Configurationally homogeneous diastereomers of a linear hexa(tertiary phosphine): Enantioselective self-assembly of a double-stranded parallel helicate of the type (P)-[Cu₃(hexaphos)₂](PF₆)₃

Abstract

Three configurationally homogeneous diastereomers of the linear hexa(tertiary phosphine) Ph₂PCH₂CH₂P(Ph)CH₂CH₂P(Ph)CH₂CH₂P(Ph)CH₂CH₂P(Ph)CH₂CH₂PPh₂ (hexaphos) have been isolated in enantiomerically pure form, namely (R,S,S,R)-, (R,S,S,S)-, and (S,S,S,S)-hexaphos. The strongly helicating (R,S,S,R)-(−) form of the ligand combines with copper(I) ions to generate by stereoselective self-assembly the P enantiomer of a parallel helicate of the type [Cu₃(hexaphos)₂](PF₆)₃, which has been characterized by x-ray crystallography. Theoretical modeling of the cation indicates that it is the relationship between the helicities of the two 10-membered rings containing the three copper ions, each of which has the twist-boat–chair–boat conformation, and the configurations of the three chiral, tetrahedral copper stereocenters of P configuration that determines the stereochemistry of the parallel and double α-helix conformers of the double-stranded trinuclear metal helicate.

The synthesis of complex, hierarchical molecular architectures containing two or more metal ions by self-assembly under equilibrium conditions is an important technique in coordination chemistry. For example, oligo-2,2′-bipyridines and related ligands combine with kinetically labile copper(I) or silver(I) ions to give solutions of stable, di- and oligo-nuclear metal helicates, grids, metallocatenanes, rotaxanes, and knots, depending on the rigidity of the spacer groups between the chelating entities (1–3). The simplest approach to the self-assembly of a particular structural motif is by the astute and selective use of rigidity in the design of the ligand (3). This approach applies also to the construction of molecular polygons and polyhedra from rigid, angular metal chelate components, such as [Pt(PEt₃)₂]²⁺, which can form the corners and apices of large two-dimensional and three-dimensional structures (4).

More subtle considerations apply to the thermodynamic self-assembly of polynuclear metal chelates derived from fully flexible ligands. Techniques available include mismatching the binding preferences of the ligand and metal to give a particular assembly (2), and the selective formation of stable chelate rings. Chiral elements within a ligand can also dramatically affect the stability of a particular diastereomer of a supramolecular chelate assembly. For example, freely flexible ligands of the type L—L′—L′—L can generate chiral and achiral diastereomers of dinuclear metal complexes of the type M₂(L—L′—L′—L)₂, chiral at the tetrahedral metal stereocenters M(L—L′)₂. The relationship between the configurational elements at donor and metal and the helicities of the metal chelate ring conformers will determine the stability of a particular stereoisomer of the complex.

In previous work, we have used these techniques for the stereoselective synthesis of dinuclear metal helicates from a flexible linear tetra(tertiary phosphine) (5) and an analogous hybrid phosphine–arsine (6), with univalent Group 11 ions. These ions form stable, but labile, tetrahedral complexes with chelating bis(tertiary phosphines and arsines) (7, 8). Chiral MP₄ stereocenters of this type are therefore potentially useful functionalities for the stereoselective synthesis of di- and oligo-nuclear metal helicates and other interesting structural motifs by thermodynamic self-assembly. Consistent with these ideas, and molecular mechanics calculations, (S,S)-Ph₂PCH₂CH₂P(Ph)CH₂CH₂P(Ph)CH₂CH₂PPh₂, (S,S)-tetraphos, spontaneously self-assembled double-stranded helicates of the type (M)-{M₂[(R,R)-tetraphos]₂}(PF₆)₂ (where M = Ag, Au; ref. 5).‡ The preferential assembly in each case of the dinuclear metal helicate was driven by the incapacity of the central ethylene spacer group in the tetra(tertiary phosphine) to stabilize the central five-membered chelate ring in the corresponding mononuclear metal complex. The overall helicity of the dinuclear metal helicate (M) is generated by the four chiral inner-phosphorus stereocenters of R configuration. These generate M configurations at the two chiral metal stereocenters and stabilize the chiral twist-boat–chair–boat (TBCB) conformation (10, 11) of the central 10-membered ring containing the two metal ions. When this ring has the λ conformation, the helicate assumes a DNA-like double α-helical structure of M helicity; when the ring has the δ conformation, a parallel double helix of the same helicity is generated. The side-by-side arrangement of the two chiral tetra(phosphine) ligands about the two metal ions in the parallel double helix conformer mimics the structural motif of the leucine repeat or zipper transcriptional proteins, wherein two polypeptide α-helices are held together by hydrogen bonding in parallel side-by-side arrangements (12). ¹H NMR measurements indicated that the double α-helix and parallel double helix conformers of the tetra(tertiary phosphine)–silver and –gold helicates were rapidly interconverting in solution; in the solid, the silver complex contains both conformers of the helicate in the unit cell and the gold complex the parallel helix only.

