Palladium-catalyzed 1,4-addition of secondary alkylphenylphosphines to α,β-unsaturated carbonyl compounds for the synthesis of phosphorus- and carbon-stereogenic compounds

Abstract

Highly stereoselective 1,4-addition of alkylphenylphosphines to α,β-unsaturated carbonyl compounds catalyzed by PCP or NCN pincer–Pd complexes is described to synthesize chiral phosphorus compounds bearing both P- and C-stereogenic centers with good to excellent enantioselectivity (up to 99.6% ee).

---

Chiral phosphines are ligands widely used in catalytic reactions to control the reactivity and enantioselectivity.¹ Among these phosphines, axially chiral, carbon-stereogenic, or planar-chiral phosphine ligands, such as binap, diop, and josiphos, are frequently used to construct optically active compounds from prochiral starting materials. By contrast, phosphorus (P)-chiral phosphines are relatively less employed in catalysis.² The first reported chiral phosphine ligand contains only one P-stereogenic center,³ likely because the preparation of P-chiral compounds is synthetically more challenging compared with other compounds.⁴ Reported methods always involve the optical resolution of racemates or desymmetrization of prochiral compounds with stoichiometric amounts of chiral reagents. These methods also require multiple-step transformations. Direct construction of a P–C bond, along with P-chiral center formation via asymmetric catalysis, appears to be a promising approach to solving this synthetic problem.^5,6 Several methods, including transition metal-catalyzed arylation and alkylation of secondary phosphines with good to excellent enantioselectivities, have been reported by Glueck et al. and Toste/Bergman et al., respectively.⁷ The asymmetric Michael addition of methylphenylphosphine to enones was recently reported to generate P- and C-chiral phosphorus compounds with up to 82% ee by Leung et al.⁸ However, certain limitations still in terms of the extent of stereoselectivity and generality of the substrates must be addressed. In the present study, we describe a palladium-catalyzed asymmetric addition of disubstituted phosphines to α,β-unsaturated carbonyl compounds for the synthesis of P- and C-stereogenic phosphorus compounds with good to excellent enantioselectivities.

We previously reported the bisphosphine (PCP) pincer Pd-catalyzed asymmetric addition of diarylphosphines to electron-deficient alkenes for the synthesis of diverse chiral phosphine compounds.⁹ A Pd-diphenylphosphido intermediate was generated from the reaction of diphenylphosphine with the Pd catalyst and proposed as the active nucleophile toward electrophiles in the catalytic cycle.^9a We hypothesized that the use of secondary phosphine nucleophiles bearing two different groups (e.g., methylphenylphosphine) could generate two Pd-phosphido diastereomers in a chiral environment induced by two methyl groups at the benzylic position of the catalyst. Subsequent functionalization of these intermediates could lead to the formation of P-stereogenic phosphorus compounds (Scheme 1).

Scheme 1 Proposed protocol for P-chiral compound synthesis.

We initiated the reaction of alkylphenylphosphines with chalcone in the presence of pincer–Pd catalysts. The reaction of methylphenylphosphine 2a with enone 1a in the presence of catalyst (S,S)-4^10,11 only afforded products with low ee and dr (Table 1, entry 1).¹² Solvent screening and temperature reduction to −30 °C did not lead to satisfactory results (entries 2–5). Changing the methyl group to ethyl and n-butyl groups in the P nucleophiles increased the ee and diastereomeric ratios of products (entries 6 and 7). Interestingly, introduction of an isopropyl group to substrate 2d significantly improved the ee of the product to 99% as well as its diastereoselectivity (entry 8; dr > 10/1). To increase the stereoselectivity in the reaction of methylphenyl phosphine with chalcone, bisimidazoline (NCN) pincer catalysts 5a–5i were synthesized and examined.¹³ Catalyst (S,S)-5a derived from (S)-phenylglycinol bearing a 4-methoxyphenyl group on the nitrogen atom afforded two diastereomers with good ee (entry 9: 74 and 83% ee; 1.3/1 dr) at −30 °C.¹⁴ By changing the substituted groups on the imidazoline ring to benzyl, isopropyl, and isobutyl groups, catalysts 5b–5d produced products with decreased enantioselectivity (entries 10–12). Investigations on temperature effects showed that reaction at room temperature yields products with 81% and 91% ee (entry 14). By changing the substituted group to 4-tolyl on the nitrogen atom or installation of a methoxy group at the phenyl ring of the catalyst, catalysts (S,S)-5e and 5f did not exert beneficial effects on the ee and dr (entries 15 and 16). The use of catalysts 5g and 5h featuring chloride or iodide anions caused a decrease in ee (entries 17 and 18). Changing KOAc to K₂CO₃ or removing KOAc in the reaction led to decreased ee (entries 19 and 20). Catalyst 5i bearing acetate anions also afforded products with lower ee than 5a (entry 21) via a slightly peculiar manner, the reason for which remains unclear at this point. Afterward, extensive examination of the solvents revealed that dichloromethane is optimal compared with other solvents (entries 22–25) at room temperature; toluene and tert-amyl alcohol afforded products with slightly low ee. Unexpectedly, using toluene as the solvent at −5 °C, products with the highest ee were isolated (entry 27: 87% and 96% ee). Further temperature reduction to −10 °C decreased the ee of both diastereomers (entry 28: 86% and 79% ee). For P nucleophiles 2b–2c, catalyst 5a only produced the corresponding products with moderate ee compared with catalyst 4 (entries 29–31).

