Synthesis of organometallic pentalenide complexes

While a number of reports have established the unique structures and electronic properties of mono- and dinuclear pentalenide complexes of s, p, d and f block elements, access to these intriguing compounds is restricted by synthetic challenges. Here we review various strategies for the synthesis, functionalisation and (trans)metalation of pentalenide complexes from a practical point of view, pointing out promising avenues for future research that may allow wider access to novel pentalenide complexes for application in many di ﬀ erent areas.


Introduction
Pentalene (Pn, C 8 H 6 ) has long fascinated theoretical and synthetic organic chemists for its anti-aromatic 8π system. 1 Unlike the flexible 8π cyclooctatetraene (COT, C 8 H 8 ) Pn is planar due to its bicyclic ring structure, enforcing its anti-aromaticity. As a result, it readily dimerises above −196°C to form two fulvene units isolated from each other by a cyclobutane linkage (Fig. 1). 2 Due to its inherent instability, Pn itself is of limited use for applications in synthetic chemistry. † However, similar to other 8π anti-aromatics like COT, double reduction of Pn to pentalenide (Pn 2− , C 8 H 6 2− ) generates a stable 10π aromatic system that presents itself as a useful π ligand for organometallic chemistry. 4 Its dianionic nature makes it a stronger donor for Lewis-acidic metals than neutral 10π hydrocarbons such as Stuart M. Boyt, Niko A. Jenek, Ulrich Hintermair Stuart M. Boyt graduated from the University of Warwick with an MChem in Chemical Biology but developed a taste for organometallic chemistry after a masters thesis with Adrian Chaplin looking at NHC complexes of group 9 metals. In 2015 he moved to the University of Bath to pursue his PhD in the Hintermair lab.
His project involves synthesizing new pentalenide ligands from readily available precursors and investigating their reactivity towards a range of s-, d-and p-block compounds.
Niko A. Jenek obtained his BSc in Chemistry from the University of Stuttgart in 2013, after which he moved to the University of Freiburg to finish his master's studies with a thesis on the fluorination of silicon surfaces with Ingo Krossing in 2017. After further fluorination adventures at the Fraunhofer Institute for Solar Energy Systems he joined the Hintermair group at the University of Bath for his PhD on novel pentalenide complexes for catalysis.
Ulrich Hintermair studied Chemistry and Chemical Engineering in Würzburg and Lyon with a stint at the University of St Andrews. After completing his PhD with Walter Leitner at Aachen he was a Humboldt postdoctoral fellow with Bob Crabtree at Yale University. In 2013 he started his independent academic career at the CSCT in Bath where he currently holds a Royal Society University Research Fellowship. Research in his group revolves around catalysis with metal complexes, including organometallic chemistry and real-time spectroscopy for mechanistic investigations.
naphthalene, and the two five-membered ring systems enable symmetrical charge distribution for reversible hapticity shifts of the metals bound to it (Fig. 2).
Due to this facile hapticity shift and a large degree of flexibility around the central C-C bridge, Pn 2− ligands exhibit some uniquely adaptive coordination abilities that neither COT nor naphthalene derivatives display. Pn 2− may wrap itself around, electron-deficient metal centres in η 8 coordination mode, or form doubly η 5 /η 3 coordinated homo-and heterobimetallic complexes with direct metal-metal interactions within syn-bimetallics and strong electronic coupling in antibimetallic systems. 5 Given these intriguing properties it may appear surprising that organometallic Pn 2− chemistry is far less explored and developed than that of its 6π congener cyclopentadienide (Cp − , C 5 H 5 − ), arguably the most important and most widely used organometallic ligand to date. 6 Whereas thousands of Cp − complexes including almost every metal in the periodic table are known 7 and widely used in numerous applications including sensing, electrochemistry, magnetism, material synthesis, and of course catalysis, only about 150 examples of variously substituted Pn 2− and HPn − complexes (including precursor salts) have been reported so far. This limitation is in no small part due to the practical challenges associated with accessing suitable synthons for Pn 2− chemistry. Historically, only few dedicated organometallic labs have developed the expertise and equipment required for pentale-nide chemistry, each following their own preferred synthetic method. However, a number of routes to suitable precursors have emerged in different parts of the chemical literature over the past 50 years. Here we summarise and compare various strategies for the synthesis and functionalisation of Pn 2− complexes that promise to give more facile access to a wider range of precursors, and thus hopefully allow more widespread exploration of the intriguing properties of organometallic pentalenide complexes in different areas in the future.

Synthesis of pentalenides
In the context of discussing synthetic pentalenide chemistry, it is useful to distinguish the 8π antiaromatic pentalene (Pn, C 8 H 6 ), the non-aromatic dihydropentalene (H 2 Pn, C 8 H 8 existing as several double-bond isomers 8

