Ferrocenylmethylation reactions with a phosphinoferrocene betaine †

A phosphinoferrocene betaine, N -{[1 ’ -(diphenylphosphino)ferrocenyl]methyl}- N , N -dimethyl-3-sulfo-1- propanaminium, inner salt, Ph 2 PfcCH 2 NMe 2 (CH 2 ) 3 SO 3 ( 2 ; fc = ferrocene-1,1 ’ -diyl), was prepared by alkyl-ation of Ph 2 PfcCH 2 NMe 2 ( 1 ) with 1,3-propanesultone, and was studied as a ferrocenylmethylation agent. The treatment of 2 with NaOH in hot water – dimethyl sulfoxide produced phosphinoalcohol Ph 2 PfcCH 2 OH ( 3 ) in a 64% yield, whereas a similar reaction with MeONa in dimethylsulfoxide – methanol furnished the corresponding ether, Ph 2 PfcCH 2 OMe ( 4 ), in a 47% yield. In subsequent experiments, betaine 2 was employed in the synthesis of phosphinoferrocene sulfones, Ph 2 PfcCH 2 SO 2 R, where R = Me ( 6a ), Ph ( 6b ), and 4-tolyl ( 6c ). Compounds 6a – c and some by-products of the ferrocenylmethylation reactions, namely alcohol 3 , 1 ’ -(diphenylphosphino)-1-methylferrocene ( 5 ), and 1-{[diphenyl(2,4-cyclo-pentadien-1-ylidene)phosphoranyl]methyl}-1 ’ -(diphenylphosphino)ferrocene ( 7 ) structurally characterised. Reactions of 6a as the representative with ZnX 2 /NaX (X = Br and I) a ﬀ orded unique coordination polymers [ZnNaX 3 ( 6a )(CH 3 OH)] n featuring tetrahedral Zn( II ) and octahedral Na( I ) centres bridged by halide ions, solvating methanol and the sulfone ligands. The reaction of 6a with ZnBr 2 /KBr produced an analogous product, [ZnKBr 3 ( 6a )(CH 3 OH)] n , while that with ZnBr 2 /LiBr furnished a di ﬀ erent, pseudodimeric complex [Zn 2 Li 2 Br 6 ( 6a ) 2 (CH 3 OH) 4 (H 2 O)]·CH 3 OH, featuring tetrahedrally coordinated Zn( II ) and Li( I ) centres bridged by 6a . Reactions of 6a with ZnBr 2 /MBr (M = Rb, Cs) and NaCl/ZnCl 2 did not yield similar products because of an easy precipitation (low solubility) of the respective alkali metal halides.


Introduction
Shortly after the discovery of ferrocene 1 and the elucidation of its real structure 2 in the early 1950s, ferrocenylmethylation was recognised as a powerful method for the preparation of various ferrocene derivatives. 3This reaction typically utilises stable starting materials capable of serving as precursors of the stabilised ferrocenylmethylium cation, 4 which is allowed to react with nucleophiles (Nu) to afford derivatives of the type FcCH 2 Nu (Fc = ferrocenyl).The most often employed ferrocenylmethylation reagents are undoubtedly FcCH 2 NMe 2 and [FcCH 2 NMe 3 ]I, with which the reaction was developed, though other compounds, e.g., [FcCH 2 PPh 3 ]I or FcCH 2 OH (the latter in combination with an acid), have also found practical applications. 3 the synthesis of phosphinoferrocene donors, 5 ferrocenylmethylation reactions have been applied only rarely because of competitive reactions affecting the phosphine moieties (alkylation). 6Therefore, the [1′-(diphenylphosphino)ferrocene-1-yl]methyl derivatives have typically been synthesised either indirectly (e.g., via late-stage lithiation/phosphinylation 7 ) or from P-protected building blocks, such as Ph 2 P(S)fcCH 2 OH 8 or the borane adduct Ph 2 PfcCH 2 OH•BH 3 . 9n view of our recent work focusing on the preparation and coordination properties of 1′-(diphenylphosphino)-1-[(dimethylamino)methyl]ferrocene (1) 10,11 and other 1′-functionalised phosphinoferrocene derivatives possessing an inserted methylene group, 9,12 we wanted to extend the hitherto unexplored synthetic chemistry of the former compound, which led us to attempt the preparation of ammonium salts derived from 1 and study their prospective synthetic applications.In this contribution, we describe the selective synthesis and structural characterisation of the phosphinoferrocene betaine Ph 2 PfcCH 2 N + Me 2 (CH 2 ) 3 SO 3 − (2; fc = ferrocene-1,1′-diyl) and its utilisation in the preparation of the known and some new 1′-functionalised phosphinoferrocene donors such as 1′-[(diphenylphosphino)ferrocenyl]methyl sulfones Ph 2 PfcCH 2 SO 2 R. Furthermore, we report on the reactions of the representative ligand, Ph 2 PfcCH 2 SO 2 Me, with zinc(II) and alkali metal halides, leading to structurally unique mixed-metal coordination polymers.
