Transition Metal Complexes Coordinated by Water Soluble Phosphane Ligands: How Cyclodextrins Can Alter the Coordination Sphere?

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Article Transition Metal Complexes Coordinated by Water Soluble Phosphane Ligands: How Cyclodextrins Can Alter the Coordination Sphere?

Michel Ferreira, Hervé Bricout, Sébastien Tilloy and Eric Monﬂier *

University of Artois, CNRS, Centrale Lille, ENSCL, University of Lille, UMR 8181, Unité de Catalyse et de Chimie du Solide (UCCS), F-62300 Lens, France; [email protected] (M.F.); [email protected] (H.B.); [email protected] (S.T.) * Correspondence: eric.monﬂ[email protected]; Tel.: +33-321-791-772; Fax: +33-321-791-717

Academic Editor: Bernard Martel Received: 9 December 2016; Accepted: 12 January 2017; Published: 17 January 2017

Abstract: The behaviour of platinum(II) and palladium(0) complexes coordinated by various hydrosoluble monodentate phosphane ligands has been investigated by 31P{1H} NMR spectroscopy in the presence of randomly methylated β-cyclodextrin (RAME-β-CD). This molecular receptor can have no impact on the organometallic complexes, induce the formation of phosphane low-coordinated complexes or form coordination second sphere species. These three behaviours are under thermodynamic control and are governed not only by the afﬁnity of RAME-β-CD for the phosphane but also by the phosphane stereoelectronic properties. When observed, the low-coordinated complexes may be formed either via a preliminary decoordination of the phosphane followed by a complexation of the free ligand by the CD or via the generation of organometallic species complexed by CD which then lead to expulsion of ligands to decrease their internal steric hindrance.

Keywords: platinum; palladium; TPPTS; cyclodextrin; hydrosoluble organometallic complexes; supramolecular chemistry

1. Introduction Biphasic aqueous organometallic catalysis is one of the greenest solutions to produce organic chemicals [1,2]. Indeed, water is not only cheap and non-toxic, but also permits one to immobilize the catalyst in an aqueous phase by the use of water-soluble ligands, leading to ease of recycling by simple decantation at the end of the reaction [3]. The most widespread ligand used in such systems is TPPTS (tris(3-sulfonatophenyl)phosphane sodium salt, Table1, entry 1) which is responsible for the industrial success of the aqueous biphasic propene hydroformylation (Ruhrchemie-Rhône Poulenc process, 1984) [4]. Attractive for partially water-soluble oleﬁns, this strategy suffers from low catalytic activity when hydrophobic substrates are used due to mass transfer limitations. The alternative approaches to overcome this drawback have been recently reviewed [5,6]. These include the use of cyclodextrins (CDs) which are widely recognized as outstanding water-soluble receptors in aqueous biphasic organometallic processes [7]. These macrocycles were ﬁrstly used as phase transfer agents between the organic and the aqueous layers by forming inclusion complexes with a hydrophobic substrate at the interface in order to convert it thanks to a water-soluble organometallic catalyst. However, CDs are more than simple receptors for hydrophobic substrates and can be now considered as polyfunctional entities in aqueous biphasic organometallic catalysis [8]. In particular, CDs can modify the catalytic species involved in the reaction. As an example, when TPPTS is combined with a rhodium precursor to catalyse the 1-decene aqueous biphasic hydroformylation reaction, a linear to branched aldehyde ratio drop is

Molecules 2017, 22, 140; doi:10.3390/molecules22010140 www.mdpi.com/journal/molecules Molecules 2017, 22, 140 2 of 25 observedMolecules when 2017, the22, 140 experiment is conducted in the presence of RAME-β-CD (=randomly methylated2 of 25 β-CD) [9]. Under CO/H2 pressure and with RAME-β-CD, equilibria displacements between the CD) [9]. Under CO/H2 pressure and with RAME-β-CD, equilibria displacements between the different different catalytic species towards the formation of phosphane low-coordinated species are observed. catalytic species towards the formation of phosphane low-coordinated species are observed. These These equilibria, displaced by TPPTS inclusion into the CD cavity, are responsible for the drop in equilibria, displaced by TPPTS inclusion into the CD cavity, are responsible for the drop in regioselectivity regioselectivity(Scheme 1) [10]. (Scheme 1)[10].

Molecules 2017, 22, 140 2 of 25 Molecules 2017, 22, 140 2 of 25 Molecules 2017, 22, 140 2 of 25

CD) [9]. Under CO/H2 pressure and with RAME-β-CD, equilibria displacements between the different CD) [9]. Under CO/H2 pressure and with RAME-β-CD, equilibria displacements between the different CD) [9]. Under CO/H2 pressure and with RAME-β-CD, equilibria displacements between the different catalytic species towards the formation of phosphane low-coordinated species are observed. These catalyticScheme species 1. Equilibria towards between the formation the different of phosphane catalytic low-coordinated species during species 1-decene are aqueousobserved. biphasic These Schemeequilibria, 1. Equilibriadisplaced by betweenTPPTS inclusio then different into the CD catalytic cavity, are species responsibl duringe for the 1-decene drop in regioselectivity aqueous biphasic equilibria,hydroformylation displaced byassisted TPPTS by inclusio RAME-n intoβ-CD. the CD cavity, are responsible for the drop in regioselectivity hydroformylation(Scheme 1) [10]. assisted by RAME-β-CD. (Scheme 1) [10]. Along the same lines, when a water-soluble triphenylphosphane derivative possessing a higher Alongaffinity thetowards same CDs lines, is wheninvolved a water-solublein a rhodium HRhCOL triphenylphosphane3 type species derivative(L = p-tBuPhP( possessingm-PhSO3Na) a higher2 afﬁnityphosphane), towards CDsunsaturated is involved catalytic in aspecies rhodium are HRhCOLalso formed3 type in the species presence (L =ofp -tBuPhP(CD even mwhen-PhSO the3 Na)2 phosphane),organometallic unsaturated complex was catalytic not exposed species to a are CO/H also2 atmosphere formed in [11]. the presence of CD even when the organometallicTable 1. complex Structure,was abbreviation not exposed of the water-soluble to a CO/H 2phosphanesatmosphere used, [11 and]. value of the association Thisconstant behaviour, (K) for the not inclusion observed complexes with between TPPTS, the wasRAME- attributedβ-CD and the to phosphane. the more stable inclusion complexEntry formed between Structure the CD and the phosphane, Name due Abbreviation to the presence of the well-recognized K (M−1) a,b p-tert-butylphenyl group. Moreover, it has been demonstrated that the combination of the same tris(3-sodium-sulfonatophenyl)phosphane 1 840 [15] ligand with another metal centre, e.g., palladium or platinum,TPPTS led to the same behaviour, that is to say formation of low-coordinated organometallic species [12].

However,Scheme the 1. combination EquilibriaEquilibria betweenbetween of a thethe palladium differentdifferenttris(4-methyl-3-sodium-sul catalyticcatalytic precursor speciesspecies with duringduring afonatophenyl)phosphane water-soluble1-decene1-decene aqueousaqueous triphenylphosphanebiphasicbiphasic 2 Scheme 1. Equilibria between the different catalytic species during 1-decene aqueous biphasic 960 [15] hydroformylation assisted by RAME-β-CD. tris(p-Me)TPPTS derivative possessinghydroformylation a p assisted-tert-butylbiphenyl by RAME-β-CD. group led to the formation of a stable second-sphere coordination adduct where the CD encapsulated the ligand directly bounded to the metal centre [13]. Along the same lines, when a water-solubletris(4-methoxy-3-sodium-sulfonatophenyl)phosphane triphenylphosphane derivative possessing a higher 3 Along the same lines, when a water-soluble triphenylphosphane derivative possessing a higher0 [15] Such speciesaffinity had towards already CDs beenis involved observed in a rhodium with a phosphaneHRhCOL3 tris(type bearingp -OMe)TPPTSspecies adamantyl(L = p-tBuPhP( groupsm-PhSO [3Na)14].2 affinity towards CDs is involved in a rhodium HRhCOL3 type species (L = p-tBuPhP(m-PhSO3Na)2 affinity towards CDs is involved in a rhodium HRhCOL3 type species (L = p-tBuPhP(m-PhSO3Na)2 phosphane), unsaturated catalytic species are also formed in the presence of CD even when the phosphane), unsaturated catalytic species are also formed in the presence of CD even when the organometallic complex was not exposed to a CO/H2 atmosphere [11]. Tableorganometallic 1. Structure, complex abbreviation was not exposed of the water-soluble to atris(6-methyl-3-sodium-sul CO/H2 atmosphere phosphanes [11]. fonatophenyl)phosphane used, and value of the association organometallic4 complex was not exposed to a CO/H2 atmosphere [11]. 0 [15] constantTable (K) for1. Structure, the inclusion abbreviation complexes of the water-soluble between the phosphanes RAME-tris(βo used,-CD-Me)TPPTS and value the phosphane. of the association Table 1. Structure, abbreviation of the water-soluble phosphanes used, and value of the association constantTable 1. Structure,(K) for the abbreviationinclusion complexes of the water-soluble between the RAME-phosphanesβ-CD used, and the and phosphane. value of the association constant (K) for the inclusion complexes between the RAME-β-CD and the phosphane. constant (K) for the inclusion complexes between the RAME-β-CD and the phosphane. −1 a,b Entry Structuretris(6-methoxy-3-sodium-sulfonatophenyl)phosphane Name Abbreviation K−1 (Ma,b ) Entry Structure Name Abbreviation K (M−1) a,b 5 Entry Structure Name Abbreviation K (M−1) a,b0 [15] Entry Structure Nametris( Abbreviationo-OMe)TPPTS K (M )

tris(3-sodium-sulfonatophenyl)phosphanetris(3-sodium-sulfonatophenyl)phosphane 1 1 tris(3-sodium-sulfonatophenyl)phosphane 840 [15]840 [15] 1 tris(3-sodium-sulfonatophenyl)phosphaneTPPTS 840 [15] 1 TPPTS 840 [15] TPPTS trisulfonated monobiphenyldiphenylphosphane c 6 9900 tris(4-methyl-3-sodium-sulP(Biph)Phfonatophenyl)phosphane2TS tris(4-methyl-3-sodium-sultris(4-methyl-3-sodium-sulfonatophenyl)phosphanefonatophenyl)phosphane 2 2 tris(4-methyl-3-sodium-sulfonatophenyl)phosphane 960 [15]960 [15] 2 tris(tris(p-Me)TPPTSp-Me)TPPTS 960 [15] tris(p-Me)TPPTS

trisulfonated bisbiphenylmonophenylphosphane 7 tris(4-methoxy-3-sodium-sulfonatophenyl)phosphane >100,000 c tris(4-methoxy-3-sodium-sulfonatophenyl)phosphanetris(4-methoxy-3-sodium-sulfonatophenyl)phosphane 3 3 tris(4-methoxy-3-sodium-sulfonatophenyl)phosphaneP(Biph)2PhTS 0 [15] 0 [15] 3 tris(tris(p-OMe)TPPTSp-OMe)TPPTS 0 [15] tris(p-OMe)TPPTS

trisulfonated trisbiphenylphosphane 8 tris(6-methyl-3-sodium-sulfonatophenyl)phosphane >100,000 c 4 tris(6-methyl-3-sodium-sultris(6-methyl-3-sodium-sulfonatophenyl)phosphaneP(Biph)fonatophenyl)phosphane3TS 0 [15] 4 tris(6-methyl-3-sodium-sulfonatophenyl)phosphane 0 [15] 4 4 tris(o-Me)TPPTS 0 [15] 0 [15] tris(tris(o-Me)TPPTSo-Me)TPPTS a In each case, the stoichiometry has been determined to be equal to 1:1 when an inclusion complex

b c was formed; K constant is an average constanttris(6-methoxy-3-sodium-sulfonatophenyl)phosphane due to the random methylation of the CD; association 5 tris(6-methoxy-3-sodium-sulfonatophenyl)phosphane 0 [15] constant5 determined between native β-CDtris(6-methoxy-3-sodium-sulfonatophenyl)phosphanetris(6-methoxy-3-sodium-sulfonatophenyl)phosphane and the phosphane.tris(o-OMe)TPPTS 0 [15] 5 5 tris(o-OMe)TPPTS 0 [15] 0 [15] tris(tris(o-OMe)TPPTSo-OMe)TPPTS

trisulfonated monobiphenyldiphenylphosphane 6 trisulfonated monobiphenyldiphenylphosphane 9900 cc 6 trisulfonated monobiphenyldiphenylphosphane 9900 c 6 P(Biph)Ph2TS 9900 c 6 P(Biph)Ph2TS 9900 P(Biph)Ph2TS

trisulfonated bisbiphenylmonophenylphosphane 7 trisulfonated bisbiphenylmonophenylphosphane >100,000 cc 7 trisulfonated bisbiphenylmonophenylphosphane >100,000 c 7 P(Biph)2PhTS >100,000 c 7 P(Biph)2PhTS >100,000 P(Biph)2PhTS

trisulfonated trisbiphenylphosphane 8 trisulfonated trisbiphenylphosphane >100,000 cc 8 trisulfonated trisbiphenylphosphane >100,000 c 8 P(Biph)3TS >100,000 c 8 P(Biph)3TS >100,000 P(Biph)3TS a In each case, the stoichiometry has been determined to be equal to 1:1 when an inclusion complex a In each case, the stoichiometry has been determined to be equal to 1:1 when an inclusion complex a In each case, the stoichiometry has been determined to be equal to 1:1 when an inclusion complex was formed; b K constant is an average constant due to the random methylation of the CD; cc association was formed; b K constant is an average constant due to the random methylation of the CD; c association was formed; b K constant is an average constant due to the random methylation of the CD; c association constant determined between native β-CD and the phosphane. constant determined between native β-CD and the phosphane.

