Carbonyl Hypoiodites as Extremely Strong Halogen Bond Donors

This is a self-archived version of an original article. This version may differ from the original in pagination and typographic details. Author(s): Title: Year: Version: Copyright: Rights: Rights url: Please cite the original version: CC BY-NC 4.0 https://creativecommons.org/licenses/by-nc/4.0/ Carbonyl Hypoiodites as Extremely Strong Halogen Bond Donors © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH Published version Yu, Shilin; Ward, Jas S.; Truong, Khai-Nghi; Rissanen, Kari Yu, S., Ward, J. S., Truong, K.-N., & Rissanen, K. (2021). Carbonyl Hypoiodites as Extremely Strong Halogen Bond Donors. Angewandte Chemie, 60(38), 20739-20743. https://doi.org/10.1002/anie.202108126 2021 Halogen Bonding Carbonyl Hypoiodites as Extremely Strong Halogen Bond Donors Shilin Yu, Jas S. Ward, Khai-Nghi Truong, and Kari Rissanen* Abstract: Neutral halogen-bonded OIN complexes were prepared from in situ formed carbonyl hypoiodites and aromatic organic bases. The carbonyl hypoiodites have a strongly polarized iodine atom with larger s-holes than any known uncharged halogen bond donor. Modulating the Lewis basicity of the selected pyridine derivatives and carboxylates leads to halogen-bonded complexes where the classical OI···N halogen bond transforms more into a halogen-bonded COO···IN+ion-pair (salt) with an asymmetric OIN moiety. X-ray analyses, NMR studies, and calculations reveal the halogen bonding geometries of the carbonyl hypoioditebased OIN complexes, confirming that in the solid-state the iodine atom is much closer to the N-atom of the pyridine derivatives than its original position at the carboxylate O-atom. Halogen bonding (XB) has become one of the most studied non-covalent interactions, more specifically electrophilenucleophile interactions, as demonstrated by the rapid increase of publications since 2007.[1–8] Halogen bonding has recently been defined to occur between halogens being electrophilic and neutral or anionic nucleophiles.[9] Despite ongoing debate about the true nature of the halogen bonding,[10–13] it is frequently used as a non-covalent interaction to construct supramolecular complexes. Owing to the similarity of the bonding geometries and directionality its kinship with hydrogen bonding is more than evident. Halogen bonding has been successfully applied to control the selfassembly of a multitude of host–guest systems (ion-pair recognition, biomolecular/chemical separations), as well as the synthesis of functional materials (porous, magnetic, phosphorescent, liquid crystals).[1,2] Crystal engineering,[1–4,14] the origin of halogen bonding, established the directionality, and specificity resulting in complex structures with appealing architectures. Owing to the demand of very precise design principles, hollow capsular molecular assemblies solely based on halogen bonding have only very recently been prepared.[15,16] Owing to its nature, halogen bonding is more directional than hydrogen bonding,[17] yet it is much more difficult to study in solution and has therefore been demonstrated mostly in the solid-state.[18–21] When an electron is removed from the halogen atom, it becomes a positively charged free ion, a halenium ion X+ (X=I, Br or Cl). These cations can be regarded as very strong bis-functional XB donors, though the reactivity of the free halenium ion effectively prevents their use as such. However, by applying suitable Lewis bases in the synthesis, the halenium ions can be trapped into a [LXL]+complex exhibiting a three-center-four-electron (3c-4e) bond. First of these, namely the iodonium bis(pyridine) complexes with a[N IN]+3c-4e bond, were reported in the 1960s by Hassel et al.,[22] Crichton et al.,[23] and Hague et al.[24] They have attracted a lot of attention, especially within the halogen bonding community and have recently been reviewed.[25,26] The iconic example, bis(pyridine)iodonium(I) tetrafluoroborate, Barluengas reagent,[27] is a mild iodination reagent and an oxidant. Barluengas reagent is a relatively stable white solid and is soluble in both organic and aqueous solutions, and its applicability in organic synthesis has been widely demonstrated.