Synthesis and Structural Characterization of Nickel Complexes

Mar 26, 2015 - Synthesis and Structural Characterization of Nickel Complexes Possessing P-Stereogenic Pincer Scaffolds and Their Application in ...
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Synthesis and Structural Characterization of Nickel Complexes Possessing P‑Stereogenic Pincer Scaffolds and Their Application in Asymmetric Aza-Michael Reactions Zehua Yang,† Delong Liu,*,† Yangang Liu,† Masashi Sugiya,§ Tsuneo Imamoto,*,§,∥ and Wanbin Zhang*,†,‡ †

School of Pharmacy and ‡School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, People’s Republic of China § Organic R&D Department, Nippon Chemical Industrial Co., Ltd., Kameido, Koto-ku, Tokyo 136-8515, Japan ∥ Department of Chemistry, Graduate School of Science, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan S Supporting Information *

ABSTRACT: Novel P-stereogenic pincer-Ni complexes {κP,κC,κP-3,5Me 2 -2,6-(Me t BuPCH 2 ) 2 C 6 H}NiCl (3), {κ P ,κ C ,κ P -3,5-Me 2 -2,6(MetBuPCH2)2C6H}NiOTf (4), [{κP,κN,κP-2,6(MetBuPCH2)2C5H3N}NiCl]Cl (7), [{κP,κN,κP-2,6(Me t BuPCH 2 ) 2 C 5 H 3 N}NiCl]BF 4 (8), and [{κ P ,κ N ,κ P -2,6(MetBuPCH2)2C5H3N}Ni(NCMe)](BF4)2 (9) were synthesized in 55−84% yields and characterized by 1H NMR, 13C{1H} NMR, 31 1 P{ H} NMR, 19F{1H} NMR, and/or single-crystal X-ray diffractions. The ORTEP diagrams of complexes 3, 7, 8, and 9 show that the coordination geometries around the Ni center in all these structures are approximately square planar but have different bond lengths and angles. These complexes were shown to be active catalysts for the asymmetric aza-Michael addition of α,β-unsaturated nitriles. For most examples good to excellent yields (up to 99%) and moderate enantiomeric excesses (up to 46% ee) were obtained. Notably, the PCP complex 3 exhibited higher catalytic activity in the aza-Michael addition than the PNP complexes 7, 8, and 9. Two achiral PCP-type pincer-Ni complexes, {κP,κC,κP-3,5-Me2-2,6-(tBu2PCH2)2C6H}NiCl (11) and {κP,κC,κP-3,5-Me2-2,6(Ph2PCH2)2C6H}NiCl (13), were also synthesized and fully characterized in order to reveal the structural differences between the chiral and achiral complexes.

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INTRODUCTION Pincer-type metal complexes have received widespread attention over the last few decades due to their rigid tridentate structural properties and tunable electron density.1 Such complexes have been used in many types of catalytic reactions.2 Chiral P-chelated pincer-metal catalysts, such as PCP-3 and PNP4-type complexes, are important chiral sources because of their potential application in asymmetric catalysis. However, the chiral centers in these structures are commonly located not on phosphorus atoms but on the pincer skeletons. Reports concerning pincer-metal complexes possessing P-stereogenic centers in which the chiral environment is closer to the metal atom catalytic center are rare. Commonly used examples utilize L-proline-derived phosphorus heterocycles, the structural complexity of which makes them difficult to synthesize (Chart 1, A).3m,5 Zhang and co-workers developed a class of phenyl- and o-anisyl-substituted P-stereogenic palladium and ruthenium pincer complexes (Chart 1, B).4b,c These complexes could be applied to asymmetric allylic alkylations and ketone hydrosilylations, providing the desired products in high yields and good enantiomeric excesses. Van Koten3f,h and MoralesMorales3g described the synthesis of phenyl- and tert-butyl- or © XXXX American Chemical Society

Chart 1. P-Stereogenic Pincer Complexes

isopropyl-substituted P-stereogenic pincer platinum, palladium, ruthenium, and iridium complexes, but their application in asymmetric hydrogen transfer reactions involving acetophenone gave the corresponding products with only 18% ee (enantiomeric excess) (Chart 1, B).3h Although the synthesis and application of pincer-type catalysts represents a promising area of research, they have thus far provided unsatisfactory Received: December 16, 2014

A

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air and moisture and does not require any special storage procedures. The 31P{1H} NMR spectrum of 3 in C6D6 shows a singlet at 48.02 ppm. The chloride anion in complex 3 was abstracted by silver salts such as AgOTf to give complex 4 as a hygroscopic brown solid. The 31P{1H} NMR spectrum of 4 also shows a singlet at 49.19 ppm, slightly downfield from that observed in 3. The singlet at −3.66 ppm observed in the 19F{1H} NMR spectrum clearly signifies the generation of an OTf anion in complex 4. The detailed structure of pincer-Ni complex 3 in the solid state was established by single-crystal X-ray diffraction (Figure 1). It shows that complex 3 crystallizes in the non-

asymmetric catalytic results. Therefore, the synthesis of new complexes with greater catalytic activity is a worthy endeavor. P-Stereogenic bidentate phosphine ligands such as QuinoxP* and BenzP*, possessing small (Me) and bulky (tert-butyl) alkyl groups, have displayed excellent activities and enantioselectivities in various catalytic asymmetric reactions.6 We envisaged that the introduction of the methyl- and tert-butyl-substituted P-stereogenic groups into the backbone of pincer complexes would enable us to develop novel P-stereogenic pincer-type catalysts with high catalytic activity (Chart 1, C).7 The enantioselective aza-Michael addition of α,β-unsaturated nitriles is a useful reaction.8 Fadini and co-workers have extensively investigated this reaction using Pigiphos as a ligand and have obtained products with very good yields and enantioselectivities.9 Schaper et al. reported a chiral zirconium bis-diketiminate complex catalyzed aza-Michael addition of α,βunsaturated nitriles, but the enantioselectivity was not higher than 19%.10 To the best of our knowledge, the use of chiral pincer complexes as catalysts for aza-Michael additions has not been reported. We have previously synthesized novel P-stereogenic PCP pincer-Pd complexes and applied them to asymmetric addition reaction of diarylphosphines to nitroalkenes. The desired products were obtained in excellent yields and with good enantioselectivities.11 Compared to other precious metals, nickel is relatively inexpensive and more abundant. Moreover, achiral PCP-type pincer-Ni complexes have proved to be efficient catalysts for the aza-Michael addition of acrylonitrile.12 Pincer-Ni complexes can therefore be expected to be economical and efficient catalysts. Herein we report the synthesis, structural characterization, and application of new P-stereogenic pincer-Ni complexes.