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CD) [9]. Under CO/H2 pressure and with RAME-β-CD, equilibria displacements between the different catalytic species towards the formation of phosphane low-coordinated species are observed. These equilibria, displaced by TPPTS inclusion into the CD cavity, are responsible for the drop in regioselectivity (Scheme 1) [10].

Scheme 1. Equilibria between the different catalytic species during 1-decene aqueous biphasic hydroformylation assisted by RAME-β-CD.

Along the same lines, when a water-soluble triphenylphosphane derivative possessing a higher affinity towards CDs is involved in a rhodium HRhCOL3 type species (L = p-tBuPhP(m-PhSO3Na)2 phosphane), unsaturated catalytic species are also formed in the presence of CD even when the organometallic complex was not exposed to a CO/H2 atmosphere [11].

Table 1. Structure, abbreviation of the water-soluble phosphanes used, and value of the association constant (K) for the inclusion complexes between the RAME-β-CD and the phosphane.

−1 a,b Entry Structure Name Abbreviation K (M−1) a,b

tris(3-sodium-sulfonatophenyl)phosphane 1 840 [15] TPPTS

tris(4-methyl-3-sodium-sulfonatophenyl)phosphane 2 960 [15] tris(p-Me)TPPTS

tris(4-methoxy-3-sodium-sulfonatophenyl)phosphane 3 0 [15] tris(p-OMe)TPPTS

Molecules 2017, 22, 140 3 of 25 tris(6-methyl-3-sodium-sulfonatophenyl)phosphane 4 0 [15] tris(o-Me)TPPTS

Table 1. Cont. tris(6-methoxy-3-sodium-sulfonatophenyl)phosphane 5 tris(6-methoxy-3-sodium-sulfonatophenyl)phosphane 0 [15] 5 tris(o-OMe)TPPTS 0 [15] Entry Structuretris( Nameo-OMe)TPPTS Abbreviation K (M−1) a,b

trisulfonated monobiphenyldiphenylphosphane trisulfonatedtrisulfonated monobiphenyldiphenylphosphane monobiphenyldiphenylphosphane c c 6 6 9900 c 9900 6 P(Biph)Ph2 TS 9900 P(Biph)Ph2TS2

trisulfonated bisbiphenylmonophenylphosphane trisulfonatedtrisulfonated bisbipheny bisbiphenylmonophenylphosphanelmonophenylphosphane c c 7 7 >100,000>100,000 c 7 2 >100,000 P(Biph)P(Biph)2PhTS2PhTS

trisulfonated trisbiphenylphosphane trisulfonatedtrisulfonated trisbiphenylphosphane trisbiphenylphosphane c 8 >100,000 c c 8 8 3 >100,000>100,000 P(Biph)P(Biph)3TSTS 3 a a In eacha In case, each the case, stoichiometry the stoichiometry has been has determinedbeen determin toed be to equal be equal to 1:1 to when 1:1 when an inclusion an inclusion complex complex was formed; b c b K constantwas formed; is an average b K constant constant is an average due tothe constant random due methylation to the random of methylation the CD; c association of the CD; c constantassociation determined betweenconstant native determinedβ-CD and thebetween phosphane. native β-CD and the phosphane.

In order to get a better insight into the interaction phenomena between the CD and transition metal complexes, we want to show in this article how RAME-β-CD can interfere with different platinum(II) or palladium(0) complexes coordinated with various hydrosoluble ligands and how specific organometallic complexes can be obtained. These ligands include TPPTS itself but also TPPTS modified phosphanes containing substituents (methyl or methoxy groups) in ortho or para position and biphenyl modified phosphanes (Table1). The interaction of the different phosphanes with RAME- β-CD has already been studied by our group [15], except for biphenylphosphane derivatives whose synthesis and catalytic properties have been exclusively published [16]. For each type of ligands, we have both examined the nature of the organometallic complex formed when mixing them with the metal precursor and the influence of the RAME-β-CD addition on these complexes.

2. Results and Discussion

2.1. Platinum Complexes

The different complexes formed by mixing the K2PtCl4 aqueous solution with 3 equiv. of phosphane were ﬁrstly analysed by 31P{1H} NMR. In a second step, RAME-β-CD has been added to the mixture in order to determine its inﬂuence on the coordination chemistry of the different ligands.

2.1.1. Complex Synthesis

TPPTS Ligand

As described in the literature [17], [Pt(TPPTS)3Cl]Cl platinum complex is quantitatively synthetized by adding three equivalents of TPPTS to a K2PtCl4 aqueous solution. As only one third of the platinum (195Pt) has a spin of 1/2, the 31P{1H} NMR spectrum of this complex is characterized 1 2 by a 1:4:1 triplet of doublets centred at δ = 24.5 ppm ( JPcis–Pt = 2491 Hz; JPcis–Ptrans = 19 Hz) corresponding to the two phosphorus atoms cis to the chloride and a 1:4:1 triplet of triplets centred at 1 2 δ = 13.3 ppm ( JPtrans–Pt = 3682 Hz; JPcis–Ptrans = 19 Hz) corresponding to the phosphorus atom trans to the chloride (Figure1). para-Substituted TPPTS Derivatives

Similarly to TPPTS, [PtL3Cl]Cl platinum complexes can be quantitatively synthetized by adding three equivalents of the para-substituted ligands tris(p-Me)TPPTS and tris(p-OMe)TPPTS to a solution of K2PtCl4 (Figure2). The two phosphorus atoms cis to the chloride appear respectively for 1 [Pt(tris(p-Me)TPPTS)3Cl]Cl and [Pt(tris(p-OMe)TPPTS)3Cl]Cl at δ = 23.3 ppm ( JPcis–Pt = 2488 Hz; 2 1 2 31 1 JPcis–Ptrans = 19 Hz) and δ = 21.8 ppm ( JPcis–Pt = 2487 Hz; JPcis–Ptrans = 18 Hz) in their P{ H} NMR 1 spectra. The phosphorus atom trans to the chloride appears at δ = 11.5 ppm ( JPtrans–Pt = 3693 Hz; 2 1 2 JPcis–Ptrans = 19 Hz) and δ = 9.8 ppm ( JPtrans–Pt = 3754 Hz; JPcis–Ptrans = 18 Hz). Molecules 2017, 22, 140 4 of 25 Molecules 2017, 22, 140 4 of 25 Molecules 2017, 22, 140 4 of 25

31 31 1 1 ◦ FigureFigureFigure 1. 1. 1.31 P{P{1H}H} NMR NMR spectrum spectrum ofof [Pt(TPPTS)[Pt(TPPTS)33Cl]Cl,Cl]Cl, [Pt] [Pt] = = 10 10 10 mM, mM, mM, 25 25 25 °C °C Cin in inD 2D DO.22O. O.

= para-substituted phosphane = para-substituted phosphane

phosphane phosphaneoxide oxide

a) a)

phosphane oxide phosphane oxide

b) 4540 3530 25 20 15 10 5 0 -5 -10 (ppm) 4540 3530 25 20 15 10 5 0 -5 -10 Figure 2. 31P{1H} NMR spectra of (a) [Pt(tris(p-Me)TPPTS) Cl]Cl and (b) [Pt(tris(p-OMe)TPPTS)(ppm) Cl]Cl, Figure 2. 31P{1H} NMR spectra of (a) [Pt(tris(p-Me)TPPTS)33Cl]Cl and (b) [Pt(tris(p-OMe)TPPTS) 3Cl]Cl,3 [Pt] = 10 mM, 25 ◦C in D O. [Pt] = 10 mM, 25 °C in D22O. Figure 2. 31P{1H} NMR spectra of (a) [Pt(tris(p-Me)TPPTS)3Cl]Cl and (b) [Pt(tris(p-OMe)TPPTS)3Cl]Cl, orthoortho-Substituted[Pt]-Substituted = 10 mM, 25 TPPTS TPPTS °C in DerivativesD Derivatives2O. ortho-SubstitutedHowever,However, attempts attemptsTPPTS toDerivatives to synthetize synthetize [Pt(tris( [Pt(tris(oo-Me)TPPTS)-Me)TPPTS)3Cl]Cl and and [Pt(tris( [Pt(tris(oo-OMe)TPPTS)-OMe)TPPTS)3Cl]Cl3Cl]Cl werewere unsuccessful. unsuccessful. Indeed, Indeed, addition addition of three of three equivalents equivalents of ligand of ligand(towards (towards platinum) platinum) to a K2PtCl to4 a However, attempts to synthetize [Pt(tris(o-Me)TPPTS)3Cl]Cl and [Pt(tris(o-OMe)TPPTS)3Cl]Cl were unsuccessful. Indeed, addition of three equivalents of ligand (towards platinum) to a K2PtCl4

Molecules 2017, 22, 140 5 of 25 Molecules 2017, 22, 140 5 of 25

Ksolution2PtCl4 solution exclusively exclusively yields to yields formation to formation of PtCl2L of2-type PtCl complex2L2-type characterized complex characterized by a 1:4:1 triplet by a 1:4:1 of tripletdoublets of doublets centred centredat δ = at20.5δ = ppm 20.5 ppmand and24.524.5 ppm, ppm, respectively, respectively, for for PtCl PtCl2(tris(2(tris(o-Me)TPPTS)o-Me)TPPTS)2 and2 and 3131 1 1 PtClPtCl2(tris(2(tris(oo-OMe)TPPTS)-OMe)TPPTS)22.. AsAs aa consequence,consequence, free free ligand ligand that that represents represents one one third third of of the the total total P{P{H}H} NMRNMR surface surface areaarea is detected (Figure (Figure 3).3). Moreover, Moreover, in in both both cases, cases, 1JP–Pt1JP–Pt coupling coupling constants constants (2750 (2750and and2590 2590 Hz Hzfor forPtCl PtCl2(tris(2(tris(o-OMe)TPPTS)o-OMe)TPPTS)2 and2 PtCland2 PtCl(tris(2o(tris(-Me)TPPTS)o-Me)TPPTS)2 respectively)2 respectively) are consistent are consistent with 1 a trans coordination when compared with cis-PtCl2(TPPTS)2 (1JP–Pt 1= 3720 Hz, Figure 4) and trans- witha trans a trans coordinationcoordination when when compared compared with withcis-PtClcis-PtCl(TPPTS)2(TPPTS) ( JP–Pt2 ( =J P–Pt3720 =Hz, 3720 Figure Hz, 4) Figure and 4trans) and- 1 PtCl2(TPPTS)2 (1JP–Pt1 = 2600 Hz) that have already been described [17]. The steric hindrance of these transPtCl-PtCl(TPPTS)2(TPPTS) ( JP–Pt2 ( J =P–Pt 2600 = Hz) 2600 that Hz) have that already have already been des beencribed described [17]. The [17 steric]. The hindrance steric hindrance of these of theseligands, ligands, which which have have a higher a higher cone cone angle angle than than their their parapara-substituted-substituted counterparts, counterparts, is isobviously obviously responsible for the formation of the observed phosphane low coordinated PtCl2L2 species. The same responsible for the formation of the observed phosphane low coordinated PtCl2L2 species. The same reasonreason can can also also explain explain the thetrans transgeometry geometry obtainedobtained for these species instead instead of of the the ciscis oneone [18]. [18].

Pt = ortho-substituted phosphane

1JP–Pt = 2590 Hz

free phosphane

1JP–Pt = 2750 Hz

free phosphane

45 35 25 15 5 -5 -15 -25 -35 -45 (ppm)

31 1 Figure 3. P{31 H}1 NMR spectra of K PtCl (3 mM) + 3 equiv. of (a) tris(o-Me)TPPTS or (b) tris(o-OMe)TPPTS Figure 3. 31P{1H} NMR spectra of2 K2PtCl4 4 (3 mM) + 3 equiv. of (a) tris(o-Me)TPPTS or (b) tris(o- at 25 ◦C in D O. OMe)TPPTS2 at 25 °C in D2O.

31 1 Figure 4.31 31P{1 1H} NMR spectrum of cis-PtCl2(TPPTS)2, [Pt] = 10 mM, 25 °C◦ in D2O. FigureFigure 4. 4. P{P{H}H} NMRNMR spectrumspectrum ofof ciscis-PtCl-PtCl2(TPPTS)(TPPTS)2, ,[Pt] [Pt] = = 10 10 mM, mM, 25 25 °C Cinin D DO.2O.

Molecules 2017, 22, 140 6 of 25 Molecules 2017, 22, 140 6 of 25

TrisulfonatedTrisulfonated Biphenylphosphane Biphenylphosphane Ligands Ligands

Again,Again, [PtL [PtL3Cl]Cl3Cl]Cl complex complex was was obtained obtained by by adding adding three three equivalents equivalents of the of monobiphenylthe monobiphenyl ligand P(Biph)Phligand P(Biph)Ph2TS to a2 KTS2PtCl to a4 Kaqueous2PtCl4 aqueous solution. solution. However, However, when when P(Biph) P(Biph)2PhTS2PhTS and and P(Biph) P(Biph)3TS3 wereTS used,were the used, complexes the complexes appeared appeared as broad as signalsbroad signals in the in31P{ the1H} 31P{ NMR1H} NMR spectra. spectra. Addition Addition of DMSO of DMSO to the previousto the previous aqueous aqueous solutions solutions achieves achieves ﬁner signals finer signals (Figure (Figure5). 5).

