(2S_p,4R,6R,8S_p)-4,6-Dimethyl-1-phenyl-diferroceno-1-phosphines

Abstract

Ferrocene-based compounds are powerful asymmetric ligands usable for chemical catalysis. We present the synthesis of six new homochiral diferroceno cycles potentially useful as P,O-, P,N- or P,S-ligands. Due to the stereoconservative nature of the S_N1 reaction at carbons adjacent to ferrocene units, we obtained a single diastereomer of the 8-membered diferroceno[c,f]heterophosphocines in all cases.

1. Introduction

Ferrocenes have been used successfully for decades in asymmetric transition-metal catalysis [1]. Metallocenes can be planar-chiral if the same Cp ring is decorated with different substituents [2]. In addition to academic research, ferrocenes have been employed industrially as well. The homochiral P,P-ligand Xyliphos is used in the industrial asymmetric hydrogenation of a metolachlor precursor [3].

With the expectation to increase the asymmetric induction, the chiral array was extended with the introduction of two ferrocene units. To date, there have been diferrocenyl ligands reported acting as N,N-ligands for Rh(I) [4], P,S-ligands for Pd [5], P,P-ligands for Rh(I) [6] and P,P,P-ligands for Ru(II) [7], Rh(III) [8] and Ni(II) [9] catalyzed reactions.

The asymmetric capabilities may be improved further by constraining the conformational freedom of the two ferrocene moieties, e.g., by ring-closing to end up with a diferroceno cycle, which would incorporate two planar-chiral ferrocene units. Xiao et al. have developed 7-membered P,N-ligands for Pd(II) and with these complexes achieved up to 86% e.e. in asymmetric allylic amination [10]. Smith et al. [11] and Barreiro et al. [12] developed 8-membered P & P,P-ligands applied in Au(I)-catalyzed hydroalkoxylation. In this article, we report the synthesis of six 8-membered cyclic phosphine ligands with two annelated ferrocene moieties and similar structural features.

2. Results and Discussion

The synthetic route towards homoannularly bridged diferrocenes 4 is shown in Scheme 1. We obtained the enantiopure diferrocenyl precursor (R,S_p,S_p,R)-1 [13,14] according to a known efficient literature procedure [12]. The phosphorous atom was protected quantitatively as phosphine oxide 2a using hydrogen peroxide or as phosphine sulfide 2b with elemental sulfur. The preparation of precursor 2b is reported in Reference [15].

Nucleophilic substitutions at the α-carbon adjacent to a ferrocene unit proceed via a carbenium ion stabilized by the aromatic system. In constrast to typical S_N1 reactions, however, these substitutions on the α-carbon take place stereo-conservatively [16]. Since preliminary experiments showed that the tertiary amino groups were inert to nucleophilic substitution, we attempted transformation of 2a and 2b to better leaving groups by methylation. Despite using a large excess (6 equiv) of methyl iodide, HRMS showed that only monoammonium salts 3a and 3b, respectively, were formed quantitatively. These salts could not be characterized by NMR, since they proved to be poorly soluble in CDCl₃, D₂O and DMSO-d₆ and were used without further purification in the follow-up experiments.

Next, we attempted to perform a Hoffmann elimination of salts 3a and 3b using Ag₂O in a water/dioxane mixture at mild conditions (50 °C) [17]. Instead of the expected mono-eliminated products, we obtained oxa-cycles 4a and 4b identified by NMR (see Supplementary Materials) in 11% and 9% yield, respectively, thus inadvertently producing 8-membered cycles potentially useful as P,O-ligands. Apparently, the Hoffmann elimination is disfavored compared to the reaction with the nucleophilic solvent. Presumably, these oxa-cycles were formed by a water molecule displacing the ammonium group intermolecularly and then displacing the amine group at the other ferrocenyl alkyl chain intramolecularly. In both cases, side products were formed as well, possibly by ring opening of the oxa cycles. In the first case, we obtained the dihydroxy hydrolytic side product 5 in 6% yield; in the latter case, we isolated the mono-eliminated decay product 6 in 6% yield.

Inspired by this finding, we attempted to cyclize mono-ammonium salts 3a and 3b with other bidentate nucleophiles. We intended to synthesize sulfur-bridged cycles 7a and 7b as well as nitrogen-bridged P,N cycles 8a and 8b by using NaHS and BnNH₂ as nucleophiles. We heated the respective nucleophile and crude ammonium salts 3a or 3b dissolved in water or ACN in a Schlenk tube following standard procedures ([10,18], respectively). In both cases we detected the desired diferroceno[c,f]heterophosphocines in the crude reaction mixture by HRMS but attempted purification via SiO₂ column chromatography merely yielded decay products formed by elimination.

A modified procedure (DMF, microwave heating) yielded less decomposed material and desired cycles were obtained by chromatography on the less acidic sorbens Al₂O₃. This allowed us to isolate and characterize all four intended cycles 7a (14%), 7b (15%), 8a (11%) and 8b (12%). In case of the N-benzyl cycles 8a and 8b, mono-eliminated side products 9 and 10 were isolated in 8% and 13% yield. In all six diferrocenocycles, impurities were detected by NMR. Repeated filtration or chromatography did not yield pure fractions.