F ig ur e 1 . O R T E P d r a w i ng o f {κ P , κ C , κ P - 3 , 5 - M e 2 - 2, 6 (MetBuPCH2)2C6H}NiCl (3). Ellipsoids are shown at the 30% probability level. Hydrogen atoms are omitted for clarity. Selected bond lengths (Å) and angles (deg): Ni1−C12 = 1.925(3); Ni1−P1 = 2.1616(9); Ni1−P2 = 2.1611(9); Ni1−Cl1 = 2.2118(10); C12−Ni1− P1 = 84.90(10); C12−Ni1−P2 = 85.36(10); P2−Ni1−P1 = 169.10(4); C12−Ni1−Cl1 = 177.93(11); P1−Ni1−Cl1 = 94.67(4); P2−Ni1−Cl1 = 95.24(4).

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RESULTS AND DISCUSSION Synthesis of P-Stereogenic PCP Pincer-Ni Complexes. The P-stereogenic PCP-type pincer-Ni complexes were prepared in two steps using an optimal “one-pot” procedure (Scheme 1). First, the boranes in compound 111 were removed

centrosymmetric space group P21 of a monoclinic crystal system. The molecular geometry of the complex indicates that there is a rigid C2-symmetric stereo environment around the nickel atom. The bond angle of P−Ni−P is 169.10(4)°, smaller than 180° due to the steric strain in the five-membered chelate rings. From this structural feature it is anticipated that the nickel atom readily coordinates with the substrates during asymmetric catalysis. The bond lengths of Ni−P [2.1616(9) and 2.1611(9) Å], Ni−C [1.925(3) Å], and Ni−Cl [2.2118(10) Å] in 3 are a little shorter than that of the corresponding Pd−P [2.278(3) and 2.269(3) Å], Pd−C [2.033(9) Å], and Pd−Cl [2.381(3) Å] in our previously reported PCPtBuMe pincer-Pd complex.11 Synthesis of P-Stereogenic PNP Pincer-Ni Complexes. The PNP pincer-Ni complexes were prepared by a similar procedure to that of the synthesis of the PCP pincer-Ni complex 3 using optically active (R,R)-2,6-bis[(borane(tertbutyl)methylphosphino)methyl]pyridine13 (5) as the starting material (Scheme 2). Thus, the boranes of 5 were removed by means of our previous synthetic route to give chiral bisphosphine pyridine 6.14 Compound 6 was directly reacted with nickel(II) chloride hexahydrate in THF at ambient temperature to afford the cationic complex 7 as a red solid, which was obtained in 59% yield from 5. The 31P{1H} NMR spectrum in CDCl3 shows a singlet centered at 51.66 ppm. The

Scheme 1. Synthetic Route to 3 and 4

using trifluoromethanesulfonic acid in degassed toluene, followed by reaction with aqueous KOH in degassed ethanol to produce bisphosphine 2. Ligand 2 was then directly reacted with nickel(II) chloride hexahydrate via C−H bond activation in a mixed solvent system of ethanol and water to give the Pstereogenic PCP pincer-Ni complex 3. The total yield for steps 1 to 3 was 73%. The resulting golden yellow solid is stable to B

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larger than that in complex 3 [169.10(4)°]. However, the length of the Ni−Cl [2.149(3) Å] bond in 7 is shorter than that in complex 3 [2.2118(10) Å], which indicates that this bond in 7 is stronger and more difficult to break. Reaction of 6 with a stoichiometric amount of Ni(dme)Cl2 (dme = 1,2-dimethoxyethane) and NaBF4 in CH2Cl2 gave a red solid 8 after 12 h in 84% total yield from 5 (Scheme 2). The 31 1 P{ H} NMR spectrum in CDCl3 showed a singlet at 40.46 ppm, which resonates at a higher field than that in complex 7 (51.66 ppm). The 1H NMR spectrum has two resonances for the pyridine backbone in the aromatic region, namely, a triplet at 7.84 ppm and a doublet at 7.54 ppm, representing the p-CH and m-CH of the pyridine backbone, respectively. The CH2 dd peak in 8 is observed at 3.74 ppm, resonating at a higher field than that in 7 (4.13 ppm). The 19F{1H} NMR spectrum in CDCl3 shows a singlet at −152.0 ppm, indicating a BF4− group as the counteranion in complex 8. Recrystallization of 8 from a mixed solvent system of CH2Cl2/EtOAc yielded dark red crystals suitable for X-ray diffraction. The ORTEP diagram for complex 8 is shown in Figure 3. The coordination geometry

Scheme 2. Synthetic Route to 7, 8, and 9

1

H NMR spectrum has a broad singlet at 7.97 ppm, denoting the pyridine backbone in the aromatic region, with an integral value equal to three protons. A dd peak is observed at 4.13 ppm with an integral of four protons representing the CH2 in the arm positions of the pincer scaffold. Crystals suitable for X-ray analysis were obtained by layering a solution of 7 in CH2Cl2 over a solvent of EtOAc. The ORTEP drawing of complex 7 is shown in Figure 2. The nickel(II) atom on 7 bonds to the phosphorus atoms, the nitrogen atom on the pyridine ring, and a chlorine atom, to form a slightly distorted square planar coordination sphere. Another chlorine atom acts as a counteranion and does not show any close contact to the metal center within the crystal packing. The P−Ni−P bond angle in 7 is 170.75(12)°, slightly

Figure 3. ORTEP drawing of [{κP,κN,κP-2,6- (MetBuPCH2)2C5H3N}NiCl]BF4 (8). Ellipsoids are shown at the 30% probability level. Hydrogen atoms and the counteranion BF4− are omitted for clarity. Selected bond lengths (Å) and angles (deg): Ni1−N1 = 1.912(5); Ni1−Cl1 = 2.152(2); Ni1−P1 = 2.1909(17); Ni1−P2 = 2.1892(16); N1−Ni1−Cl1 = 179.87(19); N1−Ni1−P1 = 86.18(16); N1−Ni1−P2 = 86.07(15); P2−Ni1−P1 = 172.23(7); Cl1−Ni1−P1 = 93.94(8); Cl1−Ni1−P2 = 93.81(7).

around Ni in complex 8 is approximately square planar and resembles that of complex 7; the P−Ni−P angle of 172.23(7)° is slightly larger than those observed in complexes 3 [169.10(4)°] and 7 [170.75(12)°]. The Ni−Cl bond length [2.152(2) Å] is similar to the corresponding value in 7 [2.149(3) Å] but shorter than that in 3 [2.2118(10) Å], indicating a strong Ni−Cl bond in 8. Complex 9 is prepared as a yellow solid in 55% total yield from 5, by mixing a stoichiometric amount of [Ni(NCMe)6](BF4)2 and compound 6 in MeCN (Scheme 2). The 31P{1H} NMR spectrum showed a singlet at 56.0 ppm. A broad singlet at 2.79 ppm with an integral value equal to three protons in the 1 H NMR reveals the existence of MeCN as a coligand in complex 9. A singlet at −145.4 ppm in the 19F{1H} NMR spectrum shows that the two BF4− counteranions are indistinguishable. Recrystallization of 9 from acetone gave a yellow needle-like crystal, and its molecular structure in the solid state is shown in Figure 4. A slightly distorted square planar geometry is observed around the Ni(II) center. The P−

