Asymmetric 1,4-Conjugate Addition of Diarylphosphines to α,β,γ,δ

Article pubs.acs.org/Organometallics

Asymmetric 1,4-Conjugate Addition of Diarylphosphines to α,β,γ,δUnsaturated Ketones Catalyzed by Transition-Metal Pincer Complexes Xiang-Yuan Yang, Wee Shan Tay, Yongxin Li, Sumod A. Pullarkat,* and Pak-Hing Leung* Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 S Supporting Information *

ABSTRACT: An enantioselective asymmetric 1,4-addition of diarylphosphines to linear α,β,γ,δ-unsaturated dienones was developed. A series of chiral PCP- and PCN-transition-metal (Pd, Pt and Ni) pincers, themselves prepared catalytically via asymmetric hydrophosphination, were sequentially screened to reveal the roles of backbone architecture and metal ion in catalyst design. The selected ester-functionalized PCP-palladium pincer afforded the chiral 1,4-phosphine adducts in excellent yields with up to >99% ee. The same catalyst when utilized for the hydrophosphination of an α,β,γ,δ-unsaturated malonate ester also revealed the critical role played by the ester functionality on the ligand backbone in dictating the enantioselectivity of the 1,6-adduct.

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INTRODUCTION The enantioselective formation of carbon−carbon bonds through conjugate addition (CA) is a practical and attractive strategy toward generating highly functionalized molecular synthons.1 However, the simultaneous control of both regioand stereoselectivity is a significant challenge in asymmetric CA, especially in the case of linear α,β,γ,δ-unsaturated Michael acceptors. Because of the presence of three potentially accessible electrophilic sites, the selective formation of 1,2-, 1,4-, or 1,6-adducts becomes inherently difficult. Nevertheless, significant progress has been achieved by the groups of Hayashi, Fillion, Feringa, and Alexakis2 in the highly regioselective construction of C−C bonds in an enantioselective manner in such scenarios. In contrast, the asymmetric formation of carbon-heteroatom bonds (such as C−Si, C−P, C−N, and C− S) involving linear α,β,γ,δ-unsaturated substrates are relatively rare in the literature.3 In the case of asymmetric C−P bond formation involving α,β,γ,δ-unsaturated substrates, this is in fact limited to just two literature reports.3d,4 Because of the wellestablished role of chiral phosphines in many areas of science such as pharmaceuticals, agrochemicals, fine chemicals, transition-metal catalysis, and organocatalysis,5 compounding interest has been generated recently in the asymmetric formation of C−P bonds via the metal-catalyzed hydrophosphination reaction on α,β-unsaturated substrates.6 This method is able to produce enantiopure tertiary phosphines in arguably the most economical, practical, and straightforward manner. The two reports of chiral phosphines produced via regioselective CA (Scheme 1) utilizing the hydrophosphination protocol, which have been reported recently by Duan et al.3d and by us,4 both conspicuously employed chiral PCP pincer catalysts (albeit generated via differing methodologies). The former report focused on the addition of diarylphosphines to © XXXX American Chemical Society

Scheme 1. Examples of Regioselective C−P Bond Formation

α,β,γ,δ-unsaturated sulfonic esters, which proceeded with 1,6regioselectivity at −60 °C, while in the latter, when employing an α,β,γ,δ-unsaturated malonate ester, viz., diethyl 2-cinnamylidenemalonate, the addition of diphenylphosphine yielded the 1,6-adduct as the major product at −80 °C. Interestingly, in the latter study, when a phosphapalladacycle was employed in the same reaction, the regioselectivity could be switched to favor the traditional 1,4-addition product, thus indicating the need to further investigate the role of catalyst design in this synthetically useful methodology. Received: September 14, 2015

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DOI: 10.1021/acs.organomet.5b00787 Organometallics XXXX, XXX, XXX−XXX

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Table 1. Screening of Catalysts in the AHP Reactiona

Herein, we report the development of an efficient protocol for the asymmetric CA of diarylphosphines to linear α,β,γ,δunsaturated dienones. The aim was to establish an efficient methodology toward the asymmetric hydrophosphination (AHP) of activated diunsaturated enones, which could also provide further insights into the role of transition-metal pincer based catalyst design in the control of regio- and stereoselectivity control in this relatively under-developed asymmetric CA.