3. Materials and Methods

3.1. General

Melting points were measured on a Reichelt Thermovar Kofler apparatus, uncorrected. Routine NMR spectra were recorded on a 400 MHz Bruker AVIII 400 spectrometer operating at 400.27 MHz (¹H), 100.66 MHz (¹³C) and 162.04 MHz (³¹P) with autosampler. ¹H-NMR spectra and ¹³C-NMR spectra used for substance characterization were recorded either on a 600 MHz Bruker AVIII 600 spectrometer operating (Bruker Biospin, Billerica, MA, USA) at 600.25 MHz (¹H) and 150.95 MHz (¹³C) or on a Bruker AVIII 700 spectrometer at 700.40 MHz (¹H) and 176.13 MHz (¹³C). ¹³C-NMR spectra were recorded in J-modulated mode. NMR chemical shifts are referenced to non-deuterated CHCl₃ residual shifts: At 7.26 ppm for ¹H-NMR, at 77.00 ppm to CDCl₃ for ¹³C-NMR and at 0.00 ppm to 85% H₃PO₄ for ³¹P-NMR. HRMS were recorded by a Bruker Maxis ESI oa-RTOF mass spectrometer equipped with a quadrupole analyzer ion guide.

MeCN and DCM were distilled from CaH₂. Reaction progress was monitored by TLC (SiO₂ or Al₂O₃ sheets with F 254 fluorescent indicator). Preparative column chromatography (MPLC) was carried out by an Biotage Isolera One automated flash chromatography instrument using self-packed columns containing either SiO₂–Macherey-Nagel silica gel 60 M (particle size 40–63 μm) or Al₂O₃–Merck aluminum oxide 90 standardized (activation grade II-III). All the other chemicals were analytical grade and used without further purification.

3.2. Synthesis

Bis{[(2S_p)-2-[(1R)-1-(dimethylamino)-ethyl]]ferrocenyl}phenyl phosphineoxide2a: [19]

Diaminophosphine 1 (630 mg, 1.02 mmol) was dissolved in MeOH (8.0 mL) and cooled in an ice bath. Aqueous H₂O₂ (30%; 210 μL, 1.85 mmol, 1.82 equiv.) was added to the orange solution. The solution was warmed to r.t. and stirred for 40 min. The reaction mixture was quenched by adding 10% aqueous NaHSO₃ solution followed by sufficient aqueous NaHCO₃ solution until pH 7 was reached. The aqueous suspension was extracted using DCM (3 × 8 mL). The combined organic fractions were dried over MgSO₄ and the solvent was removed under reduced pressure to yield diaminophosphineoxide 2a (647 mg, quant.) as an orange solid. The highly polar product was pure enough for the next step.

¹H-NMR (600 MHz, CDCl₃) δ = 7.80 (dd, J = 11.4, 8.0 Hz, 2H, C₆H₅); 7.43–7.35 (m, 3H, C₆H₅); 4.52 (q, J = 6.8 Hz, 1H, C₂H₄); 4.49 (m, 1H, C₅H₃); 4.44 (m, 1H, C₅H₃); 4.36 (m, 1H, C₅H₃); 4.33 (m, 1H, C₅H₃); 4.28 (m, 1H, C₅H₃); 4.25 (m, 1H, C₅H₃); 4.23 (s, 5H, C₅H₅); 3.73 (s, 5H, C₅H₅); 3.31–3.26 (m, 1H, C₂H₄); 2.26 (s, 6H, NCH₃); 1.53 (s, 6H, NCH₃); 1.47 (d, J = 6.8 Hz, 3H, C₂H₄); 1.21–1.15 (m, 3H, C₂H₄) ppm. ¹³C-NMR δ = 130.07 (d, J_CP = 9.2 Hz, CH, C₆H₅); 129.44 (CH, C₆H₅); 127.20 (CH, C₆H₅); 89.90 (C_q, C₅H₃); 85.23 (C_q, C₅H₃); 75.14 (C_q, C₅H₃); 73.60 (CH, C₅H₃); 71.89 (CH, C₅H₃); 71.25 (C_q, C₅H₃); 71.72 (d, J_CP = 14.9 Hz, CH, C₅H₃); 70.34 (CH, C₅H₅); 70.20 (CH, C₅H₅); 69.59 (d, J_CP = 9.8 Hz, CH, C₅H₃); 69.32 (CH, C₅H₃); 67.91 (CH, C₅H₃); 55.17 (CH, C₂H₄); 40.97 (CH₃, NCH₃); 34.66 (CH, C₂H₄); 14.93 (CH₃, NCH₃); 13.05 (CH₃, C₂H₄); 13.04 (CH₃, C₂H₄) ppm; 1 C_q not observed. ³¹P-NMR δ = 29.59 (s) ppm. HRMS: m/z calculated for C₃₄H₄₁Fe₂N₂OP [M + H]⁺: 637.1734, found: 637.1726.

