A donor-supported silavinylidene and silylium ylides: boroles as a flexible platform for versatile Si(ii) chemistry

Electron-deficient, anti-aromatic 2,5-disilyl boroles are shown to be a flexibly adaptive molecular platform with regards to SiMe3 mobility in their reaction with the nucleophilic donor-stabilised precursor dichloro silylene SiCl2(IDipp). Depending on the substitution pattern, selective formation of two fundamentally different products of rivalling formation pathways is achieved. Formal addition of the dichlorosilylene gives the 5,5-dichloro-5-sila-6-borabicyclo[2.1.1]hex-2-ene derivatives. Under kinetically controlled conditions, SiCl2(IDipp) induces 1,3-trimethylsilyl migration and adds exocyclically to the generated carbene fragment giving an NHC-supported silylium ylide. In some cases interconversion between these compound classes was triggered by temperature or NHC-addition. Reduction of silaborabicyclo[2.1.1]hex-2-ene derivatives under forcing conditions gave clean access to recently described nido-type cluster Si(ii) half-sandwich complexes of boroles. Reduction of a NHC-supported silylium ylide gave an unprecedented NHC-supported silavinylidene which rearranges to the nido-type cluster at elevated temperatures.

To corroborate this reasoning, we directly reacted the free borole B-Ph* with SiCl 2 (IDipp). NMR spectroscopic monitoring of the reaction mixture indeed revealed dominating (>95%) conversion to the anticipated 5,5-dichloro-5-sila-6-borabicyclo [2.1.1]hex-2-ene 1B-Ph* along with free IDipp and again a redorange colour. This distinct colour could however not be routed back to [Si 2 (IDipp) 2 ]. Upon crystallization from the crude mixture, we were able to identify this "coloured impurity" as a minor share of orange-red crystals aside to colourless specimen of 1B-Ph* (of which the structure is deposited and documented in the ESI †). X-ray diffractometric examination of these mediocrely diffracting orange-red crystals clearly revealed the unexpected connectivity pattern and molecular structure of an SiCl 2 (IDipp) adduct to a rearranged borole-scaffold which results from the migration of a SiMe 3 -group (2B-Ph*, Scheme 2). The determined molecular structure of 2B-Ph*(see ESI †) indicated a unique bonding situation. Unfortunately, further corroboration of the structure of 2B-Ph* by NMR remained impaired by low-concentrations in crude mixtures and broad, poorly dened signals sets resulting from steric congestion (vide infra).

Substitution-dependent selectivity and mechanistic proposal
The intriguing electronic bonding situation of the NHCsupported silylium ylide 2B-Ph* prompted us to investigate synthetic strategies for the selective formation of such species. We therefore probed the outcome of the reaction of SiCl 2 (IDipp) with a series of differently substituted free 2,5-disilylboroles iteratively tuning both the B-bound residue R (R = Cl, Me, Xyl [3,5-Me 2 (C 6 H 3 )], p-Xyl [2,5-Me 2 (C 6 H 3 )], Ph*) and the 3,4-bound aryls (Xyl, vs. Ph*) and thus changing electronic and steric proles of the respective free boroles. The results of this screening are tabulated in Scheme 3.
From this experimental insight a few observations can be summarized: (1) the steric prole of the borole backbone, i. e. system A or B, has no major inuence on the selectivity; (2) for small substituents at the boron-atom (Cl, Me), the NHC-Chart 1 Borole substitution patterns under investigation.
supported silylium ylide 2 are obtained selectively (entries 1, 2 and 7, 8); (3) only very bulky substituents such as Ph* result in clear favourisation of 1 (entries 5, 12) making our initially probed system a particularly unfortunate case; (4) boron-bound aryl-substituents with one ortho-methyl group (such as pXyl) partially blocking one hemisphere of the borole plane completely circumvent silyl migration and formation of the silylium ylide 2 in favor of 1 (entries 6, 14); (5) systems with a similar steric prole but non-p-plane interfering B-bound aryl group (such as m-Xyl vs. p-Xyl) are suitably balanced to give rise to both products 1 and 2 in almost equal shares at room temperature (20°C, entries 3, 9); (6) conducting these unselective reactions at low temperatures notably increases the formation of NHC supported silylium ylide 2 in the obtained reaction mixtures indicating 2 to be a kinetically favored product (entries 9-11); (7) potential p-donation interactions from Cl atoms in chloroboroles do not inuence the selectivity. Taking these observations into account we propose the following rivalling reaction pathways for the formation of 1 and 2, summarized in Scheme 4.