The 1 H and 13 C NMR spectra of 2 combine the signals due to the phosphinoferrocenyl moiety with those of the NMe 2 group and the propane-1,3-diyl bridge.The 31 P NMR resonance is observed at δ P −18.1 ppm, suggesting that the phosphine moiety remained intact.In its IR spectrum, betaine 2 shows strong signals attributable to the vibrations of the terminal sulfonate moiety (ν s 1037 cm −1 and ν as 1189 cm −1 ), whereas the electrospray ionisation (ESI) mass spectrum reveals signals of the pseudomolecular ions [M + X] + , where M = H, Na, and K, and of the characteristic fragment 15 ions due to the substituted ferrocenylmethylium cation [Ph 2 PfcCH 2 ] + at m/z 383.
The possible synthetic applications of betaine 2 were first examined by its conversion into the known alcohol 3 12a and the corresponding methyl ether 4 9 via reactions with the respective nucleophiles (Scheme 1).These ferrocenylmethylation reactions were carried out similarly to the literature 13,16 but carefully optimised.For solubility reasons, dimethyl sulfoxide was chosen as the solvent, and the reactions were performed at temperatures above 100 °C since lower reaction temperatures markedly reduced the yield of the substitution product (N.B. unreacted 2 could be recovered from the reaction mixture in such cases).The reaction time was maintained at minimum (typically 1 h) in order to prevent decomposition and oxidation of the phosphine moiety.
For the preparation of alcohol 3, the best reaction conditions were found to consist of refluxing the solution of betaine 2 in a mixture of DMSO and 2 M aqueous NaOH (1 : 1; the concentration of NaOH in the resulting solution was 1 M) for 1 h.Product 3 was isolated by extraction and purified by column chromatography, resulting in a 64% yield (at the 2 mmol scale).A small amount of a less polar side-product was also isolated, being identified as 1′-(diphenylphosphino)-1-methyl-ferrocene, Ph 2 PfcMe (5; typically ca.5%).This rather unexpected product probably results via "quenching" of the intermediate cation Ph 2 PfcCH 2 + upon attack of other C-H bonds (acid-base equilibria) rather than by interaction with any proton source in the reaction system.The etherification reaction was similarly performed in a mixture of dimethyl sulfoxide and methanolic MeONa (1 M MeONa in the reaction system) at lower temperatures (but still under reflux conditions) for 2 h, affording phosphinoether 4 in a 47% isolated yield.

The crystal structures of 2•CH 3 OH and 5
The solvate 2•CH 3 OH, isolated after crystallisation by liquidphase diffusion of tetrahydrofuran and diethyl ether into a solution of the betaine in methanol, crystallises with the symmetry of the triclinic space group P1 ˉ.Its structure is presented in Fig. 1, and the relevant geometric data are summarised in Table 1.
The carbons surrounding the positively charged nitrogen atom in 2 constitute a regular tetrahedral environment, with the C-N distances and associated bond angles (C-N-C) in the range of 1.497(2)-1.525(2)Å and 106.9(1)-111.0(1)°,respectively.The environment of the sulfur atom is somewhat distorted, presumably because of the different sizes of the bonded atoms and, also, a repulsion of the oxygen atoms (S-C > SvO and OvSvO > C-SvO; see parameters in Table 1).
The individual molecules constituting the crystals of 2•CH 3 OH assemble into dimers of inversion-related molecules through charge-supported hydrogen bonds between two oxygen atoms of the negatively charged sulfonate group and the CH 3 hydrogens polarised by the positively charged nitrogen (Fig. 2).The solvating methanol forms an O-H⋯O hydrogen bond with the remaining sulfonate oxygen.Additional C-H⋯O interactions further interconnect the (2) 2 (CH 3 OH) 2 units into columnar stacks oriented along the crystallographic a-axis.