{[(2S_p)-2-[(1R)-1-(dimethylamino)-ethyl]]ferrocenyl}{[(2S_p)-2-[(1R)-1-(trimethylammonium)-ethyl]]ferrocenyl}phenyl phosphineoxide iodide (3a): [20]

Diaminophosphineoxide 2a (642 mg, 1.01 mmol) was dissolved in 15 mL of dry MeCN and 15 mL of dry DCM in a flame-dried Schlenk tube under Ar. MeI (375 μL, 6.00 mmol, 5.94 equiv.) was added to the solution and stirred for 2 h at r.t. Precipitation of ammonium iodide 3a was induced by adding Et₂O (10 mL) yielding the salt as an orange powder (780 mg, quant.). HRMS: m/z calculated for C₃₅H₄₄Fe₂IN₂OP [M − I]⁺: 651.1885, found: 651.1868.

{[(2S_p)-2-[(1R)-1-(dimethylamino)-ethyl]]ferrocenyl}{[(2S_p)-2-[(1R)-1-(trimethylammonium)-ethyl]]ferrocenyl}phenyl phosphinesulfide iodide (3b):

Similar procedure as given for 3a yielded 3b from 2b in quantitative yield.

HRMS: m/z calculated for C₃₅H₄₄Fe₂IN₂PS [M − I]⁺: 667.1662, found: 667.1644.

(2S_p,4R,6R,8S_p)-4,6-Dimethyl-1-phenyl-diferroceno-5-oxa-1-phosphineoxide (4a):

Ammonium iodide salt 3a (87 mg, 0.11 mmol) was dissolved in water (1.5 mL) and dioxane (1 mL). The solution was warmed to 50 °C and Ag₂O (19 mg, 0.08 mmol, 1.5 equiv.) was added. The resulting suspension was stirred for 1 h. After complete consumption of the ammonium iodide salt 3a the mixture was cooled to r.t. and the solid material was removed by filtration. The solution was extracted with DCM (3 × 3 mL) and the combined organic fractions were washed with water (10 mL) and brine (10 mL) and dried (MgSO₄). The solvent was removed under reduced pressure and the residue was purified by MPLC (SiO₂, 75→100% EtOAc in heptane) yielding oxa cycle 4a (7 mg, 11%) as a glassy orange solid and dihydroxyphosphineoxide 5 (4 mg, 6%).

4a: ¹H-NMR (600 MHz, CDCl₃) δ = 8.02–7.95 (m, 2H, C₆H₅); 7.51–7.47 (m, 3H, C₆H₅); 5.13 (s, 1H, C₅H₃); 4.65 (q, J = 6.5 Hz, 1H, C₂H₄); 4.52 (s, 1H, C₅H₃); 4.45 (s, 1H, C₅H₃); 4.43 (s, 1H, C₅H₃); 4.38–4.36 (m, 1H, C₅H₃); 4.36–4.34 (m, 1H, C₅H₃); 4.24 (s, 5H, C₅H₅); 4.12 (q, J = 7.2 Hz, 1H, C₂H₄); 3.73 (s, 5H, C₅H₅); 1.53 (d, J = 6.5 Hz, 3H, C₂H₄); 1.51 (d, J = 6.4 Hz, 3H, C₂H₄) ppm. ¹³C-NMR δ = 138.11 (d, J_CP = 112.4 Hz, C_q, C₆H₅); 131.56 (d, J_CP = 10.0 Hz, CH, C₆H₅); 131.14 (d, J_CP = 2.6 Hz, CH, C₆H₅); 127.79 (d, J_CP = 12.3 Hz, CH, C₆H₅); 91.83 (d, J_CP = 13.2 Hz, C_q, C₅H₃); 88.93 (d, J_CP = 14.1 Hz, C_q, C₅H₃); 76.12 (d, J_CP = 10.2 Hz, C_q, C₅H₃); 75.32 (C_q, C₅H₃); 74.74 (d, J_CP = 10.6 Hz, CH, C₅H₃); 73.78 (d, J_CP = 13.5 Hz, CH, C₅H₃); 70.44 (CH, C₅H₅); 70.17 (d, J_CP = 11.1 Hz, CH, C₅H₃); 70.16 (CH, C₅H₅); 69.88 (d, J_CP = 10.2 Hz, CH, C₅H₃); 69.15 (d, J_CP = 9.8 Hz, CH, C₅H₃); 69.01 (d, J_CP = 10.1, CH, C₅H₃); 68.31 (CH, C₂H₄); 66.13 (CH, C₂H₄); 20.93 (CH₃, C₂H₄); 20.78 (CH₃, C₂H₄) ppm. ³¹P-NMR δ = 31.13 (s) ppm. HRMS: m/z calculated for C₃₀H₂₉Fe₂O₂P [M + Na]⁺: 587.0502, found: 587.0507; [2M + Na]⁺ 1151.1106, found: 1151.1113.