A more detailed account on the computational assessment of this mechanistic proposal including transition states for a sterically reduced model system (S1: R,R ′ = Me; NHC: 1,3-Me 2imidazol-2-ylidene, Scheme 4) and a graphical depiction of relative energies of proposed species in the course of the reaction is documented in the ESI. † However, as sterics are most likely to play an important role, only relative free energies (BP86/def2-TZVPP and benzene solvation model) of intermediates with experimentally probed substitution patterns are given here. The anticipated initial step is an adduct formation of the Lewis-base SiCl 2 (IDipp) with free borole S1. This would intuitively add to the Lewis-acidic boron atom to give I1. So reported an example of a silylene-donor adduct to pentaphenyl borole. 57 An alternative target for a nucleophilic attack at boroles is the C a atom which reveals a vinylogous connection to the boron-site to result in a zwitter-ionic boratabutadiene-type adduct I2. 36 For example, Braunschweig previously reported on a reversible B-/ C a -atom adduct formation of 2,6-lutidine to boroles. 58,59 Formation of both I1 (ca. −17 kcal mol −1 ) and I2 (ca. −2 kcal mol −1 ) would be exergonic. However, these putative intermediates I1 and I2 have not been experimentally observed in the course of the reaction, suggesting that subsequent processes must have low barriers. We propose the decisive forking of the pathway to occur at this stage.
Pathway I (Scheme 4) assumes an energetically uphill dissociation of the NHC. Computational NHC removal from both adducts I1 and I2 affords the identical structure I3 aer optimization. I3 can be described as an adduct of an ambiphilic dichlorosilylene to the equally ambiphilic borole. The dissociation free energy at 298 K of the NHC from I1 is high for A-Xyl (18 kcal mol −1 ) and almost prohibitively high for A/B-Me (ca. 24 kcal mol −1 ). For our model system low barriers (ca. 1 kcal mol −1 ) for the formation of the bicyclic I4 from I3 and conversion/isomerization of I4 to the bicyclic product P1 are suggested. The overall free energies of the formation of P1 are exergonic by ca. −10 kcal mol −1 .
We propose the pathway II to originate from the C a -adduct I2 from which a 1,2-SiMe 3 migration from C a to the B-atom occurs forming the silyl borate intermediate I5. Experimentally, no direct evidence for the involvement of a species of the I5-type were observed. However, the complete suppression of trimethylsilyl migration in systems with ortho-methyl substituted aryls at boron (A/B-pXyl) is considered as a strong indirect proof for a migration via the boron atom. Subsequent 1,2-SiMe 3 -migration provides silylium ylide product class P2 and again small barriers (ca. 1 kcal mol −1 ) are suggested for the reduced model system for this step.
An example for comparable sigmatropic 1,2-and 1,3-shis of hydrogen in borole-NHC adducts have been described by Braunschweig and coworkers. 35 For all substitution variants probed, despite considerable steric bulk and thus repulsive interactions involved, the NHC-supported silylium ylides P2 were the global energy minimum (ca. −30 kcal mol −1 vs. S1) of all species investigated and much more favoured than the bicyclic species P1 (−10 kcal mol −1 vs. S1). For further details, see the ESI. † A key experimental nding is that mixing the starting materials in the cold favors the formation of the NHCsupported silylium ylides, suggesting that a decisive energy barrier at an early stage aer bifurcation must be lower on the path towards P2. It seems reasonable that the NHC dissociation to form the I3 is the key barrier process.
The seemingly ideal test system, A-Xyl allowed us to develop protocols toward separation of either product from the respective mixtures. However, achieving rigorous separation to yield pure isolated products 1/2 from mixtures oen remained a tedious task affecting the yields. The NHC supported silylium ylides 2 reveal considerable dipolar moment and are less soluble in hexane. Careful extraction of crude product mixtures with hexane thus resulted in removal of the more soluble 1. Removal of remaining free IDipp can be achieved by addition of ZnCl 2 to solutions of 1 in hexane and precipitation of IDipp(ZnCl 2 ). This protocol can also be applied for further purication and isolation of the other product.
