Efficient and stereoselective synthesis of monomeric and bimetallic pincer complexes containing Pd-bonded stereogenic carbons

Abstract

Enantiopure pyridyl-functionalized tertiary phosphines and diphosphines containing one or two stereogenic carbon centers were prepared efficiently by catalytic asymmetric hydrophosphination. The tertiary phosphines were oxidized to the corresponding oxides or sulfides by treatment with aq. H₂O₂ or elemental sulfur respectively. Chemoselective cyclopalladation of the phosphorus(V) species under mild reaction conditions generated the corresponding monomeric or bimetallic N–C(sp³)–E (E = O, S) Pd pincer complexes in high isolated yields (63–97%). All the new pincer complexes contain palladium-bound stereogenic carbons which are generated stereospecifically via the metal complexation process.

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Introduction

Since the first reports in the 1970s,¹ transition metal pincer complexes have enjoyed growing attention due to their well-defined structures and reactivities.² These complexes frequently possess exceptional thermal and chemical stabilities, and have found wide applications as catalysts.³ Of all the transition metals, palladium pincer complexes are regarded as one of the most important and valuable tools in modern organic synthesis.^2c Highly versatile, their electronic and stereogenic properties may be modified at multiple sites such as the donor atoms E, pendant arms R, metal center M and counteranion/ancillary ligand X (Fig. 1). Intriguingly, while the pincer architecture can accommodate a wide variety of donors (E = O,⁴ N, P, S⁵ etc.), aryl EC(sp²)E pincer complexes dominate the literature possibly due to the ease of their syntheses.² Instances of aliphatic pincer complexes with C(sp³)–M bonds are visibly lacking,⁶ even more so for palladium variants.^6b,7

Fig. 1 Typical structures of square planar ECE′-type pincer complexes.

The aliphatic EC(sp³)E palladium pincer complexes face considerable challenges in their syntheses, and direct cyclometalation via C(sp³)–H activation is notoriously challenging.⁷ Consequently, of the limited reports on aliphatic transition metal pincer complexes with C(sp³)–M bonds, PC(sp³)HP-type preligands comprising of –PPh₂,⁸ –PtBu₂,⁹ –PiPr₂ ¹⁰ etc. as the donor arms formed the majority of these synthetically challenging complexes. The presence of the phosphorus donor atoms allow pre-coordination to the metal center, hence facilitating the interaction of PC(sp³)HP-type preligand with the metal and subsequently, activation of the C–H bond.¹¹ Other donors (E = N, S, O etc.) are correspondingly scarce in literature, for both symmetrical EC(sp³)E and unsymmetrical EC(sp³)E′ palladium pincer complexes. In addition, chiral variants of these aliphatic palladium pincer complexes are notably lacking,^7f,g despite the inherent prochirality of the central-carbon in E–C(sp³)H₂–E′ pincer preligands. Similar to P-chiral ligands, introduction of controlled chirality around donor atoms may bear heavily on the design of auxiliaries for chiral metal catalysts.

Moreover, chiral unsymmetrical pincer complexes pose considerable challenges which can complicate the syntheses of optically pure aliphatic EC(sp³)E′ pincer complexes.¹² The flexible aliphatic carbon backbones might allow possible hydride migration pathways as reported with iridium and ruthenium complexes,¹³ which contributes to further complications. However, due to unusual singular properties arising from the aliphatic pincer architecture,¹⁴ much interest has been generated towards such complexes. In general, aliphatic C(sp³) palladium pincer complexes have been known to: (1) undergo α-hydride abstraction to form carbene complexes,^11a and (2) possess higher electron densities on the metal centers due to the electron-rich aliphatic backbones,^14a thus (3) resulting in higher reactivities as compared to their aryl C(sp²)-counterparts.^14b,c

Furthermore, it is noteworthy that preparation of optically pure cyclopalladated complexes with Pd–C*(sp³) stereogenic centers have traditionally been reported with chiral resolving agents (such as amino acids or palladacycles), followed by physical separation techniques (such as recrystallization or column chromatography), consequently affording the chiral complexes in low yields.^4,15

Due to limited instances in which the properties of C(sp³)–M bonds have been studied and/or successfully applied in literature, we believe that overcoming challenges associated with the syntheses of aliphatic EC(sp³)E′ pincer complexes is of paramount importance towards the development and exploration of their unique architectures and applications in catalysis.

Herein, we report the efficient syntheses, purification and characterization of optically pure aliphatic NC(sp³)E-type (E = O, S) Pd pincer complexes generated under mild conditions. The general synthetic procedure was applied to a series of different substrates, and of notable interest is the enantioselective formation of several novel bimetallic NC(sp³)E complexes bearing C-stereogenic centers. The C-stereogenic centers on the preligands were installed via an efficient asymmetric catalytic P–H bond addition reaction, achieving >99% ee and/or de without the need for optical resolution of the isomers, which is inherently time-consuming, inefficient and laborious.

Results and discussion

Syntheses of optically pure NC(sp³)E monomeric and bimetallic pincer complexes

The pyridyl-substituted enone 1 was subjected to a catalytic hydrophosphination reaction in the presence of palladacycle (S)-2 to afford the chiral tertiary phosphine (Scheme 1).^7g,16 The tertiary phosphine was oxidized/sulfurized to afford the corresponding air-stable ligand precursor (R)-3a/b with >99% ee and in high yields (88–94%). The C(sp³)–H activation process was achieved under mild conditions upon stirring ligand precursor (R)-3 with PdCl₂(NCMe)₂ in the presence of NaOAc, resulting in the formation of the desired NC(sp³)E (E = O, S) pincer complexes (S,S)-4a/b in excellent isolated yields (92–97%). Stereoselective cyclopalladation was efficiently directed by the C-stereogenic center on ligand precursor 3, and there were no detectable generation of diastereomers (by ¹H and ³¹P{¹H} NMR studies) upon stereoselective formation of the C(sp³)–Pd bond. It should be noted that an analogous NC(sp³)O complex of 4a was prepared previously in 35% isolated yield at RT over 18 h.^7f Complexes 4 were observed to be stable in air and moisture with no noticeable degradation over a prolonged period of standing at room temperature in the solid state. Single X-ray quality crystals of complex 4b were obtained from a mixture of DCM/n-hexane. Fig. 2 shows the molecular structure and the absolute stereochemistry of complex 4b. According to the Cahn–Ingold–Prelog (CIP) sequence rule,¹⁷ both chiral carbon centers in complex 4b adopted the (S)-absolute configurations. The chirality of the tertiary carbon center in ligand precursor 3 controls the stereochemistry of the metal complexation process, thus leading to the exclusive adoption of the (S)-chirality at the new palladium-bound carbon center (Fig. 3). This three-step synthetic procedure exhibits several remarkable features for the systematic production of the aforementioned Pd pincer complexes. Firstly, the enantiopure ligand was generated via a one-pot catalytic procedure without the need for further optical resolution. Secondly, syntheses of these unsymmetrical pincer complexes circumvented traditional lengthy arm-by-arm modular construction of individual pendant arms. Lastly, direct C(sp³)–H activation (possibly promoted by the presence of the adjacent carbonyl group) was achieved at room temperature under mild conditions, remarkably even in the absence of coordinating phosphine moieties. Chirality on the C(sp³) donor atom was introduced through this C(sp³)–H activation process. Despite the presence of both α- and β-hydrogens, complex (S,S)-4a/b retained its structural integrity even upon prolonged standing under atmospheric conditions.