Figure 2. ORTEP drawing of [{κP,κN,κP-2,6- (MetBuPCH2)2C5H3N}NiCl]Cl (7). Ellipsoids are shown at the 30% probability level. Hydrogen atoms and the counteranion Cl− are omitted for clarity. Selected bond lengths (Å) and angles (deg): Ni1−N1 = 1.939(8); Ni1−Cl1 = 2.149(3); Ni1−P1 = 2.201(2); Ni1−P2 = 2.187(3); N1− Ni1−Cl1 = 178.4(3); N1−Ni1−P1 = 87.7(2); N1−Ni1−P2 = 85.6(2); P2−Ni1−P1 = 170.75(12); Cl1−Ni1−P1 = 93.57(11); Cl1−Ni1−P2 = 93.27(13). C

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complex 3 (48.02 ppm). However, the 31P{1H} NMR spectrum for complex 13 shows a singlet at 35.45 ppm, resonating at a higher field than that in 3. Crystals suitable for single-crystal Xray diffraction were obtained by recrystallization from a mixed solvent system of CH2Cl2/n-hexane. The ORTEP drawing for complexes 11 and 13 are shown in Figure 5 and Figure 6,

Figure 4. ORTEP drawing of [{κP,κN,κP-2,6- (MetBuPCH2)2C5H3N}Ni(NCMe)](BF4)2 (9). Ellipsoids are shown at the 30% probability level. Hydrogen atoms and the counteranion BF4− are omitted for clarity. Selected bond lengths (Å) and angles (deg): Ni1−N1 = 1.904(5); Ni1−N2 = 1.864(5); Ni1−P1 = 2.2061(17); Ni1−P2 = 2.2018(18); N2−Ni1−N1 = 179.1(3); N2−Ni1−P2 = 94.03(18); N1−Ni1−P2 = 86.46(15); N2−Ni1−P1 = 93.35(17); N1−Ni1−P1 = 86.16(15); P2−Ni1−P1 = 172.60(7).

Ni−P bond angle is 172.60(7)°, similar to that in complex 8 [172.23(7)°] but larger than that in complexes 3 [169.10(4)°] and 7 [170.75(12)°]. The P−Ni bond lengths in 9 [2.2061(17) and 2.2018(18) Å] are slightly longer than those in 3 [2.1616(9) and 2.1611(9) Å], 7 [2.201(2) and 2.187(3) Å], and 8 [2.1909(17) and 2.1892(16) Å]. The shorter Ni−N2 bond length [1.864(5) Å] in 8 also indicates a strong chemical bond that is difficult to break. Synthesis of Achiral PCP Pincer-Ni Complexes. In order to clearly differentiate structural features between the chiral and achiral metal center of the pincer-metal complexes, we prepared two similar PCP pincer-Ni complexes bearing two tert-butyl or phenyl groups on the phosphorus atoms (Scheme 3) according to the literature methods.15 Complex 11 was

F ig ur e 5 . O R T E P d r a w i ng o f {κ P , κ C , κ P - 3 , 5 - M e 2 - 2, 6 (tBu2PCH2)2C6H}NiCl (11). Ellipsoids are shown at the 30% probability level. Hydrogen atoms are omitted for clarity. Selected bond lengths (Å) and angles (deg): Ni1−C1 = 1.960(15); Ni1−P1 = 2.192(2); Ni1−P1A = 2.192(2); Ni1−Cl1 = 2.204(5); C1−Ni1−P1 = 85.38(10); C1−Ni1−P1A = 85.38(10); P1A−Ni1−P1 = 170.8(2); C1−Ni1−Cl1 = 180.000(3); P1−Ni1−Cl1 = 94.62(10); P1A−Ni1− Cl1 = 94.62(10).

respectively. The coordination geometries around the Ni center in complexes 11 and 13 are similar to the aforementioned chiral complexes, i.e., approximately square planar. However, a large difference was observed between the P−Ni−P angles of complexes 11 [170.8(2)°] and 13 [166.30(3)°].

Scheme 3. Synthetic Route to 11 and 13

obtained as a golden solid using a similar method to that of the synthesis of 3 from 1,3-bis[(di-tert-butylphosphino)methyl]4,6-dimethylbenzene (10).16 Similarly, complex 13 was prepared as a yellow solid by the reaction of 1,3-bis[(diphenylphosphino)methyl]-4,6-dimethylbenzene (12)17 with nickel(II) chloride hexahydrate in 2-methoxyethanol in 57% yield. The 31P{1H} NMR spectrum of 11 in C6D6 shows a singlet at 65.44 ppm, which resonates further downfield than that in

F ig ur e 6 . O R T E P d r a w i ng o f {κ P , κ C , κ P - 3 , 5 - M e 2 - 2, 6 (Ph2PCH2)2C6H}NiCl (13). Ellipsoids are shown at the 30% probability level. Hydrogen atoms are omitted for clarity. Selected bond lengths (Å) and angles (deg): Ni1−C3 = 1.944(3); Ni1−P1 = 2.1621(7); Ni1−P2 = 2.1647(7); Ni1−Cl1 = 2.2136(8); C3−Ni1−P1 = 83.85(7); C3−Ni1−P2 = 82.89(7); P2−Ni1−P1 = 166.30(3); C3− Ni1−Cl1 = 177.86(7); P1−Ni1−Cl1 = 95.14(3); P2−Ni1−Cl1 = 97.99(3). D

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Organometallics Ni-Catalyzed Asymmetric Aza-Michael Addition of α,β-Unsaturated Nitriles. We attempted the asymmetric azaMichael addition of α,β-unsaturated nitriles by using the above P-stereogenic pincer-Ni complexes 3, 4, 7, 8, and 9. Thus, the asymmetric aza-Michael addition of methacrylonitrile with morpholine was carried out in different conditions (Table 1).

useful for the asymmetric aza-Michael addition (entries 9 and 10). Increasing the temperature to 50 °C gave the same yield but a lower ee value (entry 11). Reducing the temperature to 0 °C resulted in a much lower yield (entry 12). Zargarian has mentioned that the use of NEt3 can improve the reaction activity of the addition of amines to α,β-unsaturated nitriles.12d However, in our case the addition of NEt3 resulted in a dramatic reduction in ee (entry 13). Therefore, subsequent reactions were carried out using complex 3 as a catalyst in the presence of AgOTf in toluene at 25 °C. The aza-Michael addition of various amines and α,βunsaturated nitriles was then investigated using the optimal reaction conditions described above (Table 2). Primary amines,

Table 1. Reaction Conditions of Aza-Michael Additiona

entry

catalyst

additive

solvent

yield (%)b

ee (%)c

1 2 3 4 5 6 7 8 9 10 11d 12e 13f

3 4 7 8 9 3 3 3 3 3 3 3 3

AgOTf

toluene toluene toluene toluene toluene EtOAc THF m-xylene toluene toluene toluene toluene toluene

83 85 nd 9 11 62 63 72 65 26 83 38 86

35 28

AgOTf AgOTf AgOTf AgOTf AgOTf AgOTf AgBF4 AgSbF6 AgOTf AgOTf AgOTf

Table 2. Substrate Scope of the Aza-Michael Additiona

8 11 17 17 32 26 27 28 33 10

a

Reaction conditions: Morpholine (1 mmol), methacrylonitrile (1 mmol), catalyst (3 mol %), solvent (3 mL), and additive (0.03 mmol), 25 °C, 12 h. bIsolated yield. cDetermined by chiral HPLC using a Daicel ChiralPak IC-3 column. dAt 50 °C. eAt 0 °C. fThe reaction was carried out in the presence of NEt3 (1 mmol).