5: ¹H-NMR (600 MHz, CDCl₃) δ = 7.95–7.90 (m, 2H, C₆H₅); 7.55–7.50 (m, 3H, C₆H₅); 5.93 (d, J = 5.4 Hz, 1H, OH); 5.22 (m, 1H, C₅H₃); 4.76 (m, 1H, C₂H₄); 4.57 (d, J = 5.4 Hz, 1H, C₅H₃); 4.56 (s, 1H, OH); 4.48 (pq, J = 2.4 Hz, 1H, C₅H₃); 4.44 (m, 1H, C₅H₃); 4.41 (m, 2H, C₅H₃, C₂H₄); 4.38 (pq, J = 2.4 Hz, 1H, C₅H₃); 4.17 (s, 5H, C₅H₅); 3.75 (s, 5H, C₅H₅); 1.64 (d, J = 6.7 Hz, 3H, C₂H₄); 1.21 (d, J = 6.7 Hz, 3H, C₂H₄) ppm. ¹³C-NMR δ = 136.54 (d, J_CP = 110.2 Hz, C_q, C₆H₅); 131.55 (d, J_CP = 2.9 Hz, CH, C₆H₅); 129.93 (d, J_CP = 9.5 Hz, CH, C₆H₅); 128.45 (d, J_CP = 12.1 Hz, CH, C₆H₅); 98.73 (d, J_CP = 10.4 Hz, C_q, C₅H₃); 97.57 (d, J_CP = 11.3 Hz, C_q, C₅H₃); 72.64 (C_q, C₅H₃); 71.85 (C_q, C₅H₃); 71.75 (d, J_CP = 14.6 Hz, CH, C₅H₃); 70.97 (d, J_CP = 15.0 Hz, CH, C₅H₃); 70.81 (d, J_CP = 10.0 Hz, CH, C₅H₃); 70.46 (CH, C₅H₅); 70.45 (CH, C₅H₅); 70.27 (d, J_CP = 11.0 Hz, CH, C₅H₃); 69.86 (d, J_CP = 11.0 Hz, CH, C₅H₃); 69.64 (d, J_CP = 9.8 Hz, CH, C₅H₃); 65.35 (CH, C₂H₄); 65.30 (CH, C₂H₄); 22.98 (CH₃, C₂H₄); 21.95 (CH₃), C₂H₄) ppm. ³¹P-NMR δ = 38.45 (s) ppm. HRMS: m/z calculated for C₃₀H₃₁Fe₂O₃P [M + Na]⁺: 605.0607, found: 605.0595; [2M + Na]⁺: 1187.1317, found: 1187.1295.

(2S_p,4R,6R,8S_p)-4,6-Dimethyl-1-phenyl-diferroceno-5-oxa-1-phosphinesulfide (4b):

Similar procedure as given for 4a yielded cycle 4b from 3b in 9% yield and 6% of eliminated side product 6.

4b: ¹H-NMR (600 MHz, CDCl₃) δ = 8.13–8.07 (m, 2H, C₆H₅); 7.45–7.38 (m, 3H, C₆H₅); 5.44 (m, 1H, C₅H₃); 4.61 (m, 1H, C₅H₃); 4.59–4.55 (m, 2H, C₂H₄); 4.47 (m, 1H, C₅H₃); 4.45–4.39 (m, 2H, C₅H₃); 4.37 (m, 1H, C₅H₃); 4.16 (s, 5H, C₅H₅); 4.00 (s, 5H, C₅H₅); 1.45 (d, J = 6.4 Hz, 3H, C₂H₄); 1.41 (d, J = 6.7 Hz, 3H, C₂H₄) ppm. ¹³C-NMR δ = 137.31 (d, J_CP = 90.0 Hz, C_q, C₆H₅); 132.51 (d, J_CP = 11.2 Hz, CH, C₆H₅); 130.82 (d, J_CP = 3.0 Hz, CH, C₆H₅); 127.33 (d, J_CP = 12.7 Hz, CH, C₆H₅); 92.84 (d, J_CP = 9.9 Hz, C_q, C₅H₃); 89.73 (d, J_CP = 10.2 Hz, C_q, C₅H₃); 77.97 (C_q, C₅H₃); 77.42 (d, J_CP = 15.5 Hz, CH, C₅H₃); 76.15 (C_q, C₅H₃); 75.04 (d, J_CP = 15.2 Hz, CH, C₅H₃); 70.82 (d, J_CP = 8.8 Hz, CH, C₅H₃); 70.81 (CH, C₅H₅); 70.41 (CH, C₅H₅); 69.58 (d, J_CP = 11.7 Hz, CH, C₅H₃); 69.41 (d, J_CP = 11.5 Hz, CH, C₅H₃); 69.33 (d, J_CP = 9.0 Hz, CH, C₅H₃); 65.79 (2 CH, C₂H₄); 21.22 (CH₃, C₂H₄); 20.56 (CH₃, C₂H₄) ppm. ³¹P-NMR δ = 43.82 (s) ppm. HRMS: m/z calculated for C₃₀H₂₉Fe₂OPS [M + Na]⁺: 603.0273, found: 603.0279; [2M + Na]⁺ 1183.0649, found: 1183.0662.