Deprotonation of dihydropentalenes
Mono-anionic 6π HPn − can easily be generated by deprotonation of H 2 Pn using a weak base, as demonstrated by Katz and Mrowca. 9 They showed that an isomeric mixture of H 2 Pn would react with KOH and Tl 2 SO 4 in water to furnish TlPnH as a precipitate in moderate yields (Fig. 4). In contrast to the neutral, unsubstituted H 2 Pn, HPn − salts are thermally stable and can be isolated and stored at room temperature like the related MCp salts (M = Li, Na, K). Jones et al. later showed TlOEt in pentane to be equally effective in generating TlPnH from H 2 Pn. 10 The first pK a of H 2 Pn must therefore be below 14, showing it to be slightly more acidic than HCp. 11 Presumably due to charge effects, deprotonation of the second ring in HPn − to furnish the fully 10π delocalised Pn 2− requires a stronger base. Katz et al. showed that Li 2 Pn can be prepared by double deprotonation of H 2 Pn with an excess of n butyllithium at −78°C (Fig. 5). 12 Although the second pK a value of H 2 Pn is not known with certainty, using two (or more) equivalents of bases with pK a values >25 usually leads to quantitative double deprotonation of all H 2 Pn doublebond isomers. While Katz's original preparation used heptane   to precipitate Li 2 Pn, Stezowski et al. later used dimethoxyethane (DME) to obtain single crystals of η 5 [Li(DME)] 2 Pn that showed both metals to adopt anti configuration around the planar Pn 2− in the solid state. 13 A recent computational study confirmed this to be the preferred geometry for all alkalimetal Pn 2− complexes in solution. 14 While these reactions look appealingly straightforward, and the utility of HPn − and Pn 2− salts for transmetalation reactions is well documented (see section 3), the difficulty lies in generating the H 2 Pn starting material. In the following subsections we review the most prominent methods reported.

Pyrolytic routes to dihydropentalenes
H 2 Pn can be obtained from controlled, anaerobic pyrolysis of suitable precursors such as isodicyclopentadiene in Katz's method (Fig. 6). 15 Isodicyclopentadiene was formed by treating dihydrodicyclopentadiene (obtained from partial hydrogenation of dicyclopentadiene) with acetic anhydride and selenium dioxide, followed by dehydration of the resulting alcohol by passing over alumina at 300°C. 16 Anaerobic pyrolysis of isodicyclopentadiene at 575°C lead to the formation of 1,4-H 2 Pn (through release of ethylene) in ∼30% yield, to which hydroquinoline had to be added immediately to prevent polymerisation. However, Kazennova et al. later reported that passing the pyrolysis distillate through a plug of solid potassium hydroxide provided pure H 2 Pn samples that were stable to polymerisation at −78°C. 17 They also demonstrated an improved synthesis of isodicyclopentadiene, reporting a 40% overall yield of H 2 Pn starting from HCp.
An alternative precursor was reported by Jones and Schwab, who showed that COT undergoes thermal rearrangement between 400-665°C to give H 2 Pn (Fig. 6) in addition to acetylene, benzene and styrene. 18 The selectivity to H 2 Pn was found to be highly temperature-dependent, with the optimum conversion occurring between 500-600°C. An optimised procedure was later reported by Cloke et al., in which a 87% yield was achieved thanks to precise temperature and residence time control during the continuous-flow pyrolysis. 19 In this set-up, the resulting H 2 Pn were condensed into a n butyllithium solution in DME/hexane at −78°C to be directly converted to the more stable [Li 2 (DME) x ]Pn salts that precipitate to be further purified by washing with cold hexane.
While both routes are reasonably well established (with lower yields and more synthetic steps starting from inexpensive (HCp) 2 , or fewer steps and higher yields starting from the more valuable COT), they are limited to the synthesis of the parent (unsubstituted) H 2 Pn. Substituted iso-CpH or COT have not been explored as pyrolysis precursors for substituted H 2 Pn, likely due to the difficulty and expense of synthesising the starting materials and/or unwanted thermal rearrangement pathways. A slightly more versatile pyrolytic method has been reported by Griesbeck, who showed the use of two protected vinyl fulvenes, synthesised by Diels-Alder reaction of HCp and acroleins followed by pyrrolidine-facilitated Knoevenagel condensation with an additional equivalent of HCp (Fig. 7). 20 Anaerobic pyrolysis of these compounds at 520°C furnished H 2 Pn (88% yield) or 2-Me-PnH 2 (50% yield) through thermal cyclisation accompanied by loss of HCp. This methodology is appealing as the precursors are straightforward to synthesise from inexpensive starting materials, and potentially provide a route to other substituted H 2 Pn through use of substituted acroleins in the first step and/or substituted HCp in the second step. However, the final pyrolysis may require optimisation for each protected vinyl fulvene.
Another pyrolytic route to H 2 Pn and 2-Me-PnH 2 has been reported by Stapersma et al., who showed that tetracyclo-oct-7enes may be rearranged by anaerobic heating between 250°C and 500°C. 21 These starting materials, derived from photolytic rearrangements of 7-carbomethoxynorbornadienes, 22 are comparatively difficult to prepare, and their pyrolysis reactions gave relatively low H 2 Pn yields of 7-16% due to the formation of a large number of side products.