The effect of different catalysts on the reaction was examined first by stirring a 1:1 molar ratio of methacrylonitrile and morpholine in dry toluene under a nitrogen atmosphere (Table 1, entries 1−5). The PCP-type pincer-Ni complexes showed good activities and moderate enantioselectivities (entries 1 and 2). However, the PNP-type pincer-Ni complexes showed lower activities and enantioselectivities (entries 3−5). Zargarian and co-workers have reported a PCP-type pincer-Ni complex with a MeCN coligand, which displays good reaction activity in azaMichael additions. However, a low yield was obtained when using PNP-type pincer-Ni complex 9 as a catalyst, probably due to the different scaffolds of the two catalysts (entry 5).12b It is noted that the catalytic activity of the catalysts has a close relationship with the Ni−Cl bond length. The Ni−Cl bond length in the PCP-type pincer-Ni catalyst 3 is longer (2.2118(10) Å) than that of the other PNP-type pincer-Ni complexes (7: 2.149(3) Å and 8: 2.152(2) Å). Therefore, 3 provides higher reaction activity than both 7 and 8.18 It appears that the longer Ni−Cl bond allows for easier abstraction of the chlorine atom by AgOTf, thus facilitating the catalyst to more effectively coordinate with the substrates. According to the catalytic activity and stability of the examined catalysts, we chose complex 3 as the catalyst in subsequent reactions. Solvent has a significant effect on the reaction outcome. When ethyl acetate and tetrahydrofuran were used, low yields and ee values were obtained (entries 6 and 7). Use of m-xylene was also examined, and a slightly lower activity and enantioselectivity were observed (entry 8). In general, toluene was found to be the best solvent for the reaction. Other additives, such as AgBF4 and AgSbF6, were not particularly

a Reaction conditions: Amine (1 mmol), α,β-unsaturated nitrile (1 mmol), 3 (3 mol %), AgOTf (0.03 mmol), and toluene (3 mL), 25 °C, 12 h. Isolated yield. ee values were determined by chiral HPLC. The absolute configuration of the enantiomerically enriched product was confirmed to be of S-configuration by comparison of the specific rotation to literature values.9f

including 1-pentanamine, cyclohexylamine, and benzylamine reacted with methacrylonitrile but gave the target product in low yields and with low ee’s (16b−d). When cyclic secondary amines were used, moderate to excellent yields were obtained (16a, 16e−h). In particular, when 1-methylpiperazine was used as a substrate, the corresponding product could be obtained in quantitative yield and with 26% ee. The steric hindrance of the α,β-unsaturated nitriles affects the enantioselectivities of the products. When 2-methylenebutanenitrile and 3-methyl-2methylenebutanenitrile were used in place of methacrylonitrile, the reaction proceeded smoothly to give the corresponding products in moderate yields of 36% and 46% ee, respectively (16i and 16j). When the substituent at the 2-position of the E

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acrylonitrile was changed to a phenyl group, the desired product was obtained in quantitative yield but with no ee (16k). α,β-Unsaturated nitriles possessing 3-position substituents reacted readily with morpholine, but only low enantioselectivities were observed (16l and 16m). We have considered the reaction pathway of this nickelcatalyzed aza-Michael addition reaction taking account of the results described above and on the basis of literature reports.12c,d The plausible mechanism is illustrated in Scheme 4. The substrate α,β-unsaturated nitrile coordinates to the