Scheme 1 Synthesis of NC(sp³)E pincer complex (S,S)-4.

Fig. 2 ORTEP of NC(sp³)S Pd pincer complex (S,S)-4b.

Fig. 3 Possible stereochemical pathway for the cyclopalladation process.

In view that C(sp³)-pincer complexes are rarely reported in literature, we were surprised that complexes (S,S)-4a/b could be obtained in such high yields (92–97%). We decided to examine if the formation of the C(sp³)–Pd bond is a general trend with similar ligands. We have previously reported the hydrophosphination reaction of dienone 5 to produce the corresponding chiral bisphosphine 6 in >99% ee and 86% de (Scheme 2).¹⁸ The bisphosphine 6 could undergo cyclopalladation to generate the P–C(sp²)–P square-planar pincer complex 7 as the sole product in 80% isolated yield,¹⁹ and it was noted that the two pyridyl groups were not involved in metal complexation. In this current work, the tertiary bisphosphine 6 was oxidized or sulfurized to generate the ligand precursor (R,R)-8a or 8b, respectively. These air-stable phosphorus(V) species could be isolated by recrystallization from DCM/n-hexane. From a structural standpoint, (R,R)-8 may form the dimeric N–C(sp³)–E pincer complexes 9 or monomeric E–C(sp²)–E species 10. Interestingly, palladation of the phosphorus(V) ligands with PdCl₂(NCMe)₂ afforded the bimetallic N–C(sp³)–E pincer complex (S,S,S,S)-9a/b as the sole product in good yields. The ³¹P{¹H} NMR spectra of the crude reaction mixtures did not indicate the presence of the symmetrical E–C(sp²)–E complex 10 (even with reduced amounts of PdCl₂(NCMe)₂). The X-ray molecular structure and the absolute stereochemistry of complex (S,S,S,S)-9b is presented in Fig. 4. The interesting facile coordination properties of the bisphosphine compound 6 is clearly demonstrated in Scheme 2. The direct treatment of the tertiary bisphosphine 6 with Pd^II generated the C(sp²)-complex 7 exclusively.¹⁹ When the two phosphorus(III) donors in 6 were oxidized to the phosphorous(V) species 8a and 8b, only the corresponding novel C(sp³)-complexes 9 were generated efficiently. Unlike bisphosphine 6, the more commonly observed C(sp²)–H activation was not observed with both ligand precursors 8a and 8b. Consequently, the C₂-symmetrical complexes 10a and 10b were not formed.²⁰ Therefore, this illustrates a versatile methodology which can deliver either the symmetrical PC(sp²)P- or NC(sp³)E-type complexes chemo-specifically from the same bisphosphine 6. To further investigate the generality of this methodology for the formation of the C(sp³)-pincer complexes from structurally similar ligand precursors, several di-pyridyl substituted substrates with different carbon-linkages were selected (Schemes 3 and 4).

Scheme 2 Synthesis of N–C(sp³)–E and P–C(sp²)–P pincer complexes.

Fig. 4 ORTEP of NC(sp³)S Pd pincer complex (S,S,S,S)-9b.

Scheme 3 Synthesis of NC(sp³)E pincer complex (S,S,S,S)-13.

Scheme 4 Synthesis of NC(sp³)E pincer complex (S,S,S,S)-16.

The asymmetric hydrophosphination reaction of the substrates 11 and 14 afforded the corresponding phosphorus(V) products 12a/b and 15a/b with high optical purities and in high yields.²¹ The subsequent treatment of bisphosphine derivatives 12 and 15 with PdCl₂(NCMe)₂ gave exclusively the bimetallic C(sp³)-pincer complexes 13 and 16, respectively. It should be noted that the generation of the palladium-bound C(sp³)-carbon is highly stereoselective; only one diastereomer was generated in each of these complexation reaction. In addition, the two adjacent pyridyl groups in ligand 15 did not form the commonly observed five-membered N,N-bidentate chelates.

Preliminary activity test

The efficient syntheses of the aforementioned C(sp³)-pincer preligands via the catalytic asymmetric hydrophosphination reaction offered a rare opportunity for the investigation of the corresponding chiral palladium-bound C(sp³)-complexes as catalysts for asymmetric transformations. As mentioned earlier, C(sp³)-pincer complexes and their C(sp²)-counterparts usually exhibit different reactivities when applied in a catalytic reaction. Interestingly, the current C(sp³)-preligands were synthesized efficiently in the presence of C(sp²)-palladacycle (S)-2 as catalyst. As such, we decided to conduct a preliminary comparison of these complexes in the P–H addition reaction of the conjugated diethyl malonate 17 (Table 1). This substrate is selected due to the possibility of the P–H addition occurring at different activated carbon atoms and thus generating distinct isomeric products. In the absence of a catalyst, no reaction was observed between Ph₂P–H and malonate 17. As illustrated in Table 1, the C(sp²)-catalyst (S)-2 is certainly the most efficient catalyst for the P–H addition reaction (Entry 10).²² It functions efficiently at −80 °C to generate the 1,4-addition product 18a regiospecifically. On the other hand, all the C(sp³)-complexes were also catalytically active in this P–H addition reaction, albeit generating the products in low yields.

Table 1 Preliminary investigations for catalytic activity of complexes^a,b

Entry	Catalyst	T (°C)	Yield^c (%)	18a : 18b^d
a Reaction conditions: malonate 17 (43.3 μmol, 1.0 eq.), HPPh2 (65.0 μmol, 1.5 eq.), catalyst (1.1 μmol, 2.5 mol%), KOAc (8.7 μmol, 20 mol%), DEE (3 mL), 24 h.b No appreciable ee's (0–10%) were obtained.c Isolated yield of 18a and 18b.d Ratio of 18a : 18b was determined by integration of their respective proton signals at 6.41 (18a) and 5.73 (18b) ppm.e 2.2 μmol (5 mol%) of catalyst was used instead.f ee of the major product 18b was determined to be 40% by chiral HPLC; see ESI Fig. s58.g Previously reported to afford the product in >99% ee with the use of NEt3 as an external base.^22
1^e	4a	RT	25	1.3 : 1
2^e	4b	RT	38	1 : 6.0
3	9a	RT	64	1 : 11.9
4	9b	RT	57	1 : 11.9
5	13a	RT	28	0 : 100
6	13b	RT	36	1 : 5.3
7	16a	RT	43	1 : 1.7
8	16b	RT	49	1 : 4.3
9^f	7	RT	69	1 : 13.0
10^g	2	−80	100	100 : 0