entry 1 2 3 4 5 6 7 8 9

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RESULTS AND DISCUSSION From the point of view of catalyst design, a major obstacle to accessing chiral variants of the pincer complexes lies in their syntheses.7 Existing methods are highly dependent on the chiral pool of starting materials such as amino acids8 and BINOL- and TADDOL-derivatives.9 For instance, the catalyst used in the aforementioned study by Duan et al.3d was prepared from an optically pure diol and required extensive protection− deprotection protocols,10 which are known to adversely affect optical purity and yield.11 The multistep synthesis ultimately afforded the PCP-pincer in a low overall yield of 32%. Leveraging on a recently developed synthetic methodology,12 we have successfully bypassed these traditional impediments to produce catalytically a series of optically pure PCP- and PCNpincer complexes in an efficient and diastereoselective manner from cheap and easily accessible achiral substrates (Figure 1,

cat. d

(S)-1 (R,R)-2a (R,R)-2b (R,R)-2c (R,R)-3a (R,R)-3b (R,R)-3c (R)-4a (R)-4b

t (h)

eeb (%)

yieldc (%)

3 3 24 4 20 24 48 24 24

24 5 2 21 69 16 4 10 3

80 80 73 79 89 86 71 85 69

Conditions: compound 5a (0.05 mmol), catalyst (R,R)-3a (2.5 μmol, 5 mol %), and HPPh2 (0.06 mmol) in 3 mL of solvent stirred at RT. b Determined by chiral HPLC. cIsolated yield. dAddition of NEt3 (1.2 equiv) as an external base was necessary. a

entries 2−9 in Table 1 allowed three main inferences to be made: (1) palladium is by far a better metal ion than both platinum and nickel in terms of reactivity, (2) the PCN pincers were inferior to their PCP counterparts in having lower reactivity along with diminished ee/yields, and (3) the esterfunctionalized PCP-pincer 3 clearly outperforms the ketofunctionalized pincers 2 and 4 in controlling the stereoselectivity of the AHP reaction. Comparing the same general ligand backbone with different transition metals thus sheds light on the contrasting reactivity between Pd, Pt, and Ni for this hydrophosphination reaction. It also shows the differing ability between the complexes to efficiently transmit the stereocontrol to the reaction site on the metal (Table 1, entries 2−3, 5−7). Another point to note is that the modification of the terminal R groups in the ketofunctionalized catalyst 2 (Table 1, entries 2, 4) had only marginal impact on both yields and enantioselectivity, possibly due to the remoteness of these groups from the metal center. It is noteworthy that, in all cases, only the 1,4-adduct 6a was formed exclusively. The pincer (R,R)-3a surpassed all other catalysts in providing the optimum balance between reactivity, ee, and yield and, hence, was shortlisted as the catalyst of choice for further optimization studies (Table 2). We were delighted to find out that, in the majority of the cases, the reaction gave high ee with moderate to excellent yields under mild conditions, albeit with varying reaction times. Acetone was selected as the solvent of choice due to the short reaction time, high ee, and excellent yield (Table 2, entry 5). To further improve enantioselectivity, the reaction was completed in 6 h at 0 °C (Table 2, entry 10), and 99% ee was achieved. In terms of both ee and reactivity, this outperformed a previously reported methyl-substituted PCP-pincer catalyzed AHP of substrate 5a to form adduct 6a (in 93% ee and 93% yield at RT over 24 h).3d In an attempt to determine if the steric bulkiness of the ester groups at the terminal ends of the PCP pincer (R,R)-3a has a direct influence on the stereochemical outcome, pincer (R,R)-3d was prepared and employed in the same catalytic scenario. The data (Table 2, entry 11) obtained suggest that modification of the steric bulk has negligible effects on stereoselectivity. With the optimal conditions established, a range of linear α,β,γ,δ-unsaturated dienones were screened (Table 3). This is the first instance in the literature wherein an AHP has been

Figure 1. Cyclometalated complexes employed.

complexes 2, 3, and 4) in isolated yields of up to 75%. Furthermore, this new catalytic preparation of optically pure pincer ligands allows the flexibility for the facile incorporation of various backbone functionalities. In the context of AHP, it also allows us to diversify from the traditional catalyst design based on the palladacycle (S)-1 and its analogues (Figure 1), which have proven potential as efficient catalysts in the AHP of α,β-unsaturated substrates. However, such protocols are routinely conducted at −80 °C, and a higher reaction temperature such as RT results in lower ee values.6f−k We initiated our current study by screening the PCP- and PCN-pincer complexes presented in Figure 1 as well as the phosphapalladacycle (S)-1 for the AHP of α,β,γ,δ-unsaturated dienone 5a with diphenylphosphine (Table 1). The reaction catalyzed by palladacycle (S)-1 (Table 1, entry 1) was encouraging in terms of reactivity and yield, but the ee achieved was substantially low when compared to the best performing pincer (Table 1, entry 5) at room temperature. As far as the pincer type catalysts were concerned, a preliminary analysis of B