Table 1 Palladium-catalyzed addition of alkylphenylphosphines 2 to chalcone 1a

Entry	Phosphine	Catalyst	Solvent	Temp (°C)	Yield^a (%)	dr^b	ee^c (%)
a Isolated yields. b Determined by ^1H NMR analysis of the crude product. c Determined by HPLC with hexane–2-propanol. d 50 mol% K2CO3 used. e Without addition of KOAc.
1	2a	(S,S)-4	Toluene	rt	83	1.7/1	22/47
2	2a	(S,S)-4	Toluene	−5	55	1.9/1	32/43
3	2a	(S,S)-4	Toluene	−30	96	3.0/1	28/32
4	2a	(S,S)-4	CH2Cl2	−30	83	3.9/1	56/28
5	2a	(S,S)-4	THF	−30	88	2.5/1	40/47
6	2b	(S,S)-4	Toluene	−5	96	11/1	86/65
7	2c	(S,S)-4	Toluene	−5	85	4.7/1	58/86
8	2d	(S,S)-4	Toluene	−5	80	>10/1	99.5
9	2a	(S,S)-5a	CH2Cl2	−30	74	1.3/1	74/83
10	2a	(S,S)-5b	CH2Cl2	−30	93	1.7/1	53/75
11	2a	(S,S)-5c	CH2Cl2	−30	93	1.8/1	44/67
12	2a	(S,S)-5d	CH2Cl2	−30	75	2.0/1	24/51
13	2a	(S,S)-5a	CH2Cl2	0	83	1.3/1	81/90
14	2a	(S,S)-5a	CH2Cl2	rt	87	1.4/1	81/91
15	2a	(S,S)-5e	CH2Cl2	rt	81	1.3/1	60/85
16	2a	(S,S)-5f	CH2Cl2	rt	83	1.4/1	78/83
17	2a	(S,S)-5g	CH2Cl2	rt	87	1.4/1	80/88
18	2a	(S,S)-5h	CH2Cl2	rt	94	1.5/1	61/75
19^d	2a	(S,S)-5a	CH2Cl2	rt	97	1.2/1	71/74
20^e	2a	(S,S)-5a	CH2Cl2	rt	94	1.4/1	61/80
21^e	2a	(S,S)-5i	CH2Cl2	rt	97	1.4/1	75/84
22	2a	(S,S)-5a	Toluene	rt	70	1.3/1	82/89
23	2a	(S,S)-5a	t-AmOH	rt	74	1.2/1	80/89
24	2a	(S,S)-5a	MeOH	rt	33	2.5/1	15/25
25	2a	(S,S)-5a	DMF	rt	77	1.5/1	58/71
26	2a	(S,S)-5a	Toluene	0	80	1.3/1	83/95
27	2a	(S,S)-5a	Toluene	−5	98	1.1/1	87/96
28	2a	(S,S)-5a	Toluene	−10	95	0.9/1	86/79
29	2b	(S,S)-5a	Toluene	−5	88	2.7/1	36/34
30	2c	(S,S)-5a	Toluene	−5	98	2.2/1	66/7
31	2d	(S,S)-5a	Toluene	−5	81	1.6/1	12/73