We report here the synthesis and isolation of three enantiomerically pure diastereomers of a flexible, linear hexa(tertiary phosphine), namely (R,S,S,R)-, (S,S,S,S)-, and (R,S,S,S)-hexaphos (Fig. 1), and the use of the strongly helicating (R,S,S,R) diastereomer of the ligand for the stereoselective self-assembly of the double-stranded trinuclear metal helicate (P)-(−)-{Cu₃[(S,R,R,S)-hexaphos]₂}(PF₆)₃⋅4C₆H₆, which has been structurally characterized in the solid state.

Figure 1.

The enantiomers (R,S,S,R)-, (R,S,S,S)-, and (S,S,S,S)-hexaphos.

Materials and Methods

Instrumental Techniques.

NMR spectra were recorded on a Varian Inova 500 spectrometer at 500 MHz (¹H) and 202.4 MHz (³¹P) at 295 K; chemical shifts are quoted with reference to Me₄Si (¹H) and 85% H₃PO₄ (³¹P). Optical rotations were measured on the specified solutions with a Perkin–Elmer Model 241 spectropolarimeter. Specific rotations were estimated to be within ±0.05 deg⋅cm²⋅g⁻¹.

Synthesis.

Manipulations of air-sensitive compounds were carried out under argon with use of Schlenk and canula techniques. The tetra(tertiary phosphine) (S,S)-tetraphos was obtained as described in ref. 5. Diphenylvinylphosphine (13) and [Cu(MeCN)₄]PF₆ (14) were prepared by literature methods.

Ligand Synthesis: (R,S,S,R)/(R,S,S,S/(S,S,S,S)-Hexaphos⋅6BH₃, (R,S,S)/(S,S,S)-Pentaphos⋅5BH₃.

The tetra(tertiary phosphine) (S,S)-tetraphos (1.95 g, 2.91 mmol) was dissolved in tetrahydrofuran (THF; 150 ml), and the solution was cooled to −78°C. A solution of sodium (0.293 g, 12.7 mmol) in liquid ammonia (60 ml, distilled off NaNH₂), cooled to −78°C, was added over 30 min to the vigorously stirred solution of the phosphine. The brown-colored reaction mixture was stirred for a further 10 min at this temperature, and then it was treated with ammonium bromide and allowed to warm to room temperature, and the ammonia was allowed to evaporate. The THF was then removed in vacuo from the almost colorless residual solution, and water (100 ml) was added to the oily residue of terminal secondary phosphines. Four extractions of the suspension with dichloromethane (25 ml) followed. The combined extracts were dried (MgSO₄), filtered, and evaporated to dryness. The oil (1.45 g, 96%) was dissolved in THF (200 ml), and diphenylvinylphosphine (1.30 g, 6.13 mmol) and potassium tert-butoxide (0.16 g, 1.43 mmol) were added to the solution, which was then heated under reflux for 6 h. The reaction mixture was cooled to room temperature, treated with Me₂S⋅BH₃ (35 ml, 0.39 mol), and then heated under reflux for 1.5 h. At this stage, the reaction mixture was cooled to room temperature, and ethanol (40 ml) was cautiously added to decompose the excess borane-sulfide. (The addition of a small quantity of silica assisted this process.) After removal of volatile components in vacuo (60°C, 0.1 mmHg), dichloromethane (50 ml) was added to the residue, and the extract was eluted through a short column of silica with use of dichloromethane as eluant. The eluate was dried (MgSO₄) and evaporated to dryness, and the residue was recrystallized from dichloromethane–methanol by slow evaporation of the dichloromethane. The product crystallized as a colorless crystalline solid (2.33 g, 78%) that was shown by HPLC to be a mixture of the desired three hexa(tertiary phosphine)-borane adducts, namely (R,S,S,R)/(R,S,S,S)/(S,S,S,S)-hexaphos⋅6BH₃ (90%), and the corresponding pair of penta(tertiary phosphine)-borane adducts, namely (R,s,S)/(S,s,S)-pentaphos⋅5BH₃ (10%). Preparative chromatography of ≈20-mg portions of this mixture on a Waters μ-Porasil column with use of n-hexane (15%)–dichloromethane as eluant gave five fractions with base-line separation (Fig. 2), from which the following five compounds were isolated as colorless crystalline solids by diffusion of diethyl ether into concentrated dichloromethane solutions of the individual samples.

