bonded nanotubes that protrude throughthe crystal.

Benzoin condensation (the term condensation is purely his-

toric, as no small molecule is eliminated in this addition reac-tion) was discovered by Liebig and Wçhler during their work

on bitter almond oil.[8] In recent years, this reaction has been

utilized in the synthesis of pharmaceutical precursors[9] and mi-croporous organic polymers;[10] enantioselective versions have

also been developed.[11]

The first attempts to extend benzoin condensation to more

complex dialdehyde precursors were performed early in thedevelopment of this reaction. Benzoin condensation of tere-

phthalaldehyde was first examined by Grimaux in 1876[12] and

then revisited by Oppenheimer (1886),[13] as well as by Jonesand Tinker (1955).[14] These studies concluded that only poly-

meric products were formed. Isomeric isophthaldehyde wasalso reported to yield only polymeric benzoin adducts. We

have very recently shown, however, that isophthaldehyde canbe converted into a single macrocyclic timer—which we

dubbed cyclotribenzoin—in 41 % yield.[15] This unexpected dis-

covery encouraged us to attempt an analogous benzoin con-densation of terephthaldehyde (1, Scheme 1).

Exposure of 1 to NaCN in a 1:1 mixture of EtOH and H2O re-sulted in a complex mixture of benzoin condensation productsin solution, as well as in the formation of some insoluble mate-

rials (which we presumed to be polymeric). Mass spectrometrysuggested the presence of a tetramer of 1 in the soluble frac-

tion, and we suspected that the tetrameric compound couldbe 2 (or its diastereomers). Unfortunately, we could not opti-mize this reaction to exclusively yield 2, and the high polarity

of the obtained products made their separation by columnchromatography impractical. Switching the reaction solvent to

a 1:1 mixture of 2-methoxyethanol and H2O, and lowering theconcentration of 1 to 0.167 m, resulted, however, in the forma-

tion of a precipitate consisting almost entirely of the tetramer.Recrystallization from DMSO/MeOH produced pure 2 in 21 %

Scheme 1. Synthesis of cyclotetrabenzoin 2.

[a] Q. Ji, H. T. M. Le, Dr. X. Wang, Dr. T. Makarenko, Prof. A. J. Jacobson,Prof. O. S. MiljanicDepartment of Chemistry, University of Houston, 112 Fleming BuildingHouston, TX 77204-5003 (USA)E-mail : miljanic@uh.edu

[b] Dr. Y.-S. ChenCenter for Advanced Radiation Source (ChemMatCARS)The University of Chicago, c/o APS/ANL9700 South Cass Drive, Argonne, IL 60439 (USA)

Chem. Eur. J. 2015, 21, 17205 – 17209 Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim17205

CommunicationDOI: 10.1002/chem.201503851

yield, and allowed us to confirm its structure using standardspectroscopic tools. We propose to name compound 2 “cyclo-

tetrabenzoin,” to emphasize its origin and cyclic tetramericstructure.

Single crystals of 2 suitable for X-ray diffraction analysiswere grown by slow vapor diffusion of MeOH into a dilute

DMSO solution of 2. Compound 2 crystalizes in the tetragonalspace group P421c with two molecules in the unit cell. The fourstereocenters of 2 have R, S, R, and S configurations. Curiously,

the molecule is achiral—even though it lacks symmetryplanes—on account of the existence of an S4 axis that passesthrough the central cavity. The molecule adopts a roughlysquare shape (Figure 1 A), with four benzene rings acting as

the sides of the square. A central cavity is clearly discernible: it

has dimensions of 6.9 Õ 6.9 æ, defined as the distances between

the centroids of two pairs of benzene rings on the oppositesides of the cyclotetrabenzoin molecule. Some twisting is ob-

servable in the planes of these benzene rings (Figure 1 B), asthey define a 40.88 angle with the benzene ring on the oppo-

site side. From this perspective, it is also visible that the foura-hydroxyketone functionalities point away from the centralcavity, a feature that plays a crucial role in the crystal packing

of 2 (vide infra, Figure 2). The molecule is not strained, as allcarbon atoms in 2 have bonding angles within �28 of their