Article

EXPERIMENTAL SECTION

General Remarks. All air- and moisture-sensitive manipulations were carried out with standard Schlenk techniques or in a glovebox under a nitrogen atmosphere. Column chromatography was performed using 200−300 mesh silica gels. All solvents were distilled from an appropriate drying agent under a nitrogen atmosphere. The other reagents were purchased from Adamas-Beta Ltd., Energy Chemical Inc., or J&K Scientific Inc. and used without further purification unless otherwise specified. The NMR spectra were recorded on a Varian Mercury Plus-400 (400 MHz, 1H; 101 MHz, 13C; 162 MHz, 31P; 376 MHz, 19F) spectrometer with chemical shifts reported in ppm relative to the residual deuterated solvents or the internal standard tetramethylsilane, 85% phosphoric acid, or trichlorofluoromethane, respectively. HRMS were performed on a SolariX XR 7.0 T hybrid quadrupole-FTICR mass spectrometer (Bruker Daltonics, Bremen, Germany), which was equipped with an ESI/APCI/MALDI ion source. Melting points were measured with an SGW X-4 micro melting point apparatus. Elemental analyses were performed on a Elementar Micro Cube automatic elemental analyzer. Optical rotations were measured on a Rudolph Research Analytical Autopol VI automatic polarimeter using a 50 mm path-length cell at 589 nm. Enantiomeric excess values were measured on a Shimadzu LC-10Avp HPLC system and using Daicel Chiralcel IC-3, OD-H, and AS-H columns with n-hexane/2-propanol/diethylamine as an eluent. Synthesis of (1S,1′S)-(4,6-Dimethyl-1,3-phenylene)bis(methylene)bis(tert-butyl(methyl)phosphine) (2). A solution of 1 (500 mg, 1.37 mmol) in degassed toluene (20 mL) was cooled to 0 °C. Trifluoromethanesulfonic acid (1.21 mL, 13.6 mmol) was added dropwise, and the mixture was stirred for 2 h at 0 °C and for 1 h at ambient temperature. A solution of potassium hydroxide (1.53 g, 27.3 mmol) in freshly degassed EtOH/water (9:1 ratio, 20 mL) was added, and the resulting mixture was stirred at 50 °C for 2 h under nitrogen before cooling to ambient temperature. The reaction mixture was partitioned by the addition of water (20 mL), and the aqueous layer was extracted with toluene (20 mL × 3), keeping the positive pressure of nitrogen. The combined organic phase was dried over anhydrous MgSO4 and filtered under a nitrogen atmosphere. The solvent was removed under reduced pressure to give 2 as a white solid, which was used in the next step without further purification. Synthesis of {κP,κC,κP-3,5-Me2-2,6-(MetBuPCH2)2C6H}NiCl (3). To a degassed water (3 mL) solution of NiCl2·6H2O (0.370 g, 1.37 mmol) was added a solution of 2 (the entire product generated in the previous step, ca. 1.37 mmol) dissolved in 17 mL of ethanol. A golden yellow precipitate began to form after 1 min. The solution was stirred at reflux temperature for 8 h. After cooling, the reaction mixture was filtered and washed with cold ethanol to give 353 mg of golden yellow needle crystals. The filtrate was purified by column chromatography (ethyl acetate/petroleum ether = 1:10) on silica gel to afford another 77 mg of yellow solid with a total yield of 73% from 1. Crystals suitable for X-ray analysis were obtained by recrystallization from CH2Cl2/nhexane. Mp: 249−250 °C. [α]25D = −75.9 (c 0.1, CHCl3). 1H NMR (400 MHz, C6D6, 25 °C): δ 6.67 (s, 1H, CarHp), 2.87 (d, 2JPH = 17.2, 2H, CH2), 2.64 (d, 2JPH = 17.0 Hz, 2H, CH2), 2.09 (s, 6H, CarCH3), 1.32 (vt, 2JPH = 3.2 Hz, 6H, PCH3), 1.10 (vt, 3JPH = 6.8 Hz, 18H, C(CH3)3). 13C{1H} NMR (101 MHz, C6D6, 25 °C): δ 159.1 (vt, 2JPC = 16.3 Hz, Car‑o), 147.7 (vt, 2JPC = 12.9 Hz, Car‑i), 130.6 (vt, 3JPC = 7.8 Hz, Car‑m), 128.7 (s, Car‑pH), 35.0 (vt, JPC = 13.1 Hz, C(CH3)3), 30.4 (vt, JPC = 11.1 Hz, CH2), 26.9 (s, C(CH3)3), 21.7 (s, CarCH3), 6.2 (vt, JPC = 10.0 Hz, PCH3). 31P{1H} NMR (162 MHz, C6D6, 25 °C): δ 48.02 (s, 2P, PNi). HRMS (ESI): calcd for C20H35NiP2 [M − Cl]+ 395.1567, found 395.1561. IR (KBr disc) ν/cm−1: 2969 (s), 2953 (s), 2919 (s), 2850 (s), 1460 (s), 1410 (m), 1394 (m), 1366 (s), 1290 (s), 1261 (m), 1014 (m), 909 (s), 888 (s), 832 (s), 736 (s), 727 (s), 431 (s). Anal. Calcd for C20H35ClNiP2: C, 55.66; H, 8.17. Found: C, 55.78; H, 8.25. Synthesis of {κP,κC,κP-3,5-Me2-2,6-(MetBuPCH2)2C6H}NiOTf (4). Silver trifluoromethanesulfonate (30.4 mg, 0.118 mmol) was added to a stirred solution of 3 (50.0 mg, 0.116 mmol) in toluene (5 mL) under nitrogen, and the resulting mixture was stirred in the dark at

Scheme 4. Proposed Reaction Pathway

catalyst 4, and the secondary amine adds to the activated double bond to form intermediate B, which leads to C via subsequent proton transfer. Finally, complex C reacts with α,βunsaturated nitrile to give the aza-Michael addition product with the regeneration of complex A.

■

CONCLUSION We have developed a series of new P-stereogenic pincer nickel complexes (3, 4, 7, 8, and 9) in 55−84% yields by using flexible synthetic approaches. These complexes were fully characterized by 1H NMR, 13C{1H} NMR, 31P{1H} NMR, 19F{1H} NMR, and/or single-crystal X-ray diffraction. The ORTEP diagrams show that the coordination geometries around the Ni center in all complexes are approximately square planar, but their bond lengths and angles differ from each other. These complexes were shown to be active catalysts for the aza-Michael addition of α,β-unsaturated nitriles, providing the products in good to excellent yields (up to 99%) and with moderate enantiomeric excesses (up to 46% ee). Two achiral PCP-type pincer-Ni complexes 11 and 13 were also synthesized and fully characterized in order to compare the structural differences between the chiral and achiral complexes. F