Synthesis and characterisation of phosphine-sulfones 6
Aiming at the preparation of new phosphinoferrocene ligands via ferrocenylmethylation, betaine 2 was subsequently reacted with sodium sulfinates to give the respective phosphino-ferrocene sulfones 6 (Scheme 2).The reactions were performed with an excess of the sulfinate salts (2 : RSO 2 Na = 1 : 2.5) in refluxing DMSO-water for 2 h, similarly to the synthesis of ferrocenylmethyl sulfones FcCH 2 SO 2 R from simple ferrocenylmethylation agents. 13,17 The yields of the sulfones after chromatographic purification were ca.30% for 6a and approximately 50% for the compounds bearing the aromatic substituents (6b and 6c), which are less than in the reactions leading to FcSO 2 R. Therefore, we sought for other reaction products to gain more detailed information regarding the course of these particular ferrocenylmethylation reactions.
In the case of the reaction of betaine 2 with MeSO 2 Na, a careful chromatographic purification of the reaction mixture led to the isolation of alcohol 3 (2%) and phosphorane 7 (Scheme 3; 12%).Together with 6a, compounds 3 and 7 account for nearly 45% of the starting material.The reactions leading to aryl sulfones 6b and 6c are more selective (isolated yields: ca.50%) but afford identical by-products (isolated yields of 3 and 7 are ca.3% and 10-15%, respectively).Apparently, the cation Ph 2 PfcCH 2 + generated in situ from 2 enters into reactions with all other available nucleophiles, including OH − or phosphines.Interaction with the latter provides cationic products (i.e., phosphonium salts arising from "selfalkylation" of the parent 2 with Ph 2 PfcCH 2 + ) and, consequently, also their decomposition products such as 7.The fact that no 7 could be detected in the reaction mixtures obtained after treatment of 2 with NaOH and NaOMe (vide supra) can well reflect the higher relative amounts of these nucleophilic reagents, that suppress the competing reactions with other nucleophiles.Attempts to isolate the anticipated cationic (and hence more polar) side products or to recover unreacted 2 during the course of chromatographic purification of crude sulfones 6 failed.
The formulation of 6a-c and 7 was inferred from NMR and IR spectra, ESI mass spectra, and elemental analysis and was unequivocally confirmed by single-crystal X-ray diffraction.The NMR spectra of sulfones 6 comprise the signals due to the (diphenylphosphino)ferrocenyl unit and its attached methylene linker (CH 2 : δ H /δ C 3.59/56.65for 6a, and ca.3.68/58.3for 6b and 6c).The signals of the sulfone substituents, as well as the 31 P NMR resonances (δ P ≈ −17 ppm), are observed in the usual ranges.The IR spectra of the sulfones display the characteristic strong bands of the sulfone moieties centred at approximately 1310 (ν as ) and 1145 cm −1 (ν s ).17a The 1 H and 13 C NMR spectra of the by-product 7 contain signals of the 1,1′-disubstituted ferrocene moiety and two sets of resonances of the non-equivalent PPh 2 groups, which is also reflected in the 31 P NMR spectrum showing two singlets at δ P −16.9 and 10.1.The presence of the cyclopentadienylidene unit 18 in 7 is manifested by a pair of multiplets at δ H 6.12 and 6.40 and a pair of doublets at δ C 113.92 and 115.83 in the 1 H and 13 C NMR spectra, respectively.The 13 C NMR signal due to C ipso in the PvC 5 H 4 moiety is observed at δ C 78.21 as a phosphorus-coupled doublet ( 1 J PC = 110 Hz).The signals of the connecting methylene group are found at δ H 3.59 (doublet with 2 J PH = 12.7 Hz) and δ C 30.01 (dd, 1 J PC = 53, J PC = 1 Hz).
Crystallisation of 6a from ethyl acetate-hexane provided crystals of a triclinic modification (denoted as 6a).Crystals of another polymorph, 6a′, were serendipitously isolated during an attempted preparation of Zn(II) complexes, i.e., upon crystallization of a 6a/ZnBr 2 mixture from methanol-diethyl ether (vide infra).The polymorphs differ by the symmetry of the crystal lattice (6a: triclinic, P1 ˉ; 6a′: monoclinic, P2 1 /c) and by the overall conformation of the molecules constituting their crystals (Fig. 4 and Table 2).Thus, whereas the molecular structures of the two polymorphs are expectedly very similar in terms of interatomic distances and angles, they differ in the mutual orientation of the substituted cyclopentadienyl rings, which are nearly synclinal eclipsed in 6a and exactly halfway between anticlinal eclipsed and antiperiplanar staggered in 6a′ (compare the C1-Cg1-Cg2-C6 angles in Table 1). 19Another less pronounced difference can be observed in the orientation of the PPh 2 units resulting from different rotations along the pivotal C6-P bond and from the tilting of the phenyl rings.