L = P(Biph)Ph2TS a) 40 35 30 25 20 15 10 5 0 -5 -10 (ppm)

phosphane oxide

L = P(Biph)2PhTS b)

phosphane oxide free L

40 35 30 25 20 15 10 5 0 -5 -10 (ppm)

phosphane oxide L = P(Biph)3TS b)

phosphane free L oxide c)

40 35 30 25 20 15 10 5 0 -5 -10 (ppm)

Figure 5. 31P{1H} NMR spectra of K PtCl solution (10 mM) + 3 equiv. of ligand (L) at 25 ◦C(a) in D O Figure 5. 31P{1H} NMR spectra of K22PtCl4 solution (10 mM) + 3 equiv. of ligand (L) at 25 °C (a) in D2O2 b d c d ( )(b in) in D 2DO/DMSO-2O/DMSO-d66 mixturemixture (50/50 vol.) vol.) (c () in) in DMSO- DMSO-d6. 6.

Molecules 2017, 22, 140 7 of 25 Molecules 2017, 22, 140 7 of 25

In pure DMSO, cis-PtCl2L2 is formed quantitatively (11JP–Pt = 3696 Hz when L = P(Biph)2PhTS In pure DMSO, cis-PtCl2L2 is formed quantitatively ( JP–Pt = 3696 Hz when L = P(Biph)2PhTS and1 1JP–Pt = 3702 Hz when L = P(Biph)3TS). The lowest DMSO polarity compared to water is probably and JP–Pt = 3702 Hz when L = P(Biph)3TS). The lowest DMSO polarity compared to water is probably responsibleresponsible for for the the formation formation of of these these non-ionic non-ionic complexes. complexes. When When the the water water quantity quantity of of the the medium medium is is increased, the polarity increases as well probably leading to the formation of [PtL3Cl]Cl. With these increased, the polarity increases as well probably leading to the formation of [PtL3Cl]Cl. With these two ligands, fast exchange between [PtL3Cl]Cl complex and water molecules would be responsible two ligands, fast exchange between [PtL3Cl]Cl complex and water molecules would be responsible for thefor signalsthe signals broadening. broadening.

2.1.2.2.1.2. RAME-RAME-ββ-CD-CD EffectsEffects onon thethe CoordinationCoordination BehaviourBehaviour ofof thethe LigandsLigands AsAs aa reminderreminder ofof ourour previousprevious work,work, TableTable1 1brings brings together together the the association association constants constants between between thethe differentdifferent hydrosolublehydrosoluble ligandsligands studiedstudied and and the the CDs CDs [ 15[15].].

TPPTSTPPTS LigandLigand

WhenWhen 1equiv.1equiv. ofof RAME-RAME-ββ-CD-CD towardtoward platinumplatinum waswas addedadded toto aa solutionsolution ofof thethe [Pt(TPPTS)[Pt(TPPTS)33Cl]ClCl]Cl complex,complex, aa downﬁelddownfield chemicalchemical shiftshift ofof thethe TPPTSTPPTS oxideoxide signalsignal waswas observedobserved andand attributedattributed toto thethe formationformation ofof anan inclusioninclusion complexcomplex withwith RAME-RAME-ββ-CD-CD [[19].19]. Moreover,Moreover, aa typicaltypical signalsignal ofof CD-includedCD-included TPPTSTPPTS appearedappeared atat− −8.8 ppm as well as a cis-PtCl2(TPPTS)(TPPTS)22 signalsignal at at 15.5 15.5 ppm ppm (Figure (Figure 66).).

phosphane oxide

CD included phosphane

PtCl2L2

40 30 20 10 0 -10 (ppm) 31 1 FigureFigure 6.6. 31P{1H}H} NMR spectra of (a) [Pt(TPPTS)33Cl]Cl (10 mM); (b)) +3+3 equiv. ofof RAME-RAME-ββ-CD-CD towardtoward ◦ PtPt ((cc)) +6+6 equiv.equiv. ofof RAME-RAME-ββ-CD-CD andand ((dd)) +12+12 equiv. ofof RAME-RAME-ββ-CD at 2525 °CC in D 2O.O.

ByBy adding increasing increasing amounts amounts of ofCD CD (3 to (3 12 to equiv.), 12 equiv.), these these signals signals are intensified. are intensiﬁed. Thus, RAME- Thus, RAME-β-CD isβ able-CD isto ablemodify to modify the equilibrium the equilibrium between between these thesetwo organometallic two organometallic species. species. In particular, In particular, the theformation formation of phosphane of phosphane low-coordinated low-coordinated organometallic organometallic species species is favoured is favoured by bythe the formation formation of ofan aninclusion inclusion complex complex between between RAME- RAME-β-CDβ-CD and and TPPTS TPPTS as as depicted depicted in in Scheme Scheme 22 (equilibrium(equilibrium (1)(1) isis displaceddisplaced byby equilibrium equilibrium (2)). (2)). Note Note that that such such behaviour behaviour is similar is similar to what to is what observed is observed by high pressureby high ◦ NMRpressure when NMR RAME- whenβ -CDRAME- is added,β-CD is under added, hydroformylation under hydroformylation conditions conditions (50 bars CO/H(50 bars2 andCO/H 802 andC),

Molecules 2017, 22, 140 8 of 25 Molecules 2017,, 22,, 140140 8 of 25

80 °C), on the HRh(CO)(TPPTS)3 rhodium complex. In that case, HRh(CO)2(TPPTS)2 species 80 °C), on the HRh(CO)(TPPTS)3 rhodium complex. In that case, HRh(CO)2(TPPTS)2 species on the HRh(CO)(TPPTS) rhodium complex. In that case, HRh(CO) (TPPTS) species combined with combinedcombined with with TPPTS TPPTS included included3 in in the the CD CD cavity cavity were were highlighted highlighted [10]. 2[10]. 2 TPPTS included in the CD cavity were highlighted [10].

Scheme 2. Equilibria between the different platinum species with TPPTS as ligand in the presence of Scheme 2. Equilibria between the different platinum speciesspecies with TPPTS as ligandligand in the presence of RAME-β-CD (species observed on the 3131P{1H}1 NMR spectrum are presented on a grey background). RAME-β-CD (species observed on the 31P{P{1H}H} NMR NMR spectrum spectrum are are presente presentedd on on a a grey grey background). background).

The conversion of [Pt(TPPTS)3Cl]Cl into cis-PtCl2(TPPTS)2 as a function of the RAME-β-CD The conversion ofof [Pt(TPPTS)[Pt(TPPTS)3Cl]Cl into ciscis-PtCl-PtCl2(TPPTS)(TPPTS)2 asas a function of thethe RAME-RAME-ββ-CD quantity (Figure 7) can be measured by3 integration of the2 31P{1H} NMR2 spectra (see ESI). As expected, quantity (Figure7 7)) can can be be measured measured by by integration integration of of the the 3131P{1H}H} NMR NMR spectra spectra (see (see ESI). ESI). As As expected, expected, the conversion increases with the quantity of RAME-β-CD in solution. The temperature also has an the conversion increases increases wi withth the the quantity quantity of of RAME- RAME-ββ-CD-CD in in solution. solution. The The temperature temperature also also has has an influence on these equilibria. Indeed, the conversion increases with the temperature, therefore, aninfluence inﬂuence on onthese these equilibria. equilibria. Indeed, Indeed, the the conversi conversionon increases increases with with the the temperature, temperature, therefore, implying that the natural dissociation of TPPTS from [Pt(TPPTS)3Cl]Cl is more affected compared to implying that the natural dissociation of TPPTS from [Pt(TPPTS)[Pt(TPPTS)3Cl]Cl is more affected compared to the inclusion complex stability. Moreover, the NMR spectrum carried3 out at room temperature after the inclusion complex stability. Moreover, thethe NMRNMR spectrum carried out at room temperature after heating gave back the signals with the same initial intensity reflecting the process reversibility and heating gave back the signals with the same initial intensity reﬂectingreflecting the process reversibility and assuming a thermodynamic control of the system. assuming a thermodynamic control of thethe system.system.

Pt conversion (%) Pt conversion (%)

T(°C) T(°C) 25 40 60 85 CD/Pt 25 40 60 85 CD/Pt 40 40 0 0 0 0 0 0 0 0 0 0 30 30 3 9.2 9.5 9.9 17.3 T (°C) 3 9.2 9.5 9.9 17.3 T (°C) 20 20 β 6 10.4 14.7 18 22.0 10 Rame- -CDβ 6 10.4 14.7 18 22.0 85 10 Rame- -CD 85 0 Pt 9 13.9 17.9 20.0 24.8 0 Pt 60 9 13.9 17.9 20.0 24.8 60 12 12 12 14.7 18.8 23.1 28.4 40 9 9 12 14.7 18.8 23.1 28.4 40 6 6 25 3 25 3 0 0 Figure 7. [Pt(TPPTS)3Cl]Cl conversion (%) into cis-PtCl2(TPPTS)2 as a function of RAME-β-CD quantity Figure 7. [Pt(TPPTS)3Cl]Cl conversion (%) into cis-PtCl2(TPPTS)2 as a function of RAME-β-CD andFigure temperature, 7. [Pt(TPPTS) [Pt]3 =Cl]Cl 10 mM, conversion D2O. (%) into cis-PtCl2(TPPTS)2 as a function of RAME-β-CD quantity and temperature, [Pt] = 10 mM, D2O. quantity and temperature, [Pt] = 10 mM, D2O. para-Substituted TPPTS Derivatives parapara-Substituted-Substituted TPPTS TPPTS Derivatives Derivatives The behaviour of tris(p-OMe)TPPTS and tris(p-Me)TPPTS towards RAME-β-CD is different. The behaviour of tris(p-OMe)TPPTS and tris(p-Me)TPPTS towards RAME-β-CD is different. Indeed,The unlikebehaviour tris( pof-OMe)TPPTS, tris(p-OMe)TPPTS tris(p -Me)TPPTSand tris(p-Me)TPPTS forms an towards inclusion RAME- complexβ-CD with is different. this CD Indeed, unlike tris(p-OMe)TPPTS, tris(p-Me)TPPTS forms an inclusion complex with this CD (K = 960 (Indeed,K = 960 unlike M−1)[ tris(15].p-OMe)TPPTS, The highest associationtris(p-Me)TPPTS constant forms of an this inclusion inclusion complex complex with compared this CD (K to = 960 the M−1) [15]. The highest association constant of this inclusion complex compared to the complex RAME- M−1) [15]. The highest association constant −of1 this inclusion complex compared to the complex RAME- complex RAME-β-CD/TPPTS−1 (K = 840 M ) is due to the deep inclusion of the tris(p-Me)TPPTS via β-CD/TPPTS (K = 840 M −)1 is due to the deep inclusion of the tris(p-Me)TPPTS via one of its aryl oneβ-CD/TPPTS of its aryl (K groups = 840 into M the) is CDdue cavity to the [20 deep]. inclusion of the tris(p-Me)TPPTS via one of its aryl groups into the CD cavity [20]. groupsGiven into thatthe CD the tris(cavityp-OMe)TPPTS [20]. does not interact with RAME-β-CD, it is not surprising to see Given that the tris(p-OMe)TPPTS does not interact with RAME-β-CD, it is not surprising to see Given that the tris(p31-OMe)TPPTS1 does not interact with RAME-β-CD, it is not surprising to see no modiﬁcations on the31 P{1 H} NMR spectrum of the [Pt(tris(p-OMe)TPPTS)3Cl]Cl organometallic no modifications on the 31P{ H}1 NMR spectrum of the [Pt(tris(p-OMe)TPPTS)3Cl]Cl organometallic complexno modifications when the on RAME- the βP{-CDH} wasNMR added spectrum (see ESI).of the Surprisingly, [Pt(tris(p-OMe)TPPTS) the same behaviour3Cl]Cl organometallic was observed complex when the RAME-β-CD was added (see ESI). Surprisingly, the same behaviour was observed withcomplex the tris(whenp-Me)TPPTS the RAME-β ligand.-CD was Indeed, added although (see ESI). theSurprisingly association, the constant same behaviour between was RAME- observedβ-CD withwith the the tris( tris(p-Me)TPPTSp-Me)TPPTS ligand. ligand. Indeed, Indeed, although although the the association association constant constant between between RAME- RAME-ββ-CD-CD andand tris( tris(p-Me)TPPTSp-Me)TPPTS is is higher higher than than the the one one between between RAME- RAME-ββ-CD-CD and and TPPTS, TPPTS, no no conversion conversion of of

Molecules 2017, 22, 140 9 of 25

Molecules 2017, 22, 140 9 of 25 and tris(p-Me)TPPTS is higher than the one between RAME-β-CD and TPPTS, no conversion of[Pt(tris( [Pt(tris(p-Me)TPPTS)p-Me)TPPTS)3Cl]Cl3Cl]Cl to PtCl to2 PtCl(tris(2(tris(p-Me)TPPTS)p-Me)TPPTS)2 was2 highlightedwas highlighted after the after addition the addition of RAME- of RAME-β-CD, evenβ-CD, at high even temperature at high temperature (see ESI) (see[21]. ESI)This [result21]. This can resultbe explained can be by explained the higher by σ the-donating higher σstrength-donating of tris( strengthp-Me)TPPTS of tris(p-Me)TPPTS ligand, compared ligand, to compared TPPTS. Consequently, to TPPTS. Consequently, the equilibrium the equilibrium (1) is shifted (1) istowards shifted the towards formation the formation of the high of thecoordinated high coordinated platinum platinum species [Pt(tris( speciesp [Pt(tris(-Me)TPPTS)p-Me)TPPTS)3Cl]Cl even3Cl]Cl in eventhe presence in the presence of RAME- ofβ RAME--CD (Schemeβ-CD (Scheme 3). 3).