We assume that this product formation is enabled by the much less bulky NHC that can attack the SiCl 2 moiety of the bicyclic compound 1 to proceed to a I2-type C a -adduct intermediate via cleavage of a Si-C bridgehead bond. The X-ray structure of 1A-pXyl reveals the ortho-methyl group of the boron-bound pXyl-group to point toward the SiCl 2 bridge (Fig. 1). We assume that a SiMe 3 migration from this so generated I2-type intermediate is now possible, because the SiCl 2 (NHC) donor and the respective ortho-methyl group of the boron-bound aryl are located on the same half sphere of the borole plane allowing the SiMe 3 group to migrate on the opposite, unblocked side. In the reactions of free pXyl-bearing boroles with the SiCl 2 (NHC) nucleophile, the SiCl 2 (NHC) adduct would, for steric reasons, always attack from the unprotected side resulting in an antiperiplanar type arrangement of the ortho-methyl group and the SiCl 2 (NHC) fragment.

Structural and spectroscopic properties of 1 and 2
Almost all derivatives based on the 3,5-t Bu 2 (C 6 H 3 )-substituted borole system B revealed very poor crystallinity and severe disorder and thus only allowed for collection of poor or mediocre data from X-ray diffraction. Derivatives of borole A however crystallized reliably. Structural features of substitution derivatives of 1 and 2, respectively, did not differ much within the series of compounds. Exemplarily representing their substitution derivatives, the solid state molecular structures of 1A-pXyl   Table 1.
The molecular structure of 3B-pXyl is shown in Fig. 3 and details are listed in Table 1. Key difference to IDipp adducts 2 is the lack of distortion of the [SiCl 2 (NHC)]-fragment from the borole plane and a planar C1-atom suggesting that the IDipp sterics impose this pyramidalisation of C1 in derivatives of 2. It is to note that the orientation of the Si-C NHC vector towards the borole-plane differs. In 2 the NHC stands syn-periplanar to a lone pair at C1 while in 3B-pXyl a chlorine atom adopts this position.
Trends for NMR spectroscopic observables will be discussed as summary for the two compound classes 1 and 2. Individual details for each compound are listed in Table 1. The most notable NMR spectroscopic property of compound class 1 is the considerably higheld shied, narrow 11  A very notable feature of the 1 H-NMR spectra of the B-Cl/Me derivatives of compound class 2 is the time-averaged presence of a mirror-plane symmetry (e.g. only one resonance for both SiMe 3 -groups) through the borole-plane, despite the solid-state structure suggests otherwise (Fig. 2). This could be rationalised by either a putative free rotation around the C1-Si1 bond or a dynamic NHC-coordination and dissociation fast enough within the timescale of the NMR experiment. The more bulky B-Ar derivatives (Ar = Xyl, Ph*) of compound class 2 show signicantly broadened and seemingly ill-dened signal patterns particularly for the most bulky aryl group Ph*, which indicates presence of reduced symmetry due to a putative sterics-impaired rotation around the C1-Si1 bond. Heating these samples to ca. 60-75°C causes sharpening of these signals.
Compounds 2 reveal a low-eld shied 11 B-NMR signal around d( 11 B) = 60 ppm. The B-chloro derivatives reveal resonances shied to lower frequencies (ca. 53 ppm) in line with an increased occupation of the empty p-orbital at the boron atom due to p-donation from the chlorine atom or increased C]B pinteraction resulting from higher Lewis-acidity caused by the electron withdrawing chlorine atom. The observed 11 B resonances lie in between the shi observed for the respective free boroles (d( 11 B) = ca. 80 ppm, tricoordinate B-atom) and a more higheld shied boratafulvene derivative that features authentic B]C double bonds (d( 11 B) = ca. 40 ppm). This indicates the B-atom in 2 to be involved in p-bonding to C1 with a partially populated p-orbital, however not to the extent of an authentic double bond. Spectroscopic characteristics of 3 except for the perceived colour and the respective absorption in the UV-vis spectra barely deviate.
