Catechol Thioesters: Ligands for Hierarchically Formed Lithium‐Bridged Titanium(IV) Helicates and Helicate‐Based Switches

Abstract The thioester moiety is introduced as a lithium binding unit for the hierarchical formation of titanium(IV) catecholate‐based lithium‐bridged helicates. In solution, the coordination compounds show a monomer–dimer equilibrium which —in comparison to the oxo esters— is significantly shifted towards the monomers. In addition, the influence of the thioester side chain on the dimerization behavior is investigated and an expansible/compressible molecular switch is synthesized. In the latter case expansion and compression are performed reversibly in methanol, whereas in DMSO spontaneous expansion occurs.


Introduction
Thioesters are the "little brothers" of oxoesters. In comparison to the oxygen homologous, they are more reactive regarding the cleavageo ft he C(=O)ÀSb ond. The C=Od ouble bond is less polarized.T he high reactivity of the thioester functionality is important in synthesis as well as in nature for trans-acylation reactions. [1] As ap rominente xample, acetyl coenzyme Aa sa n importants yntheticb uilding block in the biosynthesis of a huge number of natural productsh as to be mentioned. [2] In 2005, we describedt he first examples of hierarchically formed helicates [3] based on triple lithium-bridged titanium(IV) triscatecholates with carbonyl moieties in 3-position of the catechol ligand.I ns olution,t he dimerich elicates are in equilibrium with the corresponding monomers.T his equilibrium can be well observed by NMR spectroscopy and kinetic as well as thermodynamic parameters can be obtained for dimer association/dissociation.H ereby,t he dimerizationt endency strongly depends on the strength of lithium binding within the helicate. This mainly is influencedb yt he solvent, the chargeo ft he monomeric unit, and by the donor ability of the carbonyl units.S cheme1shows that the poor aldehyde donorr esults in al ower dimerization constantc ompared to the better ketone donora nd the much better ester donor. [4] Additionally,i ntersubstituent interactions as well as solvophobic/solvophilic effects do contribute to the dimer stabilization. [5] In more recent studies, the lithium-dependent dimerization of carbonyl substituted titanium(IV) triscatecholate complexes has been used as am olecular switch to control the selectivity of aD iels-Alder reaction [6] or for the development of ah elicate systemw hich is able to expand or compress depending on some externalstimulis howing some spring-type behavior. [7] In the present study as eries of thioester-substituted catechols has been synthesized and has been used to preparet he correspondingt itanium(IV) complexes. [8] It is expectedt hat the thioesters show somed istinct differences in the stability of the hierarchical helicates compared to the ester complexes.T his is due to the lower polarization of C=Oo ft he thioester and a correspondingw eaker binding of the lithium cations in the dimer. [9] Scheme1.The monomer-dimer equilibrium which is observed for hierarchically assembled titanium(IV) triscatecholate helicates showing the dimerization constants of the aldehyde, the methylketone, and the methylester. In addition, an example for an expansible/compressible helicate based on an alkyl-bridged bis(catecholt hioester)i sd escribed and as pecial spontaneous expansion behavior is observed in [D 6 ]DMSO.
The X-ray structure analysiss hows the dimericc entral part of the hierarchically formedh elicate with two titanium and three lithium cations( Ti···Ti = 5.53, Ti···Li = 3.38-3.49, and Li···Li = 3.46-3.49 )v ery similar to the one observed for the corresponding aldehyde, ketone,o ro xoesterd erivatives. [4,5] However,t he C-S-C angle at the sulfur atom (97.8-100.88)i s smaller than observed for the corresponding oxoesters. In ad-dition, the thioesters show short distances of the protons of the methylene group to the neighboring catechol unit (H···C arom = 2.8-3.2 )c ontributing significantly to the stability of the dimer.T his has been also observed for the oxygen homologues. [5] In [D 4 ]MeOH solution both, the dimer as wella st he monomer can be observed by 1 HNMR spectroscopy ( Figure 2). In [D 6 ]DMSO,only peaks of the monomeric triscatecholate titanium(IV) complex are found due to the high lithium cation-coordinating ability of the solvent. Removal of lithium cations from the dimer results in its full dissociation. Characteristic for the monomer is the observation of the CH 2 group at sulfur as one single peak due to fast inversiono ft he stereochemistry at the complex unit. In the dimer,t he stereochemistry at the complex is locked and diastereotopic protons are detected for SCH 2 . [13] This is observed for the major specieso fL i[Li 3 (1c) 6 Ti 2 ] = [Li 2 (1c) 3 Ti]i n[ D 4 ]MeOH. The minor species is the monomer which does not show this diastereotopic behavior.A tt he room-temperature equilibrium state of the monomer/dimer equilibrium in [D 4 ]MeOH, the dimerization constantc an be easily obtained from the NMR integration (see Ta ble 1a nd Figure3,aconcentration of 1 m is used as reference state in the determination of K dim ).   Following remarkable aspects can be realizedf rom the collection of dimerization constantso ft he thioester-derived complexes: 1) In case of the methyl versusthe ethyl oxoesters, the dimerization constant in [D 4 ]MeOH of the corresponding dimeric coordination complexes raises dramatically from methyl (25 600) to ethyl (only dimer observed) due to stronger electron-donating properties of the ethyl compared to the methyl substituent. [5,14] In case of the thioesters, the methyl (Li[Li 3 (1a) 6 Ti 2 ], K dim = 6650), ethyl (Li[Li 3 (1b) 6 Ti 2 ], K dim = 7380) and n-propyl thioester dimers (Li[Li 3 (1c) 6 Ti 2 ], K dim = 8170) are significantly lower and are only slightly increasing with the chain length. This showsastrong electronic isolation of the ester carbonyl and the alkyl substituent by the sulfur atom.
2) For the nBu, nPent, nHept, and nOctt hioesters relatively high K dim values are observed in [D 4 ]MeOH,w hereas the hexyl thioester resultsi nad ramaticd ecrease. This drop has been also observed for the corresponding hexyl oxoester in [D 6 ]DMSO, [5] although it has not been as dramatic as with the thioester.T his effect is assigned to as pecial conformation of the n-hexylc hain.
3) For nNon and nDodect hioesters, low dimer stability is observed.Asimilare ffect has been observed for the oxoesters and there has been attributed to al oss of entropy due to sidechain aggregation. [5] The aggregation of the chains occurs due to solvophobicity of the alkyl groups.C hain aggregation minimizes the contact area with the solvent.
4) The branched iPr and iBu, as well as the cyclic cyPent and cyHex, thioester derivatives show relatively high dimerization constantsw hichm ay be due to some dispersive interactions [15] between thes ide chains in addition to solvophobic effects.