Thermal cyclisations of vinyl fulvenes
A mild thermal synthesis of H 2 Pn has been described by Gajewski and Cavender, who found that neat 6-vinyl fulvene will undergo thermal cyclisation at 110°C (Fig. 8). 23 This procedure gave exclusively the 1,5-PnH 2 isomer due to facile 1,5hydride shifts occurring.
6-Propenylfulvene was reported to undergo a thermal reaction at 65°C, however, analysis of the products obtained was limited and no isolated yields were reported. The relatively low temperatures required to induce these rearrangements promise practical benefits over the higher temperature pyrolysis reactions discussed above. However, 6-vinyl fulvene is again not trivial to synthesise. Neuenschwander reported two preparations: the first reacting 1-hydroxymethyl-spiro-[2,4]hepta-4,6-diene with HCl, 24 the second reacting NaCp with 3-acetoxy-3-chloro-1-propene. 25 Both routes give low yields (10% and 20%, respectively) due to significant side reactions occurring. Erden et al. describe an improved protocol, starting with condensation of HCp with 3-(methylthio)propanal, followed by oxidation with NaIO 4 and sulfoxide elimination with DBU. The reported yield across the three steps was 37% including a purification after each step. 26 Kaiser and Hafner showed that 6-(2-aminovinyl)fulvenes would undergo a solution-phase thermal cyclisation and isomerisation in boiling piperidine to give 3-amino-PnH 2 in high yields (Fig. 9). 27 These species could be reduced with LiAlH 4 to give an organoaluminium species that, upon hydrolysis, underwent amine elimination at room temperature to yield H 2 Pn. The syntheses of some mono-and di-substituted H 2 Pn were also described, using 6-substituted amino fulvenes in the first step, and using alkyl/aryl lithiums in the following reduction/elimination step. However, purification procedures for these compounds were not described.
Similar to the above case of vinyl fulvenes, the amino-vinyl fulvene starting materials (derived from condensation of HCp   with di(alkyl)-aminoacroleins) are difficult to handle due to their thermal instability. 28 In theory, starting from substituted HCp could produce more stable amino-vinyl fulvenes and provide access to more highly substituted H 2 Pn. However, it is difficult to predict whether these species would follow the same thermal rearrangement pathways. While some of the thermal routes reviewed above have been shown to be quite efficient in generating H 2 Pn precursors suitable for double deprotonation to Pn 2− , the limitations of these rearrangement reactions are obvious: their precursors rely on multi-step syntheses and/or utilise expensive starting materials, they often require special apparatus, conditions need to be carefully controlled and optimised, and they are rather limited in scope.

Solution-phase rearrangement reactions
Several solution-phase syntheses of H 2 Pn that do not involve pyrolytic steps have been described in the literature. Jones et al. reported the synthesis of Li 2 Pn starting with the conversion of cycloheptatriene to 8,8-dibromobicyclo[5.1.0]octa-2,4diene using bromoform and KO t Bu (Fig. 10). 10 Reacting this species with methyllithium triggered a carbene-induced rearrangement to give H 2 Pn which was trapped with n butyllithium in DME/pentane to give [Li 2 (DME) x ]Pn.
Although the overall yields are quite low (<12%), this solutionphase method can be performed with standard laboratory equipment.
The Skattebøl rearrangement of the transient carbene generated from the geminal dihalo-cyclopropane unit allows for some variability in the substitution pattern. Cycloheptatriene can be converted to 7-alkylcycloheptatrienes through hydride abstraction, formation of the ethyl ether with EtOH and NaHCO 3 , then finally substitution of the ether with a Grignard reagent. Although 7-tert-butyl-cycloheptatriene was found not to react with CHBr 3 and KO t Bu, the methyl, ethyl and isopropyl variants did undergo this transformation (albeit with low yields of 9-15%). Treating the gem-dibromo cyclopropane unit in these species with methyllithium furnished 1-alkyl substituted H 2 Pn, which gave high yields of Li 2 [1-alkyl-Pn] upon double deprotonation with n butyllithium (53-70%). 10 Another synthesis of H 2 Pn via carbene rearrangement has been reported by Brinker and Fleischhauer. 29 trans-1,2-Bis(2.2dibromocyclopropyl)ethane, formed by twofold reaction of trans-1,3,5-hexatriene with CHBr 3 and KO t Bu, was found to rearrange to H 2 Pn when treated with methyllithium in diethyl ether. However, significant side products were formed, and attempts to separate the mixture using vapour-phase chromatography proved unsuccessful.
Ashley et al. developed a solution-phase synthesis of hexamethylpentalenide, Pn* 2− , the pentalenide analogue of pentamethylcyclopentadienide (Cp* − ). 30 The starting material for this preparation is the so-called 'Weiss-H 4 ' compound, obtained from reaction of dimethyl-1,3-acetonedicarboxylate with glyoxal. 31 Reacting the 'Weiss-H 4 ' compound with an excess of methyl iodide and K 2 CO 3 , followed by hydrolysis/decarboxylation with concentrated HCl yielded 2,4,6,8-tetramethylbicyclo[3.3.0]octane-3,7-dione (Fig. 11). The so-obtained diketone could be oxidised with bromine in MeOH, then reacted with 'methylcerium dichloride' (derived from methyllithium and cerium trichloride) at −78°C in THF. The resulting alcohol is prone to polymerisation and thus extremely sensitive to acid. The final dehydration reaction therefore required an aprotic method, and it was found that LiCl in DMSO was effective in producing 1,3,4,5,6-pentamethyl-2-methylene-1,2dihydropentalene, Me 6 -Pn or Pn*, an exocyclic isomer of hexamethylpentalene. This compound is stable due to its vinylic fulvene structure preventing cyclic conjugation of an otherwise anti-aromatic 8π system, and marks the only pentalenide synthon where the 8π Pn* is stable whereas the non-aromatic H 2 Pn* is unknown. As outlined in Fig. 3, to transform the Pn* into Pn* 2− it must be doubly reduced. Direct reaction with alkali metals lead to degradation of the starting material  through polymerisation, but reaction with a bulky trialkyl borohydride (LS-selectride) allowed for 1,4-addition of a hydride to yield LiHPn* (Fig. 12). 32 Use of the less sterically demanding L-selectride resulted in a mixture of 1,2-and 1,4addition products. LiHPn* is reportedly insoluble in most organic solvents, requiring solubilisation with pyridine for NMR analysis. The final deprotonation of LiHPn* however was performed in a refluxing hexane slurry with n butyllithium and TMEDA to afford the TMEDA adduct of Li 2 Pn*. In order to obtain single crystals suitable for XRD analysis [Li 2 (TMEDA) x ]Pn* had to be converted into a bis-stannyl derivative using Me 3 SnCl (see Fig. 39, section 3.3), and transmetallated again using methyllithium in neat TMEDA. 32 Despite requiring multiple steps involving several sensitive intermediates, the overall synthesis of [Li 2 (TMEDA) x ]Pn* is well developed and gives access to a valuable synthon for organometallic pentalenide chemistry without the use of special apparatus. Using different electrophiles (for example, ethyl iodide or isopropyl bromide) in the first step could in principle allow for incorporation of different substituents into these four positions, but this change would likely require downstream modification of the overall synthesis. So far there is no report of such variants.