DOI: 10.1021/acs.organomet.5b00787 Organometallics XXXX, XXX, XXX−XXX

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Organometallics Table 2. Optimization of the Reaction Conditionsa entry

solvent

t (h)

eeb (%)

yieldc (%)

1 2 3d 4d 5 6 7 8 9 10e 11f

toluene MTBE MeOH THF acetone MeCN DEE EA benzene acetone acetone

15 8 24 24 5 22 4 4 12 6 6

92 93 16 80 97 94 92 91 90 99 95

88 83 51 62 84 81 81 76 82 92 88

proceeded smoothly to afford the desired products without any visible changes in reactivity. The sterically bulkier phosphine (HP(o-tolyl)2) (Table 3, entry 21) was also successful in generating the 1,4-adduct in 97% ee. As aforementioned, Duan et al.3d had reported the regioselective addition of phosphines to α,β,γ,δ-unsaturated sulfonic esters to afford the 1,6-adduct as the only products. Subsequently, our group had published an article investigating the control of regioselectivity by the appropriate choice of palladium catalyst for α,β- and α,β,γ,δ-unsaturated malonate esters. However, when the keto-based pincer (R,R)-2a was employed as catalyst, 1,6-adducts were obtained regioselectively but with low ee’s (22−70%).4 Encouraged by the excellent results obtained in the current study where 1,4-adducts were regioselectively generated with the ester-based pincer (R,R)-3a, we decided to further investigate the underlying factors which caused the dramatic regioselectivity reversal observed. We, therefore, set up a model reaction involving the AHP of diethyl-2-cinnamylidenemalonate 7, but this time employing both pincers (R,R)-2a and (R,R)-3a for comparison (Table 4).

Conditions: compound 5a (0.05 mmol), catalyst (R,R)-3a (2.5 μmol, 5 mol %), and HPPh2 (0.06 mmol) in 3 mL of solvent stirred at RT. b Determined by chiral HPLC. cIsolated yield of adduct 6a. d Incomplete conversion of HPPh2. eReaction was done at 0 °C. f Catalyst (R,R)-3d was used. a

Table 3. Substrate Scope of the AHP Reactiona

Table 4. Catalytic AHP of Substrate 7a entry

R

R1

T (°C)

6

eeb (%)

yieldc (%)

1 2 3 4d 5 6 7 8 9 10 11d 12 13 14 15 16 17 18 19 20 21f

Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph Et Ph

4-PhC6H4 4-PhC6H4 3-NO2C6H4 3-NO2C6H4 3-NO2C6H4 4-CF3C6H4 3,4-ClC6H3 2-naphthyl 2-furyl 4-pyrenyl 4-pyrenyl 4-pyrenyl 4-BrC6H4 4-FC6H4 2-NH2C6H4 4-OMeC6H4 2,5-ClC6H3 2-pyridinyl 2-thionyl Ph Ph

RT 0 RT RT 0 0 0 0 0 RT RT 0 0 0 0 0 0 0 0 0 RT

6b 6b 6c 6c 6c 6d 6e 6f 6g 6h 6h 6h 6i 6j 6k 6l 6m 6n 6o 6p 6q

90 94 95 94 >99 >99 >99 >99 99 93 96 97 >99(S)e 97 98 >99 96 >99 97 97 97

81 86 84 89 92 86 88 85 78 90 89 86 90 91 82 85 88 88 89 91 84

entry

cat.

8a:8a′

eeb (%)

yieldc (%)

1 2

(R,R)-2a (R,R)-3a

0:100 0:100

37 >99

79 81

a Conditions: compound 7 (0.05 mmol), catalyst (2.5 μmol, 5 mol %), and HPPh2 (0.06 mmol) in DCM (3 mL). bDetermined by chiral HPLC. cIsolated yield.