idealized geometries.The crystal packing diagram of 2 is shown in Figure 2. In the

solid state, the key intermolecular interaction is a bifurcatinghydrogen bond established between the benzoin O¢H hydro-gen and oxygen atoms from both the carbonyl (C=O ; O···H dis-

tance 2.11 æ)[16] and hydroxyl groups (O¢H; O···H distance2.16 æ) in the neighboring molecule of 2. Each macrocycle acts

as both a hydrogen-bond donor and acceptor, resulting in aninfinite „tape“ of hydrogen bonds along the crystallographic

c axis (highlighted in green in Figure 2 A). This relationship isrepeated four times on all four sides of the macrocycle. When

viewed along the crystallographic c axis, this arrangement re-sults in a remarkably ordered square grid (Figure 2 B), wherein

individual molecules of 2 are stacked perfectly on top of eachother, resulting in square-shaped nanotubes. These nanotubes

are then bundled through hydrogen bonds established be-tween edge benzoin functionalities. Notably, the strong [O¢H···O] hydrogen bonds are established between molecules

from adjacent nanotubes. Molecules within each individualnanotube engage in comparatively weaker [C¢H···O] interac-

tions between the benzoin carbonyl group (C=O) oxygenatoms and hydrogen atoms from the aromatic ring as well asthe a-protons of the benzoin functionality (with H···O distancesbetween 2.40 and 3.00 æ). Single-crystal X-ray diffraction also

determined that no solvent molecules were present in thecavity.

The extended structure of 2 (Figure 2 B) is unique and im-portant from several viewpoints. First, it is a rare example of anintrinsically porous organic molecule, organized into a crystal

structure with 10 % void volume.[2, 17] Secondly, its highly polaroutside groups and nonpolar internal cavities could serve as

interesting platforms for transport of species through crystals

and membranes. Third, its infinitely hydrogen-bonded nano-tubular subunits may play a role in the development of novel

ferroelectric materials.[18] Finally, it is aesthetically pleasing, asits square-grid structure resembles that of a well-planned city ;

in fact, it superimposes remarkably well (see the Table of Con-tents graphic) onto the satellite image of Eixample, a district of

Figure 1. X-ray crystal structure of 2. A: A top-down view of the tetramer,showing all a-hydroxyketone functional groups pointing away from themacrocycle cavity. B: A side view showing the twisted orientation of thebenzene rings on the opposite sides of the square tetramer. Thermal ellip-soids shown at 50 % probability. Element colors : C (gray), O (red), H (white).

Figure 2. Crystal packing of 2. A: Two parallel columns of molecules of 2 es-tablish an infinite tape of hydrogen bonds, highlighted in green. Moleculeson the left are colored by element, those on the right are colored to high-light separate nanotubes. B: Segment of the extended crystal structure of 2,viewed along the crystallographic c axis. This view of the structure showsthe arrays of hydrogen-bonded nanotubes, and the intrinsic pores of 2. Ele-ment colors : C (gray), O (red), H (white).

Chem. Eur. J. 2015, 21, 17205 – 17209 www.chemeurj.org Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim17206

Communication

Barcelona known for its visionary urban plan designed by Ilde-fons Cerd�.[19, 20]

Macrocycle 2 is microcrystalline after recrystallization; thepowder X-ray diffraction (PXRD) pattern of as-synthesized 2(Figure 3, bottom) is in excellent agreement with the PXRDpattern simulated from the single-crystal X-ray data (Figure 3,

top).The thermal stability of compound 2 was evaluated using

TGA under N2, with a heating rate of 2 8C min¢1. The TGA trace

(Figure 4) shows no weight loss until approximately 250 8C. Be-

tween 250 and 320 8C, a small (<3 %) weight loss is observed;this is followed by a rapid loss of approx. 15 % of the original

weight in the 320–360 8C range, and a relatively featurelessTGA trace above 360 8C, likely indicative of full decomposition.