[28] Erdlyi[29–34] has demonstrated that the [NIN]+ halogen bond by very precise and comprehensive studies in solution, supplemented with computational calculations confirming that the [NIN]+halogen bond is symmetric with the iodine atom located in the center between the N-atoms. The anionic analogue [OIO],viz. dioxoiodane compounds, have recently applied as reagents in organic synthesis.[35] The most studied of the Barluenga-type halonium ion complexes[36–39] are the symmetrical [NXN]+(X =Br or I) complexes.[24,27] Asymmetric heteroleptic halonium complexes have been prepared by Erdlyi and co-workers,[30] with the help of molecular clefts. Only very recently the first unrestrained heteroleptic [N1IN2]+complexes have been reported in the solid-state[40] and solution.[41] Apart from the above mentioned charged XB complexes, also neutral NI···N and NI···ON XB complexes are easily prepared from suitable haloimides and halosulfonimides as the XB donors and pyridine derivatives or pyridine-N-oxides as the XB acceptors, extensively studied by Fourmigu[42,43] and Rissanen.[19–21,44] Inspired by the above-mentioned work, we sought to probe the RCOOI molecules, namely carbonyl hypoiodites, as a potential new motif of halogen bond donors. To the best of our knowledge, carbonyl hypoiodites which were stabilized by pyridine were first studied by Carlsohn in his habilitation in 1932.[45] In 1940s, Kleinberg, Zingaro and coworkers reported the preparation of a series of iodine(I) salts by the reaction of different silver carboxylates and iodine in the presence of pyridine, 2-picoline or 4-picoline as the stabilizing ligand.[46–49] Some of these salts were effectively utilized as iodination reagents with interesting antibacterial properties.[43] Furthermore, the two known single crystal [*] Dr. S. Yu, Dr. J. S. Ward, Dr. K.-N. Truong, Prof. K. Rissanen Department of Chemistry, University of Jyvaskyla Survontie 9 B, 40014 Jyvskyl (Finland) E-mail: kari.t.rissan[email protected] Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.202108126.  2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. A ngewandte Chemi e Communications How to cite: International Edition: doi.org/10.1002/anie.202108126 German Edition: doi.org/10.1002/ange.202108126 1Angew. Chem. Int. Ed. 2021,60, 1 – 6  2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH These are not the final page numbers! Ü Ü structures manifesting pyridine benzoyl hypoiodite 1b [named as benzoato-pyridine-iodine(I)] and bis-pyridine phthaloyl hypoiodite [phthalato-bis(pyridine-iodine(I)], were reported 40 years ago by Hartl.[50] In addition to their synthesis,[27] use of structurally related anionic complexes [RCOOI OOCR], which should be considered as the anionic-type 3c-4e XB complexes with two oxygen atoms as XB acceptors,[25] have been utilized as dynamic axles in the construction of rotaxanes.[51] Herein, we report the investigations on neutral OIN complexes, treated as new examples of halogen-bonded complexes, where the carbonyl hypoiodites act as XB donors. The results clearly show that carbonyl hypoiodites are very promising as strong halogen bond donors, giving unambiguous NMR spectra and manifesting very strong salt-like character (at least in the solid-state) where the iodine has jumped from the carboxyl oxygen to the N-atom of the pyridine derivative forming a very strongly halogen-bonded [RCOO][+IN(py)] ion-pair. The synthesis route to the neutral hypoiodite OIN complexes is illustrated in Scheme 1.[47,49] Characterization and details of the synthesis and the NMR studies of all twelve hypoiodite complexes (1b,1d,2a–2d,3a,3b,3d,4a,4band 4d) from pyridine and its selected derivatives, silver carboxylates, and elemental iodine are presented in the Supporting Information (SI). The 15N NMR chemical shift values based on the 1H-15N HMBC measurements (SI) of the pyridinic nitrogen of 2a–2d and free ligand 2are summarized in the Table 1. The complexation-induced chemical shift change, DdN, defined as d(15NOIN)d(15NL), with OIN as the halogen-bonded complexes and Las free 1–4, is very large and manifests a dramatic change in the chemical environment of the pyridinic N-atom during the complexation. With increasing Lewis basicity of the carboxylates the DdNincreases. The stable N-methyl-DMAP cation [2CH3]+, as the PF6salt, has aDdNbetween 2c and 2d (Table 1). Compared with the corresponding trifluoroacetate salt of DMAP ([2H]TFAc), the hypoiodite complex 2dhas a much larger DdN(129.4 vs. 85.6 ppm, Table S1), which indicates a bigger increase of the electron density around pyridinic nitrogen in 2d.