Annulation reactions of cyclopentadienes
As already exemplified in some of the previous thermal rearrangement reactions, HCp provide a convenient starting material for the synthesis of pentalene derivatives. In the following section we review examples where selective 1,2 annulation reactions of HCp have been accomplished via mild solution-phase methods. An early example was provided by Hafner and Süss, who used Li[ t BuCp] to synthesise t Bu 3 Pn through its reaction with an iminium salt derived from 5-dimethylamino-2,2,6,6-tetramethyl-4-hepten-3-one and triethyloxonium tetrafluorborate (Fig. 13). 33 The resulting deep blue species had to be purified by chromatography on alumina at −75°C using pentane as the eluent. Kitschke and Lindner were later able to obtain crystals of t Bu 3 Pn for XRD analysis by recrystallisation from hexane. 34 Its stability is interesting in that although normally one would not approach the synthesis of an organometallic Pn 2− ligand via its 8π Pn version, this might be a viable approach in the case of sterically demanding substitution patterns such as 1,3,5-tris(tert-butyl) that are effective in blocking dimerization pathways. Ashley et al. have shown that a permethylated Pn system may be reduced using a bulky borohydride to give HPn − and then Pn 2− upon deprotonation (Fig. 11), 32 so similar chemistry might be possible with other bulky Pn such as Hafner's t Bu 3 Pn.
Due to their known stability and ease of deprotonation, routes that give access to H 2 Pn synthons are still preferable in most cases. Retrosynthetic analysis shows that Hafner's HCp annulation strategy to synthesise t Bu 3 Pn is well suited to give access to H 2 Pn as well: 1,4-Michael addition by a Cp − to an electrophilic conjugated carbonyl species would yield a β-cyclopentadiene-functionalised ketone/aldehyde intermediate that is set up to undergo an intramolecular Knoevenagel condensation (Fig. 14). Compatible HCp merely require two adjacent unsubstituted carbons in order to accommodate the final ring-closing step. Thus, a wide range of mono-, 1,2 and 1,3 di-, as well as 1,2,3-trisubstituted HCp may be transformed into the corresponding H 2 Pn pro-ligands by reaction with simple enones (chalcones).  The simplest unsubstituted H 2 Pn is currently not accessible by such a transformation, as HCp and acrolein are known to undergo a Diels-Alder reaction instead of the required Michael addition. 35 However, Griesbeck showed that moving to slightly higher substituted reaction partners, and using pyrrolidine to activate the chalcone towards 1,4 nucleophilic attack via its enamine, indeed furnishes substituted H 2 Pn in good yields from a single step reaction under mild conditions (Fig. 15). 36 The six different 1,3-disubstituted H 2 Pn thus prepared were air-stable compounds that did not polymerise and could be purified by high-vacuum distillation. The initially obtained 1,2 double-bond isomers were found to isomerise to the more stable 1,5 form when contacted with Brønsted acids (e.g. trifluoroacetic acid or activated alumina) or when heated above 500°C. Curiously, none of the 1,3-disubstituted H 2 Pn reported in this study have been taken forward to the Pn 2− form by double deprotonation or used as organometallic synthons in other reports so far.
Another, more highly substituted example of this strategy has been reported by Le Goff, 37 who reported the fluoride-catalysed condensation of 1,2,3-Ph 3 CpH and 1,2,3-triphenylenone to yield Ph 6 PnH 2 (Fig.  16). Oxidation with N-bromosuccinimide reportedly afforded the corresponding Ph 6 Pn as another example of an 8π pentalene stabilised by suitable substitution pattern, as inferred from its UV-vis spectrum.
Its corresponding Ph 6 Pn 2− would make an interesting organometallic ligand, however, this two-page single-author communication does not contain any synthetic or analytical details, and the synthesis has never been replicated in later literature.

Annulation reactions of fulvenes
In cases where the required chalcone is either difficult to access or does not display the desired reactivity, a step-wise approach to H 2 Pn synthesis via HCp annulation is also possible. Condensation of a HCp with an aldehyde yields a 6-substituted fulvene that may be attacked by an enolate to ring-close via an intramolecular Knoevenagel condensation (Fig. 17). Although apparently introducing an additional reaction step, it eliminates the need for synthesising the enone in the first place. Formation of the fulvene intermediate from HCp and aldehyde follows a straightforward condensation reaction using pyrrolidine in MeOH as described by Stone and Little (Fig. 18). 38   6-Substituted fulvenes are stable enough to be isolated, however, with their exocyclic double bond being polarised to enable nucleophilic attack by a range of nucleophiles (Fig. 18). 28 Coskun et al. have demonstrated the utility of this reactivity for H 2 Pn synthesis (Fig. 19). 39 Reaction of HCp with a range of different aldehydes afforded 6-substituted fulvenes that cleanly condensed with acetone (used as the solvent for this transformation) at room temperature in the presence of pyrrolidine to give variously substituted 1,3-RMe-PnH 2 in good yields. The air-stable products were obtained after evaporation of solvent and side products (mainly from cross-condensation of acetone) followed by flash chromatography on silica, which was reported not to induce any double bond isomerisation.
Again, none of the H 2 Pn synthesised have been deprotonated to the corresponding Pn 2− in this or other studies. Coskun et al. only describe the reactivity of 6-methyl fulvene, but it could be supposed that fulvenes derived from substituted HCp and various aldehydes could be reacted in an analogous manner to give a variety of more highly substituted H 2 Pn as outlined in Fig. 16. However, like the concerted double-condensation reaction using chalcones described above, the parent (unsubstituted) H 2 Pn is not likely to be accessible via this step-wise condensation method either due to the instability of its hypothetical reaction partners (unsubstituted fulvene and acetaldehyde).
In another example, Bailey et al. 44 described the PdCl 2 catalysed cyclotetramerisation of phenylacetylene to Ph 4 PnH 2 (Fig. 21). However, of the two isomeric products obtained from this reaction only one would be suitable for deprotonation into a Ph 4 Pn 2− , and the report does not include methods of preparative work up and isolation.
Although interesting examples of an alternative, potentially elegant synthetic approach of accessing H 2 Pn from simple alkyne starting materials, the generality and versatility of these methods remain to be explored more systematically.