As it is synthesized under aqueous conditions, cyclotetraben-zoin is obviously also stable to water.[21]

Gas sorption of 2 was probed using N2 as the guest (degass-

ing conditions: 160 8C, 15 h, under 10 mmHg). Based on the iso-therm (Figure 5), the Brunauer–Emmett–Teller (BET) and Lang-

muir surface areas of 2 were determined to be 42 and52 m2 g¢1, respectively. The isotherm can be categorized as

a hybrid between the type I isotherm—characteristic for micro-porous systems, and a small contribution from the type II iso-

therm.[2m, 22] Cyclotetrabenzoin adsorbs a similar volume of H2

at 77 K (corresponding to 0.18 wt %) and a slightly largervolume of CO2 at 195 K.

In conclusion, cyclotetrabenzoin may be a progenitor for an

entire class of easily synthesized, shape-persistent, intrinsicallyporous all-organic macrocycles. Its extensively oxygenated rim

allows the molecule to engage in strong hydrogen bonds,which on one hand plays a role in its assembly in the solid

state, and on the other could be utilized to bind discrete mo-lecular guests. While its surface area is small, its chemical and

thermal stability are superior to the previously reported intrins-

ically porous organic cages based on imine, boronate esters,and boroxine functional groups. Our present focus is on build-

ing an isoreticular series of analogues of 2 by switching thecentral p-phenylene motif of terephthaldehyde for longer bi-

phenylene- or triphenylene-based precursors. Additionally,since benzoin condensation is a reversible reaction,[23] we will

explore whether this dynamic process can be steered toward

formation of other cyclic oligomers of terephthaldehyde. Re-sults of these studies will be reported in due course.

Experimental Section

Synthesis of compound 2

Terephthaldehyde (1, 6.80 g, 50.0 mmol), 2-methoxyethanol(150 mL), and deionized H2O (150 mL) were added to a 500 mLround-bottomed flask equipped with a stirring bar, and the mix-ture was heated at 100 8C under nitrogen until all of 1 had dis-solved. At that point, NaCN (253 mg, 5.00 mmol) was added intothe round-bottomed flask, and the heating at reflux was continuedfor 48 h. The precipitate was subjected to a hot filtration and thenwashed with deionized H2O (200 mL), MeOH (200 mL), and Et2O(200 mL). After drying in vacuo, yellowish crude product (2.70 g,40 %) was obtained. This crude material was suspended in DMSO(400 mL) under nitrogen, and heated to 50 8C for 12 h. The result-ing yellowish solution was filtered and transferred to a 1 L round-bottomed flask. Boiling MeOH (500 mL) was then carefully layeredon top of the DMSO solution, and the entire mixture was left to

Figure 3. Comparison of PXRD patterns of compound 2 : simulated fromsingle-crystal X-ray data (top) and measured from a freshly recrystallizedsample of 2 (bottom).

Figure 4. Thermogravimetric analysis of compound 2.

Figure 5. Adsorption and desorption of N2 (*/*), H2 (&/&), and CO2 (^/^)within the pores of 2, measured at 77 K for N2 and H2, and at 195 K for CO2.Solid symbols correspond to adsorption, hollow ones to desorption.

Chem. Eur. J. 2015, 21, 17205 – 17209 www.chemeurj.org Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim17207

Communication

cool to 20 8C. The round-bottomed flask was sealed with a septumand filled with N2. After 7 d, a precipitate was obtained; it was fil-tered and washed with MeOH (100 mL) and Et2O (100 mL), to givepure 2 as an off-white solid (1.40 g, 21 %, m.p. 299–300 8C, with de-composition). 1H NMR ([D6]DMSO, 600 MHz): d= 7.83 (d, J = 8.4 Hz,2 H), 7.34 (d, J = 8.4 Hz, 2 H), 6.22 (d, J = 5.4 Hz, 2 H), 5.91 ppm (d,J = 4.8 Hz, 2 H); 13C NMR ([D6]DMSO, 125 MHz): d= 197.40, 144.59,132.95, 129.44, 127.12, 76.36 ppm; UV/Vis (DMSO): lmax (log e) =261 (4.68), 318 nm (3.28); FTIR (KBr pellet): n= 3456 (s, br), 3057(w), 2937 (w), 1930 (w), 1807 (w), 1679 (s), 1606 (s), 1413 (m), 1255(s), 1188 (m), 1122 (m), 1095 (s), 1018 (w), 981 (s), 841 (s), 818 (s),744 (s), 704 cm¢1 (s) ; CI-HRMS: m/z : calcd for C32H24O8 : 536.1471;found [M++H]+ : 537.1548.