The geometry of the (methylsulfonyl)methyl moiety in 6a and 6a′ agrees well with that of, e.g., phenyl methyl sulfone, 4-methoxyphenyl methyl sulfone, 20 and (benzylsulfonyl)methanol. 21Similar to these compounds, the O1-S-O2 angle is the most opened and the C11-S-C24 angle is the most acute among the bond angles around the sulfur atoms in 6a and 6a′, most likely due to an electrostatic repulsion of the electronegative oxygen atoms.
The main difference between the molecular structures of sulfones 6b and 6c (Fig. 5 and Table 2) can also be found in the conformation of the 1,1′-disubstituted ferrocene unit, which is intermediate between anticlinal staggered and anticlinal eclipsed for 6b and synclinal eclipsed for 6c.In both cases, the CH 2 SO 2 Ar (Ar is an aryl) pendants extend away from the ferrocene core but adopt different orientations as indicated by the torsion angle C1-C11-S-C24 (see Table 2) and the dihedral angles of the C(1-5) and C(24-29) ring planes of 45.93(8)°and 33.5(1)°for 6b and 6c, respectively.On the other hand, the compounds comprise regular ferrocene moieties (tilt angles below ca.3°) and show similar individual interatomic distances and angles that do not depart substantially from those of 6a/6a′ and benzylsulfones of the type ArCH 2 SO 2 Ar (Ar = an aryl). 22e ferrocene cyclopentadienyls in the structure of byproduct 7 (Fig. 6) are tilted by 2.6(1)°and assume a conformation near synclinal eclipsed, as evidenced by the C1-Cg1-Cg2-C6 torsion angle of 79.3(1)°.The individual Fe-C distances are in the range of 2.026(2)-2.050(2)Å.The cyclopenta-   Preparation and structure of mixed-cation complexes with 6a Coordination preferences of the newly prepared phosphinoferrocene sulfones were studied in reactions of 6a as the model representative, with zinc(II) halides.These salts were chosen mainly due to the position of the Zn(II) ion at the borderline between hard and soft metal ions 27 and due to its closed (d 10 ) coordination sphere, which makes it structurally variable because of the absence of crystal-field stabilisation. 28o our disappointment, repeated experiments aiming at the preparation of defined products by co-crystallisation of zinc(II) halides with 6a were unsuccessful.In one case, the crystallisation of a ZnBr 2 -6a mixture in methanol/diethyl ether provided crystals of monoclinic 6a′.Eventually, the attempted preparation of a Zn(II) complex by reacting ZnBr 2 and 6a at a 1 : 1 molar ratio in methanol-chloroform, followed by evaporation and crystallisation from CHCl 3 /methyl tert-butyl ether, yielded a few crystals of 8b, which were used directly for X-ray structure determination. 29The intriguing structure of this rather unexpected product (vide infra) led us to study the formation of such complexes systematically by changing the halide in ZnX 2 /NaX (NaCl-NaBr-NaI) and then also the alkali metal cation in ZnBr 2 /MBr (M = Li, Na, K, Rb, and Cs).
Attempts to isolate any mixed-cation compound from the 6a/ZnCl 2 /NaCl system failed, presumably because of the ionic nature of NaCl, which limits its solubility in organic solvents.The experiments furnished only crystals of uncoordinated 6a.On the other hand, the reactions of 6a with NaX/ZnX 2 , where X = Br and I (all in equimolar amounts), in methanol followed by crystallisation upon layering the reaction mixture with methyl tert-butyl ether produced the respective coordination polymers 8a (X = Br) and 8b (X = I) as orange, nicely crystalline, and air-stable solids in good yields (Scheme 4).