We reason that the mild pyramidalization at C1 stems in part from the localisation of a lone pair of electrons, which is only partially delocalised into the accepting p-orbital at the boron atom to form a B1 = C1 double bond. This is corroborated by the respective notably shortened B-C contact. The lone pair of  Table 1. electrons at C1 is attracted by both p-accepting moieties: the borane as well as the adjacent vinyl moiety. (Allylic) delocalisation into the vinyl moiety explains the rather short C1-C2 contact. Feasible deviation from planarity to account for steric pressure of the C-Si vector is only reasonable if no Si]C double-bond character of the ylide vs. ylene is assumed, which is in line with the coordination number at Si. A similar mildly pyramidalised carbon atom with a lone pair of electrons delocalised between two accepting boron-atoms was recently described by Erker. 73 The experimental properties advocate for a description of 2 as NHC-supported silylium ylide in which the ylide is further internally stabilised by adjacent p-accepting moieties. The cationic charge is mostly localised on the imidazolium moiety. Suitable mesomeric descriptions (I.-III.) for the Lewis-structure of 2 are summarised in Scheme 6. The short Si-C contact is thus a consequence of coulombic attraction rather than p-bonding.
A to some extent comparable electronic situation has been previously described by Berndt and coworkers for their true (i.e. unsupported) germene/stannene derivatives of cyclic diborylsubstituted methylene fragments or respective phosphine adducts. [74][75][76][77][78] A somewhat related 1,3-silyl migration was described by Erker and coworkers who noted the formation of an unusual ketene derivative from reaction of 2,5-disilylboroles with carbon monoxide. 36 However, compared to the essentially purely sdonating SiCl 2 (IDipp), CO is a potent p-acceptor readily forming an electronically trivial, authentic C]C double-bond.

Electronic structure of silylium ylides 2
To further elucidate the electronic structure of the silyliumylides 2, these structures were probed computationally using DFT. 79,80 Structure optimisation with RI-BP86-D3(BJ)/def2-TZVP model chemistry reproduced the experimentally found features very well, including the deviation from planarity at C1. [81][82][83][84][85] The results for 2A-Me are presented and discussed exemplarily for all experimentally accessed derivatives as deviations are only marginal. NBO analyses 86,87 on 2A-Me corroborated electronic structure II. (Scheme 6) with a cyclic boratabutadiene moiety as the leading Lewis-structure. However, the C]B double bond is strongly polarised towards the C-atom, both in its s-(72%) and even more in its p-contribution (82%), the latter NBO being only occupied by 1.6 electrons. Second order perturbation theory nds no signicant delocalisation toward the Si-atom (a potential silene resonance structure) but a strong (28 kcal mol −1 ) delocalisation of the C]B pelectron density into the p*-orbital of the C]C doublebond in the boratabutadiene moiety. This is in line with an allyl-type a In Å, following the numbering scheme shown in Fig. 1 and 2. b In nm (toluene solutions) -TDDFT calculations using RI-CAM-B3LYP/def2SVP/J. c In ppm. d Crystals diffracted poorly and structure could not be determined to allow extensive discussion. e The species is only present in solution in very small quantities with broad ill-dened spectra potentially due to dynamic equilibria which do not allow unambiguous identication by NMR spectroscopy. f Two molecules in the asymmetric unit. g Shoulder.
delocalisation of a C1-centered lone pair of electrons (as in resonance structure III., Scheme 6) in line with structural parameters. The respective intrinsic bonding orbital (IBO) 88 essentially represents a lone pair of electrons in a C1-centered porbital mildly polarised into the three adjacent atoms (Fig. 4). The canonical frontier molecular orbitals reveal the boratabutadiene p-system to be the HOMO with the LUMO located on the imidazolium NCN p*-orbital with a fairly small energy gap (0.86 eV for 2A- Me, Fig. 4). The intense red to purple colour observed for these NHC-supported silylium ylides 2 goes back to respective p/p* HOMO to LUMO transitions as corroborated by TD-DFT calculations that reproduce these electronic spectra in the Vis range. An alternative description of compounds 2 other than NHC-supported silylium ylides would be an internally p-accepting boryl-substituted carbene fragment that is stabilized by a nucleophilic silylene donor.