[52,53] The DdNof three benzoate-based OIN complexes (1b, 2band 3b) was also compared, as shown in Table 1. When the nucleophilicity of the used base increases, the larger the 15N NMR chemical shift change. The complex 1bhas the smallest 15N NMR chemical shift change value, which is still bigger than that for pyridinium trifluoroacetate ([1H]TFAc) (81.0 vs. 70.0 ppm, Table S1). The single crystals of the complexes 1b,2a,2b,2c,2d,3b, 3d,4a and 4d were grown either from dichloromethane or chloroform upon slow evaporation or by vapor diffusion of pentane, diethyl ether or petroleum ether into dichloromethane, chloroform or acetonitrile. The crystallographic details are presented in the SI (Table S1). The DMAP- (2a, 2b,2c, and 2d) and benzoate-based (1b,2b, and 3b)O IN complexes will be discussed as two directly comparable series of complexes. The OI bonds for 2a,2b and 2c (Table 1, Figure 1) are very similar to each other (ca. 2.21 ) and identical for the OIO bonds (cf. 2.20 ) in the anionic dioxoiodane complexes.[35] The IN bond distances (Table 1) for 2a,2b, and 2c are all equal (ca. 2.23 ) and very much resemble those observed for previously reported 3c-4e [NI N]+halogen-bonded iodonium complexes.[22,37,40,54,55] A notable exception is the 2d where the IN bond length of 2.173(4)  is much too short to be a conventional 3c-4e halogen bond. The iodine is about 0.08  closer to the pyridinic nitrogen in 2dthan in a typical halonium ion [NI N]+complex and 0.04  closer than in the NISac-DMAP (2NISac) (inner)-salt complex reported by Fourmigu (cf. 2.218(2) ).[34] Apart from the short IN bond in 2d, the OI bond is elongated by 0.323  from the 1.989  obtained from the DFT calculations of the hypoiodite d(SI, Table S1) versus 2.312(4)  from the SCXRD. This value is analogous to the strongest I···O halogen bonds observed in N-iodosaccharinpyridine-N’-oxide halogen-bonded complexes,[19–21,44] and thus the OI bond in 2d is better described as an I···O halogen Scheme 1. Synthesis of the OIN complexes, with DMAP (2) and Agbenzoate given as an example (2b). Table 1: The OI and IN distances from SCXRD and DFTstudies and the 15N NMR chemical shifts for 1b,2,2a–2d,3b,[2CH3]PF6,[2I2]PF6, and 2-NISac. Complex d(OI) [] (XRD/DFT) d(IN) [] (XRD/DFT) d15N[b] [ppm] Dd[c] [ppm] 1b 2.159(5)/2.133 2.299(7)/2.301 148.7 81.0 2––108.6 – 2a 2.203(11)/2.15 2.234(14)/2.27 204.7 96.1 2b 2.210(3)/2.171 2.241(3)/2.247 209.5 100.9 2c 2.21(1)[a]/2.18 2.22(1)[a]/2.24 212.2 103.6 2d 2.312(4)/2.248 2.173(4)/2.189 238.0 129.4 [2CH3]PF6––224.0 115.4 [2I2]PF6––216.1 107.5 2-NISac[42] 2.292(2)[d]/2.314 2.218(2)/2.247 200.8 92.2 3b 2.230(4)/2.164 2.232(4)/2.2.257 202.1 102.5 [a] Average of four crystallographically independent complexes in the asymmetric unit. [b] The 1H-15N HMBC NMR chemical shift of pyridinic nitrogen in [OIN] complexes or free ligands in CD2Cl2. [c] The 15N NMR chemical shift change upon complexation. [d] (Sac)NI bond length. A ngewandte Chemi e Communications 2www.angewandte.org  2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH Angew. Chem. Int. Ed. 2021,60,1–6 Ü Ü These are not the final page numbers! bond. The OIN bond lengths in the solid-state for 2d support its description as an ion-pair of the N-iodo-N’,N’- dimethylaminopyridinium cation, and a trifluoroacetate anion, stabilized by a very strong N+I···OC halogen bond. The shortest IN bond of 2.167(4)  was observed for complex 4d, and similarly, the longest IO bond length was for 2das previously stated, though virtually the same as in 4d(cf. 2.308(4) ). Consistent with the general linearity of halogen bonds, the angles of the OIN moieties in all hypoiodite complexes fall within the range of 172.9(5)–178.1(1) 8 and are closer to the halogen bond angles observed for the N-iodosaccharinpyridine-N’-oxide halogen-bonded complexes[19–21,44] than to the strictly linear 3c-4e [NIN]+halogen bonds.