The reactions of 6a with ZnBr 2 with other alkali metal bromides were performed similarly to the preparation of the mentioned Na-Zn complexes but in solvent mixtures with an optimised chloroform/methanol ratio to ensure sufficient solubility of the alkali metal halide and not suppress separation of the product after the addition of methyl tert-butyl ether. 30ttempted reactions with RbBr and CsBr did not afford any M-Zn complex because these salts separated from the reaction mixture, whereas the analogous reaction of 6a with ZnBr 2 and KBr produced K-Zn complex 9a (Scheme 4), which adopts the structure of its sodium congener.In contrast, the reaction 6a with ZnBr 2 and LiBr produced a Zn-Li complex [Zn 2 Li 2 -Br 6 (6a) 2 (CH 3 OH) 4 (H 2 O)]•CH 3 OH (10a•CH 3 OH).In its structure, the phosphinoferrocene ligands coordinate the terminal ZnBr 3 units via their phosphine groups (similarly to the mentioned Na-Zn and K-Zn complexes) and further bind solvated Li + ions via the sulfone oxygens to form a discrete pseudodimeric assembly (Scheme 5). 31he M-Zn complexes (M = alkali metal cation) disintegrate upon dissolving in donor solvents.This was evidenced by the 1 H and 31 P{ 1 H} NMR spectra recorded for solutions of crystal-line 8a in CD 3 OD that reveal the exclusive presence of uncoordinated 6a in solution (δ P −16.3 ppm) and also by the ESI mass spectra showing only signals due to 6a and its fragments (see Experimental).The same applies to the elusive 6a-ZnBr 2 complexes (intermediates) as similar features have been observed in the NMR and ESI MS spectra of a residue obtained by evaporation of a 1 : 1 mixture of 6a-ZnBr 2 .Hence, the characterisation of the mixed-metal complexes had to be confined to solid-state techniques.Unfortunately, the IR spectra were of little diagnostic value because of their relative complexity (see ESI, Fig. S1 †) and only marginal shifts of the diagnostic bands upon coordination (e.g., the bands due to the sulfone moiety as compared to uncoordinated 6a).Nonetheless, the IR spectra of 8a, 8b and 9a were very similar, suggesting analogous structures for these compounds, and displayed additional broad bands attributable to ν OH vibrations at ca. 3470-3490 cm −1 , attributable to the "solvating" methanol.Nonetheless, unequivocal structural information was gained from single-crystal X-ray diffraction analysis.
Compounds 8a and 8b are essentially isostructural, and the minor differences in the lattice parameters and atomic coordinates are associated with the different sizes of the halide anions.Compound 9a also has practically the same structure, albeit described by different cell parameters because even a small variation in the cell angles near 90°as in this particular case can result in another reduced triclinic cell setting. 32The structure of 8a is depicted in Fig. 7, and the displacement ellipsoid plots for all three compounds are presented in the ESI (Fig. S2-S4 †).Pertinent geometric parameters are given in Table 3.
Compounds 8a and 8b are one-dimensional coordination polymers in which the ZnX 3 (6a-κP) units coordinate the Na(I) ions via two halide ions (bridging X2 and X3) and the sulfone oxygen O1.The coordination sphere of the Na(I) ion is completed by the sulfone O2 located in an adjacent ZnX 3 (6a-κP) moiety, related by crystallographic inversion, and also by a methanol molecule and its inversion-related counterpart.The solvating methanol further stabilises the structure through a hydrogen bond with the Zn-bound halide (O1S-H1O⋯X1, see Fig. 7).
As indicated above, the structure of 9a is very similar to its Na congener 8a, with the observed differences reflecting the larger size of the alkali metal cation present in the structure.The geometry of the PZnBr 3 moiety remains virtually unchanged upon going from 8a to 9a; the interligand angles span the range 102.97(1)-113.11(2)°andfollow the trend described for 8a though not with the same differences between the individual values.Although the overall coordination environment of the K + ion also remains seemingly the same (cis-interligand angles: 74.02(1)-107.97(5)°), the coordination sphere is expanded because of the longer potassiumdonor bonds (by approximately 0.21-0.34Å in the respective pairs).
The structure of 10a•CH 3 OH (Fig. 8, parameters in Table 4) reveals that the replacement of Na + with the Li + ion, which is smaller and prefers a tetrahedral coordination environment, results in an opening of the polymeric structure and incorporation of solvent molecules as additional donors into the struc-ture.One of the Li + cations (Li1) is coordinated by a sulfonate oxygen (O2) and three methanol molecules (OnS, n = 1-3) constituting a tetrahedral donor set.The other Li + cation (Li2) has a similar coordination, binding two sulfonate oxygens (from different molecules of 6a), methanol (O4S) and water molecule (O1W).It is noteworthy that the asymmetric environment of the sulfur atoms renders the structure chiral.