Scheme 3. EquilibriaEquilibria between between the the different different platinum platinum species species with with tris( tris(p-Me)TPPTSp-Me)TPPTS as ligand as ligand in the in thepresence presence of RAME- of RAME-β-CDβ-CD (species (species observed observed on onthe the 31P{311H}P{1 H}NMR NMR spectrum spectrum are are presented presented on on a agrey grey background). background).

Ortho-Substituted-Substituted TPPTSTPPTS DerivativesDerivatives Since the ortho-substituted-substituted ligandsligands dodo notnot interactinteract withwith RAME-RAME-ββ-CD [[15,20],15,20], addition of CDCD diddid not modify the 3131P{P{11H}H} NMR NMR spectra. spectra.

Trisulfonated BiphenylphosphaneBiphenylphosphane LigandsLigands Phosphanes possessing one, two or three sulfonated biphenyl groups strongly interact with the β-CD. Indeed, complexation studiesstudies betweenbetween thesethese ligandsligands andand nativenative ββ-CD showed a deep inclusion of theirtheir biphenylbiphenyl moiety moiety in in the the CD CD cavity. cavity. In allIn cases,all cases, stoichiometries stoichiometries were were determined determined to be to equal be equal to 1:1 andto 1:1 association and association constants constants were particularly were particularly high (Table high1 and (Table Supplementary 1 and Supplementary Materials). Consequently, Materials). theConsequently, influence of the such influence association of such towards association the platinum towards organometallic the platinum organometallic complexes was complexes investigated. was 31 1 investigated.In the case of P(Biph)Ph2TS, modifications on the P{ H} NMR spectra are observed with RAME-In theβ-CD case addition. of P(Biph)Ph Complexation2TS, modifications of the phosphane on the 31P{1H} oxide NMR by spectra the CD are is observed in fact detected with RAME- by its chemicalβ-CD addition. shift modification. Complexation Moreover, of the phosphane a broadening oxide of by [PtL the3Cl]Cl CD is signals in fact isdetected observed by concurrently its chemical withshift themodification. lack of peak Moreover, corresponding a broadening to free orof CD-complexed[PtL3Cl]Cl signals phosphane is observed (in theconcurrently region going with from the 0lack to −of10 peak ppm) corresponding (Figure8). The to free explanation or CD-compl for thatexed isphosphane the interaction (in the between region going RAME- fromβ-CD 0 to and−10 [Pt(P(Biph)Phppm) (Figure2TS) 8).3Cl]Cl The withoutexplanation inducing for dissociation that is the of the interaction ligand from between the metal RAME- centre. Thisβ-CD theory and was[Pt(P(Biph)Ph confirmed2TS) by3 theCl]Cl 2D without T-ROESY inducing experiment dissociation of a 1:1 βof-CD:[Pt(P(Biph)Ph the ligand from 2TS)the 3metalCl]Cl [centre.22] mixture This whichtheory exhibitedwas confirmed intense by cross-peaks the 2D T-ROESY between experiment the phosphane of a aromatic1:1 β-CD:[Pt(P(Biph)Ph protons and the2TS) internal3Cl]Cl [22] CD protonsmixture (Hwhich3 and exhibited H5). In thatintense case, cross-peaks an organometallic between complex the phosphane formation aromatic where theprotons CD plays and the roleinternal of coordination CD protons second(H3 and sphere H5). In ligand that case, is highlighted an organometallic (Scheme4 complex). Thus, contraryformation to where TPPTS, the three CD equivalentsplays the role of RAME-of coordinationβ-CD with se respectcond sphere to Pt areligand not ableis highlighte to transformd (Scheme the [PtL 4).3Cl]Cl Thus, complex contrary into to PtClTPPTS,2L2 threecomplex equivalents when P(Biph)Ph of RAME-2TSβ-CD is used.with respect Nevertheless, to Pt are further not able increase to transform in the the CD [PtL quantity3Cl]Cl ◦ (12complex equivalents into PtCl of2 RAME-L2 complexβ-CD when relative P(Biph)Ph to Pt) and2TS temperatureis used. Nevertheless, (85 C) lead further to a dissociationincrease in the of CD the ligandquantity from (12 the equivalents metal centre of RAME- confirmedβ-CD both relative by the to CD-included Pt) and temperature phosphane (85 signal °C) lead observed to a dissociation at −3 ppm andof the the ligand formation from ofthe low-coordinated metal centre confirmed PtCl2L2 speciesboth by (Figure the CD-included8c). phosphane signal observed at −3On ppm the and other the hand,formation when of P(Biph) low-coordinated2PhTS and PtCl P(Biph)2L2 species3TS were (Figure used, 8c). addition of large amounts of CDOn to the the other complexes hand, synthetizedwhen P(Biph) by2PhTS adding and three P(Biph) equivalents3TS were of used, the previous addition ligands of large to amounts a K2PtCl of4 aqueousCD to the solution complexes did notsynthetized lead to a by signal adding improvement three equivalents (obtained of spectrathe previous were comparableligands to a toK2 thosePtCl4 presentedaqueous solution in Figure did5(a)), not so lead in theseto a signal cases, improv it is difficultement to (obtained conclude. spectra were comparable to those presented in Figure 5(a)), so in these cases, it is difficult to conclude.

Molecules 2017, 22, 140 10 of 25 Molecules 2017, 22, 140 10 of 25

31 1 Figure 8. P{ H} NMR spectra of (a) [Pt(P(Biph)Ph2TS)3Cl]Cl 10 mM; (b) +3 equiv. of RAME-β-CD Figure 8. 31P{1H} NMR spectra of (a) [Pt(P(Biph)Ph2TS)3Cl]Cl 10 mM; (b) +3 equiv. of RAME-β-CD ◦ c β ◦ d towardtoward Pt atPt 25 at 25C( °C) (c +12) +12 equiv. equiv. of of RAME- RAME-β-CD toward toward Pt Pt at at 85 85 °C C((d) 2D) 2D T-ROESY T-ROESY spectrum spectrum of a of a solution containing β-CD (10 mM) and [Pt(P(Biph)Ph TS) Cl]Cl (10 mM) at 25 ◦C in D O. solution containing β-CD (10 mM) and [Pt(P(Biph)Ph2TS)2 3Cl]Cl3 (10 mM) at 25 °C in D2O. 2

Molecules 2017, 22, 140 11 of 25 Molecules 2017, 22, 140 11 of 25

Molecules 2017, 22, 140 11 of 25 Molecules 2017, 22, 140 11 of 25 MoleculesMoleculesMolecules 2017, 201722 2017, 140, ,22 22 , ,140 140 11 of 251111 of of 25 25

(1)(1)

++ (2) (3)(3) (2) P(Biph)Ph TS P(Biph)Ph2 2TS

Scheme 4. Equilibria between the different platinum species with P(Biph)Ph2TS as ligand in the Scheme 4. Equilibria between the different platinum species with P(Biph)Ph TS as ligand in the 31 1 2 presence of 3 equiv. of RAME-β-CD toward Pt (species observed on the 31P{ H}1 NMR spectrum are presence of 3 equiv. of RAME-orβ-CD toward Pt (species observed on the P{ H} NMR spectrum are presented on a grey background).or presented on a grey background). Scheme 4. Equilibria between the different platinum species with P(Biph)Ph2TS as ligand in the Scheme 4. Equilibria between the different platinum species with P(Biph)Ph2TS as ligand in the AScheme short 4.overview Equilibria of between this platinum the different study platinum is presented species within Table P(Biph)Ph 2. To2TS sum as31 ligandup,1 low-coordinated in the SSchemechemepresence 4. 4. EquilibriaEquilibria of 3 equiv. between between of RAME- the the different differentβ-CD toward platinum platinum Pt (species species species observed with with 31 P(Biph)Ph P(Biph)Ph1 on the2 TS2TSP{ asH} as ligand ligandNMR spectrum in in the the are presence of 3 equiv. of RAME-β-CD toward Pt (species observed on the 31P{1H} NMR spectrum are catalyticA shortpresence speciespresence overview of presented3 equiv.PtClof 3 ofequiv.2L of2 thison RAME-are aof grey platinumformedRAMEβ background).-CD-β toward-CDwhen study toward Pt ortho (species is Pt presented-substituted (species observed observed in onTPPTS Table the on theP{2derivativ. H} To3131P{ NMR1 sumH}1 NMRes spectrum up,are spectrum low-coordinatedused are or are when presentedpresence on a ofgrey 3 equiv. background). of RAME -β-CD toward Pt (species observed on the P{ H} NMR spectrum are catalyticTPPTS-basedpresented speciespresentedpresented complexeson PtCl a greyon on2 La a 2greybackground). greyare are background) background) formedcombined when. .with orthoRAME--substitutedβ-CD (trans TPPTSand cis geometry derivatives respectively). are used In or the when A short overview of this platinum study is presented in Table 2. To sum up, low-coordinated TPPTS-basedfirst case,A short these complexes overview species areof are this combinedobviously platinum withformed study RAME- is due presented toβ the-CD larger in (trans Table coneand 2. anglesTocis sumgeometry of up, these low-coordinated respectively).ortho-substituted In the ligands.A short InAA catalytic theshort shortoverview second overview overview species case,of this of PtClofthe thisplatinum this relative2L 2platinum platinumare formed studyσ-donating study study is whenpr is esentedis powerpresented presentedortho -substitutedin of Table the in in TableTPPTSTable 2. To TPPTS2. 2. sum ligand,To To sum up,sumderivativ through low-coordinatedup, up, low lowes -thearecoordinated-coordinated presenceused or when ﬁrstcatalytic case, these species species PtCl2 areL2 are obviously formed when formed ortho due-substituted to the larger TPPTS cone derivativ angleses of are these usedortho or when-substituted catalyticcatalytic speciesTPPTS-based species PtCl 2PtClL2 complexesare2L2 formedare formed are when combined when ortho ortho-substituted with- substitutedRAME- TPPTSβ-CD TPPTS ( transderivativ derivativesand cises geometryare used are used respectively).or when or when In the ligands.ofTPPTS-based the Incatalytic attractive the second complexes species meta case,sodium PtCl are the2L combined2 sulfonatoare relative formed with σgroups,-donating when RAME- makesorthoβ-CD power-substituted the (trans ligand-metal of and the TPPTScis TPPTS geometry bond derivatives ligand, weak respectively). through and are hence used In the or theRAME- presence when TPPTS-basedTPPTSTPPTSfirst-based-based complexes case, complexes complexes these are species combined are are combined combined are obviously with with RAME-with RAMEformed RAMEβ-CD- β-dueβ -(CD-transCD to ( trans( transtheand larger cisand and geometry cis cis cone geometry geometry angles respectively). respectively). ofrespectively). these orthoIn the In-substituted In the the βfirst-CD case, is able these to shift metaspecies the are equilibria obviously between formed the due diff toerent the larger organometallic cone angles species of these towards ortho-substituted the formation of thefirst attractive firstcase, case, theseligands. these species In species sodiumthe are second obviously are sulfonatoobviously case, formed the formedrelative groups, due duetoσ-donating the makes to larger the larger power the cone ligand-metalcone angles of the angles TPPTSof these of thligand, bond orthoese ortho-substituted weakthrough-substituted and the presence hence ofligands. low-coordinatedfirst In case, the secondthese speciesspecies case, the are by relative obviously the formationσ-donating formed dueofpower inclusion to theof the larger TPPTScomplex cone ligand, angles with through of the th eseligand. the ortho presence- substitutedHowever, RAME-ligands.βligands.-CD In ofthe is Inthe ablesecond the attractive second to case, shift metacase, the the relative sodiumthe equilibria relative σsulfonato-donating σ-donating between groups, power power the makesof the different of TPPTSthe the ligand-metal TPPTS ligand, organometallic ligand, through bond through weak the species presence the and presence hence towards RAME- althoughof theligands. attractive the associationIn metathe second sodium constant case, sulfonato the between relative groups, σtris(- donatingmakesp-Me)TPPTS the power ligand-metal andof the RAME- TPPTS bondβ weakligand,-CD andis throughhigher hence than RAME-the presence the one the formationof theof attractive the attractiveβ-CD of low-coordinatedmeta is able meta sodium to sodium shift sulfonato the sulfonato equilibria species groups, groups, between by makes the makes formationthe the diff ligand-metal theerent ligand oforganometallic- inclusionmetal bond bond weak complexweak species and henceand towards withhence RAME- theRAMEthe formation ligand.- betweenβ-CDof is theable TPPTS attractive to shift and the metaRAME- equilibria sodiumβ-CD, between sulfonato low-coordinated the groups, different makes platinum organometallic the ligand complexes-metal species bond are towards not weak observed. the and formation hence RAME - β-CDβ -isCD able isof ableto low-coordinated shift to shift the equilibria the equilibria species between between by the the diff the formationerent different organometallic p organometallicof inclusion species complex species towards towardswith theβ the formation the ligand. formation However, However,of low-coordinatedβ- althoughCD is able theto shiftspecies association the equilibriaby the constant formation between between the of differentinclusion tris( organometallic-Me)TPPTS complex with and species the RAME- ligand. towards-CD However, the is formation higher than of low-coordinatedofTable low although2.-coordinated Organometallic thespecies association species speciesby the by constantformed formation the formation by between adding of inclusion of tris(3 equiv. inclusionp-Me)TPPTS complexof ligand complex andtowith a RAME-K with 2thePtCl theligand.4 βaqueous-CD ligand. isHowever, higher solution However, than the one the onealthough betweenof low the- coordinatedassociation TPPTS and constant species RAME- between byβ -CD, the formationtris( low-coordinatedp-Me)TPPTS of inclusion and platinum RAME- complexβ-CD complexes with is higher the are ligand.than not the observed.However, one althoughalthough(10 mM) thebetween andassociation the afterassociation TPPTS RAME- constant and βconstant-CD RAME- between addition betweenβ-CD, tris( (1 low-coordinatedto ptris( -Me)TPPTS12 equiv.p-Me)TPPTS toward and platinum andRAME-platinum). RAME βcomplexes-CD -β -isCD higher is are higher notthan observed. than the one the one betweenalthough TPPTS the and association RAME-β -CD,constant low-coordinated between tris( platinump-Me)TPPTS complexes and RAME are not-β-CD observed. is higher than the one betweenTablebetbet 2.weenween TPPTSOrganometallic TPPTS TPPTS and andRAME- and RAME RAME speciesβ-CD,-β-β- formedCD,-low-coordinatedCD, low low by-coordinated-coordinated adding platinum 3 equiv. platinum platinum complexes of ligand complexes complexes toare a not Kare arePtCl observed.not not observed. observed.aqueous solution Table 2. OrganometallicPlatinum species Complex formed by adding 3New equiv. Species of ligand Obtained2 to a K42PtCl 4 aqueous solution Table 2. OrganometallicLigand species formed by adding 3 equiv. of ligand to a K2PtCl4 aqueous solution (10 mM)TableTable and 2. Organometallic after2.(10 Organometallic mM) RAME- and βspeciesafterObtained-CD speciesRAME- addition formed without formedβ-CD by (1 additionadding to byCD 12 adding equiv. 3 (1 equiv. to 3 12 towardequiv. ofequiv.after ligand of platinum).RAME-towardligand to a Ktoplatinum).β2-CD PtCla K2 4PtClAddition aqueous 4 aqueous solution solution (10 mM)Table and 2. after Organometallic RAME-β-CD species addition formed (1 to 12by equiv. adding toward 3 equiv. platinum). of ligand to a K2PtCl4 aqueous solution (10 mM) and after RAME-β-CD addition (1 to 12 equiv. toward platinum). (1(100 m mM)M) and and after after RAME RAME-β-[PtLβ-CD-CD3 Cl]Claddition addition = (1 (1 to to 12 12 equiv. equiv. toward toward platinum). platinum). Platinum Complex cis-PtClNew 2SpeciesL2 = Obtained LigandPlatinum Complex New NewSpecies Species Obtained Obtained LigandLigand Platinum ComplexObtained without CD New Speciesafter Obtained RAME-β -CD Addition Ligand ObtainedPlatinumPlatinum without Complex Complex CD after afterRAME-NewNew RAME- Species βSpecies-CDβ Addition-CD Obtained Obtained Addition TPPTSLigandLigand Obtained without CD after RAME-β-CD Addition ObtainedObtained without without[PtL3Cl]Cl CD CD = afterafter RAME RAME-β-β-CD-CD Addition Addition [PtL[PtL33Cl]Cl = cis-PtCl2L2 = [PtL3Cl]Cl = cis-PtCl2L2 = [PtL[PtL 3Cl]Cl3Cl]Cl = = cis-PtCl2L2 = ciscis-PtCl-PtCl2L2L2 2 = = TPPTS TPPTSTPPTS tris(pTPPTS-Me)TPPTSTPPTSTPPTS [PtL3Cl]Cl - cis-PtCl L = tris(p-OMe)TPPTS [PtL3Cl]Cl 2 2-