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Generally, the NC(sp³)S complexes 4b, 13b and 16b (Entries 2, 6 and 8) afforded the products in slightly higher yields as compared to their analogous NC(sp³)O complexes (Entries 1, 5 and 7), with the exception of complexes 9 (Entries 3 and 4). Notably, the aryl PC(sp²)P complex 7 and the aliphatic NC(sp³)E complexes 9, which were derived from the same bisphosphine 6, exhibited comparable reactivities and regioselectivities. However, the major adduct 18b was obtained in moderate ee of 40% with pincer complex 7 acting as catalyst (complexes 9 afforded product 18b as racemic mixtures). Overall, the C(sp³)-complexes were less regioselective as mixtures of 1,4- and 1,6-addition products were generally obtained, except for pincer complex 13a, in which only the 1,6-adduct was obtained. From this preliminary test, it is suggested that the aryl C(sp²)- and aliphatic C(sp³)-catalysts show slight differences in terms of reactivities and regioselectivities in the P–H addition reaction. Nevertheless, the aryl C(sp²) complex 7 outperformed its aliphatic C(sp³)-counterparts to achieve significantly higher ee. Further investigations and optimization of the reaction conditions will be required to improve on the enantioselectivities of the C(sp³)-complexes.

Conclusions

The syntheses of novel aliphatic NC(sp³)E pincer complexes were accomplished with an efficient synthetic procedure that leveraged on a palladacycle-catalyzed asymmetric hydrophosphination reaction. The protocol involved the catalytic generation of the enantioenriched phosphine compounds, followed by oxidation/sulfurization, and then cyclopalladation via C(sp³)–H activation of the ligand precursors. This robust protocol could efficiently control the stereoselective formation of the chiral centers, across a range of structurally-dissimilar compounds. Evidently, a lack of literature examples on aliphatic unsymmetrical pincer complexes is preventing the advancement of these structurally unique mono- and bi-metallic complexes with palladium-bound C-chiral centers in catalytic applications. Efforts are underway in our laboratory to develop the application of the C(sp³)-complexes in various types of asymmetric organic transformations.

Experimental

All reactions were carried out under a positive pressure of nitrogen using standard Schlenk techniques. NMR spectra were recorded on Bruker AV 300, AV 400 and AV 500 spectrometers. Chemical shifts were reported in ppm and referenced to an internal SiMe₄ standard (0 ppm) for ¹H NMR, chloroform-d (77.23 ppm) for ¹³C NMR, and an external 85% H₃PO₄ for ³¹P{¹H} NMR. DCM, DCE, DEE, toluene, acetone, acetonitrile and MeOH were purchased from their respective companies and used as supplied. THF was distilled prior to use. Solvents were degassed when necessary. A Low Temp Pairstirrer PSL-1800 was used for controlling low temperature reactions. Column chromatography was carried out with Silica gel 60 (Merck). Melting points were measured using SRS Optimelt Automated Point System SRS MPA100. Optical rotation were measured with JASCO P-1030 Polarimeter in the specified solvent in a 0.1 dm cell at 22.0 °C. Elemental analyses were performed on EuroVector EA3000 Elemental Analyzer operated with Callidus software.

Preparation of compound (R)-3a or (R)-3b

A Schlenk tube was charged with Ph₂PH (41.0 mg, 0.22 mmol, 1.1 equiv.), catalyst (S)-2 (6.90 mg, 0.011 mmol, 5 mol%) in toluene (15 mL) and stirred for 10 minutes before cooling to −80 °C. Enone 1 (41.8 mg, 0.20 mmol, 1.0 equiv.) was added followed by the addition of NEt₃ (27.9 μL, 0.20 mmol, 1.0 equiv.) in toluene (1 mL) dropwise. The solution was stirred at −80 °C and the completion of the reaction was monitored by ³¹P{¹H} NMR. Upon completion, the solution was allowed to warm up to room temperature. For the generation of compound 3a, aq. H₂O₂ (31% w/w, 0.1 mL) was added and stirred for 30 min. For the generation of compound 3b, S₈ (12.8 mg, 0.05 mmol, 0.25 equiv.) was added and stirred for 30 min. Volatiles were removed under reduced pressure and the crude product was purified by silica gel column chromatography. Compound (R)-3a. Yield: 77.3 mg, 0.19 mmol, 94%. Eluted with EA to afford white solid. [α]_D = +107.4 (c 0.1, DCM). Mp: 218–219 °C. ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 33.6 (s). ¹H NMR (CDCl₃, 400 MHz): δ 8.62–8.61 (m, 1H, Ar), 8.02–7.97 (m, 2H, Ar), 7.83–7.81 (m, 1H, Ar), 7.71 (td, 1H, ³J = 7.7 Hz, ⁴J = 1.7 Hz, Ar), 7.51–7.46 (m, 5H, Ar), 7.41–7.36 (m, 2H, Ar), 7.35–7.31 (m, 2H, Ar), 7.27–7.23 (m, 2H, Ar), 7.14–7.08 (m, 3H, Ar), 4.48–4.41 (m, 1H, PCHCH₂), 4.39–4.34 (m, 1H, O=CCH₂), 3.58 (ddd, 1H, ²J = 17.5 Hz, ³J_PH = 9.9 Hz, ³J = 1.4 Hz, O=CCH₂). ¹³C NMR (CDCl₃, 125 MHz): δ 199.0 (d, 1C, ³J_PC = 12.9 Hz, C=O), 153.0 (1C, Ar), 149.1 (2C, Ar), 136.8–121.9 (20C, Ar), 41.8 (d, 1C, ¹J_PC = 68.2 Hz, PCH), 38.4 (1C, O=CCH₂). Anal. calcd for C₂₆H₂₂NO₂P: C, 75.90; H, 5.39; N, 3.40. Found: C, 76.20; H, 5.69; N, 3.44%. HRMS (+ESI) m/z: (M + H)⁺ calcd for C₂₆H₂₃NO₂P, 412.1466; found, 412.1464. Compound (R)-3b. Yield: 75.2 mg, 0.18 mmol, 88%. Eluted with n-hexane : DCM (1 : 1 to 1 : 10) to afford white solid. [α]_D = +241.2 (c 0.1, DCM). Mp: 94–96 °C. ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 51.5 (s). ¹H NMR (CDCl₃, 400 MHz): δ 8.63–8.61 (m, 1H, Ar), 8.23–8.18 (m, 2H, Ar), 7.80 (d, 1H, ³J = 7.8 Hz, Ar), 7.68 (td, 1H, ³J = 7.7 Hz, ⁴J = 1.7 Hz, Ar), 7.54–7.49 (m, 5H, Ar), 7.39–7.35 (m, 1H, Ar), 7.33–7.25 (m, 3H, Ar), 7.23–7.19 (m, 2H, Ar), 7.08–7.05 (m, 3H, Ar), 4.87 (td, 1H, ²J_PH = 10.6 Hz, ³J = 2.6 Hz, PCHCH₂), 4.51 (ddd, 1H, ²J = 18.2 Hz, ³J_PH = 10.9 Hz, ³J = 6.2 Hz, O=CCH₂), 3.51 (ddd, 1H, ²J = 18.4 Hz, ³J_PH = 11.6 Hz, ³J = 2.7 Hz, O=CCH₂). ¹³C NMR (CDCl₃, 100 MHz): δ 198.8 (d, 1C, ³J_PC = 15.1 Hz, C=O), 152.9 (1C, Ar), 149.2 (1C, Ar), 136.8–121.8 (21C, Ar), 42.1 (d, 1C, ¹J_PC = 52.9 Hz, PCH), 38.6 (1C, O=CCH₂). Anal. calcd for C₂₆H₂₂NOPS: C, 73.05; H, 5.19; N, 3.28. Found: C, 72.87; H, 5.02; N, 3.60%. HRMS (+ESI) m/z: (M + H)⁺ calcd for C₂₆H₂₃NOPS, 428.1238; found, 428.1235.