It was noted that both the keto-functionalized (R,R)-2a (Table 1, entry 2) and ester-functionalized (R,R)-3a (Table 1, entry 5) afforded the 1,4-adduct 6a with ee values of 5% and 69% respectively.When extended to the bulkier substrate 7, pincer (R,R)-2a yielded the 1,6-adduct 8a′ in a highly regioselective manner, but with moderate ee (Table 4, entry 1). The pincer (R,R)-3a, however, yielded the same 1,6-adduct regioselectively with >99% ee (Table 4, entry 2). Modifying the substrate bulk predictably resulted in the exclusive formation of the 1,6-adduct 8a′, whereas the ketone 5a selectively formed the traditionally favored (in terms of activation toward nucleophilic attack) 1,4-adduct 6a. This is in agreement with earlier reports which explained that the regioselectivity is controlled by the sterically unfavorable interaction of the pincer with the bulkier ester functionalities on substrate 7 during the course of the catalytic reaction.4 In addition, an analogous methyl-substituted analogue of pincer (R,R)-2a could only afford the adducts 8a and 8a′ in a 1:9 ratio with 43% ee.3d From the viewpoint of the PCP pincers, we could infer that the methyl-substituted pincer experienced less steric interactions with substrate 7 compared with pincers (R,R)-2a and (R,R)-3a, which contributes to better regioselective control. Notably, we have observed that pincer (R,R)-3a achieves higher enantio-discrimination than its analogous complex (R,R)-2a with both substrates 5a and 7. Pincer (R,R)-3a gave ee values of 69% for ketone 5a and >99% for substrate 7 (Table 1, entry 5 and Table 4, entry 2), while pincer (R,R)-2a gave 5% (ketone 5a, Table 1, entry 2) and 37% (substrate 7, Table 4,

Conditions: compound 5 (0.05 mmol), catalyst (R,R)-3a (2.5 μmol, 5 mol %), and HPAr2 (0.06 mmol) in 3 mL of solvent. bDetermined by chiral HPLC. cIsolated yield of product. dCatalyst (R,R)-3d was used. eAbsolute configuration determined by X-ray analysis; see the Supporting Information. fHP(o-tolyl)2 (0.06 mmol) was used. a

attempted on such a wide range of functionalized conjugated dienones. The pincer (R,R)-3a was found to exhibit appreciable substrate tolerance, furnishing only the 1,4-adduct 6 in high ee’s (90−99%) and isolated yields of 78−92% across a broad spectrum of functional groups at the position adjacent to the keto moiety such as substituted aryls and heterocyclic rings. Notably present were both electron-donating groups such as amino (Table 3, entry 15) or methoxy (Table 3, entry 16) groups and an electron-withdrawing moiety such as nitro (Table 3, entries 3−5). In all of these instances, the reaction C

DOI: 10.1021/acs.organomet.5b00787 Organometallics XXXX, XXX, XXX−XXX

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Organometallics entry 1) under the same reaction conditions. To investigate the origin for the superior stereochemical control exhibited by pincer (R,R)-3a as compared to complex (R,R)-2a, their steric properties were first conveniently analyzed from the perspective of their characteristic twist angle, θ (Figure 2).13

Figure 2. Diagrammatic representation of the twist angle θ.

For a particular pincer system, a larger θ with a smaller P→ M←P angle will reflect a more compact conformation, which potentially limits the access of a reactant to the metal center in the direction trans to the M−C bond axis.14 A comparison of the single-crystal X-ray structures12 of the chloro derivatives (R,R)-2a′ and (R,R)-3a′ revealed that both solid-state structures have identical θ (19.64°) and similar P→Pd←P angles ((R,R)-2a′ = 162.24(4)° and (R,R)-3a′ = 161.05(2)°). Bond lengths, bond angles, and geometry of the atoms around the metal centers of both pincers are also identical, therefore, suggesting that the contrasting stereoselectivity of the pincer complexes might be directly related to the substituents on the C-stereogenic centers. The X-ray crystal structure of complex (R,R)-3a′ (Figure 3) shows two five-membered chelate rings, each bearing a C-

Figure 4. 2D 1H−1H NOESY NMR spectrum of complex 3a′.

assigned to their respective protons based on their chemical shifts, multiplicities, and integral ratios (Table 5 and Figure 5). Table 5. Essential 1H NMR Assignments of Complex 3a′ δ (ppm)

multiplicity

integral

assignment

7.09 6.94 4.84−4.80 3.84 3.18 2.68a

doublet triplet multiplet doublet of doublet singlet singlet

2 1 2 2 6 6

H(4) H(3) H(1) H(2) Me(2) Me(1)

a

Assignment is supported by the ring-shielding effect,15 in which protons on C(10) and C(28) will be shielded by the central aryl ring.