Figure 2.

Typical HPLC trace of hexaphos/pentaphos–6/5-borane mixture (band 1 fastest moving).

(R,S,S)-Pentaphos⋅5BH₃ (Band 1).

Colorless rosettes, 0.108 g (4.2%). M.p. 211°C; [α] = −11.8 (c = 1.0, CH₂Cl₂); ¹H NMR (CD₂Cl₂): δ = 0–1.4 (br m, 15 H; BH₃), 1.5–2.5 (br m, 16 H; CH₂), 7.35–7.80 (br m, 35 H; ArH); ³¹P{¹H} NMR (CD₂Cl₂): δ = 18.1 to 19.3 (br m, 2 P; terminal P), 22.2 to 23.4 (br m, 3 P; internal P; elemental analysis calc (%) for C₅₀H₆₆B₅P₅: C 68.56; H 7.59; found: C 68.54; H 7.81.

(S,S,S)-Pentaphos⋅5BH₃ (Band 2).

Colorless rosettes, 0.104 g (4.1%). M.p. 217–219°C; [α] = −0.1 (c = 1.0, CH₂Cl₂); ¹H NMR (CD₂Cl₂): δ = 0–1.4 (br m, 15 H; BH₃), 1.5–2.5 (br m, 16 H; CH₂), 7.35–7.80 (br m, 35 H; ArH); ³¹P{¹H} NMR (CD₂Cl₂): δ = 18.1 to 19.4 (br m, 2 P; terminal P), 22.1 to 23.4 (br m, 3 P, internal P); elemental analysis calc (%) for C₅₀H₆₆B₅P₅: C 68.56; H 7.59; found: C 68.24; H 7.81.

(S,S,S,S)-Hexaphos⋅6BH₃ (Band 3).

Colorless plates, 0.476 g (16.0%). M.p. > 208°C (decomp.); [α] = +8.7 (c = 1.0, CH₂Cl₂); ¹H NMR (CD₂Cl₂): δ = 0–1.4 (br m, 18 H; BH₃), 1.5–2.5 (br m, 20 H; CH₂), 7.35–7.80 (br m, 40 H; ArH); ³¹P{¹H} NMR (CD₂Cl₂): δ = 18.0 to 19.4 (br m, 2 P; terminal P), 22.0 to 23.4 (br m, 4 P, internal P); elemental analysis calc (%) for C₅₈H₇₈B₆P₆: C 67.90; H 7.66; found: C 66.67; H 7.82.

(R,S,S,S)-Hexaphos⋅6BH₃ (Band 4).

Colorless needles, 0.965 g (32.4%). M.p. > 205°C (decomp.); [α] = −2.5 (c = 1.0, CH₂Cl₂); ¹H NMR (CD₂Cl₂): δ = 0–1.4 (br m, 18 H; BH₃), 1.5–2.5 (br m, 20 H; CH₂), 7.35–7.80 (br m, 40 H; ArH); ³¹P{¹H} NMR (CD₂Cl₂): δ = 17.9 to 19.4 (br m, 2 P; terminal P), 21.8 to 23.6 (br m, 4 P, internal P); elemental analysis calc (%) for C₅₈H₇₈B₆P₆: C 67.90; H 7.66; found: C 67.85; H 7.95.