Preparation of complex (S,S)-4a or (S,S)-4b

A mixture of compound 3a or 3b (0.47 mmol, 1.0 equiv.), PdCl₂(NCMe)₂ (0.12 g, 0.47 mmol, 1.0 equiv.) and NaOAc (38.6 mg, 0.47 mmol, 1.0 equiv.) in DCM (50 mL) was stirred for 12 h at RT. On removal of the solvent, the residue was purified by silica gel column chromatography to afford yellow solid of complex 4a or 4b respectively. Complex (S,S)-4a. Yield: 251.4 mg, 0.46 mmol, 97%. Eluted with EA : DCM (2 : 1) to afford yellow solid. [α]_D = +240.4 (c 0.1, DCM). Mp: 176–178 °C. ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 73.2 (s). ¹H NMR (CDCl₃, 400 MHz): δ 9.05 (d, 1H, ³J = 5.4 Hz, Ar), 7.93–7.88 (m, 1H, Ar), 7.85–7.80 (m, 2H, Ar), 7.61–7.55 (m, 2H, Ar), 7.54–7.48 (m, 5H, Ar), 7.43–7.35 (m, 3H, Ar), 7.17–7.11 (m, 3H, Ar), 6.96–6.94 (m, 2H, Ar), 5.17 (dd, 1H, ³J = 9.6 Hz, ³J_PH = 4.2 Hz, PdCH), 4.89 (dd, 1H, ²J_PH = 16.4 Hz, ³J = 9.6 Hz, PCH). ¹³C NMR (CDCl₃, 100 MHz): δ 192.7 (d, 1C, ³J_PC = 13.5 Hz, C=O), 157.2 (1C, Ar), 151.2 (1C, Ar), 139.6–122.6 (21C, Ar), 55.8 (1C, PdCH), 48.6 (d, 1C, ¹J_PC = 72.1 Hz, PCH). Anal. calcd for C₂₆H₂₁ClNO₂PPd: C, 56.54; H, 3.83; N, 2.54. Found: C, 56.55; H, 3.44; N, 2.15%. HRMS (+ESI) m/z: (M − Cl)⁺ calcd for C₂₆H₂₁NO₂PPd, 516.0345; found, 516.0342. Complex (S,S)-4b. Yield: 245.4 mg, 0.43 mmol, 92%. Eluted with EA : DCM (1 : 1) to afford yellow solid. X-ray quality crystals was obtained from DCM/n-hexane. [α]_D = +148.3 (c 0.1, DCM). Mp: 236–238 °C (dec.). ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 66.4 (s). ¹H NMR (CDCl₃, 400 MHz): δ 9.20 (d, 1H, ³J = 5.2 Hz, Ar), 7.97–7.91 (m, 3H, Ar), 7.67–7.62 (m, 2H, Ar), 7.58–7.47 (m, 6H, Ar), 7.39–7.34 (m, 2H, Ar), 7.21–7.13 (m, 3H, Ar), 7.03–7.01 (m, 2H, Ar), 5.18 (dd, 1H, ²J_PH = 13.8 Hz, ³J = 8.6 Hz, PCH), 4.96 (dd, 1H, ³J = 8.4 Hz, ³J_PH = 6.9 Hz, PdCH). ¹³C NMR (CDCl₃, 100 MHz): δ 193.7 (d, 1C, ³J_PC = 14.5 Hz, C=O), 156.1–122.6 (23C, Ar), 55.4 (1C, PdCH), 52.6 (d, 1C, ¹J_PC = 59.2 Hz, PCH). Anal. calcd for C₂₆H₂₁ClNOPPdS: C, 54.94; H, 3.72; N, 2.46. Found: C, 55.07; H, 4.08; N, 2.09%. HRMS (+ESI) m/z: (M − Cl)⁺ calcd for C₂₆H₂₁NOPPdS, 532.0116; found, 532.0118.