[22,37,40,54,55] The SCXRD data for 2a–2d demonstrates the dynamic bonding situation for the OIN moiety, with shorter IN bond lengths reflecting an increase in the N-iodopyridinium character of the pyridine derivative, concomitantly with an elongation of the OI bond length reflecting an increase in the anionic character of the carboxylate component. As expected, substituted pyridines such as DMAP (2) and 4piperidinopyridine (4), that are stronger nucleophiles, are better able to induce this increased N-iodopyridinium character in the OIN complexes described herein. Estimation of the N-iodopyridinium character is difficult as no Niodopyridinium cation X-ray structure is known (only the N-fluoropyridinium cation is known).[56] In the 3c-4e [NI N]+halogen-bonded symmetric halonium complex [2I 2]PF6, the relative N-iodopyridinium character can be considered to be 50% (NI: 2.250 , NN: 4.500 ),[36,40,57] while for the [2I]+cation the IN bond distance can only be obtained with computational methods (SI, section 3). The DFT computed value for the IN bond distance in [2I]+is 2.042 . Using these two values and the SCXRD measured I N distances, the relative N-iodopyridinium character can be estimated for the Fourmigu reported 2-NISac complex[34] (56.5%), 2d (67.6%), 3d (62.4%) and 4d (69.1%) in the solid-state. Due to the dynamic nature[51] of the OIN moiety in solution, no clear correlation about the N-iodopyridinium character in the solid-state and in solution can be given. When keeping the trifluoroacetyl hypoiodite moiety constant but changing the pyridine moiety, namely complexes 2d,3d, and 4d, no apparent differences in the halogen bonding geometries were observed, as in all complexes the OI(2d: 2.312(4) , 3d: 2.282(5) , 4d: 2.308(4)) , the IN bond distances (2d: 2.173(4) , 3d: 2.194(5) , 4d: 2.167- (4) ) and the OIN angles (2d: 175.5(2) 8 ,3d: 172.1(2) 8 , 4d: 175.0(1) 8 ) are very similar. This is very likely due to the fact that all 2,3and 4are very strong Lewis bases and act as very strong XB donors enhancing the ion-pair formation in the solid-state. For comparison of the halogen bonding geometries from the SCXRD and DFT calculations (SPARTAN’18,[58] M062X, def2-TZVP) with non-polar solvent model (DCM) were performed. The detailed experimental SCXRD and calculated DFT geometries are given in SI (Table S1). The DFT calculated bond geometries are extremely close to those experimentally determined by SCXRD. This is a convincing proof that the computational values obtained for the nonsingle crystalline complexes are feasible and can be used to discuss the dynamic bonding behavior of the OIN system. The hypoiodites a–dshowed no trend on the OI bond distance as in all cases it is 1.99  (DFT, Table S1). Drastic elongation of the OI bond occurs during the OIN complex formation as the OI bond get longer by 0.17– 0.34 , and correspondingly the IN bonds shorten (Table S1). The N···O distance in all OIN complexes also remains virtually unchanged (4.43–4.48 ). The molecular electrostatic surface potential maps (MEPS, Figure 2) of the hypoiodites a–dreveal very large s-holes, ranging from +170.41 kJmol1(a)to +234.55 kJmol1(d). Due to the strong polarizing power of the carboxylate moiety these values are large when compared to some common strong halogen bond donors like trifluoroiodomethane (+139.50 kJmol1), iodoacetylene (+165.47 kJmol1), ICl (+182.41 kJmol1) and N-iodosaccharin (+226.36 kJmol1) (SI, Figure S75). Figure 1. The X-ray crystal structures of 2a,2b,2c and 2d (top to bottom; thermal ellipsoids at 50% probability).