On the other hand, the halide anion is transferred to the zinc(II) centre, which thus gains a distorted tetrahedral PBr 3 coordination as observed for the Na/K-Zn complexes discussed above.Both ZnBr 3 units in the structure of 10a assume a sterically loose staggered orientation with respect to their bonding PC 3 moieties and do not exert any pronounced angular distortion (cf. the interligand angles ranging 105.64(4)-114.28(4)°forZn1 and 104.54(3)-112.79(4)°forZn2).

Conclusion
][8][9][10][11] Compound 6a, chosen as a representative phosphinosulfone donor, was shown to form unprecedented 34 alkali metal-Zn coordination polymers of the general formula [ZnMX 3 (6a)(CH 3 OH)] n (M/X = Na/Br, Na/I, and K/Br), in which the ferrocene-based ligand coordinates the softer Zn(II) ion via its phosphine substituent and the alkali metal cation through the sulfone oxygen atoms, while the methanol molecules complete octahedral coordination around the alkali metal ions.These compounds are zwitterions combining negatively charged ZnBr 3 units with cationic centres represented by the alkali metal cations in their structures.In the case of ZnBr 2 -LiBr, the analogous reaction with 6a provides [Br 3 Zn(6a) Li 2 (CH 3 OH) 4 (H 2 O)(6a)ZnBr 3 ] (methanol solvate), a pseudodimeric complex comprising two chemically different, tetrahedral Li + centres coordinated by the sulfonate oxygens, solvating methanol and a water molecule, and the phosphinecoordinated ZnBr 3 units.

Materials and methods
All reactions were performed under an argon atmosphere by standard Schlenk techniques.Amine 1 was prepared as reported previously. 10Benzene and chloroform were dried by standing over sodium metal and CaH 2 , respectively, and distilled under argon.Dimethyl sulfoxide was distilled under vacuum.Methanol was dried with an in-house PureSolv MD5 Table 4 Selected distances and angles for 10a•CH 3 OH (in Å and °)a solvent-drying system (Innovative Technology, USA).A solution of sodium methoxide was prepared by dissolving the appropriate amount of sodium metal in anhydrous methanol.Other chemicals and solvents were obtained from commercial suppliers (Sigma-Aldrich or Lachner, Czech Republic) and were used without any additional purification.
NMR spectra were recorded at 25 °C on a Varian Unity INOVA spectrometer operating at 399.95 MHz for 1 H, 100.58 MHz for 13 C, and 161.92 MHz for 31 P.The chemical shifts (δ in ppm) are given relative to internal tetramethylsilane ( 1 H and 13 C) or to external 85% aqueous H 3 PO 4 ( 31 P).IR spectra were obtained on a Nicolet Magna 6700 FTIR spectrometer in the range of 400-4000 cm −1 .Electrospray ionisation mass spectra (ESI MS) were acquired with a Bruker Esquire 3000 spectrometer using samples dissolved in HPLC-grade methanol.

Syntheses
Synthesis of betaine 2. A solution of propane-1,3-sultone (1.221 g, 10 mmol) in dry benzene (30 mL) was slowly introduced into a solution of amine 1 in the same solvent (4.272 g, 10 mmol in 20 mL).The resultant mixture was stirred at room temperature overnight (15 h), during which time a fine yellow precipitate deposited.The reaction mixture was diluted with methanol (50 mL) and carefully evaporated.The residue was purified by column chromatography over silica gel, eluting first with dichloromethane-methanol (5 : 1) to remove the less polar impurities.The polarity of the eluent was then increased (dichloromethane-methanol 3 : 1) to elute a salt containing the protonated amine 1 as the cation, very likely hydrochloride [1H]Cl. 35Finally, the eluent was changed to dichloromethanemethanol 1 : 1, which removed the major orange band of the desired product.Following evaporation and drying under vacuum over sodium hydroxide, betaine 2 was isolated as an air-stable orange solid (4.476 g, 81%).An analytical sample, in the form of the defined solvate 2•CH 3 OH, was obtained upon crystallisation from methanolic solution layered with tetrahydrofuran and diethyl ether.