Functionalisation of pentalenides
Although most solution-phase syntheses of H 2 Pn are easier for more highly substituted starting materials, the opposite is true for pyrolytic pathways. However, post-synthetic functionalisation of the parent (unsubstituted) H 2 Pn obtained from e.g. FVP is also possible to some degree. Cloke et al. for instance demonstrated the functionalisation of Li 2 Pn with of trialkylsilyl-groups (Fig. 22), which in addition to modifying their electronic and steric parameters imparts the complexes with enhanced solubility in hydrocarbon solvents. 19 [Li(DME)] 2 Pn was shown to react regio-selectively with two equivalents of TMS-Cl in THF to give 1,4-TMS 2 PnH 2 as a mixture of syn and anti isomers. These could be doubly deprotonated again with n butyllithium in DME/pentane to give the corresponding [Li(DME)] 2 [1,4-TMS 2 Pn] for subsequent transmetalation reactions. When introduction of additional substituents was attempted at this stage, by further reaction of 1,4-TMS 2 Pn 2− with another two equivalents of TMS-Cl, 1,1,4,4-TMS 4 PnH 2 was obtained exclusively. Due to the two bis-silylated sp 3 carbons in the 1 and 4 positions this compound cannot be converted into a Pn 2− by way of deprotonation any more, limiting how much functionality may be introduced through this strategy. [Li(DME)] 2 Pn failed to react analogously with tris( i propyl)silyl chloride, but did react with the more activated tris( i propyl)silyl triflate to give the corresponding 1,4-TIPS 2 PnH 2 , forming the anti isomer only, presumably due to steric reasons in this case. Reacting this compound with KNH 2 in Et 2 O gave high yields of K 2 [1,4-TIPS 2 Pn], a useful ligand for use in f-block chemistry where lithium salts tend to form 'ate' complexes (see section 3.3). 19 The regioselectivity of the reaction of Pn 2− with hard electrophiles is a consequence of its charge distribution. In  addition to the fully delocalised (aromatic) η 8 form and the partially delocalised (allylic) η 3 form that govern reactivity with soft Lewis acids, its ground state η 1 resonance structure conjugates both charges to the 1 and 4 positions (Fig. 23). Thus, post-synthetic functionalisation of Pn 2− is often limited to these two positions.

Synthesis of pentalenide complexes of p-, d-and f-block metals
As mentioned in section 2.1 ( Fig. 4 and 5), deprotonative metalation of H 2 Pn with suitably strong bases gives straightforward access to stable HPn − and Pn 2− salts that can be used for transmetalation on to p-, d-, and f-block metals in the desired oxidation state. Before we review selected cases of these in section 3.3, there are also some examples of direct metalation reactions of neutral precursors via redox reactions (as in related HCp chemistry) that deserve mentioning. At present these appear less generally applicable than transmetalation from HPn − and Pn 2− salts, but serve to illustrate the rich coordination chemistry of pentalenide ligands.