(R,S,S,R)-Hexaphos⋅6BH₃ (Band 5).

Colorless needles, 0.484 g (16.2%). M.p. > 205°C (decomp.); [α] = −12.7 (c = 1.0, CH₂Cl₂); ¹H NMR (CD₂Cl₂): δ = 0–1.4 (br m, 18 H; BH₃), 1.5–2.5 (br m, 20 H; CH₂), 7.35–7.80 (br m, 40 H; ArH); ³¹P{¹H} NMR (CD₂Cl₂): δ = 18.0 to 19.2 (br m, 2 P; terminal P), 22.0 to 23.3 (br m, 4 P, internal P); elemental analysis calc (%) for C₅₈H₇₈B₆P₆: C 67.90; H 7.66; found: C 67.25; H 7.75.

(S,S,S,S)-Hexaphos.

The adduct (S,S,S,S)-hexaphos⋅6BH₃ (0.476 g) was dissolved in morpholine (75 ml), and the solution was heated at 35°C for 12 h, then stirred at room temperature for 48 h. The morpholine was removed in vacuo, and the colorless solid remaining was heated with methanol (5 ml) and water (20 ml). After stirring for 30 min, the mixture was filtered through a glass frit, and the filtrate was diluted with water (20 ml). Additional solid precipitated. The combined solid was dissolved in dichloromethane (20 ml), and the solution was dried (Na₂SO₄). The dried solution was filtered, and the filtrate was evaporated to dryness. The residue was recrystallized by diffusion of diethyl ether into a concentrated dichloromethane solution of the crude product, thus affording the pure hexa(tertiary phosphine) as colorless prisms. Yield: 0.424 g (97%). M.p. 192–193°C; [α] = +12.1 (c = 1.0, CH₂Cl₂); ¹H NMR (CD₂Cl₂): δ = 1.46–1.70 (br m, 16 H; CH₂), 1.87, 1.96 (d of m, 4 H, CH₂), 7.24–7.92 (br m, 40 H; ArH); ³¹P{¹H} NMR (CD₂Cl₂): δ = −12.5 (d, ³J(P,P) = 28.1 Hz, 2 P; terminal P), −15.9 to −16.9 (m, 4 P, internal P); elemental analysis calc (%) for C₅₈H₆₀P₆: C 73.88; H 6.41; found: C 73.64; H 6.30.

(R,S,S,S)-Hexaphos.

Procedure as for (S,S,S,S)-hexaphos. Colorless needles, 0.816 g (92%). M.p. 128–129°C; [α] = +0.2 (c = 1.0, CH₂Cl₂); ¹H NMR (CD₂Cl₂): δ = 1.42–1.71 (br m, 16 H; CH₂), 1.89, 1.98 (d of m, 4 H, CH₂), 7.24–7.32 (br m, 40 H; ArH); ³¹P{¹H} NMR (CD₂Cl₂): δ = −12.2 to −12.9 (m, 2 P; terminal P), −15.5 to −16.9 (m, 4 P, internal P); elemental analysis calc (%) for C₅₈H₆₀P₆: C 73.88; H 6.41; found: C 73.68; H 6.54.

(R,S,S,R)-Hexaphos.

Procedure as for (S,S,S,S)-hexaphos. Colorless needles, 0.378 g (85%). M.p. 124–125°C; [α] = −15.3 (c = 1.0, CH₂Cl₂); ¹H NMR (CD₂Cl₂): δ = 1.46–1.68 (br m, 16 H; CH₂), 1.86–2.02 (m, 4 H, CH₂), 7.24–7.32 (br m, 40 H; ArH); ³¹P{¹H} NMR (CD₂Cl₂): δ = −12.65 (d, ³J(P,P) = 28.1 Hz, 2 P; terminal P), −15.7 to −16.6 (m, 4 P, internal P); elemental analysis calc (%) for C₅₈H₆₀P₆: C 73.88; H 6.41; found: C 73.69, H 6.48.

Preparation of (−)-{Cu₃[(S,R,R,S)-Hexaphos]₂}(PF₆)₃⋅4C₆H₆.