6: ¹H-NMR (600 MHz, CDCl₃) δ = 8.10 (dd, J = 17.6, 10.8 Hz, 1H, C₂H₃); 7.87–7.81 (m, 2H, C₆H₅); 7.51–7.42 (m, 3H, C₆H₅); 5.49 (dd, J = 17.6, 1.6 Hz; 1H, C₂H₃); 5.23–5.17 (m, 1H, C₅H₃); 5.20 (dd, J = 10.8, 1.7 Hz, 1H, C₂H₃); 4.88 (m, 1H, C₅H₃); 4.49 (m, 1H, C₅H₃); 4.34 (s, 5H, C₅H₅); 4.33 (m, 1H, C₅H₃); 4.24 (m, 1H, C₅H₃); 4.17 (s, 5H, C₅H₅); 3.77 (m, 1H, C₅H₃); 3.71 (m, 1H, OH); 2.41 (d, J = 5.3 Hz; 1H, C₂H₄); 1.26 (d, J = 6.6 Hz, 3H, C₂H₄) ppm. ¹³C-NMR δ = 135.30 (d, J_CP = 87.1 Hz, C_q, C₆H₅); 134.25 (CH, C₆H₅); 132.10 (d, J_CP = 10.3 Hz, CH, C₆H₅); 131.38 (d, J_CP = 2.8 Hz, CH, C₆H₅); 127.96 (d, J_CP = 12.1 Hz, CH, C₂H₃); 111.74 (CH₂, C₂H₃); 94.90 (d, J_CP = 12.3 Hz, C_q, C₅H₃); 88.43 (d, J_CP = 11.8 Hz, C_q, C₅H₃); 78.56 (d, J_CP = 95.4 Hz, C_q, C₅H₃); 75.05 (d, J_CP = 12.0 Hz, CH, C₅H₃); 74.97 (d, J_CP = 12.6 Hz, CH, C₅H₃); 73.48 (d, J_CP = 96.0 Hz, C_q, C₅H₃); 71.22 (CH, C₅H₅); 71.00 (d, J_CP = 9.7 Hz, CH, C₅H₃); 70.72 (CH, C₅H₅); 70.10 (d, J_CP = 10.4 Hz, CH, C₅H₃); 68.38 (d, J_CP = 9.1 Hz, CH, C₅H₃); 68.04 (d, J_CP = 10.5 Hz, CH, C₅H₃); 64.38 (CH, C₂H₄); 21.91 (CH₃, C₂H₄) ppm. ³¹P-NMR δ = 40.51 (s) ppm. HRMS: m/z calculated for C₃₀H₂₉Fe₂OPS [M]⁺ 580.0376, found: 580.0360; [M + Na]⁺ 603.0273, found: 603.0273; [M + K]⁺ 619.0013, found: 619.0018.

(2S_p,4R,6R,8S_p)-4,6-Dimethyl-1-phenyl-diferroceno-5-sulfa-1-phosphineoxide (7a):

Ammonium iodide salt 3a (75 mg, 0.10 mmol) and NaHS·H₂O (7.5 mg, 0.10 mmol, 1.0 equiv.) were dissolved in 8 mL of DMF and heated for 8 min at 100 °C in a microwave oven. The mixture was cooled to r.t., 10 mL of DCM were added and the organic layer was washed four times with 50 mL of water each, once with 20 mL of brine and dried over MgSO₄. The solvent was removed under reduced pressure and the residue was purified by column chromatography (Al₂O₃; 0→100% EtOAc in heptane) yielding 14% of the intended sulfidephosphineoxide diferrocenyl cycle 7a (8 mg) as a glassy orange solid.

¹H-NMR(700 MHz, CDCl₃) δ = 7.92–7.85 (m, 2H, C₆H₅); 7.52–7.48 (m, 3H, C₆H₅); 5.30 (s, 1H, C₅H₃); 5.11 (s, 1H, C₅H₃); 4.52 (s, 1H, C₅H₃); 4.37 (s, 1H, C₅H₃); 4.36 (s, 1H, C₅H₃); 4.35 (s, 5H, C₅H₅); 4.24 (s, 1H, C₅H₃); 3.83 (s, 5H, C₅H₅); 3.74 (q, J = 6.9 Hz, 1H, C₂H₄); 3.21 (q, J = 7.1 Hz, 1H, C₂H₄); 1.58 (d, J = 7.2 Hz, 3H, C₂H₄); 1.51 (d, J = 7.0 Hz, 3H, C₂H₄) ppm. ¹³C-NMR δ = 138.59 (d, J_CP = 111.7 Hz, C_q, C₆H₅); 131.81 (d, J_CP = 9.8 Hz, CH, C₆H₅); 131.17 (d, J_CP = 2.7 Hz, CH, C₆H₅); 127.66 (d, J_CP = 12.1 Hz, CH, C₆H₅); 96.88 (d, J_CP = 13.2 Hz, C_q, C₅H₃); 92.56 (d, J_CP = 13.8 Hz, C_q, C₅H₃); 74.83 (d, J_CP = 37.5 Hz, C_q, C₅H₃); 74.20 (d, J_CP = 42.9 Hz, C_q, C₅H₃); 73.50 (d, J_CP = 10.7 Hz, CH, C₅H₃); 73.32 (d, J_CP = 13.8 Hz, CH, C₅H₃); 70.36 (CH, C₅H₅); 70.32 (d, J_CP = 11.8 Hz, CH, C₅H₃); 70.11 (d, J_CP = 10.1 Hz, CH, C₅H₃); 69.95 (CH, C₅H₅); 67.45 (d, J_CP = 9.6 Hz, CH, C₅H₃); 67.43 (d, J_CP = 10.0 Hz, CH, C₅H₃); 36.62 (CH, C₂H₄); 35.71 (CH, C₂H₄); 20.28 (CH₃, C₂H₄); 20.20 (CH₃, C₂H₄) ppm. ³¹P-NMR δ = 29.47 (s) ppm. HRMS: m/z calculated for C₃₀H₂₉Fe₂OPS [M]⁺: 580.0376, found: 580.0369.