Single crystals of 2 were grown as follows. Crude 2 (40 mg) wasdissolved in DMSO (20 mL) under heating. The resulting solutionwas cooled to 20 8C and filtered. Different volumes of the filtrate(0.1–0.5 mL) were added to five small vials (0.8 mL). These vialswere then placed inside a larger scintillation vial (20 mL) contain-ing MeOH (4 mL) as the diffusing solvent. The vial was closed andkept at 20 8C for 14 d. Colorless needle-shaped crystals were ob-tained from all vials, and the best ones were selected for analysis.

The X-ray diffraction data were collected at ChemMatCARS beam-line at Advanced Photon Source in Argonne National Laboratory. Acolorless needle-shaped crystal measuring 0.10 Õ 0.01 Õ 0.01 mm3

was mounted on a glass fiber and cooled to 100 K using Cryojet(Oxford instrumentation). The diffraction data was collected ona Bruker D8 diffractometer with an APEX-II CCD detector using phiscans. Crystal-to-detector distance was 110 mm and the exposuretime was 0.3 s per frame using a scan width of 0.58. The diffractionwavelength was 0.40651 nm. Data collection was 98.2 % completeto 14.1178 in q. A total of 24 222 reflections were collected, cover-ing the indices: ¢21�h�21, ¢21�k�21 and ¢8� l�8. A totalof 2018 reflections were found to be symmetry independent, withan Rint of 0.1760. Crystal data of 2 : Tetragonal P�4c; a = b =

14.507(3), c = 5.8300(10) æ; V = 1226.9(5) æ3 ; Z = 2; 1calcd =1.452 Mg m¢3 ; crystal size 0.10 Õ 0.01 Õ 0.01 mm3 ; T = 100(2) K; m=0.046 mm¢1; R1[I>2s(I)] = 0.0562; wR2 = 0.1162, GOF= 1.051.

CCDC-1060952 contains the supplementary crystallographic datafor this paper. These data can be obtained free of charge from TheCambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

Acknowledgements

This research was supported by the University of Houston and

its Grant to Advance and Enhance Research (to O.S M.), the Na-tional Science Foundation (award DMR-1507664 to O.S.M.), and

the Welch Foundation (awards E-0024 to A.J.J. and E-1768 toO.S.M.). O.S.M. is a Cottrell Scholar of the Research Corporation

for Science Advancement. ChemMatCARS Sector 15 is princi-pally supported by the National Science Foundation under

grant number CHE-1346572. Use of the Advanced PhotonSource was supported by the U. S. Department of Energy,

Office of Science, Office of Basic Energy Sciences, under Con-

tract No. DE-AC02-06CH11357. Parts of this manuscript werewritten at New York University Abu Dhabi (NYUAD), where

O.S.M. was on a sabbatical stay.

Keywords: adsorption · benzoin condensation · dynamic

combinatorial chemistry · macrocycles · shape-persistentmacrocycles

[1] For reviews, see: a) W. Zhang, J. S. Moore, Angew. Chem. Int. Ed. 2006,45, 4416 – 4439; Angew. Chem. 2006, 118, 4524 – 4548; b) M. J. MacLa-chlan, Pure Appl. Chem. 2006, 78, 873 – 888; c) S. Hçger, Chem. Eur. J.2004, 10, 1320 – 1329; d) D. Zhao, J. S. Moore, Chem. Commun. 2003,807 – 818; e) J. S. Moore, Acc. Chem. Res. 1997, 30, 402 – 413; f) M. K.Smith, O. S. Miljanic, Org. Biomol. Chem. 2015, 13, 7841 – 7845.