---

The scope of substrates was examined under optimum conditions, and the results are shown in Table 2. Methylphenylphosphine reacted with enones bearing diverse substituted groups (i.e., alkyl, methoxy, halide, and nitro) smoothly, thereby yielding a series of phosphorus compounds with good to excellent enantiomeric excess (Table 2: entries 1–9). For substrates bearing an isopropyl moiety at the β-position, the ee of products is lower than that in the case of aryl groups (entry 10). α,β-Unsaturated N-acyl pyrroles have been reported to be good acceptors in asymmetric addition reactions.¹⁵ The pyrrole group can be easily converted into various moieties.¹⁶ Experimental results indicate that various α,β-unsaturated N-acyl pyrroles show properties comparable to those of enones in terms of ee and dr (entries 11–17), which further extends the applicability of the current catalytic system. Table 3 summarizes the reactions of isopropylphenylphosphines with α,β-unsaturated enones and N-acyl pyrroles. All of the products were isolated with almost perfect enantioselectivities and moderate to good diastereomeric ratios (Table 3: entries 1–8; 98 to 99.6% ee). To illustrate the utility of the current method, a bisenone was reacted with a secondary phosphine 2d to yield a chiral bisphosphine bearing four stereogenic centers in 99% ee (Scheme 2); this biphosphine is a useful ligand for the preparation of P-chiral pincer metal catalysts.^6q,17

Scheme 2 Synthesis of an optically pure P-stereogenic bisphosphine.

Table 2 Palladium-catalyzed asymmetric addition of methylphenylphosphines to α,β-unsaturated carbonyl compounds

Entry	R^1	R^2	Yield (%)/(dr)^a^,^b	ee of the major and minor product^c^,^d (%)
a Isolated yields. b Determined by ^1H NMR analysis of the crude product. c Determined by HPLC with hexane–2-propanol. d The absolute configurations of products were determined to be S,Sp for major diastereomers and S,Rp for minor diastereomers by X-ray crystal diffraction of 1,4-adducts in entries 9 and 17 (see ESI for details).^18
1	Ph	Ph	98 (1.1/1)	87/96
2	Ph	4-MeC6H4	97 (1.1/1)	88/95
3	Ph	4-MeOC6H4	92 (1.2/1)	89/95
4	Ph	3-BrC6H4	94 (1.1/1)	87/96
5	Ph	4-BrC6H4	98 (1.1/1)	83/96
6	Ph	4-O2NC6H4	94 (1.2/1)	87/97
7	Ph	4-CF3C6H4	86 (1.3/1)	81/95
8	4-BrC6H4	Ph	88 (1.2/1)	89/94
9	Me	4-BrC6H4	98 (1.7/1)	89/94
10	Ph	i-Pr	91 (2.6/1)	72/85
11	1-Pyrrolyl	Ph	84 (1.2/1)	86/93
12	1-Pyrrolyl	4-MeC6H4	97 (1.2/1)	84/93
13	1-Pyrrolyl	2-Naphthyl	91 (1.2/1)	85/93
14	1-Pyrrolyl	4-MeOC6H4	95 (1.1/1)	83/92
15	1-Pyrrolyl	4-NO2C6H4	97 (1.1/1)	85/93
16	1-Pyrrolyl	3-BrC6H4	98 (1.2/1)	84/95
17	1-Pyrrolyl	4-BrC6H4	96 (1.2/1)	86/96

---

Table 3 Palladium-catalyzed asymmetric addition of isopropylphenylphosphine to α,β-unsaturated carbonyl compounds

Entry	R^1	R^2	Yield (%)/(dr)^a^,^b	ee^c^,^d (%)
a Isolated yields. b Determined by ^1H NMR analysis of the crude product. c Determined by HPLC with hexane–2-propanol. d The absolute configurations of products were determined to be S,Rp by X-ray crystal diffraction of the 1,4-adduct in entry 1 (see ESI for details).^18
1	Ph	Ph	80 (>10/1)	99.5
2	Ph	4-MeOC6H4	84 (>10/1)	98
3	Ph	4-NO2C6H4	85 (>10/1)	99
4	3-BrC6H4	Ph	88 (>10/1)	99.4
5	1-Pyrrolyl	Ph	83 (7/1)	98
6	1-Pyrrolyl	4-BrC6H4	80 (5/1)	99.6
7	1-Pyrrolyl	3-BrC6H4	81 (6/1)	99
8	1-Pyrrolyl	2-Naphthyl	78 (5/1)	>99.5

---

In summary, we have described the enantioselective addition of alkylphenylphosphines to α,β-unsaturated carbonyl compounds catalyzed by PCP and NCN pincer Pd catalysts to yield chiral phosphorus compounds bearing both P- and C-stereogenic centers with good to excellent enantioselectivity under mild conditions. Further studies will elucidate the stereochemistry-determining factors and applications of P-chiral compounds as ligands to transition metals in catalysis.