Figure 3. Single-crystal X-ray structure of complex (R,R)-3a′.4

stereogenic center. The bulky −CO2Me groups are located on the axial plane, and the stereogenic protons are found at the equatorial position. This arrangement will avoid major steric repulsions between the −CO2Me groups and the adjacent central aryl ring as well as the −PPh2 groups. It was noted that the two phenyl substituents on each P atoms are nonequivalent. In order to investigate if the structural features of the pincer complex in the solid state is retained in solution, a twodimensional 1H−1H nuclear Overhauser effect spectroscopy (NOESY) experiment was conducted on the chloro derivative (R,R)-3a′ of pincer (R,R)-3a (Figure 4). Special attention was directed to the study on the rotation of the −CO2Me groups along the C(25)−C(26) and C(7)−C(8) bond axes, as well as the rigidity of the ring conformation in solution. Prior to the analysis of the 2D 1H−1H NOESY NMR spectrum, it is essential to assign the key 1H NMR signals of the complex (R,R)-3a′. Six of the 1H NMR signals are unambiguously

Figure 5. Representative numbering scheme of complex 3a′.

From the 1H−1H NOESY NMR spectrum, crystal structure, and model studies of complex (R,R)-3a′, the presence of the signals A−I are noted in Table 6. In particular, signals F−I suggest the existence of unique structural features in the complex. First, if the chelate ring undergoes δ and λ conversion in solution, NOE interactions of Me(2) with both H(5) and H(6) as well as H(2) with both H(5) and H(6) will be detected. However, the absence of NOE interactions corresponding to Me(2)−H(5) and H(2)−H(5) indicate that the two fivemembered chelate rings adopt a fixed δ conformation in solution (Figure 6). A model study revealed that the rotations of the CH(CO2Me)2 groups along the C(25)−C(26) and C(7)−C(8) D

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tolerate a wide range of functionalities on the ketone substrate. A comparative study conducted subsequently revealed how the combination of substrate selection in conjunction with catalyst choice can provide excellent control on enantio- and regioselectivity (1,4- vs 1,6-addition) in the case of AHP. The origin of the enhanced stereoselectivity exhibited by pincer (R,R)-3a was also revealed.

Table 6. Important NOE Interactions in Complex 3a′ signal

NOE interaction

A B C D E F G H I

H(1)−H(4) H(1)−H(5) H(1)−H(6) H(5)−H(6) H(1)−H(2) H(2)−H(6) Me(1)−H(5) Me(1)−H(4) Me(2)−H(6)

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EXPERIMENTAL SECTION

General Information. All reactions were carried out under a positive pressure of nitrogen using a standard Schlenk technique. Solvents were purchased from their respective companies and used as supplied. Where necessary, solvents were degassed prior to use. A Low Temp Pairstirrer PSL-1800 was used for controlling low-temperature reactions. Column chromatography was done on Silica gel 60 (Merck). Melting points were measured using an SRS Optimelt Automated Point System SRS MPA100. Optical rotation were measured with a JASCO P-1030 polarimeter in the specified solvent in a 0.1 dm cell at 21.0 °C. 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. HPLC analysis was done with an Agilent Technologies 1200 Series HPLC machine. The palladacycle (S)-1,6g (R,R)-2a−c, (R,R)-3a−d, and (R)-4a−b12 were prepared according to literature methods. All other reactants and reagents were used as supplied. General Procedure for Preparation of Wittig Reagents. Arylsubstituted 2-bromoethanone (5.00 mmol, 1.0 equiv) and PPh3 (1.44 g, 5.50 mmol, 1.1 equiv) were refluxed in THF (10 mL) for 4 h. Upon cooling, volatiles were removed, and the solids were redissolved in DCM, extracted with aq. NaOH (20% w/w in H2O, 1 × 20 mL), washed with water (1 × 20 mL), dried over MgSO4, filtered, and evaporated to dryness. The crude product was purified by silica gel chromatography (2 EA:1 n-hexane) to afford the pure product. General Procedure for Preparation of αβγδ-Unsaturated Substrates. Method A: Wittig Reaction. A solution of aldehyde (7.57 mmol, 1.0 equiv) and Wittig reagent (8.32 mmol, 1.1 equiv) in toluene (30 mL) was refluxed for 24 h. The mixture was cooled and extracted with EA (3 × 40 mL), washed with H2O (1 × 40 mL), dried over MgSO4, filtered, and evaporated to dryness. The crude product was purified by silica gel chromatography (2 n-hexane:1 DCM) to afford the pure product. Method B: Aldol Condensation. To a solution of NaOH (0.11 g, 2.75 mmol, 1.2 equiv) in H2O (20 mL) and aromatic ketone (2.29 mmol, 1.0 equiv) in ethanol (12 mL) at 0 °C was gradually added aromatic aldehyde (0.30 g, 0.29 mL, 2.29 mmol, 1.0 equiv). The mixture was allowed to warm to room temperature and stirred for 4 h, after which the precipitate of the product was collected by suction filtration on a Buchner funnel and washed repeatedly with cold water. The residue was redissolved in DCM and extracted, washed with H2O (1 × 40 mL), dried over MgSO4, filtered, and evaporated to dryness. The crude product was purified by silica gel chromatography (2 n-hexane:1 DCM) to afford the pure product. General Procedure for Catalytic AHP Reaction. The catalyst (2.25 mg, 2.5 umol, 5 mol %) was added to a solution of diarylphosphine (0.06 mmol, 1.2 equiv) in the stated solvent (3 mL) and brought to the desired temperature. The substrate (0.05 mmol, 1.0 equiv) was subsequently added and stirred at the stated temperature. Completion of the reaction was determined by the disappearance of the phosphorus signal attributed to diphenylphosphine (−40 ppm) or di(o-tolyl)phosphine (−60 ppm) in the 31P{1H} NMR spectrum. Upon completion of the reaction, aq. H2O2 (0.1 mL, 31% v/v) was added to form the respective product. The volatiles were removed under reduced pressure and the crude product was directly loaded onto a silica gel column (ethyl acetate:n-hexane = 3:2) to afford the pure product.