[2] For reviews, see: a) G. Zhang, M. Mastalerz, Chem. Soc. Rev. 2014, 43,1934 – 1947; b) M. Mastalerz, Synlett 2013, 781 – 786; < lit c>M. Masta-lerz, Angew. Chem. Int. Ed. 2010, 49, 5042 – 5053; Angew. Chem. 2010,122, 5164 – 5175. For notable examples, see: d) T.-H. Chen, I. Popov, Y.-C.Chuang, Y.-S. Chen, O. S. Miljanic, Chem. Commun. 2015, 51, 6340 –6342; e) H. Yang, Y. Du, S. Wan, G. D. Trahan, Y. Jin, W. Zhang, Chem. Sci.2015, 6, 4049 – 4053; f) G. Zhang, O. Presly, F. White, I. M. Oppel, M. Mas-talerz, Angew. Chem. Int. Ed. 2014, 53, 5126 – 5130; Angew. Chem. 2014,126, 5226 – 5230; g) G. Zhang, O. Presly, F. White, I. M. Oppel, M. Masta-lerz, Angew. Chem. Int. Ed. 2014, 53, 1516 – 1520; Angew. Chem. 2014,126, 1542 – 1546; h) S. M. Elbert, F. Rominger, M. Mastalerz, Chem. Eur. J.2014, 20, 16707 – 16720; i) T. Mitra, K. E. Jelfs, M. Schmidtmann, A.Ahmed, S. Y. Chong, D. J. Adams, A. I. Cooper, Nat. Chem. 2013, 5, 276 –281; j) M. W. Schneider, H.-J. S. Hauswald, R. Stoll, M. Mastalerz, Chem.Commun. 2012, 48, 9861 – 9863; k) M. W. Schneider, I. M. Oppel, M. Mas-talerz, Chem. Eur. J. 2012, 18, 4156 – 4160; l) J. T. A. Jones, T. Hasell, X.Wu, J. Bacsa, K. E. Jelfs, M. Schmidtmann, S. Y. Chong, D. J. Adams, A.Trewin, F. Schiffmann, F. Cora, B. Slater, A. Steiner, G. M. Day, A. I.Cooper, Nature 2011, 474, 367 – 371; m) M. Mastalerz, M. W. Schneider,I. M. Oppel, O. Presly, Angew. Chem. Int. Ed. 2011, 50, 1046 – 1051;Angew. Chem. 2011, 123, 1078 – 1083; n) S. Jiang, J. T. A. Jones, T. Hasell,C. E. Blythe, D. J. Adams, A. Trewin, A. I. Cooper, Nat. Commun. 2011, 2,DOI: 10.1038/ncomms1207; o) M. Mastalerz, Chem. Commun. 2008,4756 – 4758; p) D. Venkataraman, S. Lee, J. S. Zhang, J. S. Moore, Nature1994, 371, 591 – 593; see also: q) A. D. Finke, D. E. Gross, A. Han, J. S.Moore, J. Am. Chem. Soc. 2011, 133, 14063 – 14070.

[3] a) K. Tahara, J. Gotoda, C. N. Carroll, K. Hirose, S. De Feyter, Y. Tobe,Chem. Eur. J. 2015, 21, 6806 – 6816; b) K. Tahara, K. Inukai, J. Adisoejoso,H. Yamaga, T. Balandina, M. O. Blunt, S. De Feyter, Y. Tobe, Angew. Chem.Int. Ed. 2013, 52, 8373 – 8376; Angew. Chem. 2013, 125, 8531 – 8534;c) K. Tahara, H. Yamaga, E. Ghijsens, K. Inukai, J. Adisoejoso, M. O. Blunt,S. De Feyter, Y. Tobe, Nat. Chem. 2011, 3, 714 – 719; d) T. Chen, G.-B. Pan,H. Wettach, M. Fritzsche, S. Hçger, L.-J. Wan, H.-B. Yang, B. H. Northrop,P. J. Stang, J. Am. Chem. Soc. 2010, 132, 1328 – 1333; e) J. Adisoejoso, K.Tahara, S. Okuhata, S. Lei, Y. Tobe, S. De Feyter, Angew. Chem. Int. Ed.2009, 48, 7353 – 7357; Angew. Chem. 2009, 121, 7489 – 7493; f) S. Lei, K.Tahara, F. C. De Schryver, M. Van der Auweraer, Y. Tobe, S. De Feyter,Angew. Chem. Int. Ed. 2008, 47, 2964 – 2968; Angew. Chem. 2008, 120,3006 – 3010; g) K. Tahara, S. Lei, W. Mamdouh, Y. Yamaguchi, T. Ichikawa,H. Uji-I, M. Sonoda, K. Hirose, F. C. De Schryver, S. De Feyter, Y. Tobe, J.Am. Chem. Soc. 2008, 130, 6666 – 6667; h) S. Hçger, K. Bonrad, A. Mour-ran, U. Beginn, M. Mçller, J. Am. Chem. Soc. 2001, 123, 5651 – 5659; i) E.Mena-Osteritz, P. B�uerle, Adv. Mater. 2001, 13, 243 – 246.