We thank the National Basic Research Program of China (973 Program 2010CB833300), the NSFC (20902099, 21172238), and SIOC for funding this work.

Notes and references

1. (a) Phosphorus Ligands in Asymmetric Catalysis: Synthesis and Applications, ed. A. Börner, Wiley-VCH, Weinheim, vol. 1–3, 2008; (b) W. Tang and X. Zhang, Chem. Rev., 2003, 103, 3029; (c) X. Cui and K. Burgess, Chem. Rev., 2005, 15, 3272; (d) J.-H. Xie, S.-F. Zhu and Q.-L. Zhou, Chem. Rev., 2011, 111, 1713; (e) D.-S. Wang, Q.-A. Chen, S.-M. Lu and Y.-G. Zhou, Chem. Rev., 2012, 112, 2557.
2. For recent examples of P-chiral ligands in catalysis, see: (a) T. Imamoto, J. Watanabe, Y. Wada, H. Masuda, H. Yamada, H. Tsuruta, S. Matsukawa and K. Yamaguchi, J. Am. Chem. Soc., 1998, 120, 1635; (b) I. D. Gridnev, N. Higashi, K. Asakura and T. Imamoto, J. Am. Chem. Soc., 2000, 122, 7183; (c) W. Tang and X. Zhang, Angew. Chem., Int. Ed., 2002, 41, 1612; (d) W. Tang, W. Wang and X. Zhang, Angew. Chem., Int. Ed., 2003, 42, 943; (e) W. Tang, W. Wang, Y. Chi and X. Zhang, Angew. Chem., Int. Ed., 2003, 42, 3509; (f) T. Imamoto, K. Sugita and K. Yoshida, J. Am. Chem. Soc., 2005, 127, 11934; (g) T. Imamoto, Y. Saitoh, A. Koide, T. Ogura and K. Yoshida, Angew. Chem., Int. Ed., 2007, 46, 8636; (h) A. M. Taylor, R. A. Altman and S. L. Buchwald, J. Am. Chem. Soc., 2009, 131, 9900; (i) T. Imamoto, K. Tamura, Z. Zhang, Y. Horiuchi, M. Sugiya, K. Yoshida, A. Yanagisawa and I. D. Gridnev, J. Am. Chem. Soc., 2012, 134, 1754; (j) G. Liu, X. Liu, Z. Cai, G. Jiao, G. Xu and W. Tang, Angew. Chem., Int. Ed., 2013, 52, 4235.
3. For early reported P-chiral ligands, see: (a) L. Horner, H. Siegel and H. Büthe, Angew. Chem., Int. Ed. Engl., 1968, 7, 942; (b) W. S. Knowles and M. J. Sabacky, Chem. Commun., 1968, 1445; (c) W. S. Knowles, M. J. Sabacky and B. D. Vineyard, J. Chem. Soc., Chem. Commun., 1972, 10; (d) W. S. Knowles, M. J. Sabacky, B. D. Vineyard and D. J. Weinkauff, J. Am. Chem. Soc., 1975, 97, 2567.
4. For reviews on preparation of P-stereogenic phosphines, see: (a) K. M. Pietrusiewicz and M. Zablocka, Chem. Rev., 1994, 94, 1375; (b) K. V. L. Crépy and T. Imamoto, Top. Curr. Chem., 2003, 229, 1; (c) K. V. L. Crépy and T. Imamoto, Adv. Synth. Catal., 2003, 345, 79; (d) P.-H. Leung, Acc. Chem. Res., 2004, 37, 169; (e) A. Grabulosa, J. Granell and G. Muller, Coord. Chem. Rev., 2007, 251, 25; (f) O. I. Kplodiazhnyi, Tetrahedron: Asymmetry, 2012, 23, 1. For representative examples, see: (g) W. B. Farnham, R. K. Murray Jr. and K. Mislow, J. Am. Chem. Soc., 1970, 92, 5809; (h) J. Donohue, N. Mandel, W. B. Farnham, R. K. Murray Jr., K. Mislow and H. P. Benschop, J. Am. Chem. Soc., 1971, 93, 3792; (i) T. Imamoto, T. Oshiki, T. Onozawa, T. Kusumoto and K. Sato, J. Am. Chem. Soc., 1990, 112, 5244; (j) S. Jugé, M. Stephan, J. Laffitte and J. Genet, Tetrahedron Lett., 1990, 31, 6357; (k) T. Oshiki and T. Imamoto, J. Am. Chem. Soc., 1992, 114, 3975; (l) A. R. Muci, K. R. Campos and D. A. Evans, J. Am. Chem. Soc., 1995, 117, 9075; (m) B. Wolfe and T. Livinghouse, J. Am. Chem. Soc., 1998, 120, 5116; (n) K. Nagata, S. Matsukawa and T. Imamoto, J. Org. Chem., 2000, 65, 4185; (o) T. Imamoto, S.