Analytical data for betaine Preparation of alcohol 3. Degassed aqueous NaOH (25 mL of 2 M solution) was slowly added to a solution of betaine 2 (1.099 g, 2.0 mmol) in dimethyl sulfoxide (25 mL) heated in an oil bath maintained at 130 °C.The refluxing reaction mixture was stirred for 1 h, during which time it darkened and deposited as a brown precipitate.The mixture was cooled to room temperature and diluted with water (50 mL), and the resulting mixture was extracted with dichloromethane (3 × 50 mL).The combined organic layers were washed with water (2 × 200 mL), dried over magnesium sulfate, and evaporated.The residue was purified by column chromatography on a silica-gel column.Elution with diethyl ether-hexane (1 : 10) resulted in a yellow band that contained compound 5, which was isolated in a 6% yield (44 mg) after evaporation.Subsequent elution with diethyl ether-hexane 2 : 1 led to the development of a major orange band due to alcohol 3, which was isolated as slowly crystallising orange oil upon evaporation under vacuum.Yield of 3: 511 mg (64%).The compound was identified by NMR spectroscopy.12a Analytical data for 5. 1 H NMR (CDCl 3 ): δ 1.81 (s, 3 H, CH 3 ), 3.92 (vt, J′ = 1.8 Hz, 2 H), 3.99 (vt, J′ = 1.8 Hz, 2 H), 4.00 (vt, J′ = 1.9 Hz, 2 H) and 4.29 (vt, J′ = 1.9 Hz, 2 H) (4 × CH of C 5 H 4 ), 7.28-7.40(m, 10 H, P(C 6 H 5 ) 2 ) ppm. 31 P{ 1 H} NMR (CDCl 3 ): δ −16.0 (s) ppm. 13 Preparation of ether 4. Betaine 2 (1.101 g, 2.0 mmol) was dissolved in dimethyl sulfoxide (25 mL) at 100 °C, and the solution was treated with 2 M MeONa in methanol (25 mL).The resulting mixture was heated under reflux for 2 h and cooled to room temperature.Then, it was diluted with water (50 mL) and extracted with dichloromethane (3 × 50 mL).The organic extracts were washed with water (2 × 200 mL), dried over magnesium sulfate, and evaporated.The crude product was purified by chromatography over a silica-gel column using diethyl ether-hexane 1 : 1 as the eluent.The major band due to the product was collected and evaporated under vacuum to yield ether 4 as a yellow-orange solid.Yield: 388 mg (47%).The NMR spectra of the product were identical with those reported in the literature. 9reparation of 6a.A solution of sodium methanesulfinate (0.534 g, 5.0 mmol) in degassed water (25 mL) was added to a chromatized Mo Kα radiation (λ = 0.71073 Å) and were corrected for absorption using routines included in the diffractometer software.
The structures were solved by the direct methods (SHELXS97) and refined by full-matrix least squares routines based on F 2 (SHELXL97). 36The non-hydrogen atoms were refined with anisotropic displacement parameters.The hydrogen atoms residing on the oxygen atoms (OH protons) in the structures of 2•CH 3 OH, 8a, 8b, and 9a were identified on the difference electron density maps and refined as riding atoms with U iso (H) set to 1.2-times U eq (O).In the case of 10a•CH 3 OH, they were placed into positions suitable for the formation of hydrogen bonds and refined similarly.Hydrogen atoms residing on the carbon atoms were included in their theoretical positions and refined analogously.
Description of the crystallization experiments and a listing of relevant crystallographic data and structure refinement parameters are available in the ESI (Table S1 †).Geometric data as well as all structural drawings were obtained with a recent version of the PLATON program. 37All numerical values are rounded with respect to their estimated standard deviations (ESDs) given with one decimal.Parameters pertaining to atoms in constrained positions are presented without ESDs.

Fig. 1
Fig. 1 PLATON plot of the phosphinobetaine molecule in the structure of 2•CH 3 OH showing the atom-labelling scheme and displacement ellipsoids at a 30% probability level.

Fig. 5
Fig.5PLATON plots of the molecular structure of the phosphinoferrocene sulfones 6b and 6c at the 30% probability level.

Fig. 8
Fig. 8 Perspective drawing of the structure of 10a•CH 3 OH.The molecule of solvating methanol and CH hydrogens are omitted for clarity.For a displacement ellipsoid plot, see the ESI (Fig. S5 †).

Table 1
Selected interatomic distances and angles for 2•CH 3 OH (in Å and °)a