[4] a) L. Zang, Y. Che, J. S. Moore, Acc. Chem. Res. 2008, 41, 1596 – 1608;b) K. Balakrishnan, A. Datar, W. Zhang, X. Yang, T. Naddo, J. Huang, J.Zuo, M. Yen, J. S. Moore, L. Zang, J. Am. Chem. Soc. 2006, 128, 6576 –6577; c) J. K.-H. Hui, P. D. Frischmann, C.-H. Tso, C. A. Michal, M. J. MacLa-chlan, Chem. Eur. J. 2010, 16, 2453 – 2460; d) A. J. Gallant, M. J. MacLa-chlan, Angew. Chem. Int. Ed. 2003, 42, 5307 – 5310; Angew. Chem. 2003,115, 5465 – 5468.

[5] a) J. N. H. Reek, S. Otto, Dynamic Combinatorial Chemistry, Wiley-VCH,Weinheim, 2010 ; b) P. T. Corbett, J. Leclaire, L. Vial, K. R. West, J.-L.Wietor, J. K. M. Sanders, S. Otto, Chem. Rev. 2006, 106, 3652 – 3711;c) S. J. Rowan, S. J. Cantrill, G. R. L. Cousins, J. K. M. Sanders, J. F. Stod-dart, Angew. Chem. Int. Ed. 2002, 41, 898 – 952; Angew. Chem. 2002, 114,938 – 993.

[6] a) Q. Wang, C. Yu, H. Long, Y. Du, Y. Jin, W. Zhang, Angew. Chem. Int. Ed.2015, 54, 7550 – 7554; Angew. Chem. 2015, 127, 7560 – 7564; b) Q.Wang, C. Zhang, B. C. Noll, H. Long, Y. Jin, W. Zhang, Angew. Chem. Int.

Chem. Eur. J. 2015, 21, 17205 – 17209 www.chemeurj.org Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim17208

Communication

Ed. 2014, 53, 10663 – 10667; Angew. Chem. 2014, 126, 10839 – 10843;c) C. Zhang, Q. Wang, H. Long, W. Zhang, J. Am. Chem. Soc. 2011, 133,20995 – 21001; d) W. Zhang, J. S. Moore, J. Am. Chem. Soc. 2004, 126,12796; e) Y. Jin, Q. Wang, P. Taynton, W. Zhang, Acc. Chem. Res. 2014,47, 1575 – 1586.

[7] a) K. Ono, K. Johmoto, N. Yasuda, H. Uekusa, S. Fujii, M. Kiguchi, N. Iwa-sawa, J. Am. Chem. Soc. 2015, 137, 7015 – 7018; b) T.-H. Chen, W. Kavee-vivitchai, N. Bui, O. S. Miljanic, Chem. Commun. 2012, 48, 2855 – 2857.

[8] a) F. Wçhler, J. Liebig, Ann. Pharm. 1832, 3, 249 – 282; for a recentreview, see: b) D. Enders, O. Niemeier, A. Henseler, Chem. Rev. 2007, 107,5606 – 5655.