[59] Figure 2. The electrostatic potential surfaces and the Vs,max (kJmol1) values calculated at the M06-2X/6–311+G(3df,2p) level on the 0.001 a.u. molecular surfaces for a–d. A ngewandte Chemi e Communications 3Angew. Chem. Int. Ed. 2021,60, 1 – 6  2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH www.angewandte.org These are not the final page numbers! Ü Ü While the asymmetric OIN halogen-bonded hypoiodite complexes are stable (with a few exceptions) under normal conditions, they can be prone to exchange reactions to the corresponding positively charged [LIL]+(L =Lewis base) halonium complex in the presence of excess Lewis base, depending on the strength of the Lewis base and the carboxylate used. This is unambiguously proven by a titration experiment monitored by 1H NMR in d2-DCM (Figure 3). The OIN hypoiodite complex 2d (Figure 3a) was titrated with DMAP to probe the displacement of the TFAc anion. Given that DMAP is a strong nucleophile, it would be expected to replace the TFAc anion to form the [2I2]+ halonium complex. This indeed happens as, with the increasing amount of DMAP, the signals of DMAP in 2d (green color) gradually diminish, while new peaks (blue color) emerge for the symmetric [2I2]+halonium complex (Figure 3b–f). The 1H NMR spectrum of a separately prepared [2I2]PF6halonium complex is shown in Figure 3h for reference. At two equivalents of 2(Figure 3g), it was observed that the signals of 2d had nearly completely disappeared. In conclusion, a series of halogen-bonded OIN hypoiodite complexes have been synthesized, and their solid-state structures investigated, to probe the dependency between the OI and IN bond lengths and the Lewis basicity of the Ndonor. The solid-state studies revealed that these OIN complexes can be described as a new class of halogen-bonded complexes, namely as a very strongly bound ion-pair comprised from an iodopyridinium cation and an anion derived from the respective acid used. The 1H–15N HMBC NMR studies reveal a drastic change in the chemical shift of the pyridinic nitrogen atom in the complexes, especially those from strong acids, resulting in a stable halogen-bonded complex. The computational calculations support their characterization, revealing very large s-holes of the parent hypoiodites. The Vs,max value (+234.55 kJmol1) of the trifluoroacetyl hypoiodite surpassed that of the previously strongest neutral halogen bond donor molecule, N-iodosaccharin (+226.36 kJmol1). The exchange reactions of the hypoiodite complex 2d (COOIN(2)) with excess of 2 results in the corresponding positively charged [2I2]+ halonium complex, with COOas the anion. Furthermore, the results provide useful knowledge for the development of XB based materials and OIN based antibacterial agents. Acknowledgements We are grateful for financial support from the Academy of Finland (K.R.: grant no. 317259), the Finnish Cultural Foundation Central Fund (J.S.W.: grant no. 00201148), the Magnus Ehrnrooth Foundation (J.S.W.), and the University of Jyvskyl. Conflict of Interest The authors declare no conflict of interest. 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[59] Deposition Numbers 2068106 (for 1b), 2068107 (for 2a), 2068108 (for 2b), 2068109 (for 2c), 2068110 (for 2d), 2068111 (for 3b), 2068112 (for 3d), 2068113 (for 4a), and 2068114 (for 4d) contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service www.ccdc. cam.ac.uk/structures. Manuscript received: June 18, 2021 Accepted manuscript online: July 16, 2021 Version of record online: && &&,&&&& A ngewandte Chemi e Communications 5Angew. Chem. Int. Ed. 2021,60, 1 – 6  2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH www.angewandte.org These are not the final page numbers! Ü Ü Communications Halogen Bonding S. Yu, J. S. Ward, K.-N. Truong, K. Rissanen* &&&& —&&&& Carbonyl Hypoiodites as Extremely Strong Halogen Bond Donors Carbonyl hypoiodites possess very strongly polarized iodine atoms, including what is now the largest known s-hole for a neutral compound, and act as strong halogen bond donors. When strong Lewis bases, for example DMAP, are used as halogen bond acceptors, the iodine atom, for all intents and purposes, transfers from the oxygen to nitrogen atom to give an ion-pair of the general form [RCOO]- [I+N(DMAP)] with an O···IN halogen bond. A ngewandte Chemi e Communications 6www.angewandte.org  2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH Angew. Chem. Int. Ed. 2021,60,1–6 Ü Ü These are not the final page numbers!