-I. Kikuchi, T. Miura and Y. Wada, Org. Lett., 2001, 3, 87; (p) Q. Xu, C.-Q. Zhao and L.-B. Han, J. Am. Chem. Soc., 2008, 130, 12648; (q) G. Wang, R. Shen, Q. Xu, M. Goto, Y. Zhao and L.-B. Han, J. Org. Chem., 2010, 75, 3890; (r) Y. Zhou, G. Wang, Y. Saga, R. Shen, M. Goto, Y. Zhao and L.-B. Han, J. Org. Chem., 2010, 75, 7924; (s) Z. S. Han, N. Goyal, M. A. Herbage, J. D. Sieber, B. Qu, Y. Xu, Z. Li, J. T. Reeves, J.-N. Desrosiers, S. Ma, N. Grinberg, H. Lee, H. P. R. Mangunuru, Y. Zhang, D. Krishnamurthy, B. Z. Lu, J. J. Song, G. Wang and C. H. Senanayake, J. Am. Chem. Soc., 2013, 135, 2474; (t) O. Berger and J.-L. Montchamp, Angew. Chem., Int. Ed., 2013, 52, 11377.
5. For reviews on the synthesis of chiral phosphorus compounds, see: (a) D. S. Glueck, Synlett, 2007, 2627; (b) D. S. Glueck, Chem. – Eur. J., 2008, 14, 7108; (c) J. S. Harvey and V. Gouverneur, Chem. Commun., 2010, 7477; (d) D. Zhao and R. Wang, Chem. Soc. Rev., 2012, 41, 2095. For leading examples, see: (e) I. Kovacik, D. K. Wicht, N. S. Grewal, D. S. Glueck, C. D. Incarvito, I. A. Guzei and A. L. Rheingold, Organometallics, 2000, 19, 950; (f) A. D. Sadow, I. Haller, L. Fadini and A. Togni, J. Am. Chem. Soc., 2004, 126, 14704; (g) C. Scriban, I. Kovacik and D. S. Glueck, Organometallics, 2005, 24, 4871; (h) C. Scriban, D. S. Glueck, L. N. Zakharov, W. S. Kassel, A. G. DiPasquale, J. A. Golen and A. L. Rheingold, Organometallics, 2006, 25, 5757; (i) A. D. Sadow and A. Togni, J. Am. Chem. Soc., 2005, 127, 17012; (j) C. Genet, S. J. Canipa, P. O'Briena and S. Taylor, J. Am. Chem. Soc., 2006, 128, 9336; (k) B. Join, D. Mimeau, O. Delacroix and A.-C. Gaumont, Chem. Commun., 2006, 3249; (l) G. Nishida, K. Noguchi, M. Hirano and K. Tanaka, Angew. Chem., Int. Ed., 2008, 47, 3410; (m) P. Butti, R. Rochat, A. D. Sadow and A. Togni, Angew. Chem., Int. Ed., 2008, 47, 4878; (n) J. S. Harvey, S. J. Malcolmson, K. S. Dunne, S. J. Meek, A. L. Thompson, R. R. Schrock, A. H. Hoveyda and V. Gouverneur, Angew. Chem., Int. Ed., 2009, 48, 762; (o) L. Hong, W. Sun, C. Liu, D. Zhao and R. Wang, Chem. Commun., 2010, 2856; (p) W. Sun, L. Hong, C. Liu and R. Wang, Org. Lett., 2010, 12, 3914; (q) M. Nielsen, C. B. Jacobsen and K. A. Jørgensen, Angew. Chem., Int. Ed., 2011, 50, 3211; (r) S. Liu, Z. Zhang, F. Xie, N. Butt, L. Sun and W. Zhang, Tetrahedron: Asymmetry, 2012, 23, 329.