(2S_p,4R,6R,8S_p)-4,6-Dimethyl-1-phenyl-diferroceno-5-sulfa-1-phosphinesulfide (7b):

Similar procedure as given for 7a yielded cycle 7b from 3b in 15% yield.

¹H-NMR (600 MHz, CDCl₃) δ = 7.95–7.90 (m, 2H, C₆H₅); 7.47–7.43 (m, 1H, C₆H₅); 7.43–7.38 (m, 2H, C₆H₅); 5.38 (m, 1H, C₅H₃); 4.64 (q, J = 2.2 Hz, 1H, C₅H₃); 4.50 (m, 1H, C₅H₃); 4.42–4.40 (m, 1H, C₅H₃); 4.40–4.38 (m, 2H, C₅H₃); 4.28 (s, 5H, C₅H₅); 4.20 (s, 5H, C₅H₅); 3.63 (q, J = 6.8 Hz, 1H, C₂H₄); 2.96 (q, J = 7.3 Hz, 1H, C₂H₄); 1.54 (d, J = 7.3 Hz, 3H, C₂H₄); 1.31 (d, J = 6.8 Hz, 3H, C₂H₄) ppm. ¹³C-NMR δ = 137.96 (d, J_CP = 88.8 Hz, C_q, C₆H₅); 132.57 (d, J_CP = 11.0 Hz, CH, C₆H₅); 131.13 (d, J_CP = 3.1 Hz, CH, C₆H₅); 127.45 (d, J_CP = 12.5 Hz, CH, C₆H₅); 96.94 (d, J_CP = 11.0 Hz, C_q, C₅H₃); 92.90 (d, J_CP = 10.6 Hz, C_q, C₅H₃); 75.32 (d, J_CP = 15.6 Hz, CH, C₅H₃); 75.02 (C_q, C₅H₃); 74.42 (C_q, C₅H₃); 73.75 (d, J_CP = 15.0 Hz, CH, C₅H₃); 70.91 (CH, C₅H₅); 70.29 (CH, C₅H₅); 70.22 (d, J_CP = 11.5 Hz, CH, C₅H₃); 70.05 (d, J_CP = 11.5 Hz, CH, C₅H₃); 68.58 (d, J_CP = 8.6 Hz, CH, C₅H₃); 68.34 (d, J_CP = 9.1 Hz, CH, C₅H₃); 37.27 (CH, C₂H₄); 35.39 (CH, C₂H₄); 20.82 (CH₃, C₂H₄); 20.79 (CH₃, C₂H₄) ppm. ³¹P-NMR δ = 42.92 (s) ppm. HRMS: m/z calculated for C₃₀H₂₉Fe₂PS₂ [M]⁺: 596.0147, found: 596.0141.

(2S_p,4R,6R,8S_p)-4,6-Dimethyl-5-benzyl-1-phenyl-diferroceno-5-amino-1-phosphineoxide (8a):

Ammonium iodide salt 3a (77 mg, 0.10 mmol) and BnNH₂ (11 μL, 0.10 mmol, 1.0 equiv.) were dissolved in 8 mL of DMF and heated for 8 min at 100 °C in a microwave oven. The reaction mixture was cooled to r.t., 10 mL of DCM were added and the organic solution was washed four times with 50 mL of water each, once with 20 mL of brine and dried over MgSO₄. The solvent was removed under reduced pressure and the residue was purified by column chromatography (Al₂O₃; 0→100% EtOAc in heptane) yielding 11% of the intended benzylic aminephosphineoxide diferroceno cycle 8a (7 mg) as a glassy orange solid as well as 8% of the sec. amine elimination product 9 (5 mg).