The ligand (R,S,S,R)-hexaphos (0.112 g, 0.118 mmol) was added to a solution of [Cu(MeCN)₄]PF₆ (0.063 g, 0.17 mmol) in acetonitrile (1 ml). The ligand dissolved to give a colorless solution to which benzene (5 ml) was carefully layered. Colorless prisms of the product crystallized from the mixture over several days, and were isolated and washed with benzene and dried. Yield: 0.154 g (97%). M.p. 243–244°C; [α] = +10.4 (c = 1.0, CH₃CN); ¹H NMR (CD₃CN), δ = 1.8–2.6 (br m, 40 H; CH₂), 7.3 (s, 24 H; 4 C₆H₆), 6.8–7.5 (m, 92 H; ArH); ³¹P{¹H} NMR (CD₃CN): δ = 3 to 21 (m, 12 P), −143.2 (sept. [CuL]⁺; ¹J(P,F) = 705 Hz, 3 P, PF). MS (ES, CH₃CN): m/z (%) 2,363–2,371(2) [Cu₃L₂(PF₆)₂]⁺, 1,005–1,008(55) [CuL]⁺; 534–537(20) [Cu₂L]²⁺; elemental analysis calc (%) for C₁₄₀H₁₄₄Cu₃F₁₈P₁₅: C 59.55; H 5.14; found: C 59.47; H 5.30.

Crystal Structure Data for (S,S,S,S)-Hexaphos.

F_W = 942.95, crystal size 0.36 × 0.19 × 0.03 mm, monoclinic, C2 (No. 5), a = 16.453(2), b = 5.457(4), c = 29.991(2) Å, β = 107.662(9)°, V = 2556(2) ų, Z = 2, ρ_calc = 1.220 g⋅cm⁻³, 2θ < 120°, μ(Cu Kα) = 22.42 cm⁻¹, T 296 K, F(000) = 996, R₁ = 0.038, wR₂ = 0.044 [for 1931 refl. I > 2σ(I)], S = 1.93, Δρ (min/max) = −0.18/0.29 e⋅Å⁻³. The data were collected on a Rigaku (Tokyo) AFC6R diffractometer, graphite monochromated Cu Kα radiation (λ = 1.54178 Å). Data were corrected for absorption (transmission factors 0.63–0.94) and decay (3.66% decline). The structure was solved by direct methods with use of SIR92 (15), and the program texsan (16) was used to refine 288 independent variables.

Crystal Structure Data for (P)-(−)-{Cu₃[(S,R,R,S)-Hexaphos]₂}(PF₆)₃⋅4C₆H₆.

F_W = 2823.9, crystal size 0.3 × 0.2 × 0.07 mm, orthorhombic, P2₁2₁2₁, a = 13.0109(1), b = 26.3154(2), c = 39.1850(4) Å, V = 13416.4(2) ų, Z = 4, ρ_calc = 1.398 g⋅cm⁻³, 2θ < 50°, μ(Mo Kα) = 7.3 cm⁻¹, T 200 K, F(000) = 5832, R₁ = 0.072, wR₂ = 0.095 [for 14,015 refl. I > 3σ(I)], S = 1.013, Δρ (min/max) = −0.44/0.59 e⋅Å⁻³. The data were collected on a Nonius Kappa charge-coupled device (CCD) area-detector diffractometer (Enraf-Nonius, Delft, The Netherlands) by using graphite monochromatized Mo K_α radiation (λ = 0.71073 Å). Data were corrected for absorption (transmission factors 0.89–0.93). The program raels00 was used to refine 451 independent variables (17). This program allows extensive use of constraints and restraints. A separate scale constant was used for the h + k odd reflections, which refined to 0.94(1) of the value for the h + k even reflections, indicating an average 0.97:0.03 ratio for disordering about the pseudo 2-fold axis of the crystal. The structure does not pack tightly and results in a large thermal motion of the three PF ions, the four benzene molecules, and some of the phenyl groups of the cation. There is a pseudoinversion center at 3/4, 1/2, 1/2, the approximate site of Cu(1), which allows the structure to be described also as an occupancy modulation of a 1:1 disordered Pmcn structure. In this structure, the Cu atoms and all C atoms of the bridging —CH₂—CH₂— groups strongly overlap resulting in an unstable refinement of the carbon atoms. A satisfactory constrained refinement strategy was to constrain all C—C bonds to the same refinable length, final value 1.534(3) Å, and to refine the orientation and centroid position of each bond. Restraints on differences between P—C distances were also used, with the final range being 1.827–1.848 Å. Details of constraints and restraints are included in the CIF that accompanies the paper.