General procedure for the asymmetric hydrophosphination of dienones 5, 11 and 14

A Schlenk tube was charged with Ph₂PH (82.0 mg, 0.44 mmol, 2.2 equiv.), catalyst (S)-2 (13.8 mg, 0.022 mmol, 5 mol% for dienone 5 or 11; 27.6 mg, 0.044 mmol, 10 mol% for dienone 14) in toluene (15 mL) and stirred for 10 minutes before cooling to −80 °C. Dienone 5, 11 or 14 (0.20 mmol, 1.0 equiv.) was added followed by the addition of NEt₃ (55.8 μL, 0.40 mmol, 2.0 equiv.) in toluene (1 mL) dropwise. The solution was stirred at −80 °C and the completion of the reaction was monitored by ³¹P{¹H} NMR. Upon completion, the solution was allowed to warm up to room temperature. For the generation of compound 8a, 12a or 15a aq. H₂O₂ (31% w/w, 0.2 mL) was added and stirred for 30 min. For the generation of compound 8b, 12b or 15b, S₈ (25.7 mg, 0.10 mmol, 0.5 equiv.) was added and stirred for 30 min. Volatiles were removed under reduced pressure and the crude product was purified by silica gel column chromatography. Compound (R,R)-8a yield: 0.14 g, 0.18 mmol, 85%. Eluted with EA : MeOH (100 : 1 to 10 : 1) to afford pale yellow solid. [α]_D = +119.6 (c 0.1, DCM). Mp: 122–124 °C. ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 33.6 (s). ¹H NMR (CDCl₃, 300 MHz): δ 8.62–8.61 (m, 2H, Ar), 7.97–7.90 (m, 4H, Ar), 7.66–7.62 (m, 4H, Ar), 7.48–7.35 (m, 13H, Ar), 7.21–7.11 (m, 8H, Ar), 6.91 (t, 1H, ³J = 7.65 Hz, Ar), 4.39–4.32 (m, 2H, PCHCH₂), 4.16–4.05 (m, 2H, PCHCH₂), 3.54 (ddd, 2H, ²J_PH = 18.2 Hz, ³J = 11.3, 3.1 Hz, O=CCH₂). ¹³C NMR (CDCl₃, 100 MHz): δ 198.0 (d, 2C, ³J_PC = 13.0 Hz, C=O), 152.9 (2C, Ar), 149.1 (2C, Ar), 136.7–121.7 (36C, Ar), 41.3 (d, 2C, ¹J_PC = 68.4 Hz, PCH), 38.7 (2C, O=CCH₂). Anal. calcd for C₄₆H₃₈N₂O₄P₂: C, 74.18; H, 5.14; N, 3.76. Found: C, 74.46; H, 5.38; N, 4.10%. HRMS (+ESI) m/z: (M + H)⁺ calcd for C₄₆H₃₉N₂O₄P₂, 745.2385; found, 745.2383. Compound (R,R)-8b yield: 0.14 g, 0.19 mmol, 88%. Eluted with DCM : EA(100 : 0 to 20 : 1) to afford white solid. [α]_D = +214.0 (c 0.1, DCM). Mp: 121–123 °C. ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 50.9 (s). ¹H NMR (CDCl₃, 400 MHz): δ 8.66–8.65 (m, 2H, Ar), 8.15–8.09 (m, 4H, Ar), 7.66–7.63 (m, 4H, Ar), 7.49–7.36 (m, 13H, Ar), 7.21–7.12 (m, 6H, Ar), 7.06–7.04 (m, 2H, Ar), 6.72 (t, 1H, ³J = 7.7 Hz, Ar), 4.72 (td, 2C, ²J_PH = 10.2 Hz, ³J = 2.6 Hz, PCHCH₂), 4.37 (ddd, 2H, ³J_PH = 18.6 Hz, ²J = 10.5 Hz, ³J = 6.4 Hz, O=CCH₂), 3.45 (ddd, 2H, ²J = 18.6 Hz, ³J_PH = 12.0 Hz, ³J = 2.7 Hz, O=CCH₂). ¹³C NMR (CDCl₃, 100 MHz): δ 197.8 (d, 2C, ³J_PC = 14.9 Hz, C=O), 152.4 (2C, Ar), 148.7 (2C, Ar), 136.7–121.2 (36C, Ar), 41.2 (d, 2C, ¹J_PC = 52.7 Hz, PCH), 39.1 (2C, O=CCH₂). Anal. calcd for C₄₆H₃₈N₂O₂P₂S₂: C, 71.12; H, 4.93; N, 3.61. Found: C, 70.85; H, 4.77; N, 3.95%. HRMS (+ESI) m/z: (M + H)⁺ calcd for C₄₆H₃₉N₂O₂P₂S₂, 777.1928; found, 777.1926. Compound (R,R)-12a yield: 0.14 g, 0.18 mmol, 90%. Eluted with EA : MeOH (100 : 1 to 10 : 1) to afford white solid. [α]_D = +135.2 (c 0.1, DCM). Mp: 200–202 °C (dec.). ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 33.5 (s). ¹H NMR (CDCl₃, 400 MHz): δ 8.58 (d, 2H, ³J = 4.2 Hz, Ar), 7.90–7.86 (m, 4H, Ar), 7.75–7.64 (m, 4H, Ar), 7.49–7.43 (m, 6H, Ar), 7.38–7.30 (m, 8H, Ar), 7.17–7.13 (m, 4H, Ar), 7.08 (s, 4H, Ar), 4.35–4.27 (m, 2H, PCHCH₂), 4.26–4.20 (m, 2H, O=CCH₂), 3.53–3.45 (m, 2H, O=CCH₂). ¹³C NMR (CDCl₃, 100 MHz): δ 198.5 (d, 2C, ³J_PC = 12.9 Hz, C=O), 152.7 (2C, Ar), 149.0 (2C, Ar), 136.6–121.6 (36C, Ar), 41.1 (d, 2C, ¹J_PC = 68.7 Hz, PCH), 38.2 (2C, O=CCH₂). Anal. calcd for C₄₆H₃₈N₂O₄P₂: C, 74.18; H, 5.14; N, 3.76. Found: C, 74.48; H, 5.31; N, 4.09%. HRMS (+ESI) m/z: (M + H)⁺ calcd for C₄₆H₃₉N₂O₄P₂, 745.2385; found, 745.2387. Compound (R,R)-12b yield: 0.14 g, 0.18 mmol, 88%. Eluted with DCM: n-hexane (1 : 2) to afford off-white solid. [α]_D = +318.3 (c 0.1, DCM). Mp: 124–126 °C. ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 51.3 (s). ¹H NMR (CDCl₃, 400 MHz): δ 8.62 (d, 2H, ³J = 4.7 Hz, Ar), 8.14–8.09 (m, 4H, Ar), 7.77 (d, 2H, ³J = 7.8 Hz, Ar), 7.69 (td, 2H, ³J = 7.6 Hz, ⁴J = 1.6 Hz, Ar), 7.50–7.49 (m, 5H, Ar), 7.40–7.33 (m, 7H, Ar), 7.24–7.20 (m, 4H, Ar), 6.94 (s, 4H, Ar), 4.68 (td, 2H, ²J_PH = 10.5 Hz, ³J = 2.4 Hz, PCHCH₂), 4.41 (ddd, 2H, ²J = 18.5 Hz, ³J_PH = 10.8 Hz, ³J = 5.7 Hz, O=CCH₂), 3.38 (ddd, 2H, ²J = 18.5 Hz, ³J_PH = 11.9 Hz, ³J = 2.4 Hz, O=CCH₂). ¹³C NMR (CDCl₃, 100 MHz): δ 198.5 (d, 2C, ³J_PC = 15.1 Hz, C=O), 152.7 (2C, Ar), 149.0 (2C, Ar), 136.8–121.7 (36C, Ar), 42.0 (d, 2C, ¹J_PC = 53.1 Hz, PCH), 38.6 (2C, O=CCH₂). Anal. calcd for C₄₆H₃₈N₂O₂P₂S₂: C, 71.12; H, 4.93; N, 3.61. Found: C, 71.29; H, 4.67; N, 3.48%. HRMS (+ESI) m/z: (M + H)⁺ calcd for C₄₆H₃₉N₂O₂P₂S₂, 777.1928; found, 777.1932. Compound (R,R)-15a yield: 0.13 g, 0.17 mmol, 80%. Eluted with DCM : EA (4 : 1 to 1 : 2) to afford white solid. [α]_D = +331.3 (c 0.1, DCM). Mp: 243–245 °C (dec.). ³¹P{¹H} NMR (CDCl₃, 121 MHz): δ 34.7 (s). ¹H NMR (CDCl₃, 400 MHz): δ 8.65 (dd, 2H, ³J = 7.2 Hz, ⁴J = 1.6 Hz, NCCH), 8.01–7.90 (m, 8H, Ar), 7.50–7.46 (m, 10H, Ar), 7.38–7.32 (m, 6H, Ar), 7.27–7.23 (m, 4H, Ar), 7.14–7.07 (m, 6H, Ar), 4.54–4.50 (m, 2H, PCHCH₂), 4.49–4.47 (m, 2H, O=CCH₂), 3.66–3.59 (m, 2H, O=CCH₂). ¹³C NMR (CDCl₃, 100 MHz): δ 198.7 (d, 2C, ³J_PC = 13.1 Hz, C=O), 154.4 (2C, Ar), 152.2 (2C, Ar), 138.2–122.3 (42C, Ar), 41.5 (d, 2C, ¹J_PC = 68.6 Hz, PCH), 38.0 (2C, O=CCH₂). Anal. calcd for C₅₂H₄₂N₂O₄P₂: C, 76.09; H, 5.16; N, 3.41. Found: C, 76.47; H, 5.38; N, 3.64%. HRMS (+ESI) m/z: (M + H)⁺ calcd for C₅₂H₄₃N₂O₄P₂, 821.2698; found, 821.2701. Compound (R,R)-15b yield: 0.15 g, 0.18 mmol, 88%. Eluted with DCM: n-hexane (1 : 2 to 5 : 1) to afford off-white solid. [α]_D = +330.9 (c 0.1, DCM). Mp: 148–150 °C. ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 51.6 (s). ¹H NMR (CDCl₃, 400 MHz): δ 8.69 (d, 2H, ³J = 7.2 Hz, NCCH), 8.19–8.15 (m, 4H, Ar), 7.98–7.89 (m, 4H, Ar), 7.55–7.50 (m, 10H, Ar), 7.35–7.25 (m, 6H, Ar), 7.23–7.21 (m, 4H, Ar), 7.08–7.07 (m, 6H, Ar), 4.90–4.84 (m, 2H, PCHCH₂), 4.70 (ddd, 2H, ²J = 18.0 Hz, ³J_PH = 10.4 Hz, ³J = 5.6 Hz, O=CCH₂), 3.59 (ddd, 2H, ²J = 18.3 Hz, ³J_PH = 12.0 Hz, ³J = 2.4 Hz, O=CCH₂). ¹³C NMR (CDCl₃, 125 MHz): δ 198.8 (d, 2C, ³J_PC = 14.7 Hz, C=O), 154.4 (2C, Ar), 152.3 (2C, Ar), 138.3–122.4 (42C, Ar), 42.1 (d, 2C, ¹J_PC = 52.7 Hz, PCH), 38.5 (2C, O=CCH₂). Anal. calcd for C₅₂H₄₂N₂O₂P₂S₂: C, 73.22; H, 4.96; N, 3.28. Found: C, 73.37; H, 5.29; N, 3.54%. HRMS (+ESI) m/z: (M + H)⁺ calcd for C₅₂H₄₃N₂O₂P₂S₂, 853.2241; found, 853.2244.