6. For catalytic asymmetric 1,4-addition of substituted phosphines or phosphine oxides to electron-deficient alkenes, see: (a) A. Carlone, G. Bartoli, M. Bosco, L. Sambri and P. Melchiorre, Angew. Chem., Int. Ed., 2007, 46, 4504; (b) I. Ibrahem, R. Rios, J. Vesely, P. Hammar, L. Eriksson, F. Himo and A. Córdova, Angew. Chem., Int. Ed., 2007, 46, 4507; (c) G. Bartoli, M. Bosco, A. Carlone, M. Locatelli, A. Mazzanti, L. Sambri and P. Melchiorre, Chem. Commun., 2007, 722; (d) X. Fu, Z. Jiang and C.-H. Tan, Chem. Commun., 2007, 5058; (e) I. Ibrahem, P. Hammar, J. Vesely, R. Rios, L. Eriksson and A. Córdova, Adv. Synth. Catal., 2008, 350, 1875; (f) D. Zhao, L. Mao, D. Yang and R. Wang, J. Org. Chem., 2010, 75, 6756; (g) S. Wen, L. Li, H. Wu, F. Yu, X. Liang and J. Ye, Chem. Commun., 2010, 4806; (h) Y. Huang, S. A. Pullarkat, L. Li and P.-H. Leung, Chem. Commun., 2010, 6950; (i) A. Russo and A. Lattanzi, Eur. J. Org. Chem., 2010, 6736; (j) X. Luo, Z. Zhou, X. Li, X. Liang and J. Ye, RSC Adv., 2011, 1, 698; (k) M.-J. Yang, Y.-J. Liu, J.-F. Gong and M.-P. Song, Organometallics, 2011, 30, 3793; (l) Y. Huang, R. J. Chew, Y. Li, S. A. Pullarkat and P.-H. Leung, Org. Lett., 2011, 13, 5862; (m) D. Zhao, L. Wang, D. Yang, Y. Zhang and R. Wang, Chem. – Asian. J., 2012, 7, 881; (n) Y. Huang, S. A. Pullarkat, S. Teong, R. J. Chew, Y. Li and P.-H. Leung, Organometallics, 2012, 31, 4871; (o) Y. Huang, S. A. Pullarkat, R. J. Chew, Y. Li and P.-H. Leung, J. Org. Chem., 2012, 77, 6894; (p) M. Hatano, T. Horibe and K. Ishihara, Angew. Chem., Int. Ed., 2013, 52, 4549; (q) B. Ding, Z. Zhang, Y. Xu, Y. Liu, M. Sugiya, T. Imamoto and W. Zhang, Org. Lett., 2013, 15, 5476.
7. For catalytic asymmetric synthesis of chiral phosphines through arylation or alkylation of substituted phosphines, see: (a) J. R. Moncarz, N. F. Laritcheva and D. S. Glueck, J. Am. Chem. Soc., 2002, 124, 13356; (b) V. S. Chan, I. C. Stewart, R. G. Bergman and F. D. Toste, J. Am. Chem. Soc., 2006, 128, 2786; (c) C. Scriban and D. S. Glueck, J. Am. Chem. Soc., 2006, 128, 2788; (d) N. F. Blank, J. R. Moncarz, T. J. Brunker, C. Scriban, B. J. Anderson, O. Amir, D. S. Glueck, L. N. Zakharov, J. A. Golen, C. D. Incarvito and A. L. Rheingold, J. Am. Chem. Soc., 2007, 129, 6847; (e) V. S. Chan, R. G. Bergman and F. D. Toste, J. Am. Chem. Soc., 2007, 129, 15122; (f) T. J. Brunker, B. J. Anderson, N. F. Blank, D. S. Glueck and A. L. Rheingold, Org. Lett., 2007, 9, 1109; (g) C. Scriban, D. S. Glueck, J. A. Golen and A. L. Rheingold, Organometallics, 2007, 26, 1788; (h) V. S. Chan, M. Chiu, R. G. Bergman and F. D. Toste, J. Am. Chem. Soc., 2009, 131, 6021; (i) T. W. Chapp, D. S. Glueck, J. A. Golen, C. E. Moore and A. L. Rheingold, Organometallics, 2010, 29, 378.
8. Y. Huang, S. A. Pullarkat, Y. Li and P.-H. Leung, Inorg. Chem., 2012, 51, 2533.