Pentalenide and hydropentalenide complexes through direct metalation of neutral precursors
An early example of a direct redox metalation of Pn with a transition metal has been provided Hafner and Weidemüller, 45 who reported that the reaction of Pn 2 with an iron(0) precursor produced a small amount of (CO) 5 Fe 2 Pn (Fig. 24). According to the contemporary ionic electron counting model, and in line with the thermodynamic driving force of forming a 10π aromatic, this reaction implies a double reduction of Pn to Pn 2− accompanied by cleavage of the dimer and oxidation of two Fe 0 centres to Fe I . Heating Pn 2 to 50°C in methylcyclohexane in the presence of Fe 2 (CO) 9 resulted in the formation of a yellow crystalline solid, supposed to be the syndiiron pentalenide complex shown based on its NMR spectro-scopic and mass spectrometric signatures. However, no XRD analysis is available to confirm the geometry, and work up details were not provided in the original paper. A mixture of isomers of [1,3-Me 2 Pn] 2 was reacted in a similar fashion to give an unidentified green diiron complex in 21% reported yield. 45 In related examples of directly metalating H 2 Pn precursors, Hunt and Russel 46 reported that reacting 3-Me 2 N-PnH 2 or 3-Ph-PnH 2 with Fe(CO) 5 would produce analogous syn bimetallic (CO) 5 Fe 2 Pn complexes in similar yields (Fig. 25). However, none of the geometries have been confirmed by XRD either.
Similar to direct metalation reactions of HCp with zerovalent metal precursors to give M(I)Cp complexes, this conversion of a H 2 Pn into a bimetallic Pn 2− complex implies a double deprotonation and proton reduction to H 2 to give two Fe I centres in the resulting complex.
Another redox metalation of a Pn has been reported by Ashley et al. 47 Refluxing Pn* (Fig. 11) with an excess of Fe 2 (CO) 9 in toluene (added in portions) furnished a brown solid upon filtration and washing. Recrystallisation from toluene/hexane produced the η 5 (CO) 5 Fe 2 Pn* complex shown in Fig. 26 in good yields. In this case the syn geometry of the two metal centres has been established by XRD analysis. The same procedure could be applied to synthesise a related dicobalt complex using a stoichiometric amount of Co 2 (CO) 8 (Fig. 26). Notably, both compounds could be synthesised on a multigram scale.
Both reactions involve a formal double reduction of the Pn* scaffold by the metal(0) precursors, accompanied by a twobond hydrogen shift to the exocyclic methylene group. The similar reactivity but increased stability and enhanced crystallinity of these Pn* 2− compounds compared to the parent Pn 2− complexes are promising and provide motivation for further exploration of other substitution patterns in organometallic pentalenide chemistry.
Redox metallations of COT accompanied by skeletal rearrangement to Pn 2− are also known for some d-block metal   complexes. Brookes et al. 48 reported the reaction of cis-[Ru (CO) 4 (GeMe 3 ) 2 ] with COT in refluxing heptane or octane (Fig. 27). Of the several compounds produced from this reaction, a small amount of the pale yellow syn bimetallic Ru 2 Pn complex shown in Fig. 27 could be isolated and analysed by XRD.
Similarly, Howard et al. 49 reported that COT would react with Ru 3 (CO) 10 in refluxing heptane to give a trinuclear RuPn complex, albeit in low yields and in a mixture with various other RuCOT complexes. Silyl-substituted COT have been reported to react in an analogous manner, giving the correspondingly substituted trinuclear RuPn complexes. 50 All of these reactions were very low yielding and no work up procedures are available, so the synthetic utility of these transformations appears limited.
Akin to the alkali metal induced and palladium catalysed alkyne oligomerisation reactions that produce substituted H 2 Pn (section 2.7), the direct formation of HPn − complexes from cyclotetramerization of acetylenes has also been reported. For example, Coffield et al. 51 showed that heating Mn 2 (CO) 10 in THF under a pressure of acetylene resulted in the formation of η 5 (CO) 3 MnPnH as a viscous yellow oil that was purified by distillation (Fig. 28). The same transformation could also be accomplished using MeMn(CO) 5 but with lower yields of 27%. Further deprotonation of the bound HPn − was not attempted.

Hydropentalenide complexes through transmetalation of hydropentalenides
As shown in Fig. 3 and section 2.4, and illustrated in some of the examples in section 3.1, the monoanionic, 6π aromatic HPn − synthon may be obtained from either hydride addition to a stable Pn or mono-deprotonation of H 2 Pn. Katz and Rosenberger provided an early demonstration of its utility as a transmetalation agent: in situ generation from H 2 Pn with 1.1 equivalents of n butyllithium in THF/hexane followed by addition of iron(II) precursors yielded the ferrocene analogue η 5 Fe[PnH] 2 as a mixture of two isomers (Fig. 30). 53 The stable compound was obtained in 54% yield after aqueous work up followed by sublimation and recrystallisation from hexane.
TlCp is known to be a useful transmetalation agent in instances where alkali metal Cp − salts are too reducing. 54 In the same manner, TlPnH (Fig. 4) has been shown to act as an efficient, mild transmetalating agent with d-block metal precursors: reaction with FeCl 2 in THF was shown to give the ferrocene derivatives shown in Fig. 30 in 47% isolated yield. 9 Similalry, reaction of TlPnH with [Rh(COD)Cl] 2 in THF smoothly yielded η 5 (COD)Rh[PnH] (Fig. 31). 9 The TlCl byproduct was easily removed by filtration, and sublimation of the product gave the pure Rh I complex in high yield. The same study also demonstrated the successful reaction of TlPnH with Me 3 PtI, but the Me 3 Pt[PnH] complex produced required gas-phase chromatography in order to furnish pure product.
Reaction of TlPnH with a suspension of [Re(CO) 3 (THF)Br] 2 in THF in the absence of light gave η 5 (CO) 3 Re[PnH] as a colourless solid after purification by chromatography on silica (Fig. 31). 10 Recrystallisation from Et 2 O yielded crystals suitable for XRD analysis. The analogous manganese complex could also be prepared through the reaction of [Mn(CO) 3 ( py) 2 Br] with TlPnH in THF to give the same product of the cyclotetramerisation of acetylene with Mn 2 (CO) 10 (Fig. 28). 5a Reacting a mixture of Tl[MePnH] isomers with [Re(CO) 3 (THF)Br] 2 in THF yielded the corresponding η 5 (CO) 3 Re[MePnH] complexes as a mixture of double bond isomers. 10 Although good combined yields were obtained after purification on silica, the isomers (distinguishable by NMR) could not be separated by chromatography or fractional crystallisation.
Direct metalation reactions of H 2 Pn with other heavy p-block metal bases has also been achieved. Ustynyuk et al. reported the synthesis of mono-and bis-Me 3 Sn derivatives of H 2 Pn using tin amides. 55 The reaction of H 2 Pn with one equivalent of Me 3 Sn(NEt 2 ) in boiling hexane produced, after distillation, a mixture of 1-and 2-η 1 -(Me 3 Sn)PnH (Fig. 32). Higher yields were obtained by stirring the reagents in heptane at room temperature for 48 hours. According to Fig. 23, the 1-isomer would be the primary reaction product from formal addition of a Me 3 Sn + moiety to the HPn − intermediate, and NMR analysis indeed showed rapid suprafacial 1-2-3 shifts of the TMT group within (Me 3 Sn)PnH (as also observed in related η 1 -TMT Cp and Ind complexes 56 ) to be responsible for formation of the 2-isomer.
The same reaction with two equivalents of Me 3 Sn(NEt 2 ) produced 1,4-(Me 3 Sn) 2 Pn in high yield without purification. A 6 : 1 mixture of anti-and syn-isomers was obtained which did not interconvert; although VT 13 C NMR analysis showed suprafacial Me 3 Sn shifts to be possible within each (Me 3 Sn) 2 Pn isomer there was no evidence for superfacial migration or intermolecular exchange. A pure sample of the anti-isomer could be obtained after separation by fractional distillation  Similar to the η 5 thallium reagents, η 1 stannylated Pn act as mild transmetalation agents in cases where alkali metal Pn 2− salts are too reducing (see below). This reactivity is not seen with the structurally related but non-fluxional η 1 silylated Pn derivatives discussed in section 2.8 due to the strength of the covalent Si-C bond, preventing the trisalkylsily substituent from acting as a leaving group.
Turner et al. demonstrated the use of mono-stannylated HPn* − as a ligand transfer agent for synthesising hydropentalenide complexes of group 4 metals (Fig. 33). 57 The reaction of LiHPn* with SnMe 3 Cl in pentane gave η 1 (Me 3 Sn)HPn* as a 1 : 1 mixture of syn and anti isomers in near quantitative yields after isolation by filtration.
Reacting (Me 3 Sn)HPn* with TiCl 4 (THF) 2 in refluxing benzene gave a single isomer of η 5 TiCl 3 [HPn*] in high yields, and single crystals for XRD analysis could be grown from diethyl ether. Chlorine-bridged, mono-nuclear zirconium and hafnium HPn* dimer complexes could also be prepared from (Me 3 Sn)HPn*. 57 Although deprotonation of the bound HPn* ligand in the Ti complex was not attempted, the reverse reaction (mono-protonation of a titanium Pn* 2− complex) was later reported by the same group (see Fig. 40).