tris(p-Me)TPPTStrans -PtCl2L2[PtL = 3Cl]Cl - tris(p p-Me)TPPTS [PtL3Cl]Cl - tris(tris(-Me)TPPTSp-Me)TPPTS [PtL3Cl]Cl - - tris(tris(pp-Me)TPPTS-tris(Me)TPPTSp-OMe)TPPTS [PtL[PtL3Cl]Cl3Cl]Cl[PtL 3Cl]Cl - - - tris(tris(po-OMe)TPPTS-Me)TPPTS [PtL3Cl]Cl - - tris(tris(p-OMe)TPPTSp-OMe)TPPTS [PtL3Cl]Cl - - tris(tris(pp-OMe)TPPTS-OMe)TPPTS 3[Pt[PtLL3Cl]Cltrans3Cl]Cl-PtCl 2L2 = - - trans-PtCl2L2 = transtrans-PtCl-PtCl2L2 = tris(o-Me)TPPTS transtrans2-PtCl-PtCl2 2L2L2 2= = - tris(o-Me)TPPTS - tris(o-OMe)TPPTS trans -PtCl2L2 - tris(tris(o-Me)TPPTSotris(-Me)TPPTStris(oo-Me)TPPTS-Me)TPPTS - -- -

tris(o-OMe)TPPTS trans-PtCl 2L2 - tris(o-OMe)TPPTS trans-PtCl2L2 - 2 2 tris(tris(o-OMe)TPPTSotris(-OMe)TPPTSo-OMe)TPPTS transtrans-PtCl-PtCltrans-PtClL 2L2 2 2 - -- P(Biph)Phtris(o-OMe)TPPTS2TS [PtLtrans3Cl]Cl2-PtCl2 L -

P(Biph)Ph2TS [PtL3Cl]Cl P(Biph)Ph2TS [PtL3Cl]Cl or P(Biph)Ph2TS [PtL3Cl]Cl P(Biph)PhP(Biph)PhP(Biph)Ph2TS2TS2TS [PtL3[PtLCl]Cl[PtL3Cl]Cl3Cl]Cl P(Biph)2PhTS n.d (broad signals) * n.d (broad signals) or or P(Biph)3TS n.d (broad signals) * n.d (broad or signals) P(Biph)2PhTS n.d (broad signals) * n.d oror or(broad signals) P(Biph)2PhTS n.d (broad signals) * n.d (broad signals) P(Biph)* Probably2PhTS [PtL3Cl]Cl n.d (broad when signals) compared * with spectrum n.d obtained (broad signals) with P(Biph)Ph 2TS. P(Biph) P(Biph)PhTSP(Biph)2PhTSP(Biph)2PhTS n.d3TS (broad n.dn.d (broad (broad signals) n.d (broadsignals) signals) * signals) * * * n.d n.dn.d (broad (broad(broad n.d (broadsignals) signals)signals) signals) P(Biph)2 3TS n.d (broad signals) * n.d (broad signals) P(Biph)3TS n.d (broad signals) * n.d (broad signals) P(Biph)P(Biph)3TS*3TS Probably n.d n.d[PtL (broad (broad3Cl]Cl signals) whensignals) compared * * with specn.dtrumn.d (broad (broad obtained signals) signals) with P(Biph)Ph2TS. P(Biph)* Probably3TS [PtL3Cl]Cl n.d (broad when compared signals) * with spectrum obtained n.d with (broad P(Biph)Ph signals)2TS. This behaviour* Probably* Probably comes [PtL3 [PtLCl]Cl from3Cl]Cl when the when compared highest compared withσ-donating withspec trumspectrum power obtained obtained of with this withP(Biph)Ph ligand P(Biph)Ph compared2TS. 2TS. to TPPTS * Probably* Probably [PtL [PtLCl]Cl3Cl]Cl when when compared compared with with spectrum spectrum obtained obtained with with P(Biph)Ph P(Biph)PhTS.2TS. through the presenceThis behaviour of the3 donatingcomes from para the methyl highest groupsσ-donating which power makes of this the ligand ligand-metal2 compared bond to TPPTS This behaviour comes from the highest σ-donating power of this ligand compared to TPPTS stronger.This ThisbehaviourFurthermore,through behaviour the comes presence comesgiven from from thattheof the highestthetris( donating highestp-OMe)TPPTS σ-donating σpara-donating methyl power does power groupsofnot this ofinteract thisligandwhich ligand comparedmakeswith compared RAME-the to ligand-metal TPPTS βto-CD, TPPTS its bond through theThis presence behaviour of comesthe donating from the para highest methyl σ- donatinggroups which power makes of this theligand ligand-metal compared bond to TPPTS throughThisthrough behaviour thestronger. presence the presence comes Furthermore, of the from of donating thethe donatinggiven highest para that paramethyl σtris(-donating methylp -OMe)TPPTSgroups groups powerwhich whichdoes ofmakes this makesnot the ligandinteract ligand-metal the ligand compared with- metalRAME- bond to bond β TPPTS-CD, its stronger.through Furthermore, the presence given of thethat donating tris(p-OMe)TPPTS para methyl does groups not whichinteract makes with theRAME- ligandβ-CD,-metal its bond throughstronger.stronger. thestronger. presenceFurthermore, Furthermore,Furthermore, of the given donating given given that thatpara thattris( p tris(methyl-OMe)TPPTS tris(pp-OMe)TPPTS-OMe)TPPTS groups does which does doesnot makes notinteract not interact interact the with ligand-metal with withRAME- RAME RAMEβ-CD, bond-β-β- CD,-CD,its stronger. its its

Molecules 2017, 22, 140 12 of 25

Furthermore, given that tris(p-OMe)TPPTS does not interact with RAME-β-CD, its coordination behaviour towards platinum(II) is not affected by the CD addition. Finally, formation of organometallic species where the RAME-β-CD plays the role of coordination second sphere ligand is observed when P(Biph)Ph2TS, which possesses a CD-recognised moiety, is used in combination with one equivalent of RAME-β-CD towards the ligand. It is important to emphasize that further increase in the CD quantity yields to the formation of low-coordinated species. The formation of organometallic species possessing more than one CD in their coordination second sphere would probably yield to a steric decompression trough the decoordination of the CD included phosphane.

2.2. Palladium Complexes The RAME-β-CD inﬂuence on organometallic species was extended to palladium (0) complexes. The palladium extraction from a toluene solution of Pd(TPP)4 to an aqueous phase by the hydrosoluble ligand yields to isolation of PdLx complexes (see “materials and methods” part). In the case of TPPTS, this study has already been published by our group [19]. It was concluded that the addition of RAME-β-CD only yields to a chemical exchange rate decrease between free TPPTS and the Pd(TPPTS)3 complex caused by the formation of the inclusion complex RAME-β-CD/TPPTS. Furthermore, no new palladium species were observed, even at high temperature (60 ◦C).

2.2.1. Para-Substituted TPPTS Derivatives

[Pd(0)/tris(p-Me)TPPTS] Complex

31 1 P{ H} NMR spectra of Pd(tris(p-Me)TPPTS)3 complexes in addition to different RAME-β-CD concentrations and at different temperatures are given in Figure9. Without CD, two different resonances are observed. Besides the minor phosphane oxide signal at 34 ppm, a broad signal was detected at 19.5 ppm which corresponds to the average signal of the Pd(tris(p-Me)TPPTS)3 complex in fast equilibrium with a small amount of free residual tris(p-Me)TPPTS ligand [19,23]. Higher temperatures have no effects on this equilibrium. Adding three equivalents of RAME-β-CD yields to an exchange rate decrease between the Pd(tris(p-Me)TPPTS)3 species, which signal becomes sharp at 21.8 ppm, and the small excess of free ligand by its encapsulation in the CD cavity (−11.2 ppm). Higher CD concentrations combined with higher temperatures do not lead to the formation of new palladium species. Hence, like what was observed with the platinum(II) complexes, addition of RAME-β-CD does not change the nature of the organometallic complex, albeit association constant between the CD and the ligand is greater than that of the RAME-β-CD/TPPTS inclusion complex.

[Pd(0)/tris(p-OMe)TPPTS] Complex Addition of large amount of RAME-β-CD (12 equiv. with respect to Pd) to the 31 1 Pd(tris(p-OMe)TPPTS)3 complex does not modify the P{ H} NMR spectrum as this ligand does not interact with the CD. In fact, even at high temperature, a broad signal at 19 ppm is detected which corresponds to the average signal of the equilibrium between the organometallic complex and free tris(p-OMe)TPPTS (Figure 10).