Molecular Mechanics Calculations.

Calculations were performed by using the molecular mechanics module of the program spartan 3.0 and force-field parameters and minimization algorithms therein (18).

Results and Discussion

Design Strategy.

The linear hexa(tertiary phosphine) Ph₂PCH₂CH₂P(Ph)CH₂CH₂P(Ph)CH₂CH₂P(Ph)CH₂CH₂P(Ph)CH₂CH₂PPh₂ (hexaphos) contains four chiral phosphorus stereocenters, which give rise to six possible, configurationally stable, E_inv 120–150 kJ⋅mol⁻¹ (19) diastereomers: four racemic pairs, namely (R*,R*,R*,R*)-(±)-, (R*,R*,R*,S*)-(±)-, (R*,R*,S*,R*)-(±)-, and (R*,S*,S*,R*)-(±)-hexaphos, and two meso forms, namely (R*,S*,R*,S*)- and (R*,R*,S*,S*)-hexaphos.§ Of these six, only the individual enantiomers of the four chiral forms are suitable for the enantioselective self-assembly of double-stranded trinuclear metal helicates of the type (±)-[M₃(hexaphos)₂]X₃ (where M = Cu, Ag, Au). Enantiomers of the two C₂ diastereomers, (R*,R*,R*,R*)-(±)- and (R*,S*,S*,R*)-(±)-hexaphos, may generate discrete double-stranded helicates of D₂ symmetry, and those of the two C₁ diastereomers, (R*,R*,R*,S*)-(±)- and (R*,R*,S*,R*)-(±)-hexaphos, mixed pairs of head-to-head and head-to-tail helicates of C₂ symmetry. Our strategy therefore was to focus on the synthesis and isolation of the C₂ enantiomers, (R,S,S,R)- and (S,S,S,S)-hexaphos.

Inspection of molecular models of {Cu₃[(S,R,R,S)-hexaphos]₂}³⁺ and {Cu₃[(R,R,R,R)-hexaphos]₂}³⁺ indicated that the binding of the two ligand strands in each case to the three metal ions in a tetrahedral helicate arrangement was stereospecific at the three chiral metal stereocenters. This result is because the eight methylene groups in the two 10-membered rings containing the three metal ions must adopt equatorial dispositions. For {Cu₃[(S,R,R,S)-hexaphos]₂}³⁺, this situation results in P configurations for each of the three metal stereocenters, a strongly helical, cooperative alignment (Fig. 3). Stereospecific coordination of (S,S,S,S)-hexaphos to give {Cu₃[(R,R,R,R)-hexaphos]₂}³⁺, however, produces the less favorable M,P,M arrangement.

Figure 3.

Schematic representation of highest symmetry (D₂) parallel double helix and double α-helix conformers of helicate ion.

The steric energies of the conformational diastereomers of (P_Cu,P_Cu,P_Cu)-{Cu₃[(S,R,R,S)-hexaphos]₂}³⁺ were calculated with use of the forcefield tripos 5.2 in the program spartan 3.0 (18). The calculations indicated that the lowest-energy diastereomers were associated with two annulated 10-membered rings having the chiral twist-boat–chair–boat (TBCB) conformation, rather than the usual achiral, boat–chair–boat (BCB) conformation (Fig. 4; ref. 11). When the twists of these two chiral rings are in the λ direction, the helicate adopts the more favorable, compact side-by-side arrangement, a parallel double helix (Fig. 5). The idealized symmetry of the cation is D₂, and the two ligand strands each complete ≈2.5 turns of a P helix. When the twists of the two 10-membered rings are in the δ direction, the double α-helix conformation of the helicate is generated. This conformer, which is more open than the nearest- energy parallel double helix conformer, also has D₂ idealized symmetry; each ligand strand completes ≈0.75 turn of a P helix, as does the overall helicate. Variations of the helicities of the six, chiral five-membered chelate rings in each structure have only a minor effect on the steric energies.