8a: ¹H-NMR (600 MHz, CDCl₃) δ = 8.11–8.06 (m, 2H, C₆H₅); 7.57–7.50 (m, 3H, C₆H₅); 7.41 (d, J = 7.4 Hz, 2H, C₇H₇); 7.28–7.24 (m, 2H, C₇H₇); 7.17 (pt, J = 7.3 Hz, 1H, C₇H₇); 4.80 (m, 1H, C₅H₃); 4.47 (m, 1H, C₅H₃); 4.39 (m, 2H, C₅H₃); 4.35 (m, 1H, C₅H₃); 4.29 (m, 1H, C₅H₃); 4.24 (s, 5H, C₅H₅); 4.04 (q, J = 6.8 Hz, 1H, C₂H₄); 3.94 (d, J = 16.4 Hz, 1H, C₇H₇); 3.90 (s, 5H, C₅H₅); 3.73 (q, J = 6.6 Hz, 1H, C₂H₄); 3.39 (d, J = 16.3 Hz, 1H, C₇H₇); 1.26 (d, J = 6.5 Hz, 3H, C₂H₄); 1.25 (d, J = 6.9 Hz, 3H, C₂H₄) ppm. ¹³C-NMR δ = 143.69 (C_q, C₇H₇); 137.02 (d, J_CP = 110.2 Hz, C_q, C₆H₅); 132.35 (d, J_CP = 9.38 Hz, CH, C₆H₅); 131.20 (d, J_CP = 2.7 Hz, CH, C₆H₅); 127.82 (CH, C₇H₇); 127.63 (d, J_CP = 5.5 Hz, CH, C₆H₅); 127.54 (d, J_CP = 6.6, CH, C₇H₇); 126.01 (CH, C₇H₇); 93.20 (d, J_CP = 13.2 Hz, C_q, C₅H₃); 93.06 (d, J_CP = 13.6 Hz, C_q, C₅H₃); 75.38 (d, J_CP = 22.2 Hz, C_q, C₅H₃); 74.62 (d, J_CP = 18.2 Hz, C_q, C₅H₃); 73.65 (d, J_CP = 11.4 Hz, CH, C₅H₃); 72.64 (d, J_CP = 13.9 Hz, CH, C₅H₃); 70.45 (CH, C₅H₅); 70.39 (d, J_CP = 10.6 Hz, CH, C₅H₃); 70.17 (CH, C₅H₅); 69.81 (d, J_CP = 11.2 Hz, CH, C₅H₃); 69.58 (d, J_CP = 9.6 Hz, 2 CH, C₅H₃); 54.66 (CH, C₂H₄); 53.55 (CH, C₂H₄); 53.12 (CH₂, C₇H₇); 21.44 (CH₃, C₂H₄); 20.52 (CH₃, C₂H₄) ppm. ³¹P-NMR δ = 29.63 (s) ppm. HRMS: m/z calculated for C₃₇H₃₆Fe₂NOP [M + H]⁺: 654.1306, found: 654.1306; [M + Na]⁺: 676.1126, found: 676.1129.

9: ¹H-NMR (600 MHz, CDCl₃) δ = 7.80–7.69 (m, 3H, C₆H₅); 7.55–7.34 (m, 2H, C₆H₅); 7.33–7.27 (m, 3H, C₇H₇); 7.16–7.10 (m, 2H, C₇H₇); 6.84–6.80 (m, 1H, C₂H₃); 5.46 (dd, J = 17.7, 1.6 Hz, 1H, C₂H₃); 5.16 (dd, J = 10.8, 10.6 Hz, 1H, C₂H₃); 4.86 (m, 1H, C₅H₃); 4.49 (m, 1H, C₂H₄); 4.41 (pq, J = 2.4 Hz, 1H, C₅H₃); 4.39 (pt, J = 2.0 Hz, 1H, C₅H₃); 4.36 (m, 1H, C₅H₃); 4.27 (s, 5H, C₅H₅); 4.24 (s, 1H, C₅H₃); 3.93 (s, 5H, C₅H₅); 3.89 (d, J = 4.3 Hz, 1H, C₅H₃); 3.20 (s, 2H, C₇H₇); 1.43 (d, J = 6.6, 3H, C₂H₄) ppm. ¹³C-NMR δ = 133.52 (C_q, C₆H₅); 131.28 (CH, C₆H₅); 130.29 (CH, C₆H₅); 128.38 (CH, C₆H₅); 128.26 (CH, C₇H₇); 128.15 (CH, C₇H₇); 127.95 (CH, C₇H₇); 111.43 (CH₂, C₂H₃); 90.13 (C_q, C₂H₃); 86.08 (C_q, C₅H₃); 71.65 (CH, C₅H₃); 71.26 (CH, C₅H₃); 71.17 (CH, C₅H₃); 70.81 (CH, C₅H₃); 70.73 (CH, C₅H₅); 70.31 (CH, C₅H₅); 70.28 (CH, C₅H₃); 69.58 (CH, C₅H₃); 67.25 (CH, C₂H₄); 53.15 (CH₂, C₇H₇); 20.56 (CH₃, C₂H₄) ppm; 4 C_q not observed. ³¹P-NMR δ = 30.54 (s) ppm. HRMS: m/z calculated for C₃₇H₃₆Fe₂NOP [M + H]⁺: 654.1306, found: 654.1314.

(2S_p,4R,6R,8S_p)-4,6-Dimethyl-5-benzyl-1-phenyl-diferroceno-5-amino-1-phosphinesulfide (8b):

Similar procedure as given for 8a yielded cycle 8b from 3b in 12% yield and side product 10 in 13% yield.