2.2.2. ortho-Substituted Ligands The same experiments were realized with the ortho-substituted ligands but the synthesis of the PdL3 complex failed. Indeed, Pd extraction from the organic phase to the aqueous phase is too low. The bulkiness of the hydrosoluble ortho-substituted are obviously responsible for the equilibrium displacement toward the organic Pd(TPP)4 complex. Again, these results are in accordance with the previous observations made with the platinum complexes study showing that these ligands hardly coordinate the metal centre. Molecules 2017, 22, 140 13 of 25 Molecules 2017, 22, 140 13 of 25

phosphane oxide Oxyde RAM Molar ratio RAME-β-CD Pd

25°C)25°C)

45°C)45°C)

PdLPdL++ L* L* PdL PdL L* + L 3 3 2 0

65°C)65°C)

85°C)85°C)

PdL3 PdL3 Oxyde CD included phosphane oxide CD includedL phosphane

25°C)25°C)

45°C)45°C)

PdLPdL3 +3 +L* L* PdL PdL2L* + LL 3

65°C)65°C)

85°C)85°C)

PdL3 PdL3

25°C)25°C)

45°C)45°C)

PdL33 + + L* L* PdL PdL22L*L* + + LL 12

65°C)65°C)

85°C)85°C)

(ppm)(ppm) 3838 3030 2222 1414 66 -2-2 -10-10 -18-18

31 1 FigureFigure 9. 9. 31P{P{1H} NMR NMR spectra spectra of Pd(tris( of Pd(tris(p-Me)TPPTS)p-Me)TPPTS)3 depending3 depending on both on temperature both temperature and RAME- and RAME-β-CDβ -CDquantity quantity in D2O in with D2O a with ligand a ligandconcentration concentration of 66 mM. of 66 mM.

MoleculesMolecules2017 2017, 22, ,22 140, 140 1414 of of 25 25

phosphane oxide

PdL3 + L* PdL2L* + L PdL3 + L* PdL2L* + L

a)a)

b)b)

c)c)

(ppm)(ppm) 38 34 30 26 2222 18 1414 10 66 2 -2 -6-6 -8

31 1 ◦ β Figure 10. P{31 H}1 NMR spectra of Pd(tris(p-OMe)TPPTS)3 at (a) 25 C; (b) +12 equiv. of RAME- -CD Figure◦ 10. P{ H} NMR spectra of Pd(tris(◦p-OMe)TPPTS)3 at (a) 25 °C; (b) +12 equiv. of RAME-β-CD at 25 C(c) +12 equiv. of RAME-β-CD at 85 C in D2O with a ligand concentration of 66 mM. at 25 °C (c) +12 equiv. of RAME-β-CD at 85 °C in D2O with a ligand concentration of 66 mM.

2.2.3.2.2.3. Biphenylphosphane Biphenylphosphane Ligands Ligands

[Pd(0)/P(Biph)Ph2TS] Complex [Pd(0)/P(Biph)Ph2TS] Complex In this case, comments are identical to the previous Pd(tris(p-Me)TPPTS)3 complex (see ESI). In this case, comments are identical to the previous Pd(tris(p-Me)TPPTS)3 complex (see ESI). That That is to say, CD addition to a Pd(P(Biph)Ph2TS)3 aqueous solution reduces the chemical exchange rate is to say, CD addition to a Pd(P(Biph)Ph2TS)3 aqueous solution reduces the chemical exchange rate between free ligand and the organometallic complex. Increasing both temperature and RAME-β-CD between free ligand and the organometallic complex. Increasing both temperature and RAME-β-CD quantity do not yield to the formation of other palladium species. However, 2D NMR T-ROESY quantity do not yield to the formation of other palladium species. However, 2D NMR T-ROESY experiment of a 1:1 β-CD:Pd(P(Biph)Ph2TS)3 mixture exhibited intense cross-peaks between the experiment of a 1:1 β-CD:Pd(P(Biph)Ph2TS)3 mixture exhibited intense cross-peaks between the phosphane aromatic protons and the internal CD protons H3 and H5 (Figure 11). The presence of phosphane aromatic protons and the internal CD protons H3 and H5 (Figure 11). The presence of only only 4% (determined by integration of the 31P{1H} NMR spectrum) of free ligand which is trapped 4% (determined by integration of the 31P{1H} NMR spectrum) of free ligand which is trapped by the by the CD in the mixture could not be responsible for such intense cross peaks. Therefore, absence CD in the mixture could not be responsible for such intense cross peaks. Therefore, absence of new of new palladium species together with strong correlation between the CD and the ligand in the 2D palladium species together with strong correlation between the CD and the ligand in the 2D T-ROESY T-ROESY NMR spectrum enable us to assume the formation of inclusion complex between the CD and NMR spectrum enable us to assume the formation of inclusion complex between the CD and the the ligand (coordinated to the palladium centre). As with the platinum complex, the P(Biph)Ph2TS ligand (coordinated to the palladium centre). As with the platinum complex, the P(Biph)Ph2TS ligand ligand allows the formation of organometallic palladium species where the cyclodextrin plays the role allows the formation of organometallic palladium species where the cyclodextrin plays the role of of coordination second sphere ligand. coordination second sphere ligand. Furthermore, intense cross-peaks between the CD internal H3 protons and Ha of the biphenyl Furthermore, intense cross-peaks between the CD internal H3 protons and Ha of the biphenyl moiety together with high correlations between the CD internal H5 protons and Hc/Hd of the biphenyl moiety together with high correlations between the CD internal H5 protons and Hc/Hd of the biphenyl moiety in the T-ROESY spectrum allow us to propose a geometry where the phosphane penetration in moiety in the T-ROESY spectrum allow us to propose a geometry where the phosphane penetration the CD cavity takes place via the primary face (Scheme5). in the CD cavity takes place via the primary face (Scheme 5). It should be noted however, that this geometry differs from the geometry of the inclusion complex It should be noted however, that this geometry differs from the geometry of the inclusion between the free ligand in solution and the CD which takes place via the CD secondary face (see ESI). complex between the free ligand in solution and the CD which takes place via the CD secondary face The spatial proximity of the palladium coordinated ligands inevitably leads to a high steric hindrance (see ESI). The spatial proximity of the palladium coordinated ligands inevitably leads to a high steric which could be responsible for such a difference in the geometry. hindrance which could be responsible for such a difference in the geometry.

Molecules 2017, 22, 140 15 of 25 Molecules 2017 22 Molecules 2017,, 22,, 140 140 1515 of of 25 25

Figure 11. 2D T-ROESY spectrum of a solution containing β-CD (11 mM) and Pd(P(Biph)Ph2TS)3 (11 Figure 11. 2D T-ROESY spectrum of a solution containing β-CD (11 mM) and Pd(P(Biph)Ph2TS)3 FiguremM) at 11. 25 2D°C inT-ROESY◦ D2O. spectrum of a solution containing β-CD (11 mM) and Pd(P(Biph)Ph2TS)3 (11 (11 mM) at 25 C in D2O. mM) at 25 °C in D2O.

NaO3S NaO3S SO3Na SO3Na

P P NaO3S P Pd P NaO3S Pd SO3Na 2 SO3Na 2 P 2 P 2 2 SO3Na SO Na2 3 SO3Na SO3Na Scheme 5. Possible geometry of the organometallic pa palladiumlladium species where CD plays the role of Schemecoordination 5. Possible second geometry spheresphere ligand.ligand. of the organometallic palladium species where CD plays the role of coordination second sphere ligand.

[Pd(0)/P(Biph)22PhTS]PhTS] Complex Complex [Pd(0)/P(Biph)2PhTS] Complex 31 11 P{P{H}H} NMR NMR spectra spectra of Pd(P(Biph)2PhTS)PhTS)33 complexescomplexes in in addition to differentdifferent RAME-RAME-ββ-CD concentrations31P{1H} NMR and spectra at different of Pd(P(Biph) temperaturestemperatures2PhTS) areare3 given givencomplexes inin FigureFigure in 12addition12.. to different RAME-β-CD concentrations and at different temperatures are given in Figure 12.

Molecules 2017, 22, 140 16 of 25 Molecules 2017, 22, 140 16 of 25

PdL3

phosphane Molar ratio oxide β PdL2 RAME- -CD Pd

25°C)

40°C)

0 60°C)

85°C) PdL3

CD included CD included phosphane oxide PdL2 phosphane

25°C)

40°C)

60°C)

85°C)

25°C)

40°C)

60°C)

85°C)

50 40 30 20 10 0 -10 -20 (ppm) 31 1 FigureFigure 12. 12. 31P{P{1H}H} NMRNMR spectraspectra of palladium complexes complexes synthetized synthetized with with P(Biph) P(Biph)2PhTS2PhTS depending depending onon both both temperature temperature and and RAME- RAME-ββ-CD-CD quantity in in D D22OO with with a aligand ligand concentration concentration of of66 66mM. mM.

At room temperature and without CD, two different broad signals corresponding to the PdL3 At room temperature and without CD, two different broad signals corresponding to the PdL3 and and PdL2 complexes in fast equilibrium with free ligand are observed. Neither temperature, nor PdL complexes in fast equilibrium with free ligand are observed. Neither temperature, nor addition of addition2 of 3 equiv. of RAME-β-CD do not allow to observe new organometallic species. Indeed, CD 3 equiv. of RAME-β-CD do not allow to observe new organometallic species. Indeed, CD addition only addition only leads to the apparition of the complexed free ligand at −7.5 ppm, a phosphane oxide leads to the apparition of the complexed free ligand at −7.5 ppm, a phosphane oxide chemical shift chemical shift trapped by the CD and a sharpening of the organometallic complexes signals which trapped by the CD and a sharpening of the organometallic complexes signals which are in equilibrium. are in equilibrium. However, addition of 12 equiv. of RAME-β-CD leads to a diminution of the PdL3 β However, addition of 12 equiv. of RAME- -CD leads to a diminution of the PdL3 species in favour Molecules 2017, 22, 140 17 of 25 Molecules 2017, 22, 140 17 of 25

2 species in favour of the PdL2 species and free ligand trapped by the CD. On the other hand, temperature increase has a negligible influence on the PdL3/PdL2 ratio. At high temperature, natural oftemperature the PdL2 species increase and has free a negligible ligand trapped influence by theon the CD. PdL On3 the/PdL other2 ratio. hand, At high temperature temperature, increase natural has dissociation increase of the PdL3 species is probably offset by the stability diminution of the inclusion adissociation negligible inﬂuenceincrease of on the the PdL PdL3 species3/PdL 2isratio. probably At high offset temperature, by the stability natural diminution dissociation of the increase inclusion of complex between the CD and the phosphane. To sum up, high CD quantity is able to shift the thecomplex PdL3 speciesbetween is the probably CD and offset the byphosphane. the stability To diminution sum up, high of the CD inclusion quantity complex is able betweento shift the equilibriumCD and the phosphane.between the To different sum up, palladium high CD quantityspecies towards is able to the shift formation the equilibrium of low-coordinated between the speciesdifferent (Scheme palladium 6). species towards the formation of low-coordinated species (Scheme6).

Scheme 6. Equilibria between the different palladium species with P(Biph)2PhTS as ligand in the Scheme 6. Equilibria between the different palladium species with P(Biph)2PhTSPhTS as ligand in the 2 31 1 presence of 12 equiv. of RAME-β-CD toward palladium (species observed on the 31P{1H} NMR presence of 1212 equiv.equiv. of RAME-RAME-β-CD towardtoward palladiumpalladium (species(species observedobserved onon thethe 31P{P{1H} NMR spectrum are presented on a grey background). spectrum are presented onon aa greygrey background).background).

3 [Pd(0)/P(Biph)3TS] Complex [Pd(0)/P(Biph)3TS] Complex 3 As already described [16], the ligand P(Biph)3TS forms a new palladium species at room As already described [16], the ligand P(Biph)3TS forms a new palladium species at room temperature:PdL4 which have a chemical shift of 15 ppm. Without CD, PdL3 and PdL4 species are in temperature:PdL4 whichwhich have have a achemical chemical shift shift of of15 15ppm. ppm. Without Without CD, CD,PdL3PdL and PdLand4 species PdL species are in slow equilibrium.4 Indeed, when the temperature is increased, the signals of both3 complexes4 are areslow in equilibrium. slow equilibrium. Indeed, Indeed, when when the temperature the temperature is increased, is increased, the the signals signals of of both both complexes complexes are broadened and merge together at 85 °C (Figure 13). Moreover, the NMR spectrum carried out at room broadened and merge together at 85 ◦°CC (Figure 13).13). Moreover, Moreover, the NMR spectrum carried out at room temperature after heating gave the same signals reflecting the reversibility of the process. temperature after heating gavegave thethe samesame signalssignals reﬂectingreflecting thethe reversibilityreversibility ofof thethe process.process.

+L PdL3 PdL4 PdL3 PdL4 -L

phosphane oxide

25 C) 25°C)

40 C) 40°C)

60 C) 60°C) +L PdL3 PdL4 PdL3 PdL4 -L

85 C) 85°C) (ppm) 50 45 40 35 30 25 20 15 10 5 0 -5 -10 -15 -20 (ppm) 50 45 40 35 30 25 20 15 10 5 0 -5 -10 -15 -20 31 1 Figure 13. 31 P{1 H} NMR spectra of palladium complexes synthetized with P(Biph)3TS depending on Figure 13. 31P{1H} NMR spectra of palladium complexes synthetized with P(Biph)3TS depending on Figure 13. P{ H} NMR spectra of palladium complexes synthetized with P(Biph)3TS depending on temperature in D2O with a ligand concentration of 66 mM. temperature in D2O with a ligand concentration of 66 mM. temperature in D2O with a ligand concentration of 66 mM.

Molecules 2017, 22, 140 18 of 25 Molecules 2017, 22, 140 18 of 25

By adding increasing amounts of RAME-β-CD, the PdL4 signal disappears concurrently with an By adding increasing amounts of RAME-β-CD, the PdL4 signal disappears concurrently with an increase of both the PdL3 signal and the free ligand trapped by the CD (Figure 14). increase of both the PdL3 signal and the free ligand trapped by the CD (Figure 14).