Figure 4.

Chiral twist-boat–chair–boat (TBCB) and achiral boat–chair–boat (BCB) conformations of 10-membered ring.

Figure 5.

ortep views of cation of (P)-(−)-{Cu₃[(S,R,R,S)-hexaphos]₂}(PF₆)₃⋅4C₆H₆ from above (a) and side (b).

Ligand Synthesis.

The diastereomers of the hexa(tertiary phosphine) were synthesized from (S,S)-tetraphos, as indicated in Scheme S1. This strategy, which preserves the configurations of the central two inner phosphorus stereocenters, leads to a statistical 1:2:1 mixture of the enantiomers of the three possible diastereomers of the hexa(tertiary phosphine), namely (R,S,S,R)-, (R,S,S,S)-, and (S,S,S,S)-hexaphos (Fig. 1), because of the non-stereoselective nature of the reactions involving the secondary phosphine intermediates. Included in the three products is the desired strongly helicating C₂ diastereomer of the ligand, viz. (R,S,S,R)-hexaphos, which will constitute 25% of hexa(tertiary phosphine) product.

Scheme 1.

Synthesis of (R,S,S,R)/(R,S,S,S)/(S,S,S,S)-hexaphos: a, Na/NH₃, THF, −78°C; b, NH₄Br; c, Ph₂PCH⩵CH₂, KOBu^t, THF, reflux 6 h; d, Me₂S⋅BH₃; e, morpholine, 35°C, 12 h.

The bis(secondary phosphine) intermediate was prepared by the slow addition of 12.7 mmol sodium in ammonia at −78°C to a solution of (S,S)-tetraphos in tetrahydrofuran at the same temperature. The resulting solution of the terminal bis(sodium phenylphosphide) was quenched with ammonium bromide, which gave the corresponding bis(secondary phosphine) as a mixture of diastereomers in high yield.¶ The product was contaminated with ≈10% of the corresponding terminal mono(secondary phosphine). The secondary phosphine mixture was converted in high yield into the diastereomeric mixture of hexa(tertiary phosphines), epimeric at P2 and P5, by the reaction with 2 equiv. diphenylvinylphosphine in the presence of potassium tert-butoxide. The mono(secondary phosphine) impurity reacted similarly to give the penta(tertiary phosphine) epimers, (R,s,S)- and (S,S)-pentaphos (Fig. 6). Without isolation, the mixture of hexa- and penta-tertiary phosphines was converted into the corresponding, air-stable, mixture of hexa- and penta-tertiary phosphine-borane adducts. Base-line separation of the five components of the mixture was achieved on a Waters μ-Porasil silica column with use of dichloromethane–n-hexane as eluant (Fig. 2). The two penta(tertiary phosphine)–pentaborane diastereomers were the first compounds to be eluted, followed by the three hexa(tertiary phosphine)–hexaborane adducts in the expected 1:2:1 ratio. Each of the five products crystallized as a high-melting crystalline solid. Isolated yields from (S,S)-tetraphos (1.95 g) of the five components were the following (in order of elution): (R,S,S)-pentaphos⋅5BH₃, 0.108 g (4.2%); (S,S,S)-pentaphos⋅5BH₃, 0.104 g (4.1%); (R,S,S,R)-hexaphos⋅6BH₃, 0.484 g (16.2%); (R,S,S,S)-hexaphos⋅6BH₃, 0.965 g (32.4%); (S,S,S,S)-hexaphos⋅6BH₃, 0.476 g (16.0%). Absolute configurations of the borane adducts were inferred from those of the free ligands (see below).

Figure 6.

The epimers (R,s,S)- and (S,S)-pentaphos.

The three enantiomerically pure hexa(tertiary phosphines) were recovered from the individual, configurationally pure hexaborane adducts by heating in morpholine for 12 h at 35°C. At the end of each reaction, the morpholine was removed by distillation under reduced pressure, and the residue was stirred in aqueous methanol to extract the morpholine-borane adduct; the free phosphine was filtered off, dried in vacuo, and recrystallized from dichloromethane–methanol. The enantiomerically pure hexa(tertiary phosphines) were thus isolated in high yields. They have the following selected physicochemical properties: (S,S,S,S)-hexaphos, mp 192–193°C, [α] = +12.1 (c = 1.0, CH₂Cl₂); (R,S,S,S)-hexaphos, mp 128–129°C, [α] = +0.2 (c = 1.0, CH₂Cl₂); (R,S,S,R)-hexaphos, mp 124–125°C, [α] = −15.3 (c = 1.0, CH₂Cl₂).