8b: ¹H-NMR (600 MHz, CDCl₃) δ = 7.91 (ddd, J = 13.6, 7.8, 1.5 Hz, 2H, C₆H₅); 7.47–7.41 (m, 3H, C₆H₅); 7.31 (d, J = 7.5 Hz, 2H, C₇H₇); 7.28–7.24 (m, 2H, C₇H₇); 7.17 (pt, J = 7.2 Hz, 1H, C₇H₇); 5.36 (m, 1H, C₅H₃); 4.65 (dd, J = 4.3, 2.4 Hz, 1H, C₅H₃); 4.57 (m, 1H, C₅H₃); 4.48 (m, 1H, C₅H₃); 4.46 (m, 1H, C₅H₃); 4.38 (m, 1H, C₅H₃); 4.21 (s, 5H, C₅H₅); 4.14 (s, 5H, C₅H₅); 3.98 (s, 1H, C₇H₇); 3.73 (q, J = 6.9 Hz, 1H, C₂H₄); 3.46 (q, J = 6.3 Hz, 1H, C₂H₄); 3.19 (d, J = 16.9 Hz, 1H, C₇H₇); 1.19 (d, J = 7.0 Hz, 3H, C₂H₄); 1.09 (d, J = 6.4 Hz, 3H, C₂H₄) ppm. ¹³C–NMR δ = 144.18 (C_q, C₇H₇); 138.58 (d, J_CP = 89.2 Hz, C_q, C₆H₅); 132.79 (d, J_CP = 11.3 Hz, CH, C₆H₅); 130.88 (d, J_CP = 3.0 Hz, CH, C₆H₅); 127.88 (CH, C₇H₇); 127.32 (d, J_CP = 12.4 Hz, CH, C₆H₅); 127.00 (CH, C₇H₇); 126.05 (CH, C₇H₇); 93.39 (d, J_CP = 11.1 Hz, C_q, C₅H₃); 92.56 (d, J_CP = 12.1 Hz, C_q, C₅H₃); 75.55 (C_q, C₅H₃); 75.47 (d, J_CP = 15.6 Hz, CH, C₅H₃); 74.93 (C_q, C₅H₃); 73.93 (d, J_CP = 15.0 Hz, CH, C₅H₃); 71.41 (d, J_CP = 9.7 Hz, CH, C₅H₃); 71.01 (CH, C₅H₅); 70.35 (CH, C₅H₅); 70.07 (d, J_CP = 11.5 Hz, CH, C₅H₃); 69.96 (d, J_CP = 9.1 Hz, CH, C₅H₃); 69.85 (d, J_CP = 11.4 Hz, CH, C₅H₃); 55.79 (CH, C₂H₄); 53.18 (CH₂, C₇H₇); 52.14 (CH, C₂H₄); 22.12 (CH₃, C₂H₄); 21.35 (CH₃, C₂H₄) ppm. ³¹P-NMR δ = 43.41 (s) ppm. HRMS: m/z calculated for C₃₇H₃₆Fe₂NPS [M + H]⁺: 670.1078, found: 670.1068.

10: M.p.: 179–180 °C (decomposition). ¹H-NMR (600 MHz, CDCl₃) δ = 7.82 (dd, J = 12.7, 6.5 Hz, 2H, C₆H₅); 7.29–7.23 (m, 3H, C₆H₅); 7.13–7.08 (m, 3H, C₇H₇); 6.80–6.76 (m, 3H, C₇H₇, C₂H₃); 5.47 (dd, J = 17.7, 1.6 Hz, 1H, C₂H₃); 5.17 (dd, J = 10.8, 1.6 Hz, 1H, C₂H₃); 4.86 (m, 1H, C₅H₃); 4.62 (q, J = 6.7 Hz, 1H, C₂H₄); 4.56 (m, 1H, C₅H₃); 4.33 (s, 5H, C₅H₅); 4.30 (m, 1H, C₅H₃); 4.24 (dd, J = 4.1, 2.6 Hz, 1H, C₅H₃); 4.12 (s, 5H, C₅H₅); 3.77 (m, 1H, C₅H₃); 3.67 (m, 1H, C₅H₃); 3.21 (dd, J = 23.6, 12.8 Hz, 2H, C₇H₇); 1.45 (d, J = 6.6 Hz, 3H, C₂H₄) ppm. ¹³C-NMR δ = 140.46 (C_q, C₇H₇); 135.15 (d, J_CP = 86.3 Hz, C_q, C₆H₅); 134.47 (CH, C₇H₇); 131.80 (d, J_CP = 10.2 Hz, CH, C₆H₅); 131.14 (d, J_CP = 2.9 Hz, CH, C₆H₅); 127.85 (CH, C₇H₇); 127.82 (d, J_CP = 11.4 Hz, CH, C₆H₅); 127.78 (CH, C₇H₇); 126.14 (CH, C₂H₃); 111.48 (CH₂, C₂H₃); 95.12 (d, J_CP = 12.7 Hz, C_q, C₅H₃); 88.55 (d, J_CP = 12.0 Hz, C_q, C₅H₃); 77.91 (d, J_CP = 95.5 Hz, C_q, C₅H₃); 75.03 (d, J_CP = 12.2 Hz, CH, C₅H₃); 74.42 (d, J_CP = 12.1 Hz, CH, C₅H₃); 73.98 (d, J_CP = 95.4 Hz, C_q, C₅H₃); 71.15 (CH, C₅H₅); 71.10 (d, J_CP = 10.1 Hz, CH, C₅H₃); 70.67 (CH, C₅H₅); 69.97 (d, J_CP = 10.2 Hz, CH, C₅H₃); 68.22 (d, J_CP = 9.1 Hz, CH, C₅H₃); 67.94 (d, J_CP = 10.6 Hz, CH, C₅H₃); 50.71 (CH₂, C₇H₇); 50.08 (CH, C₂H₄); 19.53 (CH₃, C₂H₄) ppm. ³¹P-NMR δ = 39.55 (s) ppm. HRMS: m/z calculated for C₃₇H₃₆Fe₂NPS [M + H]⁺: 670.1078, found: 670.1075.