Pentalenide complexes through transmetalation of pentalenides
Due to their stability and ease of preparation, alkali metal Pn 2− salts are the most prevalent reagents for synthesising organometallic pentalenide complexes. Again similar to MCp chemistry, Jonas et al. reported that [Li 2 (DME) x ]Pn would react cleanly with Cp 2 VCl by substitution of one Cp − ligand and chloride. 58 The resulting η 5 CpVη 8 Pn complex (Fig. 34) is air sensitive but could be sublimed under vacuum to give pure product in high yields. η 5 Cp*Vη 8 Pn and η 5 IndVη 8 Pn could be prepared in the same manner, and recrystallisation from hexane at low temperatures gave samples suitable for XRD analysis.
The reaction of CpTiCl 2 with [Li 2 (DME) x ]Pn yielded η 5 CpTiη 8 Pn in high yield, and the analogous reaction of Cp 2 ZrCl 2 gave η 5 CpClZrη 8 Pn (Fig. 34). 59 However, details of solvents for these transformations is missing from these reports.
Jones et al. managed to access several new bimetallic group 7 carbonyl Pn 2− complexes by way of transmetalation. 60 The reaction of [Li 2 (DME) x ]Pn with 2 equivalents of [Mn  (CO) 3 ( py) 2 Br] in THF gave exclusively the anti-isomer of η 5 [(CO) 3 Mn] 2 Pn (Fig. 35), which after extraction and filtration in air was purified by chromatography on silica. When the analogous reaction was performed with one equivalent of [Re(CO) 3 (THF)Br] 2 , a mixture of syn-and anti η 5 [(CO) 3 Re] 2 Pn was obtained, with the ratio being dependent on the reaction temperature. The two isomers could be separated through fractional crystallisation. Katz et al. showed that dinuclear Pn 2− sandwich complexes of cobalt and nickel could be synthesised by reacting their respective dihalide salts with [Li 2 (DME) x ]Pn in THF (Fig. 35). 61 Both compounds were obtained in low yields after purification by sublimation. The analogous reaction with FeCl 2 however did not produce the analogous dinuclear sandwich complex ("double ferrocene"), 61b but a mononuclear sandwich complex with two bridging HPn − ligands instead. 62 Binding et al. were later able to synthesise the dinuclear sandwich complex [FePn*] 2 by reacting [Li 2 (TMEDA) x ]Pn* with Fe(acac) 2 in THF at room temperature, 63 providing yet another example of the utility of more highly substituted pentalenide scaffolds.
Manriquez et al. showed that Cp*Fe(acac), generated in situ from LiCp* and Fe(acac) 2 in THF, would react smoothly with [Li 2 (DME) x ]Pn to produce anti η 5 [Cp*Fe]η 8 Pn (Fig. 35). 64 The complex was obtained in high yields after recrystallization from toluene; analogous cobalt, nickel and ruthenium complexes could be prepared in the same manner.
Exploring Pn 2− complexes of f-block metals, Cloke at al successfully synthesised thorium and uranium complexes of 1,4-(TIPS) 2 Pn 2− by way of transmetallation. 65 The reaction of ThCl 4 and K 2 [1,4-(TIPS) 2 Pn] suspended in THF yielded a bright orange solid containing a mixture of staggered and eclipsed isomers of η 8 [1,4-(TIPS) 2 Pn] 2 Th (Fig. 36). The product could be purified by sublimation, and crystals for XRD analysis were grown from pentane. The same reaction with UCl 4 produced a dark green product as the analogous isomeric mixture of η 8 [1,4-(TIPS) 2 Pn] 2 U again in high yields.     67 In another example of a substituted Pn 2− transmetallation reaction, Cooper et al. described the reactivity of Pn* 2− with group 4 metal halides. 68 ZrCl 4 and HfCl 4 mixed with [Li 2 (TMEDA) x ]Pn* in benzene gave, after filtration and recrystallization, halide-bridged dinuclear η 8 complexes of zirconium and hafnium as LiCl adducts (Fig. 37). Attempts to remove coordinated THF via high vacuum lead to decomposition.
When the analogous reaction was performed with titanium(IV) precursors, no titanium complex could be obtained but ligand degradation was observed instead. Reaction of [Li 2 (TMEDA) x ]Pn* with TiCl 3 and subsequent oxidation with PbCl 2 did give a dinuclear Ti IV complex, however, only in 8% yield.
In order to access Ti IV 2 Pn* complexes, less reducing transmetalation agents were required. [Li 2 (TMEDA) x ]Pn* was thus reacted with two equivalents of Me 3 SnCl to give η 1 (Me 3 Sn) 2 Pn* derivatives (Fig. 38), analogous to those reported for the parent H 2 Pn (section 3.2, Fig. 32), in an extension to the η 1 (Me 3 Sn)HPn* shown in Fig. 33. 68 Interestingly, the use of a non-polar solvent such as benzene lead to formation of the syn product, whereas the use of THF exclusively gave the anti-isomer. Both could be isolated in very high yields after filtration and recrystallisation from toluene or pentane. It was proposed that the second lithiation step in the synthesis of [Li 2 (TMEDA) x ]Pn* initially precipitated the syn dilithio complex as the kinetic product, which when reacted further in a benzene slurry produced syn TMT derivatives, whereas the use THF allowed interconversion to the thermodynamic anti dilithio configuration during the dissolution, producing anti TMT derivatives. This represents an interesting opportunity to steer the face selectivity of M 2 Pn reagents in transmetalation reactions in general, but remains to be explored for other pentalenide reagents than [Li 2 (TMEDA) x ]Pn*.
In terms of transmetalation ability, reaction of syn η 1 (Me 3 Sn) 2 Pn* with TiCl 4 in toluene indeed smoothly produced η 8 [TiCl 2 Pn*] 2 in high yields after recrystallization (Fig. 39). 68 The  analogous reactions with ZrCl 4 and HfCl 4 failed to produce the desired complexes, suggesting the presence of LiCl is required to stabilise the Zr/Hf Pn* complexes shown in Fig. 37.
In a controlled hydrolysis experiment, Clement et al. showed that reacting [TiCl 2 Pn*] 2 with one equivalent of 2,6xylenol ( pK a ∼10) in toluene resulted in clean mono-protonation of the bound Pn* ligand and cleavage of the dimer by coordination of the alkoxide (Fig. 40), giving a single isomer of the mono-nuclear hydropentalenide complex Ti(OR)Cl 2 [HPn*] in 68% yield. 69 This transformation represents an interesting example of accessing a HPn − complex via protonation of a Pn 2− complex, but on its own does not allow commenting on the reversibility of the reaction.
In a further demonstration of the usefulness of (Me 3 Sn) 2 Pn* as mild transmetalation agent, Chadwick et al. successfully synthesised dinuclear Pn* 2− complexes of easily reducible rhodium(I) and iridium(I) precursors. 70 Reactions of [M(CO) 2 Cl] 2 (M = Rh, Ir) with syn η 1 (Me 3 Sn) 2 Pn* (generated in situ) selectively produced the corresponding syn η 5 [(CO) 2 M] 2 Pn* complexes (Fig. 41). Both the rhodium and   iridium complexes have been analysed by XRD, with suitable crystal samples grown from hexane at low temperatures. Whether the observed syn selectivity of the transmetalation was a result of using syn (Me 3 Sn) 2 Pn* or due to the dimeric nature of the metal precursor is not clear, however.