General procedure for the preparation of complexes 9, 13 and 16

A mixture of compound 8a/8b/12a/12b/15a/15b (0.19 mmol, 1.0 equiv.), PdCl₂(NCMe)₂ (96.0 mg, 0.38 mmol, 2.0 equiv.) and NaOAc (30.9 mg, 0.38 mmol, 2.0 equiv.) in DCM (50 mL) was stirred for 24 h at RT. On removal of the solvent, the residue was purified by silica gel column chromatography to afford complex 9a/9b/13a/13b/16a/16b respectively. Complex (S,S,S,S)-9a yield: 127.0 mg, 0.12 mmol, 66%. Eluted with EA : MeOH (20 : 1 to 10 : 1) to afford yellow solid. [α]_D = +227.1 (c 0.1, DCM). Mp: 222–223 °C (dec.). ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 72.4 (s). ¹H NMR (CDCl₃, 400 MHz): δ 9.11 (d, 2H, ³J = 5.2 Hz, Ar), 8.01 (td, 2H, ³J = 7.70 Hz, ⁴J = 1.08 Hz, Ar), 7.83–7.79 (m, 4H, Ar), 7.67–7.65 (m, 5H, Ar), 7.60–7.49 (m, 6H, Ar), 7.44–7.39 (m, 4H, Ar), 7.32–7.27 (m, 5H, Ar), 6.95 (t, 1H, ³J = 7.66 Hz, Ar), 6.83 (s, 1H, Ar), 6.78 (d, 2H, ³J = 7.36 Hz, Ar), 4.92 (dd, 2H, ³J = 9.32 Hz, ³J_PH = 3.82 Hz, PdCH), 4.75 (dd, 2H, ²J_PH = 16.04 Hz, ³J = 9.34 Hz, PCH). ¹³C NMR (CDCl₃, 100 MHz): δ 192.8 (d, 2C, ³J_PC = 12.8 Hz, C=O), 157.3 (2C, Ar), 151.7 (2C, Ar), 139.6 (2C, Ar), 134.8–122.6 (26C, Ar), 56.0 (2C, PdCH), 48.6 (d, 2C, ¹J_PC = 71.9 Hz, PCH). Anal. Calcd for C₄₆H₃₆Cl₂N₂O₄P₂Pd₂: C, 53.82; H, 3.53; N, 2.73. Found: C, 53.93; H, 3.90; N, 2.82%. HRMS (+ESI) m/z: (M − Cl)⁺ calcd for C₄₆H₃₆ClN₂O₄P₂Pd₂, 988.9908; found, 988.9906. Complex (S,S,S,S)-9b yield: 143.0 mg, 0.14 mmol, 72%. Eluted with EA : MeOH (100 : 0 to 70 : 1) to afford yellow solid. X-ray quality crystals was obtained from DCM/n-hexane. [α]_D = +216.2 (c 0.1, DCM). Mp: 253–255 °C (dec.). ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 65.0 (s). ¹H NMR (CDCl₃, 400 MHz): δ 9.21 (d, 2H, ³J = 5.2 Hz, Ar), 8.00–7.95 (m, 6H, Ar), 7.69–7.54 (m, 10H, Ar), 7.33–7.26 (m, 5H, Ar), 7.26–7.22 (m, 6H, Ar), 6.83–6.79 (m, 1H, Ar), 6.72–6.70 (m, 2H, Ar), 5.09 (dd, 2H, ²J_PH = 12.8 Hz, ³J = 7.6 Hz, PCH), 4.76 (dd, 2H, ³J = 7.6 Hz, ³J_PH = 7.6 Hz, PdCH). ¹³C NMR (CDCl₃, 100 MHz): δ 194.1 (d, 2C, ³J_PC = 12.8 Hz, C=O), 155.7 (2C, Ar), 149.2 (2C, Ar), 139.6–122.5 (36C, Ar), 55.3 (2C, d, 2C, ²J_PC = 5.6 Hz, PdCH), 51.1 (d, 2C, ¹J_PC = 58.6 Hz, PCH). Anal. calcd for C₄₆H₃₆Cl₂N₂O₂P₂Pd₂S₂: C, 52.19; H, 3.43; N, 2.65. Found: C, 52.11; H, 3.15; N, 2.45%. HRMS (+ESI) m/z: (M − Cl)⁺ calcd for C₄₆H₃₆ClN₂O₂P₂Pd₂S₂, 1020.9452; found, 1020.9455. Complex (S,S,S,S)-13a yield: 131.0 mg, 0.13 mmol, 68%. Eluted with EA : MeOH (20 : 1 to 10 : 1) to afford yellow solid. [α]_D = +321.2 (c 0.1, DCM). Mp: 238–239 (dec.). ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 71.8 (s). ¹H NMR (CDCl₃, 400 MHz): δ 9.03 (d, 2H, ³J = 5.3 Hz, Ar), 7.98–7.95 (m, 2H, Ar), 7.85–7.80 (m, 3H, Ar), 7.70–7.39 (m, 19H, Ar), 7.30–7.18 (m, 4H, Ar), 6.88–6.84 (m, 3H, Ar), 5.06 (dd, 2H, ³J_PH = 8.4 Hz, ³J = 3.2 Hz, PdCH), 4.80 (dd, 2H, ³J = 9.0 Hz, ²J_PH = 14.4 Hz, PCH). ¹³C NMR (CDCl₃, 100 MHz): δ 192.8 (d, 2C, ³J_PC = 12.0 Hz, C=O), 157.1 (2C, Ar), 151.5 (2C, Ar), 139.7–122.6 (36C, Ar), 55.9 (2C, PdCH), 47.9 (d, 2C, ¹J_PC = 71.8 Hz, PCH). Anal. calcd for C₄₆H₃₆Cl₂N₂O₄P₂Pd₂: C, 53.82; H, 3.53; N, 2.73. Found: C, 54.20; H, 3.28; N, 2.39%. HRMS (+ESI) m/z: (M − Cl)⁺ calcd for C₄₆H₃₆ClN₂O₄P₂Pd₂, 988.9908; found, 988.9909. Complex (S,S,S,S)-13b yield: 147.0 mg, 0.14 mmol, 74%. Eluted with EA : DCM (1 : 1) to afford yellow solid. [α]_D = +178.5 (c 0.1, DCM). Mp: 153–155 °C (dec.). ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 65.7 (s). ¹H NMR (CDCl₃, 400 MHz): δ 9.18 (d, 2H, ³J = 5.2 Hz, Ar), 7.95–7.88 (m, 6H, Ar), 7.67–7.64 (m, 4H, Ar), 7.59–7.56 (m, 4H, Ar), 7.51–7.48 (m, 4H, Ar), 7.38–7.34 (m, 4H, Ar), 7.26–7.21 (m, 4H, Ar), 6.84 (s, 4H, Ar), 5.08 (dd, 2H, ²J_PH = 12.5 Hz, ³J = 8.2 Hz, PCH), 4.82 (dd, 2H, ³J = 7.4 Hz, ³J_PH = 7.4 Hz, PdCH). ¹³C NMR (CDCl₃, 75 MHz): δ 193.8 (t, 2C, ³J_PC = 7.0 Hz, C=O), 155.9 (2C, Ar), 149.3 (2C, Ar), 139.6–122.6 (36C, Ar), 55.3 (2C, PdCH), 38.6 (d, 2C, ¹J_PC = 60.4 Hz, PCH). Anal. calcd for C₄₆H₃₆Cl₂N₂O₂P₂Pd₂S₂: C, 52.19; H, 3.43; N, 2.65. Found: C, 52.11; H, 3.74; N, 2.51%. HRMS (+ESI) m/z: (M − Cl)⁺ calcd for C₄₆H₃₆ClN₂O₂P₂Pd₂S₂, 1020.9452; found, 1020.9450. Complex (S,S,S,S)-16a yield: 130.4 mg, 0.12 mmol, 63%. Eluted with EA : MeOH (10 : 1) to afford pale yellow solid. [α]_D = +118.2 (c 0.1, DCM). Mp: 231–232 (dec.). ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 67.5 (s). ¹H NMR (CDCl₃, 400 MHz): δ 8.47–8.42 (m, 4H, Ar), 7.90–7.87 (m, 2H, Ar), 7.78–7.76 (m, 6H, Ar), 7.67–7.65 (m, 5H, Ar), 7.55–7.53 (m, 2H, Ar), 7.38–7.35 (m, 3H, Ar), 7.28–7.24 (m, 4H, Ar), 7.15–7.12 (m, 4H, Ar), 7.01–6.97 (m, 6H, Ar), 6.85 (dd, 2H, ²J_PH = 8.7 Hz, ³J = 3.2 Hz, PCH), 4.90 (dd, 2H, ³J_PH = 6.8 Hz, ³J = 3.3 Hz, PdCH). ¹³C NMR (CDCl₃, 100 MHz): δ 190.5 (d, 2C, ³J_PC = 4.0 Hz, C=O), 159.7 (2C, Ar), 156.4 (2C, Ar), 139.6–123.3 (42C, Ar), 61.9 (d, 2C, ²J_PC = 4.6 Hz, PdCH), 47.1 (d, 2C, ¹J_PC = 69.4 Hz, PCH). Anal. Calcd for C₅₂H₄₀Cl₂N₂O₄P₂Pd₂: C, 56.65; H, 3.66; N, 2.54. Found: C, 56.68; H, 3.88; N, 2.77%. HRMS (+ESI) m/z: (M − Cl)⁺ calcd for C₅₂H₄₀ClN₂O₄P₂Pd₂, 1065.0221; found, 1065.0222. Complex (S,S,S,S)-16b yield: 144.8 mg, 0.13 mmol, 68%. Eluted with EA : MeOH (15 : 1) to afford yellow solid. [α]_D = −198.3 (c 0.1, DCM). Mp: 215–216 (dec.). ³¹P{¹H} NMR (CDCl₃, 162 MHz): δ 61.7 (s). ¹H NMR (CDCl₃, 400 MHz): δ 8.49–8.44 (m, 4H, Ar), 7.95–7.86 (m, 6H, Ar), 7.83–7.81 (m, 2H, Ar), 7.63–7.59 (m, 8H, Ar), 7.42–7.38 (m, 2H, Ar), 7.27–7.13 (m, 14H, Ar), 6.06 (dd, 2H, ²J_PH = 13.7 Hz, ³J = 2.4 Hz, PCH), 5.44 (dd, 2H, ³J_PH = 8.2 Hz, ³J = 2.3 Hz, PdCH). ¹³C NMR (CDCl₃, 100 MHz): δ 192.6 (d, 2C, ³J_PC = 3.8 Hz, C=O), 158.1 (2C, Ar), 156.1 (2C, Ar), 139.3–123.4 (42C, Ar), 58.2 (2C, PdCH), 48.6 (d, 2C, ¹J_PC = 56.6 Hz, PCH). Anal. calcd for C₅₂H₄₀Cl₂N₂O₂P₂Pd₂S₂: C, 55.04; H, 3.55; N, 2.47. Found: C, 55.42; H, 3.54; N, 2.58%. HRMS (+ESI) m/z: (M − Cl)⁺ calcd for C₅₂H₄₀ClN₂O₂P₂Pd₂S₂, 1096.9765; found, 1096.9700.