9. (a) J.-J. Feng, X.-F. Chen, M. Shi and W.-L. Duan, J. Am. Chem. Soc., 2010, 132, 5562; (b) D. Du and W.-L. Duan, Chem. Commun., 2011, 47, 11101; (c) Y.-R. Chen and W.-L. Duan, Org. Lett., 2011, 13, 5824; (d) J.-J. Feng, M. Huang, Z.-Q. Lin and W.-L. Duan, Adv. Synth. Catal., 2012, 354, 3122; (e) M. Huang, C. Li, W.-L. Duan and S. Xu, Chem. Commun., 2012, 48, 11148; (f) D. Du, Z.-Q. Lin, J.-Z. Lu, C. Li and W.-L. Duan, Asian J. Org. Chem., 2013, 2, 392; (g) C. Li, W.-X. Li, S. Xu and W.-L. Duan, Chin. J. Org. Chem., 2013, 33, 799; (h) J. Lu, J. Ye and W.-L. Duan, Org. Lett., 2013, 15, 5016; (i) J. Lu, J. Ye and W.-L. Duan, Chem. Commun., 2014, 50, 698; (j) J. Huang, M.-X. Zhao and W.-L. Duan, Tetrahedron Lett., 2014, 55, 629.
10. For synthesis and application of the chiral PCP-PdCl complex, see: (a) J. M. Longmire and X. Zhang, Tetrahedron Lett., 1997, 38, 1725; (b) J. M. Longmire, X. Zhang and M. Shang, Organometallics, 1998, 17, 4374.
11. For reviews on pincer Pd catalysts, see: (a) M. Albrecht and G. van Koten, Angew. Chem., Int. Ed., 2001, 40, 3750; (b) N. Selander and K. J. Szabó, Chem. Rev., 2011, 111, 2048.
12. Due to the oxygen sensitivity of phosphines, the 1,4-adducts were converted to the corresponding phosphine borane complexes for analysis.
13. For the use of imidazoline pincer catalysts in asymmetric phosphorus addition reactions, see ref. 6k.
14. 50 mol% KOAc was used in the reaction to replace the bromide on the palladium atom with acetate. The acetate anion on the palladium atom is very important to achieve high ee. For similar observations in catalysis, see ref. 6k, q and 9a.
15. α,β-Unsaturated N-acylpyrrole was first introduced into asymmetric 1,4-addition by Shibasaki et al., see: (a) T. Kinoshita, S. Okada, S.-R. Park, S. Matsunaga and M. Shibasaki, Angew. Chem., Int. Ed., 2003, 42, 4680; (b) T. Mita, K. Sasaki, M. Kanai and M. Shibasaki, J. Am. Chem. Soc., 2005, 127, 514; (c) N. Yamagiwa, H. Qin, S. Matsunaga and M. Shibasaki, J. Am. Chem. Soc., 2005, 127, 13419.
16. D. A. Evans, G. Borg and K. A. Scheidt, Angew. Chem., Int. Ed., 2002, 41, 3188.
17. (a) B. S. Williams, P. Dani, M. Lutz, A. L. Spek and G. von Koten, Helv. Chim. Acta, 2001, 84, 3519; (b) D. Morales-Morales, R. E. Cramer and C. M. Jensen, J. Organomet. Chem., 2002, 654, 44; (c) S. Medici, M. Gagliardo, S. B. Williams, P. A. Chase, S. Gladiali, M. Lutz, A. L. Spek, G. P. M. van Klink and G. van Koten, Helv. Chim. Acta, 2005, 88, 694.
18. CCDC 981792, 981793 and 981794 contain the supplementary crystallographic data for this paper.

---

Footnote

† Electronic supplementary information (ESI) available: Detailed experimental procedures and analytical data for all new compounds. CCDC 981792, 981793 and 981794. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4qo00017j

---