Diastereomer Identification.

The identities of the two C₂ diastereomers of the ligand, isolated in equal amounts, were confirmed by the determination of the crystal structure of the less soluble, higher melting form, mp 192–193°C, which crystallizes as colorless platelets in the monoclinic space group C2 (No. 5). Absolute configurations at phosphorus in the diastereomer are S,S,S,S.

Metal Complex.

The copper(I) complex was prepared by reacting (R,S,S,R)-hexaphos with 1.5 equiv. [Cu(MeCN)₄]PF₆ in acetonitrile. Large, colorless prisms of (−)-{Cu₃[(S,R,R,S)-hexaphos]₂}(PF₆)₃⋅4C₆H₆ were obtained by layering the acetonitrile solution with benzene and allowing crystallization to proceed over several days.

Crystal Structure of (P)-(−)-{Cu₃[(S,R,R,S)-hexaphos]₂}(PF₆)₃⋅4C₆H₆.

A crystal of the complex was mounted and transferred directly to the coldstream of the diffractometer. The complex crystallizes in the orthorhombic space group P2₁2₁2₁. The structure of the cation is shown in Fig. 5. Distances and angles around the copper ions are unexceptional and similar to those in (M)-(−)-{Cu[(R,R)-tetraphos]}PF₆⋅EtOH (5).

The structure of the cation is that of a parallel double helix with each strand of the hexa(tertiary phosphine) completing ≈2.5 turns of a P helix around three tetrahedral copper ions of P configuration (Fig. 7). Assignments for the configurational and conformational elements in the cation are given in Fig. 8. The two annulated 10-membered rings linking the three copper stereocenters have the chiral twist-boat–chair–boat (TBCB) conformation, which was also found in the structures of the dinuclear metal helicates (M)-{M₂[(R,R)-tetraphos]₂}(PF₆)₂ (where M = Ag, Au; ref. 5). In the present structure, the direction of the helicity of each 10-membered ring is left-handed (λ), which negates the right-handed (P) twists of the three MP₄ stereocenters and generates the parallel double helix conformer of the helicate. The distance between the copper ions is 6.015(3) Å.

Figure 7.

Schematic end-elevation of helicate ion showing parallel double helix arrangement.

Figure 8.

Full stereochemical assignment for helicate of cation in solid state.

The trication has inherent D₂-222 symmetry. One of the 2-fold axes is parallel to a and is in the correct position for the crystal structure to be regarded as a displacive modulation away from a C222₁ parent structure with the trication located about a crystallographic 2-fold axis. There is an origin displacement of ±1/4 a between the standard settings for the two sets of equivalent positions. Within the cation, atoms related by the pseudocrystallographic 2-fold axis parallel to a are primed. The second and third PF ions are similarly related. The first anion lies on a pseudo 2-fold axis parallel to b of C222₁. The pseudoequivalence under the 2-fold axes parallel to a relates benzene molecules 1 and 2 and benzene molecules 3 and 4. Their somewhat larger displacement from pseudoequivalence is associated with the reduction of 2-fold equivalence of some of the phenyl rings' orientations, as can be seen in Fig. 5.

Conclusions

The fully flexible ligand (R,S,S,R)-hexaphos can be used for the enantioselective self-assembly of a parallel double helix of the type (P)-[Cu₃(hexaphos)₂](PF₆)₃. This type of helicate, which mimics the structural motif of certain proteins, cannot be synthesized from semirigid ligands. The two ligand strands bind stereospecifically to the three copper(I) ions to give three tetrahedral metal stereocenters of P configuration that are linked by two annulated, 10-membered, twist-boat–chair–boat rings of λ conformation in the solid state. Each ligand strand completes ≈2.5 turns of an α-helix of P configuration in the idealized cation of D₂ symmetry.