General procedure for the asymmetric hydrophosphination of malonate 17

A Schlenk tube was charged with HPPh₂ (12.1 mg, 65.0 μmol, 1.5 equiv.), NC(sp³)E (E = O, S) complex (2.2 μmol, 5 mol% for mono-metallic complex; 1.1 μmol, 2.5 mol% for bi-metallic complex), KOAc (0.86 μg, 8.7 μmol, 20 mol%), malonate 17 (10.7 μL, 43.3 μmol, 1.0 equiv.), solvent (3 mL) and stirred at RT for 24 h. Subsequently, aq. H₂O₂ (31% w/w, 0.1 mL) was introduced to the mixture. The volatiles were removed and the crude product loaded directly onto silica gel column (1 n-hexane: 2 EA) to afford pure white solid(s) of 18a (1,4-adduct) and/or 18b (1,6-adduct).

Acknowledgements

We wish to acknowledge the funding support for this project from Nanyang Technological University under the Undergraduate Research Experience on CAmpus (URECA) programme.

Notes and references

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3. For selected examples, see: (a) E. M. Schuster, M. Botoshansky and M. Gandelman, Angew. Chem., Int. Ed., 2008, 47, 4555–4558; (b) S. Bonnet, M. Lutz, A. L. Spek, G. van Koten and R. J. M. K. Gebbink, Organometallics, 2010, 29, 1157–1167; (c) J. L. Bolliger and C. M. Frech, Adv. Synth. Catal., 2009, 351, 891–902; (d) B. Inés, R. SanMartin, F. Churruca, E. Domínguez, M. K. Urtiaga and M. I. Arriotua, Organometallics, 2008, 27, 2833–2839; (e) S. Perdriau, D. S. Zijlstra and H. J. Heeres, Angew. Chem., Int. Ed., 2015, 54, 4236–4240; (f) V. Pandarus and D. Zargarian, Organometallics, 2007, 26, 4321–4334; (g) T. T. Metsänen, D. Gallego, T. Szilvási, M. Driess and M. Oestreich, Chem. Sci., 2015, 6, 7143–7149; (h) J. M. Longmire and X. Zhang, Organometallics, 1998, 17, 4374–4379; (i) B. S. Williams, P. Dani, M. Lutz, A. L. Spek and G. van Koten, Helv. Chim. Acta, 2001, 84, 3519–3530; (j) I. Göttker-Schnetmann, P. White and M. Brookhart, J. Am. Chem. Soc., 2004, 126, 1804–1811.
4. For an example on aliphatic C(sp³) pincer complex with O- and N-donors, see: A. Yoneda and T. Hakushi, Organometallics, 1994, 13, 4912–4918.
5. For selected reviews on aryl C(sp²) pincer complexes with N-, P- or S-donors, see: (a) M. Albrecht and G. van Koten, Angew. Chem., Int. Ed., 2001, 40, 3750–3781; (b) J. T. Singleton, Tetrahedron, 2003, 59, 1837–1857 . For an example on aryl C(sp²) pincer complexes with N-, P- or S-donors, see:; (c) C. M. Jensen, Chem. Commun., 1999, 2443–2449.
6. For examples of aliphatic C(sp³) pincer complexes with Rh, Ir, Ru or Os, see: (a) D. Gelman and S. Musa, ACS Catal., 2012, 2, 2456–2466 . For examples of aliphatic C(sp³) pincer complexes with Pd, Pt, Ni, Rh, Ir, Ru and Os, see:; (b) D. Gelman and R. Romm, Top. Organomet. Chem., 2013, 40, 289–318.
7. (a) Q. Zhang, X.-S. Yin, K. Chen, S.-Q. Zhang and B.-F. Zhang, J. Am. Chem. Soc., 2015, 137, 8219–8226; (b) M.-T. Chicote, C. Rubio, D. Bautista and J. Vicente, Dalton Trans., 2014, 43, 15170–15182; (c) F. Cocco, A. Zucca, S. Stoccoro, M. Serratrice, A. Guerri and M. A. Cinellu, Organometallics, 2014, 33, 3413–3424; (d) P. Saxena, N. Thirupathi and M. Nethaji, Organometallics, 2013, 32, 7580–7593; (e) F. Juliá-Hernández, A. Arcas, D. Bautista and J. Vicente, Organometallics, 2012, 31, 3736–3744; (f) X.-Q. Hao, J.-J. Huang, T. Wang, J. Lv, J.-F. Gong and M.-P. Song, J. Org. Chem., 2014, 79, 9512–9530; (g) X.-Y. Yang, W. S. Tay, Y. Li, S. A. Pullarkat and P.-H. Leung, Chem. Commun., 2016, 52, 4211–4214.
8. For an example on PC(sp³)P Ru pincer complex, see: (a) S. Musa, S. Fronton, L. Vaccaro and D. Gelman, Organometallics, 2013, 32, 3069–3073 . For an example on PC(sp³)P Ir pincer complex, see:; (b) G. A. Silantyev, O. A. Filippov, S. Musa, D. Gelman, N. V. Belkova, K. Weisz, L. M. Epstein and E. S. Shubina, Organometallics, 2014, 33, 5964–5973.
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20. To investigate the possible reasons for the preferred formation of the five-membered NC(sp³)E complexes 9 instead of the six-membered EC(sp²)E complexes 10, the analogous bisphosphine sulfide and oxide derivatives containing phenyl-substituents instead of the pyridyl-substituents were synthesized and isolated. By removing the N-donors, the formation of the five-membered NC(sp³)E complexes will be prevented, thus allowing the plausible formation of the six-membered EC(sp²)E complexes via C(sp²)–H activation. The cyclopalladation of the bisphosphine derivatives were attempted with PdCl₂(NCMe)₂ in the presence of NaOAc in DCM at RT. Unfortunately, no reaction was observed by ³¹P{¹H} NMR spectroscopy even after 4 days. This leads us to conclude that the formation of the six-membered EC(sp²)E complexes are not favorable in this instance.
21. For a detailed discussion of determination of ee and de by ³¹P{¹H} NMR techniques, see ESI Fig. s56 and s57†.
22. X.-Y. Yang, J. H. Gan, Y. Li, S. A. Pullarkat and P.-H. Leung, Dalton Trans., 2015, 44, 1258–1263.

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Footnote

† Electronic supplementary information (ESI) available: Experimental and spectral data and crystallographic refinement data. CCDC 1457086 ((S,S)-4b) and 1457085 (S,S,S,S)-9b. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra16721g

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