Contrary to conventional widely applied nucleophilic carbenes such as NHC, this putative intermediate carbene fragment would be electrophilic an thus readily stabilised by the nucleophilic [:SiCl 2 (IDipp)] donor. Similar descriptions were previously suggested by Berndt. 78 In situ generation of a sdonating cAAC by 1,2-H migration in a cyclic alkene induced by a borane was observed previously by Kinjo and coworkers for a 2,3-dihydro-1H-1,2-azaborole derivative to nally form an adduct of the carbene to the borane. 89 Reduction of compounds 1 and 2 Our initial investigations aimed at more efficient approaches toward the synthesis of neutral Si(II) half-sandwich compounds (such as 4B-Ph*, Scheme 1) circumventing the necessity of two equivalents of [Cp*Si] + reagents. 41 We therefore attempted the reduction of the now straightforwardly available dichlorosilylene addition derivatives 1 and 2.
While our attempts to achieve successful reductions of 1 with common reducing agents (Li(naph), 5% Na on NaCl, KC 8 ) revealed only unsatisfyingly poor selectivity, a rather clean (as monitored by NMR spectroscopy) reliable conversion was achieved by 1 equiv. of Jones' and Stasch's [ Mes Nacnac(Mg I )] 2 reagent. 90,91 Starting from 1B-Ph* we were able to selectively form the previously described Si(II) borole compound 4B-Ph*. The reverse reaction, an oxidative conversion of the halfsandwich to a bicyclic 5-sila-6-borabicyclo[2.1.1]hex-2-ene was previously observed by formal protonation of the Si-cluster 4B-Ph*. 41 Accordingly, we converted 1A-pXyl into the respective new Si(II) cluster 4A-pXyl by reduction with 1 equiv. of [ Mes Nacnac(Mg I )] 2 reagent (Scheme 7). NMR monitoring suggested clean conversions, however due to the high solubility of the resulting clusters, poor isolated yields of crystallized  Table 1.  compounds 4 (ca. 20%) were obtained. The Si(II) cluster 4A-pXyl was obtained as a colorless compound revealing a mixture of two conformers (with regards to rotation around the B-pXyl bond) in a ratio of ca. 15 : 85 as observed by NMR spectroscopy. The X-ray structure of 4A-pXyl is shown in Fig. 5 and only reveals the trans-type conformer where the apical Si-atom and the orthomethyl group occupy different half-spheres of the borole plane.
The key bond lengths of the nido-clusters [C 4 B]Si moiety are, within the error, identical to those previously described for 4B-Ph* and feature the essential bond length homologisation that is to be expected when a free borole (with localized single-and double bonds) is reduced to a borole dianion, isoelectronic to Cp − . The 11 B resonance is found at d( 11 B) = 30.6 ppm (31.5 ppm, in 4B-Ph*) and the characteristically high eld shied 29 Si resonances are found at d( 29 Si) = −354.8 ppm (minor conformer) and −355.7 ppm (major conformer). The latter also clearly reveals the loweld-shied shoulder at −355.6 ppm assigned to the 10 B-29 Si isotopologue.
Strikingly, when we attempted the reduction of derivatives of 2 we found rather unselective formations of intractable mixtures however, for 2B-Me a rather clean reduction was observed with lithium naphthalenide (Scheme 8).
Carefully allowing to warm the coloured reaction mixture from −95°C to ca. −30°C led to an intensely blood red colourisation and we were able to isolate the unprecedented NHCsupported silavinylidene 5B-Me featuring an authentic C]Si: double bond. A number of donor-stabilised heavier homologs of vinylidenes have been reported in the last decade (R 2 Ge = Ge*, 92,93 R 2 Si = Ge*, 94,95 R 2 Ge = Si*, 96 R 2 Si = Si*; 97,98 asterisks denote further donor-stabilisation of the atom). To the best of our knowledge, silavinylidene 5B-Me is the rst example for the lightest heavier congener of (donor-stabilised) vinylidenes. Filippou recently reported a NHC-and isonitrile donor-stabilised Si 0 atom which reveals the structural motif of a NHCsupported :Si=CNR fragment. 99 The molecular structure of 5B-Me is shown in Fig. 6.