[9] a) Y.-J. Kim, N. Y. Kim, C.-H. Cheon, Org. Lett. 2014, 16, 2514 – 2517; b) P.Dìnkelmann, D. Kolter-Jung, A. Nitsche, A. S. Demir, P. Siegert, B.Lingen, M. Baumann, M. Pohl, M. Mìller, J. Am. Chem. Soc. 2002, 124,12084 – 12085; c) G. R. Pettit, J. W. Lippert III, D. L. Herald, J. Org. Chem.2000, 65, 7438 – 7444; d) M. C. Pirrung, L. Fallon, D. C. Lever, S. W. Shuey,J. Org. Chem. 1996, 61, 2129 – 2136.

[10] Y.-C. Zhao, T. Wang, L.-M. Zhang, Y. Cui, B.-H. Han, ACS Appl. Mater. Inter-faces 2012, 4, 6975 – 6981.

[11] a) L. Baragwanath, C. A. Rose, K. Zeitler, S. J. Connon, J. Org. Chem.2009, 74, 9214 – 9217; b) D. Enders, U. Kallfass, Angew. Chem. Int. Ed.2002, 41, 1743 – 1745; Angew. Chem. 2002, 114, 1822 – 1824; c) R. L.Knight, F. J. Leeper, J. Chem. Soc. Perkin Trans. 1 1998, 1891 – 1894; d) D.Enders, K. Breuer, J. H. Teles, Helv. Chim. Acta 1996, 79, 1217 – 1221.

[12] E. Grimaux, Compt. Rend. 1876, 83, 826.[13] H. Oppenheimer, Ber. Dtsch. Chem. Ges. 1886, 19, 1814 – 1818.[14] J. I. Jones, P. B. Tinker, J. Chem. Soc. 1955, 1286 – 1287.[15] Q. Ji, L. H. Do, O. S. Miljanic, Synlett 2015, 26, 1625 – 1627.

[16] All O¢H bond lengths have been normalized to a neutron-diffraction-determined internuclear distance of 0.993 æ. See: T. Steiner, Angew.Chem. Int. Ed. 2002, 41, 48 – 76; Angew. Chem. 2002, 114, 50 – 80.

[17] PLATON (C) 1980 – 2011 A. L. Spek, Utrecht University, Padualaan 8, 3584CH, Utrecht, The Netherlands.

[18] A. S. Tayi, A. Kaeser, M. Matsumoto, T. Aida, S. Stupp, Nat. Chem. 2015,7, 281 – 294.

[19] J. Ramoneda, Cerd� and the Barcelona of the Future : Reality versus Proj-ect. CCCB, Barcelona, 2009.

[20] Satellite image of Eixample district of Barcelona was obtained usingGoogle Earth, Google Inc.

[21] For hydrolytically stable cages obtained by reduction of imine-basedcages, see: a) M. Liu, M. A. Little, K. E. Jelfs, J. T. A. Jones, M. Schmidt-mann, S. Y. Chong, T. Hasell, A. I. Cooper, J. Am. Chem. Soc. 2014, 136,7583 – 7586; b) Y. Jin, B. A. Voss, R. D. Noble, W. Zhang, Angew. Chem.Int. Ed. 2010, 49, 6348 – 6351; Angew. Chem. 2010, 122, 6492 – 6495.

[22] K. S. W. Sing, D. H. Everett, R. A. W. Haul, L. Moscou, R. A. Pierotti, J. Rou-qu¦rol, T. Siemieniewska, Pure Appl. Chem. 1985, 57, 603 – 619.

[23] Exposure of 2 to an excess of 4-methylbenzaldehyde in the presence ofcatalytic NaCN resulted in its complete decomposition to a number ofproducts. This outcome is consistent with retrobenzoin opening of 2,followed by unselective cross-benzoin condensations between tereph-thaldehyde (or its benzoin dimer or trimer) and 4-methyl-benzaldehyde.Small amounts of terephthaldehyde were detected in the reaction mix-ture.

Received: September 25, 2015Published online on October 14, 2015

Chem. Eur. J. 2015, 21, 17205 – 17209 www.chemeurj.org Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim17209

Communication