5) Aromatic units (Ph, Bn)s howh igh solphophilicity in [D 4 ]MeOH andt hus K dim is low.
The observedl ithium-dependentd imerization of the thioester-derived triscatechol titanium(IV) complexes shows ome behavior as observed for the oxoesters [5] but also some different distinct features whichc an be attributedt ot he sulfur atom of the thioester moiety.
In addition to the hierarchical helicates, ac lassical helicate Li[Li 3 (2) 3 Ti 2 ]h as been prepared by tethering two thioesters by ad ecyl-bridge. Coordination of three internal lithium cations results in ac ompressed structure. Corresponding complexes with oxoesters have been earlier prepared and showthe ability  Chem. Eur.J. 2020,26,[3829][3830][3831][3832][3833] www.chemeurj.org 2020 The Authors. Published by Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim to be switched from the compressed to the expanded state or vice versa by simply removing or adding lithium cations.W ith the oxoesters the switching proceeds smoothly in [D 6 ]DMSO solution. [7] The compressed lithium-containing complex Li[Li 3 (2) 3 Ti 2 ]d isplays ah ighly dominating signal in the negative ESI MS at m/z = 1539.294f or [Li 3 (2) 3 Ti 2 ] À (calcd: m/z = 1539.295). The 1 HNMR in [D 4 ]MeOH reveals characteristic signals for aromatic protons at d = 7.25 (dd, 1H)a nd 6.56 (m, 2H)a nd of the diastereotopic SCH 2 protons at d = 2.59 (m, 1H), and 1.99 ppm (m, 1H). Addition of [2.1.1]cryptand changes the spectrums ignificantly which can be best observed following the aromatic protons ( Figure 4). They now appear for the dominating species as three separate signals at d = 6.95, 6.42, and 6.35 ppm. A similar spectrum has been obtained for K 4 [(2) 3 Ti 2 ]. This indicates the expansion of the spring type complex to form [(2) 3 Ti 2 ] 4À .U pon addition of an excess of lithium chloride, the spectrum of the compressed compound [Li 3 (2) 3 Ti 2 ] À is restored again. This behaviori st he same as has been observed for the oxoesters in DMSO. [7] Directly after dissolution of Li[Li 3 (2) 3 Ti 2 ]i n [D 6 ]DMSO,atypical spectrum of the compressed helicate Li[Li 3 (2) 3 Ti 2 ]i so bserved with aromatic catechol signals found at d = 7.1, 6.5, and 6.4 ppm. With time, the signali ntensity decreasesa tr oom temperature and an ew set of signals grows in at d = 6.8, 6.2, and 6.1 ppm until full conversion is obtained. The new signals are similar to those observed fort he expanded potassium complex K 4 [(2) 3 Ti 2 ]. Following the kinetics of the expansion for as olution of 2 10 À3 mol L À1 ,arate constant of k = 2.2 AE 0.4 10 À4 s À1 is obtained for the first-order expansion reaction at room temperature ( Figure 5).

Conclusions
Herein, we introduced the thioester moiety as an ew functionality to facilitate the lithium-dependent hierarchical formation of dinuclear triscatecholate titanium(IV) based helicates. Dimerization constants of the thioester derivatives are much lower than observed for corresponding oxoesters but highert han for corresponding ketones.D imerization constants strongly dependo nt he solvent as well as on the kind of thioester substituent.F or the thioesters, the substituents are electronically well isolated from the carbonyl unit and K dim within the series of complexes is mainly influenced by side-chain-side-chain interactions caused by solvophobicity/solvophilicity or maybe by dispersion interactions.
Regarding the oxoesters, am olecular switch was createdb y introducing an alkyl tether at the complex units whiche asily can be switchedi nm ethanol between an expanded and compressed state. However,D MSO as solvent is as trongc ompetitor for lithium-cation binding so that in this solvent the complex spontaneously releases lithium cationsa nd expands.T he kinetics of this process can be easily followed by NMR spectroscopy.
Herein, an ew class of compounds is added to the family of hierarchically formed dinuclear titanium(IV) catecholates. Those show ad istinct different dimerization behavior compared to . This process is reversible in [D 4 ]MeOHa tr oom temperature, as can be seen by followingthe signals of the catechol protons.The quality of the NMRs pectra decreases in each switching step due to the addition of excess cryptand or LiCl to the NMR tube(bottom). the earlier investigated oxoesters, ketones,a nd aldehydes, which is important for the development of functional switches and switchable catalysts with tunable switching properties.