Conclusion
From the selected examples reviewed it is clear that a number of different synthetic routes to pentalenide complexes exist. Unsubstituted H 2 Pn is mostly synthesised by controlled anaerobic pyrolysis of various starting materials, whereas several relatively straightforward solution-phase methods for substituted H 2 Pn exist. It is interesting that not all of these, mostly developed in the realm of organic synthesis, have been put to use in organometallic pentalenide chemistry yet. Symmetrically substituted H 2 Pn appear most desirable to reduce the number of possible isomers, which may be hard to separate or transform selectively from a mixture. Given that their reactivity is mostly governed by their core π electronic system, it is not unreasonable to expect that most new substituted H 2 Pn would be amenable to the same deprotonation, functionalisation and transmetalation methods developed for the two archetypical synthons, unsubstituted H 2 Pn and permethylated Pn*. This would allow a wider range of novel Pn 2− complexes to be synthesised for a more systematic study of Pn 2− ligand effects on their electronic structure and reactivity. Thallium salts and Me 3 Sn derivatives have proven to be mild and effective transmetalation agents in addition to the alkali metal salts, but the development of less toxic alternatives would be desirable for practical reasons. The prospect of controlling the face selectivity of Pn 2− double metalation via either kinetically controlled deprotonation or installation of syn-configured leaving groups represents an exciting opportunity for selectively synthesising syn-dinuclear half-sandwich complexes with interesting properties for binding and activating various ligands across the two metal sites. The stability of mono-deprotonated HPn − and its metal complexes may even allow consecutive installation of different metals to synthesise heterodinuclear compounds in a controlled manner. In general, the flexible and adaptive nature of Pn 2− to bind a range of different metals together with the ability of bringing two metals together in close proximity with electronic coupling hold great potential for future applications in sensing, electrochemistry, and homogeneous catalysis.

Conflicts of interest
The authors declare no conflict of interests.