Direct comparison of bond length in 5B-Me with the set of structural features of the silylium ylides reveals only minor changes with a slight elongation of the C1-B1, C1-Si1 and Si1-C NHC distances being most notable. The elongation of the Si1 distances may be a result of the larger covalent radius of the reduced Si-atom. The Si1]C1 distance found is identical to Scheme 7 Reduction of 1 to give Si(II) half-sandwich compounds.    Table 1.
what Filippou reported. 99 The C1-B1 elongation may hint at a reduced p-interaction of the formerly ylidic lone-pair with the boron atom as p-bonding to the Si1 atom can now be established. The 11 B-NMR signal of 5B-Me is found at d( 11 B) = 61.3 ppm, barely shied from 2B-Me. The structural data are in line with a Lewis-structure as depicted in Scheme 8 which is also corroborated by NBO analysis. The comparably short C1-C2 and C1-B1 can be rationalised with some delocalisation of the C1] Si1 p-density into the adjacent accepting vinyl and boryl moieties. This is corroborated by second order perturbation theory in NBO that nds donation from the C1]Si1 NBO (populated by 1.58e) into the boron p-orbital (11 kcal mol −1 ) and the C3]C4 p*-NBO (29 kcal mol −1 ). The lone-pair at Si is predicted to be high in s-orbital character (72%). The canonical HOMO-1 represents the Si-based lone-pair, while the HOMO is located on the silabutadiene moiety. The LUMO is a p-type orbital on the Si-NHC-vector (Fig. 7).
The most obvious change is observed for the 29 Si-resonance that shis drastically to higher frequencies and is found at  100 The intensely blood-red 5B-Me reveals a respective absorption band at 496 nm with a shoulder at 436 nm.
When solutions of 5B-Me were heated at ca. 70°C for several days, we observed a very clean and complete conversion of the deep red silavinylidene to the colourless Si(II) half-sandwich compound 4B-Me and free IDipp which becomes unequivocally clear from the respective characteristic heteronuclear NMR pattern with d( 29 Si) = −347.6 ppm and d( 11 B) = 31.4 ppm. The isomerisation of NHC-supported silavinylidene 5B-Me to 4B-Me and IDipp was computationally approximated to be endergonic at 298 K (4.3 kcal mol −1 ). The conversion of the silavinylidene 5 into the half-sandwich compounds including a remigration of the silyl groups further highlights the mobility of silicon atoms on the borole-platform. Further inspection revealed that the half-sandwich compound was also present as a minor side product in the crude reduction reaction mixture of 5.
Therefore, reductions of both products of the reaction of free boroles with SiCl 2 (IDipp) ultimately allow access to the Si(II)centered, nucleophilic nido-cluster 4 allowing for the development of more straightforward synthetic procedures than introducing Si(II) via [Cp*Si] + .

Conclusions
This study gives a detailed account on the reactivity of antiaromatic free boroles with SiCl 2 (IDipp) as a low-valent silicon precursor. They either react in a formal [4 + 1] cycloaddition reaction to give sila-borabicyclo[2.1.1]hex-2-ene derivatives or induce silyl migration to generate NHC-supported silylium ylides. Mechanistic proposals corroborated by computational assessment and experimental derivatizations have been presented for the diverging product formation pathways. We have been able to show, that the borole platform allows for facile and reversible migration of silyl groups. Depending on the substitution pattern and reaction conditions selective formation of either of these products was achieved. It was shown that the NHC-supported silylium ylides can be thermally converted into the bicyclic products but addition of small NHC to the bicycles can induce trimethyl silyl migration leading to new NHCsupported silylium ylides. Finally examples for both species, sila-borabicyclo[2.1.1]hex-2-ene and NHC-supported silylium ylides were successfully reduced to borole-based half-sandwich compounds of Si(II), our initial target structure. In the case of the reduction of silylium ylides, an unprecedented silavinylidene was isolated and identied as a key intermediate in the formation of the Si(II) half-sandwich cluster. This study perfectly complements to most recent ndings by the groups of Nakamoto and Scheschkewitz that found virtually identical silyl migration in anti-aromatic cyclobutadienes by addition of nucleophilic silylenes to give donor-supported silenes. 39 Reduction of such silenes gave Si(II) nido-clusters (silapyramidanes). Our work suggests that silavinylidenes could also be relevant intermediates in the formation of silapyramidanes.

Data availability
Synthetic details and analytical data, including depictions of all spectra and detailed accounts on the methods applied are documented in the ESI. † Crystallographic data is made available via the CCDC. Coordinate data of all computationally optimised species is provided as a separate xyz-le as accompanying ESI. †  acquired and analysed X-ray data. DS and CPS acquired funding and provided resources and supervision. CPS managed the project, performed computations, wrote the original dra. The manuscript was further reviewed and edited from contributions of JS, TH and PNR.

Conflicts of interest
There are no conicts to declare.