DOI: 10.1021/om501287k Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics room temperature for 6 h. The reaction mixture was filtered through Celite, washed with dichloromethane (5 mL), and concentrated under vacuum to afford the product 4 as a brown solid (56.9 mg, 90% yield). Mp: 344−346 °C. 1H NMR (400 MHz, C6D6, 25 °C): δ 6.52 (s, 1H, CarHp), 2.51 (vt, 2JPH = 3.2 Hz, 4H, CH2), 1.94 (s, 6H, CarCH3), 1.30 (vt, J = 3.2 Hz, 6H, PCH3), 0.92 (vt, 3JPH = 7.0 Hz, 18H, C(CH3)3). 13 C{1H} NMR (101 MHz, C6D6, 25 °C): δ 147.7 (vt, 2JPC = 12.1 Hz, Car‑i), 146.9 (vt, 2JPC = 17.2 Hz, Car‑o), 130.6 (vt, 3JPC = 7.2 Hz, Car‑m), 129.2 (s, Car‑p), 127.6 (q, 1JFC = 133.3 Hz, CF3), 32.6 (vt, 1JPC = 14.5 Hz, C(CH3)3), 30.6 (vt, 1JPC = 11.5 Hz, CH2), 27.0 (s, C(CH3)3), 21.3 (s, CarCH3), 5.8 (vt, 1JPC = 9.2 Hz, PCH3). 31P{1H} NMR (162 MHz, C6D6, 25 °C): δ 49.19 (s, 2P, PNi). 19F{1H} NMR (376 MHz, C6D6, 25 °C): δ −3.66 (s, 1F, CF3). Anal. Calcd for C21H35F3NiO3P2S: C, 46.26; H, 6.47; S, 5.88. Found: C, 46.42; H, 6.59; S, 5.76. Synthesis of [{κP,κN,κP-2,6-(MetBuPCH2)2C5H3N}NiCl]Cl (7). A THF solution (10 mL) of compound 614 (156 mg, 0.5 mmol) was added to a THF solution (10 mL) of NiCl2·6H2O (107 mg, 0.45 mmol), and the reaction mixture was stirred for 12 h at room temperature, affording a brown suspension. The solvent was removed in vacuo, and the residue was purified by column chromatography (CH2Cl2/MeOH = 10:1) on silica gel to afford complex 7 as a red solid (130 mg, 59% from compound 5). Single crystals suitable for X-ray analysis were obtained from a solution of 7 in dichloromethane layered with ethyl acetate. Mp: 144−145 °C. [α]25D = +260 (c 0.1, CHCl3). 1H NMR (400 MHz, CDCl3, 25 °C): δ 7.97 (br s, 3H, CH-Py), 4.13 (dd, 4H, 2 JPH = 39.0 Hz, 2JHH = 17.9 Hz, CH2), 1.77 (s, 6H, PCH3), 1.32 (s, 18H, C(CH3)3). 13C{1H} NMR (101 MHz, CDCl3, 25 °C): δ 164.5 (s, CH-Pyo), 141.8 (s, CH-Pyp), 124.2 (s, CH-Pym), 36.9 (s, C(CH3)3), 32.8 (s, CH2), 27.3 (s, C(CH3)3), 6.1 (s, PCH3). 31P{1H} NMR (162 MHz, CDCl3, 25 °C): δ 51.66 (s, 2P, PNi). HRMS (MALDI): calcd for C17H31ClNNiP2 [M − Cl]+ 404.0974, found 404.0971. IR (KBr disc) ν/cm−1: 3385 (s), 2957 (s), 2868 (s), 1603 (s), 1560 (s), 1464 (m), 1370 (m), 1293 (m), 1194 (m), 1018 (m), 902 (s), 883 (s), 844 (m), 745 (m). Anal. Calcd for C17H31Cl2NNiP2: C, 46.30; H, 7.09; N, 3.18. Found: C, 46.15; H, 6.98; N, 3.30. Synthesis of [{κP,κN,κP-2,6-(MetBuPCH2)2C5H3N}NiCl]BF4 (8). A solution of Ni(dme)Cl2 (303 mg, 1.47 mmol) in CH2Cl2 (25 mL) was added to a solution of 6 (459 mg, 1.47 mmol) and NaBF4 (162 mg, 1.47 mmol) in CH2Cl2 (50 mL) at room temperature. The solution quickly turned reddish and was thereafter stirred for 12 h. Filtration and evaporation left a red crude solid. Recrystallization from 2-propanol yielded scarlet crystals of complex 8 (612 mg, 84% from 5). Single crystals suitable for X-ray analysis were obtained from a solution of 8 in dichloromethane layered with ethyl acetate. Mp: 223− 224 °C. [α]25D = +313 (c 0.1, CHCl3). 1H NMR (400 MHz, CDCl3, 25 °C): δ 7.84 (t, 3JHH = 7.8 Hz, 1H, CH-Pyp), 7.54 (d, 3JHH = 7.7 Hz, 2H, CH-Pym), 3.74 (dd, 2JPH = 48.3 Hz, 2JHH = 18.7 Hz, 4H, CH2), 1.61 (s, 6H, PCH3), 1.25 (vt, 3JPH = 6.2 Hz, 18H, C(CH3)3). 13C{1H} NMR (101 MHz, CDCl3, 25 °C): δ 164.6 (vt, 2JPC = 5.8 Hz, CH-Pyo), 141.5 (s, CH-Pyp), 123.1 (s, CH-Pym), 36.7 (vt, 1JPC = 10.0 Hz, C(CH3)3), 32.0 (vt, 1JPC = 11.9 Hz, CH2), 26.4 (s, C(CH3)3), 4.5 (vt, 1 JPC = 13.9 Hz, PCH3). 31P{1H} NMR (162 MHz, CDCl3, 25 °C): δ 40.46 (s, 2P, PNi). 19F{1H} NMR (376 MHz, CDCl3, 25 °C): δ −152.0 (s, 4F, BF4). HRMS (MALDI): calcd for C17H31ClNNiP2 [M − BF4]+ 404.0974, found 404.0969. IR (KBr disc) ν/cm−1: 3401 (w), 2958 (m), 1605 (m), 1560 (m), 1465 (s), 1396 (m), 1370 (m), 1289 (m), 1054 (s), 969 (m), 904 (s), 882 (s), 842 (m), 744 (m). Anal. Calcd for C17H31BClF4NNiP2: C, 41.47; H, 6.35; N, 2.85. Found: C, 41.45; H, 6.19; N, 2.88. Synthesis of [{κP,κN,κP-2,6-(MetBuPCH2)2C5H3N}Ni(NCMe)](BF4)2 (9). A solution of compound 6 (156 mg, 0.5 mmol) in MeCN (4 mL) was added dropwise to a solution of [Ni(NCMe)6](BF4)2 (239 mg, 0.5 mmol) in MeCN (2 mL) by means of a cannula at room temperature. The resultant blue solution turned a khaki color within 1 min and was subsequently stirred for 2 h. Filtration and evaporation of solvent in vacuo left a yellow solid. Recrystallization of 9 from acetone gave yellow crystals (160 mg, 55%). Mp: 297−299 °C. [α]25D = +119.8 (c 0.1, CHCl3). 1H NMR (400 MHz, (CD3)2CO, 25 °C): δ 8.13 (t, 3JHH = 7.9 Hz, 1H, CH-Pyp), 7.71 (d, 3JHH = 7.8 Hz, 2H, CHPym), 4.38 (d, 2JHH = 17.2 Hz, 2H, CH2), 4.02 (d, 2JHH = 17.9 Hz, 2H,