PdL3 PdL4 CD included Ligand Molar ratio oxide RAME-β-CD Phosphane

0.2

0.4

CD included phosphane oxide

PdL2

(ppm) 5045 40 35 30 25 20 15 10 5 0 -5 -10 -15 -20 Figure 14. 31P{1H} NMR spectra effect of RAME-β-CD quantity on the equilibrium of the different Figure 14. 31P{1H} NMR spectra effect of RAME-β-CD quantity on the equilibrium of the different ◦ palladium species formed with the ligand P(Biph)3TS in D2O at 25 C with a ligand concentration of palladium species formed with the ligand P(Biph)3TS in D2O at 25 °C with a ligand concentration of 66 mM. 66 mM.

WhenWhen the CD quantity quantity reaches reaches four four equivalents equivalents of of ligand, ligand, species species PdL PdL2 appears.2 appears. Similarly Similarly to the to theabove-mentione above-mentionedd Pd(P(Biph) Pd(P(Biph)2PhTS)2PhTS)3 complex,3 complex, temperature temperature has has a anegligible negligible influence inﬂuence on on thethe PdLPdL33/PdL2 2ratioratio when when P(Biph) P(Biph)3TS3 TSis used is used (Figure (Figure 15). Again, 15). Again, RAME- RAME-β-CD isβ able-CD to is shift able the to equilibria shift the equilibriabetween the between different the palladium different palladium organometallic organometallic species when species P(Biph) when3TS P(Biph) is used3TS as is ligand. used as ligand. AA shortshort overview overview of of this this palladium palladium study study is presented is presented in Table in Table3. To sum3. To up, sum the differentup, the different ligands usedligands in thisused study in this can study be classiﬁed can be classified in three categories:in three categories:

(1)(1) ligands forming forming palladium palladium complexes complexes not not affected affected by the by RAME- the RAME-β-CDβ addition-CD addition (TPPTS, (TPPTS, tris(p- Me)TPPTStris(p-Me)TPPTS and tris( andp-OMe)TPPTS) tris(p-OMe)TPPTS) (2)(2) ligands forming palladium complexes where the CD couldcould playplay thethe rolerole ofof coordinationcoordination secondsecond sphere ligand (P(Biph)Ph2TS) sphere ligand (P(Biph)Ph2TS) (3) ligands forming palladium complexes which are transformed by the presence of RAME-β-CD. (3) ligands forming palladium complexes which are transformed by the presence of RAME-β-CD. Indeed, P(Biph)2PhTS and P(Biph)3TS spontaneously form respectively PdL3/PdL2 and Indeed, P(Biph)2PhTS and P(Biph)3TS spontaneously form respectively PdL3/PdL2 and PdL4/PdL3 organometallic complexes which are converted in PdL2 complexes when CD is added PdL4/PdL3 organometallic complexes which are converted in PdL2 complexes when CD is due to shift equilibria between the different organometallic species. However, formation of added due to shift equilibria between the different organometallic species. However, formation species where the CD acts as coordination second sphere ligand could not be avoided as the of species where the CD acts as coordination second sphere ligand could not be avoided as the biphenyl moiety is well recognised by its cavity. In these cases, the organometallic complexes biphenyl moiety is well recognised by its cavity. In these cases, the organometallic complexes formed would naturally evolve to low-coordinated species through steric decompression by formed would naturally evolve to low-coordinated species through steric decompression by ligand decoordination. ligand decoordination.

Molecules 2017, 22, 140 19 of 25 Molecules 2017, 22, 140 19 of 25

PdL CD included 3 CD included phosphane oxide PdL Ligand CD included 3 CD included phosphane oxide Ligand PdL2

PdL2

25°C) 25°C)

40°C) 40°C)

60°C) 60°C)

85°C)

(ppm) 8550°C) 45 40 35 30 25 20 15 10 5 0 -5 -10 -15 -20

(ppm) 50 45 40 35 30 25 20 15 10 5 0 -5 -10 -15 -20 31 1 Figure 15. P{ H} NMR spectra of palladium complexes synthetized with P(Biph)3TS depending on Figure 15. 31P{1H} NMR spectra of palladium complexes synthetized with P(Biph)3TS depending on temperature in the presence of 4 equiv. of RAME-β-CD towards the phosphane in D2O with a ligand temperature in the31 presence1 of 4 equiv. of RAME-β-CD towards the phosphane in D2O with a ligand concentrationFigure 15. of 66P{ mM.H} NMR spectra of palladium complexes synthetized with P(Biph)3TS depending on concentrationtemperature of 66 inmM. the presence of 4 equiv. of RAME-β-CD towards the phosphane in D2O with a ligand Tableconcentration 3. New organometallic of 66 mM. species observed after RAME-β-CD addition (1 to 12 equiv. toward Table 3. New organometallic species observed after RAME-β-CD addition (1 to 12 equiv. toward palladium) to a solution of the palladium complexes formed by extraction with an aqueous ligand palladium) to a solution of the palladium complexes formed by extraction with an aqueous ligand solutionTable (66 mM).3. New organometallic species observed after RAME-β-CD addition (1 to 12 equiv. toward solutionpalladium) (66 mM). to a solution of the palladium complexes formed by extraction with an aqueous ligand solution (66 mM). PalladiumPalladium Complex Complex New SpeciesNew Species Obtained Obtained Ligand Ligand Obtained without CD after RAME-β-CD Addition ObtainedPalladium without ComplexCD after RAME-Newβ Species-CD Addition Obtained Ligand TPPTSTPPTS ObtainedPdL PdL3 3 without CD after RAME-- β- -CD Addition tris(p-Me)TPPTS PdL3 - tris(p-Me)TPPTSTPPTS PdL3PdL3 -- 3 tris(p-OMe)TPPTStris(p-Me)TPPTS PdL PdL3 - - tris(p-OMe)TPPTS PdL3 - tris(o-Me)TPPTStris(p-OMe)TPPTS No palladium extractionPdL3 - - tris(o-Me)TPPTS No palladium extraction - tris(o-OMe)TPPTStris(o-Me)TPPTS No palladiumNo palladium extraction extraction - - tris(o-OMe)TPPTStris(o-OMe)TPPTS No palladiumNo palladium extraction extraction - -

P(Biph)Ph2TS PdL3

P(Biph)PhP(Biph)Ph2TS2TS PdL3PdL3

P(Biph)2PhTS PdL3 + PdL2 [PdL2] increase 3 4 3 3 2 P(Biph)P(Biph)TS 2PhTS PdL +PdL PdL3 + PdL2 [PdL ] increase[PdL + PdL2] increase formed P(Biph)2PhTS PdL3 + PdL2 [PdL2] increase P(Biph)3TS PdL4 + PdL3 [PdL3] increase + PdL2 formed 2.3. ComparisonP(Biph) of the Results3TS Obtained with PdL Palladium4 + PdL3 and Platinum[PdL Complexes3] increase + PdL2 formed An2.3. overview Comparison of theof the results Results is presentedObtained with in Table Palladium 4. and Platinum Complexes 2.3. Comparison of the Results Obtained with Palladium and Platinum Complexes An overview of the results is presented in Table 4. An overview of the results is presented in Table4.

Molecules 2017, 22, 140 20 of 25

Table 4. Effects of RAME-β-CD addition on the platinum and palladium complexes obtained with the ◦ different phosphanes (in D2O, at 25 C); CD = RAME-β-CD; L@CD = Ligand included in the CD cavity.

Entry Ligand (L) Inﬂuence of CD on Pt Complexes Inﬂuence of CD on Pd Complexes [PtL Cl]Cl + CD → cis-PtCl L + L@CD 1 TPPTS 3 2 2 PdL unchanged with CD CD = decoordination promotor 3 tris(p-Me)TPPTS 2 [PtL Cl]Cl unchanged with CD PdL unchanged with CD tris(p-OMe)TPPTS 3 3 [PtL Cl]Cl impossible to obtain; Ligand unable to extract Pd tris(o-Me)TPPTS 3 3 trans-PtCl L was formed from the organic layer tris(o-OMe)TPPTS 2 2 with or without CD with or without CD [PtL Cl]Cl + CD → [(L@CD)PtL Cl]Cl PdL + CD → (L@CD)PdL 4 P(Biph)Ph TS 3 2 3 2 2 CD = second sphere ligand CD = second sphere ligand

PdL3 + CD → PdL*2 + L@CD L* = L or L@CD 5 P(Biph) PhTS n.d. (broad signals with or without CD) 2 CD = decoordination promotor and second sphere ligand

PdL4 + CD → PdL*3 + L@CD PdL*3 + CD → PdL*2 + L@CD 6 P(Biph)3TS n.d. (broad signals with or without CD) L* = L or L@CD CD = decoordination promotor and second sphere ligand

Firstly, tris-ortho-substituted hydrosoluble phosphanes led to low coordinated platinum species and are unable to extract palladium from a Pd(TPP)4 toluene solution (Table4, entry 3). These two behaviours are probably due to the steric hindrance around their phosphorous atom making them poor ligands. Apart from this peculiar case and the results obtained with platinum for P(Biph)2PhTS 31 1 and P(Biph)3TS ligands (broad signals in P{ H} NMR) (entries 5 and 6), three CD behaviours towards [PtL3Cl]Cl and PdLn complexes were noticed:

• The CD can have no inﬂuence on the organometallic species. That is what is observed with para-substituted hydrosoluble phosphanes for both palladium and platinum complexes (entry 2) and also with TPPTS, only in the case of palladium (entry 1). For the para-substituted hydrosoluble phosphanes, this behaviour could be explained by the lack of interaction between the CD and the phosphane (tris(p-OMe)TPPTS), or by a too strong metal-phosphorus bond coming from a high σ-donor ligand (tris(p-Me)TPPTS). However, the fact that the PdL2 species is not formed after CD addition on the PdL3 complex not only for tris(p-OMe)TPPTS and tris(p-Me)TPPTS but also for − TPPTS probably comes from the too unstable PdL2 (14e species) in the case of TPPTS derivatives. • The CD can act as a phosphane decoordination promotor. This property was emphasised with TPPTS as ligand in the [PtL3Cl]Cl complex (entry 1), and with P(Biph)2PhTS and P(Biph)3TS ligands in the case of PdLn type complexes (entries 5 and 6). The fact that TPPTS can be removed from Pt by addition of CD, contrary to tris(p-OMe)TPPTS and tris(p-Me)TPPTS, comes not only from its ability to be included in the CD cavity but also to its lower coordination power (less basic ligand). • The CD can act as a second sphere ligand by including the metal-bound phosphane. This property was undoubtedly highlighted for both platinum and palladium complexes with the P(Biph)Ph2TS ligand whose p-sodiosulfobiphenyl group is well recognized by the CD. Because of this identical group present in their structure, making them accessible for a cyclodextrin even when bound to a metal, it is also important to say that P(Biph)2PhTS and P(Biph)3TS based organometallic species form also surely supramolecular complexes with CD. This property plays probably a role in the observed decoordination of P(Biph)2PhTS and P(Biph)3TS from palladium, the CD being able to stabilize the low-coordinated resulting organometallic species. More concretely, this property can explain the observation of PdL2 type species when P(Biph)3TS ligand was used, species not formed with TPPTS ligand. Indeed, TPPTS structure doesn’t permit complexation when bound to the metal. Molecules 2017, 22, 140 21 of 25