Figure 6. Conformation of chelate ring in complex 3a′.

bond axes are sterically hindered by the equatorial Ph moieties on the P atoms. The NOESY NMR spectrum shows long-range NOE interactions of Me(1) with H(5) (signal G), but not with H(6). In contrast, Me(2) has an NOE interaction with H(6) (signal I), but not with H(5). The absence of Me(2)−H(4) NOE interaction suggests the possibility of restricted rotation of the CH(CO2Me)2 groups. If the chiral functionalities are rotatable along the C(25)−C(26) and C(7)−C(8) bond axes, both Me(1) and Me(2) should exhibit NOE interactions with H(4), H(5), and H(6). Overall, all the data collated is indicative of a favorable disposition of the pendant arms bearing the ester moieties around the active site of complex (R,R)-3a′, which is not observed for pincer (R,R)-2a′. The unique arrangement of the carboxylate groups together with the nonequivalent Ph substituents on each P atom serves to regulate the approach of the reactants during the course of the catalytic cycle. NOE signals corresponding to the protons on the terminal carboxylate groups and the aromatic protons on the −PPh2 groups suggest a close spatial proximity of the ester groups to the P atoms of the P→Pd←P moiety. In addition, restricted rotation of the groups in the pendant arms of pincer (R,R)-3a′ due to the sterically bulkier ester moieties may exert more stereocontrol over the accessibility of the substrate to the active site, which translates into enantio-discrimination.

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CONCLUSIONS In summary, we have screened a series of enantiopure PCPand PCN-pincer complexes (themselves generated via an efficient catalytic methodology)12 in the asymmetric P-H addition of diarylphosphines to linear α,β,γ,δ-unsaturated dienones. It should be reiterated that the new methodology developed provides substantial improvement in reactivity while allowing the AHP to be conducted on a wide range of functionalized conjugated ketones. The study provided key insights into the molecular structure required in terms of metal ion and backbone functionalities for an efficient catalyst design. A straightforward preparation of synthetically useful chiral allylic phosphines was achieved in high yields (81−92%) with excellent enantioselectivity (94% to >99%) under mild reaction conditions catalyzed by pincer (R,R)-3a. The protocol could E

DOI: 10.1021/acs.organomet.5b00787 Organometallics XXXX, XXX, XXX−XXX

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Organometallics

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.5b00787. Detailed experimental procedures for the syntheses of substrates and products; crystal and refinement data for complex (S)-6i; and 1H, 13C, 31P{1H} NMR spectra and HPLC spectra (PDF) Crystallographic data for (S)-6i (CIF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (S.A.P.). *E-mail: [email protected] (P.-H.L.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We wish to acknowledge the funding support for this project from Nanyang Technological University (NTU). X.-Y.Y thanks NTU for the award of a scholarship, and W.S.T. thanks the NTU Undergraduate Research Experience on CAmpus (URECA) program for the support.

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REFERENCES

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DOI: 10.1021/acs.organomet.5b00787 Organometallics XXXX, XXX, XXX−XXX