CH2), 2.79 (s, 3H, NCCH3), 1.92 (s, 6H, PCH3), 1.31 (s, 18H, C(CH3)3). 13C{1H} NMR (101 MHz, (CD3)2CO, 25 °C): δ 165.8 (s, CH-Pyo), 142.6 (s, CH-Pyp), 123.0 (s, CH-Pym), 35.3 (vt, 1JPC = 11.3 Hz, C(CH3)3), 32.4 (vt, 1JPC = 11.3 Hz, CH2), 25.2 (s, C(CH3)3), 3.0 (vt, 1JPC = 9.1 Hz, PCH3). 31P{1H} NMR (162 MHz, (CD3)2CO, 25 °C): δ 56.00 (s, 2P, PNi). 19F{1H} NMR (376 MHz, (CD3)2CO, 25 °C): δ −145.4 (s, 8F, BF4). HRMS (MALDI): calcd for C18H31N2NiP2 [M − 2(BF4−) − Me+]+ 395.1316, found 395.1312. IR (KBr disc) ν/ cm−1: 3419 (s), 2956 (s), 2901 (s), 2866 (s), 2245 (m, CN), 1604 (m), 1561 (m), 1464 (s), 1369 (w), 1294 (m), 1058 (s), 903 (m), 883 (m), 842 (m), 744 (m), 533 (m). Anal. Calcd for C19H34B2F8ClN2NiP2: C, 39.03; H, 5.86; N, 4.79. Found: C, 39.12; H, 5.81; N, 4.62. Synthesis of {κP,κC,κP-3,5-Me2-2,6-(tBu2PCH2)2C6H}NiCl (11). To a degassed water (3 mL) solution of NiCl2·6H2O (264 mg, 1.11 mmol) was added a solution of 10 (469 mg, 1.11 mmol) dissolved in 17 mL of ethanol. The solution was heated at reflux temperature for 16 h. After cooling to room temperature, precipitated solid was collected and washed with cold ethanol to give 237 mg of golden yellow crystals. The filtrate was purified by column chromatography (ethyl acetate/ petroleum ether = 1:10) on silica gel to afford another 25 mg of yellow solid (total yield 46%). Crystals suitable for X-ray analysis were obtained by recrystallization from CH2Cl2/n-hexane. Mp: 316−318 °C. 1H NMR (400 MHz, C6D6, 25 °C): δ 6.63 (s, 1H, CarHp), 2.85 (vt, 2JHH = 3.6 Hz, 4H, CH2), 2.09 (s, 6H, CarCH3), 1.45 (vt, 3JPH = 6.4 Hz, 36H, C(CH3)3). 13C{1H} NMR (101 MHz, C6D6, 25 °C): δ 156.7 (vt, 2JPC = 15.2 Hz, Car‑o), 148.7 (vt, 2JPC = 12.7 Hz, Car‑i), 130.1 (vt, 3 JPC = 7.7 Hz, Car‑m), 128.5 (s, Car‑pH), 34.7 (vt, JPC = 6.8 Hz, C(CH3)3), 31.7 (vt, JPC = 11.6 Hz, CH2), 29.7 (s, C(CH3)3), 21.9 (s CarCH3). 31P{1H} NMR (162 MHz, C6D6, 25 °C): δ 65.44 (s, 2P, PNi). HRMS (ESI): calcd for C26H47NiP2 [M − Cl]+ 479.2506, found 479.2515. IR (KBr disc) ν/cm−1: 2990 (m), 2976 (m), 2961 (s), 2935 (s), 2895 (s), 2862 (s), 1449 (s), 1367 (s), 1178 (s), 1017 (m), 887 (s), 835 (m), 809 (m), 779 (m), 590 (m), 455 (m). Anal. Calcd for C26H47NiP2Cl: C, 60.55; H, 9.19. Found: C, 60.74; H, 9.38. Synthesis of {κP,κC,κP-3,5-Me2-2,6-(Ph2PCH2)2C6H}NiCl (13). A solution of 12 (940 mg, 1.87 mmol) dissolved in 40 mL of 2methoxyethanol was added to a 100 mL Schlenk flask that was charged with NiCl2·6H2O (445 mg, 1.87 mmol), whereupon the color of the solution immediately changed to golden yellow. The reaction mixture was heated to 60 °C for 3 h before diisopropylethylamine (0.37 mL, 2.24 mmol) was added carefully, and the reaction mixture was heated at reflux for another 12 h. After cooling to room temperature, the solvent was removed and the product was recrystallized from ethanol to isolate 341 mg of a yellow powder of 13. The filtrate was purified by column chromatography (ethyl acetate/petroleum ether = 1:8) on silica gel to afford another 288 mg of yellow solid (total yield 57%). Crystals suitable for X-ray analysis were obtained by recrystallization from CH2Cl2/n-hexane. Mp: 283−285 °C. 1H NMR (400 MHz, CDCl3, 25 °C): δ 7.87−7.82 (m, 8H, PCarHo), 7.44−7.36 (m, 12H, PCarHm and PCarHp), 6.69 (s, 1H, CarHp), 3.73 (vt, 2JHH = 4.3 Hz, 4H, CH2), 2.22 (s, 6H, CarCH3). 13C{1H} NMR (101 MHz, CDCl3, 25 °C): δ 157.6 (vt, 2JPC = 17.2 Hz, Car‑o), 146.8 (vt, 1JPC = 13.8 Hz, PCar‑i), 133.3 (vt, 2JPC = 6.0 Hz, Car‑i), 132.6 (s, PCar‑m), 132.4 (s, PCar‑p), 130.4 (s, Car‑o), 129.5 (s, PCar‑m), 128.7 (s, Car‑pH), 40.3 (vt, 1 JPC = 15.9 Hz, CH2), 22.1 (s, CarCH3). 31P{1H} NMR (162 MHz, CDCl3, 25 °C): δ 35.45 (s, 2P, PNi). HRMS (ESI): calcd for C34H31NiP2 [M − Cl]+ 559.1254, found 559.1238. IR (KBr disc) ν/ cm−1: 3052 (m), 2930 (m), 1482 (s), 1435 (s), 1103 (s), 1028 (m), 999 (m), 889 (s), 740 (s), 692 (s), 510 (s). Anal. Calcd for C34H31NiP2: C, 68.55; H, 5.25. Found: C, 68.49; H, 5.12. Typical Procedure for Catalytic Asymmetric Aza-Michael Addition of α,β-Unsaturated Nitriles. Pincer-Ni catalyst (0.03 mmol) and AgOTf (7.71 mg, 0.03 mmol) were added to a dry 10 mL Schlenk tube under a N2 atmosphere. Toluene (3 mL) was added by syringe, and the reaction mixture was stirred at 25 °C for 1 h. α,βUnsaturated nitrile (1 mmol) and amine (1 mmol) were added by syringe, and the mixture was stirred at 25 °C for a predetermined length of time (normally 12 h), which was then filtered through a plug of Celite. Purification by column chromatography (ethyl acetate/ G