The three evoked behaviours of CD in the presence of a phosphane bound to a metal depend on different equilibria whose evolution is assumed to be under thermodynamic control. Indeed, in all the experiments conducted in this study, the temperature had always a reversible effect on the Molecules 2017, 22, 140 21 of 25 system. More concretely, the modification of spectra sometimes observed by heating disappeared systematically by recovering the room temperature. The threeBasically, evoked by behaviours considering of a CD simplified in the presence system consisting of a phosphane of a cyclodextrin bound to a (CD) metal and depend a phosphane on different(L ligand) equilibria coordinated whose to evolution a metal (Met), is assumed i.e., a “Met to be ← under L + CD” thermodynamic system, several control. evolutions Indeed, are in possible. all the experimentsFirstly, the phosphane conducted can in naturally this study, leave the the temperature metal by decoordination had always a reversible and lead to effect a “Met on the + L + CD” system.system More (Scheme concretely, 7a, the 1). This modification last system of spectracan then sometimes be transformed observed by inclusion by heating of the disappeared free ligand in the systematicallyCD cavity by (Scheme recovering 7a, the 2). roomStarting temperature. from the same initial system (“Met ← L + CD”), another evolution Basically,can be the by consideringcomplexation a simplifiedof ligand bound system to consisting the metal ofto areach cyclodextrin a “Met ← (CD) L@CD” and asystem phosphane in which the (L ligand)CD coordinated acts as a second to a metal sphere (Met), ligand i.e., a(Scheme “Met ← 7a,L + 3). CD” In system,this complex, several the evolutions “L@CD” are part possible. constitutes a Firstly,supramolecular the phosphane can ligand naturally which leave can therefore the metal also by decoordination leave the metal and to lead lead to to a “Met + LL@CD” + CD” system system(Scheme (Scheme 7a,7a, 1). 4). This The last fore system‐mentioned can then besystems transformed are in by equilibrium inclusion of theand free their ligand proportions in the are CD cavityconsequently (Scheme7a, driven 2). Starting by their from free the enthalpy, same initial the more system stable (“Met system← L +being CD”), the another more represented evolution one. can be the complexationSo, when the “Met of ligand ← L” bound starting to organometallic the metal to reach species a “Met stays← perfectlyL@CD” stable system in in the which presence of the CDCD, acts it as means a second that sphere the free ligand enthalpy (Scheme of the7 a,“Met 3). In ← this L + complex,CD” system the is “L@CD” very low part compared constitutes to the other a supramolecularpossible systems ligand which(Scheme can 7b). therefore Different also reasons leave the can metal produce to lead this to asituation: “Met + L@CD”basicity system of the ligand (Schememaking7a, 4). The the fore-mentioned“Met ← L” bond systems very strong, are in ligand equilibrium poorly and recognized their proportions by the CD... are consequently driven by theirIn the free same enthalpy, way, thewhen more CD stable is proved system to beingbe a decoordination the more represented promotor one. by being able to do an So,inclusion when the complex “Met ← withL” startingthe phosphane, organometallic it means species that the stays “Met perfectly + L@CD” stable system in theis relatively presence close to of CD,the it means “Met that← L the+ CD” free initial enthalpy system, of the in “Metterms ←of Lfree + CD”enthalpy system (Scheme is very 7(c)). low In compared this case, to the the “Met + other possibleL@CD” systems system can (Scheme be reached7b). Different either by reasons preliminary can produce natural this decoordination situation: basicity of the of phosphane the ligand via the making“Met the “Met + L← + L”CD” bond system very strong,(Scheme ligand 7(c)), poorly mechanism recognized with by the the successive CD... steps 1 and 2) or by Inpreliminary the same way, complexation when CD is of proved the organometallic to be a decoordination species by promotor the CD (Scheme by being 7(c), able mechanism to do an with inclusionsteps complex 3 and with4 successively). the phosphane, This itsecond means mechanism that the “Met is probably+ L@CD” favoured system iswhen relatively the CD close is able to to the “Metinclude← theL + ligand CD” initial bound system, to the inmetal, terms i.e., of when free enthalpy the free (Schemeenthalpy7 (c)).of the In Met this ← case, L@CD the is low. “Met +Therefore, L@CD” system one can can think be reached that TPPTS either decoordination by preliminary from natural [PtL decoordination3Cl]Cl species by of CD the proceed phosphane via the “1, via the2 “Met “ mechanism+ L + CD” (Met system ← L@CD (Scheme species7(c)), is mechanism too high in withfree enthalpy the successive to be easily steps 1reached and 2) in or the by case of preliminaryTPPTS) complexation and that biphenyl of the organometallic phosphanes decoordination species by the CD from (Scheme palladium7(c), mechanism species proceed with stepsby the “3, 4” 3 and 4mechanism successively). (Met This ← second L@CD mechanismis easy to form). is probably favoured when the CD is able to include the ligand boundFinally, to the the metal, “Met i.e., ← when L@CD” the species free enthalpy can be ofobtained the Met from← L@CD the initial is low. “Met Therefore, ← L + CD” one cansystem via think thatdirect TPPTS complexation decoordination (scheme from 7(d), [PtL step3Cl]Cl 3) speciesor via preliminary by CD proceed formation via the “1,of the 2 “ mechanism“L@CD” inclusion (Met ←complexL@CD speciesin solution is too (Scheme high in 7(d), free steps enthalpy 1, 2 and to ‐ be4). easily reached in the case of TPPTS) and that biphenylThe phosphanes simple rationalization decoordination of the from different palladium transformations species proceed observed by the in “3, this 4” study mechanism for platinum (Met ←andL@CD palladium is easy tocomplexes form). in the presence of RAME‐β‐CD can be refined by taking into account the Finally,fact that the several “Met ← ligandsL@CD” are species systematically can be obtained present on from the the metal. initial In particular, “Met ← L for + CD” ligands system allowing a via directcomplexation complexation by (schemeCD when 7(d), coordinated step 3) or to via the preliminary metal (biphenyl formation phosphanes, of the “L@CD” in this study), inclusion relatively complexstable in solution organometallic (Scheme7 (d),species steps 1,possessing 2 and -4). two spheres of coordination (phosphane and CD, Therespectively) simple rationalization may be obtained. of the different However, transformations in these species, observed the steric in this hindrance study for generated platinum by the and palladiumcomplexation complexes by the in theCD presenceconstitutes of RAME-a possibleβ-CD reason can be explaining refined by that taking the into included account ligand the or a fact thatneighbour several ligands ligand arecan systematically be expulsed to present reach a onmore the stable metal. system In particular, (Scheme for 8, pathway ligands allowing (a)). a complexationConversely, by CD when for ligands coordinated not accessible to the metal for (biphenyl a CD when phosphanes, bound to a in metal this study), (TPPTS, relatively in this study), stable organometallicthe only way speciesto explain possessing an observed two spheres decoordination of coordination in the (phosphane presence andof CD CD, is respectively) undoubtedly the may bepreliminary obtained. However, decoordination in these of species, the ligand the from steric the hindrance metal (Scheme generated 8, pathway by the complexation (b)). by the CD constitutes a possible reason explaining that the included ligand or a neighbour ligand can be expulsed to reach a more stable system (Scheme8, pathway (a)). Conversely, for ligands not accessible for a CD when bound to a metal (TPPTS, in this study), the only way to explain an observed decoordination in the presence of CD is undoubtedly the preliminary decoordination of the ligand from the metal (Scheme8, pathway (b)).

MoleculesMolecules2017 2017, 22, 22, 140, 140 2222 of of 25 25 Molecules 2017, 22, 140 22 of 25

SchemeSchemeScheme 7. Different7.7. DifferentDifferent possible possiblepossible mechanisms mechanismsmechanisms for the cyclodextrinfor the cyclodextrin assisted generation assistedassisted ofgenerationgeneration new organometallic ofof newnew speciesorganometallicorganometallic from a metal speciesspecies coordinated fromfrom aa metameta byll coordinatedcoordinated a ligand (Met by a← ligandL species); (Met(Met ←← Met LL species);species); = metal, MetMet L == metal, Phosphanemetal, L L = = , L@CDPhosphane,Phosphane, = ligand L@CD L@CD included = = ligand ligand in the inincludedcluded CD cavity. inin thethe CD cavity.

L@CDL@CD L@CD Met Met L@CD GrowingGrowing Met L Met L@CD L L@CD StericSteric hindrance hindrance PathwayPathway(a)(a)

LL MetL@CD MetL@CD  FINALFINAL SYSTEM SYSTEM STARTINGSTARTING SYSTEM SYSTEM   MetMet Met L@CD Met L@CD LL + L ++ L@CDL@CD (Biphenylphosphanes(Biphenylphosphanes type type ligand) ligand)

PathwayPathway(b)(b) MetL  FINAL SYSTEM MetMetL+L+ LL FINAL SYSTEM + L@CD (TPPTS(TPPTS typetype ligand) ligand)

SchemeSchemeScheme 8. 8. 8.Two Two Two possible possible possible pathways pathways pathwaysof ofof generation generationgeneration ofof low coordinated organometallicorganometallic organometallic species species species thanks thanks thanks to to to

a cyclodextrinaa cyclodextrin cyclodextrin from from from a a speciesa species species bearing bearing bearing several severalseveral ligands ligands (symbolized(symbolized by by “MetL“MetL 222”):”):”): ( (aa ()a) via )via via supramolecular supramolecular supramolecular organometallicorganometallicorganometallic species; species; species; ( b ((b)b) via) viavia preliminary preliminarypreliminary decoordinationdecoordinationdecoordination ofof aa ligand;ligand; MetMet Met == = metal,metal, metal, L L L= = =Phosphane, Phosphane, Phosphane, L@CDL@CDL@CD = = ligand= ligand ligand included included included inin in the thethe CD CDCD cavity. cavity.cavity.

Molecules 2017, 22, 140 23 of 25

3. Materials and Methods

3.1. General Remarks The 1H and 31P{1H} NMR spectra were recorded on an Avance 300 DPX instrument (Bruker, Karlsruhe, Germany) at 300.13 and 121.49 MHz, respectively. Organic compounds were purchased from Fisher Scientiﬁc (Pittsburgh, PA, USA) in their highest purity and used without further puriﬁcation. Potassium tetrachloroplatinate(II) and tetrakis(triphenylphosphane)palladium(0) were purchased from Strem Chemicals (Newburyport, MA, USA). Ultrapure water was used in all experiments (Fresenius Kabi, Bad Homburg, Germany; γ = 72.0 mN.m−1 at 25 ◦C). Pharmaceutical grade RAME-β-CD (Cavasol® W7 M) was purchased from Wacker Chemie GmbH (München, Germany) and was used as received. Randomly methylated β-cyclodextrin (RAME-β-CD) is a partially methylated cyclodextrin and its degree of substitution was equal to 1.8 (1.8 methyl groups per glucopyranose unit). TPPTS [24], tris(o-Me)TPPTS [25], tris(o-OMe)TPPTS [25], tris(p-Me)TPPTS [15] and tris(p-OMe)TPPTS [26], P(Biph)Ph2TS [16], P(Biph)2PhTS [16] and P(Biph)3TS [16] were prepared as reported in the literature. The purity of these water-soluble phosphanes was controlled by 1H, 13C{1H} and 31P{1H} NMR analysis.

3.2. 31P{1H} NMR Study on Platinum and Palladium Complexes

Platinum complexes were synthetized by dissolving K2PtCl4 (8.3 mg, 0.02 mmol) in degassed deuterated water (2 mL). Three equiv. of the corresponding ligand (0.06 mmol) were added to the solution, which was then stirred for 15 min at room temperature under nitrogen. Studies in the presence of RAME-β-CD were conducted as follows: the required amount of cyclodextrin was introduced into 500 µL of the above solution. After 15 min of stirring, the solution was transferred into a NMR tube and analysed. Palladium complexes were synthetized according to a modiﬁed literature procedure [27]. Pd(PPh3)4 (103 mg, 0.089 mmol.) was dissolved in 2 g of degassed toluene into a Schlenk tube under nitrogen. The corresponding phosphane (1.5 equiv., 0.133 mmol) was dissolved in 2 g of D2O and cannulated onto the palladium solution. The mixture was stirred for 30 min at room temperature. After decantation, the organic phase was removed and a new degassed Pd(PPh3)4 solution was added to the previous aqueous solution which underwent again a 30 min stirring period to ensure an optimal extraction of the palladium by the hydrosoluble ligand. After decantation, the aqueous 31 1 phase was recovered. The obtained PdLn (n = 2, 3 or 4) solution was then used for the P{ H} NMR study. The previous solution usually contained a small excess of free ligand. Study in the presence of RAME-β-CD was conducted as follow: to 1 mL of the above solution was introduced under nitrogen the required amount of RAME-β-CD. After 15 min of stirring, the solution was transferred via cannula into a nitrogen pressurized 5 mm NMR tube.

4. Conclusions A 31P{1H} NMR study of platinum(II) and palladium(0) complexes coordinated with two different groups of hydrosoluble monodentate phosphane ligands (including TPPTS, meta-trisulfonated triphenylphosphane derivatives bearing one methyl (or methoxy) group on the aromatic ring and trisulfonated biphenylphosphanes) has been described. The effect of randomly methylated β-cyclodextrin (RAME-β-CD) addition on these complexes has been examined. It has been shown that the interaction of the free phosphane with RAME-β-CD is a prerequisite to observe any effect of the CD on the organometallic species (case of tris(p-OMe)TPPTS: no interaction, thus no effect). However, the stereoelectronic properties of the ligand are also of great importance. On the one hand, ligands whose phosphorous atom is hindered by ortho-substituted meta-sulfophenyl groups lead, without CD, to low coordinated organometallic species, even with an excess of ligand; the lack of free volume in the coordination sphere of these species doesn’t permit the coordination of another ligand (case of tris(o-Me)TPPTS and tris(o-OMe)TPPTS, with platinum). On the other hand, Molecules 2017, 22, 140 24 of 25 a high σ-donating ligand can be difficult to be removed from the metal by CD because of the stability of its metal-phosphorous bond (case of tris(p-Me)TPPTS, with platinum as well as palladium). More generally, two interesting behaviours of CD have been highlighted: the CD can act as a second sphere ligand by including the metal-bound phosphane without denaturing the organometallic species or as a phosphane decoordination promotor. These two behaviours are under thermodynamic control. Depending on the used ligand structure, the decoordination observed in the presence of CD may proceed either via a preliminary decoordination of the phosphane followed by a complexation of the free ligand by the CD (case of TPPTS) or via the generation of organometallic species complexed by CD which then lead to expulsion of ligands to decrease their internal steric hindrance (cases of biphenylphosphanes). Such modifications of organometallic complexes by a CD, i.e., inclusion of organometallic species into the cyclodextrin cavity by one of its ligand or decoordination of a ligand from the metal, can be efficient strategies to obtain new catalysts possessing original activities and selectivities.

Supplementary Materials: The following are available online at http://www.mdpi.com/1420-3049/22/1/140/s1: Figures S1–S12. Acknowledgments: This work was supported by the Centre National de la Recherche Scientifique (CNRS). M. Ferreira is grateful to the Ministère de l’Education et de la Recherche for financial support (2005–2008). Author Contributions: M.F. performed the experiments; M.F., H.B., S.T. and E.M. analyzed the data and wrote the paper. Conflicts of Interest: The authors declare no conflict of interest.

References and Notes

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Sample Availability: Samples of the water-soluble phosphanes are available from the authors.

© 2017 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).