DOI: 10.1021/om501287k Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics petroleum ether) on silica gel afforded the pure product. Known compounds were confirmed by comparison of their spectra to literature data (see the Supporting Information). Characterizations of the new products are given below. 2-Methyl-3-(pentylamino)propanenitrile (16b): colorless oil (65.7 mg, 41%). [α]25D = +4.0 (c 0.1, CHCl3). 1H NMR (400 MHz, CDCl3, 25 °C): δ 2.89−2.69 (m, 3H, CH and CHCH2), 2.69−2.53 (m, 2H, NHCH2CH2), 1.47 (dt, 3JHH = 12.7, 4JHH = 7.6 Hz, 3H, CHCH3), 1.34−1.28 (m, 6H, CH2CH2CH2CH3), 0.89 (t, 3JHH = 7.0 Hz, 3H, CH2CH3). 13C{1H} NMR (101 MHz, CDCl3, 25 °C): δ 122.6 (s, CN), 52.8 (s, CHCH2), 49.7 (s, NHCH2CH2), 30.0 (s, CHCH2), 29.6 (s, CH 2 CH 2 CH 2 CH 3 ), 26.9 (s, CH 2 CH 2 CH 2 CH 3 ), 22.9 (s, CH2CH2CH2CH3), 15.9 (s, CH2CH3), 14.3 (s, CHCH3). HRMS (ESI): calcd for C9H19N2 [M + H]+ 155.1548, found 155.1537. IR (KBr disc) ν/cm−1: 3320 (m, NH), 2957 (s), 2930 (s), 2858 (s), 2241 (m, CN), 1648 (w), 1466 (s), 1380 (m), 1260 (w), 1140 (s), 796 (m). 730 (m). Anal. Calcd for C9H18N2: C, 70.08; H, 11.76; N, 18.16. Found: C, 69.97; H, 11.82; N, 17.95. HPLC Daicel ChiralPak AS-H, nhexane/i-PrOH = 98/2, 210 nm, 0.5 mL/min, tR1 = 16.0 min (major), tR2 = 21.2 min (minor), ee = 7%. 2-(Morpholinomethyl)butanenitrile (16i): colorless oil (104 mg, 62%). [α]25D = +7.6 (c 0.1, CHCl3). 1H NMR (400 MHz, CDCl3, 25 °C): δ 3.75−3.66 (m, 4H, OCH2), 2.72−2.58 (m, 2H, NCH2CH), 2.57−2.47 (m, 4H, NCH2CH2), 2.43−2.47 (m, 1H, CHCN), 1.66− 1.57 (m, 2H, CHCH2CH3), 1.10 (t, 3JHH = 7.4 Hz, 3H, CH2CH3). 13 C{1H} NMR (101 MHz, CDCl3, 25 °C): δ 121.8 (s, CN), 67.1 (s, OCH2), 59.9 (s, NCH2CH), 53.9 (s, NCH2CH2), 32.0 (s, CH), 23.8 (s, CH2CH3), 11.7 (s, CH2CH3). HRMS (ESI): calcd for C9H17N2O [M + H]+ 169.1341, found 169.1326. IR (KBr disc) ν/cm−1: 2965 (s), 2815 (s), 2240 (s, CN), 1727 (m), 1456 (s), 1359 (s), 1295 (s), 1273 (m), 1209 (m), 1149 (s), 1118 (s), 1071 (s), 1017 (s), 926 (m), 867 (s), 797 (s), 629 (m). Anal. Calcd for C9H16N2O: C, 64.25; H, 9.59; N, 16.65. Found: C, 64.37; H, 9.69; N, 16.47. HPLC Daicel ChiralPak IC-3, n-hexane/i-PrOH = 75/25, 210 nm, 0.8 mL/min, tR1 = 32.2 min (minor), tR2 = 67.8 min (major), ee = 36%. 3-Methyl-2-(morpholinomethyl)butanenitrile (16j): colorless oil (74.7 mg, 41%). 1H NMR (400 MHz, CDCl3, 25 °C): δ 3.71 (t, 3JHH = 4.6 Hz, 4H, OCH2), 2.70−2.57 (m, 2H, NCH2CH), 2.56−2.37 (m, 5H NCH2CH2 and CHCN), 1.99−1.91 (m, 1H, CH(CH3)2), 1.06 (dd, 3JHH = 13.0 Hz, 4JHH = 6.8 Hz, 6H, CH(CH3)2). 13C{1H} NMR (101 MHz, CDCl3, 25 °C): δ 120.7 (s, CN), 67.1 (s, OCH2), 58.6 (s, NCH2CH), 53.9 (s, NCH2CH2), 37.6 (s, CHCN), 28.6 (s, CH(CH3)2), 21.5 (s, CH(CH3)2), 18.5 (s, CH(CH3)2). HRMS (ESI): calcd for C10H19N2O [M + H]+ 183.1497, found 183.1482. IR (KBr disc) ν/cm−1: 3587 (w), 2963 (s), 2856 (s), 2814 (s), 2689 (m), 2239 (s, CN), 1458 (s), 1392 (s), 1373 (s), 1358 (s), 1276 (s), 1239 (s), 1147 (s), 1118 (s), 1071 (s), 1035 (s), 914 (s). 868 (s), 803 (m), 635 (m). Anal. Calcd for C10H18N2O: C, 65.90; H, 9.95; N, 15.37. Found: C, 65.93; H, 9.88; N, 15.19. HPLC Daicel ChiralPak IC-3, nhexane/i-PrOH = 75/25, 210 nm, 0.8 mL/min, tR1 = 13.1 min (minor), tR2 = 16.8 min (major), ee = 46%. [α]25D = +14.0 (c 0.2, CHCl3). 3-Morpholino-3-phenylpropanenitrile (16m): colorless oil (45.4 mg, 21%). [α]25D = +7.5 (c 0.2, CHCl3). 1H NMR (400 MHz, CDCl3, 25 °C): δ 7.41−7.30 (m, 5H, C6H5), 3.71 (t, 3JHH = 4.7 Hz, 4H, OCH2), 3.58 (t, 3JHH = 6.2 Hz, 1H, NCH), 2.82 (dd, 3JHH = 6.3 Hz, 3 JHH = 1.8 Hz, 2H, CH2CN), 2.50−2.39 (m, 4H, NCH2). 13C{1H} NMR (101 MHz, CDCl3): δ 138.4 (s, C6H5), 129.1 (s, C6H5), 128.7 (s, C6H5), 128.0 (s, C6H5), 117.9 (s, CN), 67.1 (s, OCH2), 66.2 (s, NCH), 51.2 (s, NCH2), 22.8 (s, CH2CN). HRMS (ESI): calcd for C13H17N2O [M + H]+ 217.1341, found 217.1325. IR (KBr disc) ν/ cm−1: 3062 (m), 3031 (m), 2961 (m), 2856 (m), 2241 (s, CN), 1600 (m), 1494 (s), 1455 (s), 1357 (m), 1273 (m), 1143 (m), 1116 (s), 1070 (m), 1034 (m), 1007 (s), 915 (s), 866 (s), 785 (s), 700 (s), 649 (m), 523 (m), 440 (m). Anal. Calcd for C13H16N2O: C, 72.19; H, 7.46; N, 12.95. Found: C, 71.95; H, 7.57; N, 12.67. HPLC Daicel ChiralPak IC-3, n-hexane/i-PrOH = 70/30, 210 nm, 0.8 mL/min, tR1 = 21.0 min (minor), tR2 = 24.2 min (major), ee = 21%. Crystal Structure Determinations. Single crystals of 3 (CCDC 860091), 11 (CCDC 1047713), and 13 (CCDC 1017024) were

obtained from a concentrated solution of dichloromethane layered by n-hexane over 5 days, whereas single crystals of 7 (CCDC 1026823) and 8 (CCDC 1017067) were obtained from a concentrated solution of dichloromethane layered by ethyl acetate, and single crystals of 9 (CCDC 1017071) were obtained by evaporation from a concentrated solution of acetone. The X-ray diffraction data were collected on an Oxford Diffraction Gemini A Ultra diffractometer with graphitemonochromated Mo Kα radiation (λ = 0.710 73 Å). The structures were solved by the direct method using the SHELXS-97 program,19 and all non-hydrogen atoms were refined anisotropically on F2 by the full-matrix least-squares technique, which used the SHELXS-97 crystallographic software package.19 Details of the crystal structure determination of complexes 3, 7, 8, 9, 11, and 13 are summarized in Table S1 in the Supporting Information.

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ASSOCIATED CONTENT

S Supporting Information *

Synthesis of new compounds, crystallographic data for 3, 7, 8, 9, 11, and 13 as cif with refinement details, NMR data of known products, and NMR and HPLC spectra of all catalytic reaction products are given in the Supporting Information. This material is available free of charge via the Internet at http:// pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. *E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was partially supported by the National Natural Science Foundation of China (No. 21172143, 21172145, 21372152, and 21472123), Nippon Chemical Industrial Co., Ltd., and Shanghai Jiao Tong University (SJTU). We thank the Instrumental Analysis Center of SJTU for HRMS analysis.

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REFERENCES

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