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Organometallics 2010, 29, 6334–6342 DOI: 10.1021/om100741m
Synthesis and Characterization of New, Chiral P-N Ligands and Their Use in Asymmetric Allylic Alkylation Kurtis E. Thiesen,† Kalyani Maitra,† Marilyn M. Olmstead,‡ and Saeed Attar*,† †
Department of Chemistry, California State University, Fresno, California 93740, United States, and ‡ Department of Chemistry, University of California, Davis, California 95616, United States Received July 27, 2010
Several new ferrocenylimines containing both planar and central chirality were prepared from (Sp)-2-(diphenylphosphino)ferrocenecarboxaldehyde and chiral primary amines. One of these compounds, (Sp,Sc)-3, induced particularly high conversions (92-99%) and enantioselectivities (91-94% ee) when applied as a P-N ligand in the asymmetric allylic alkylation (AAA). In addition, a precatalyst complex was formed from (Sp,Sc)-3 and di-μ-chlorobis[(η3-C3H5)palladium(II)] and isolated after anion exchange with NaBF4 to give [Pd(η3-C3H5)((Sp,Sc)-3)]BF4 (4). High conversions (99%) and enantioselectivities (90-93% ee) were also observed when the isolated precatalyst (4) was used in the AAA reaction. Crystal structures were obtained for all three ligands prepared for this study ((Sp,Sc)-1-3) and for the isolated precatalyst (4). These compounds were also investigated by CD spectroscopy.
Introduction The usefulness of organometallic, palladium-containing compounds in asymmetric catalysis cannot be understated. In particular, ferrocene-based compounds have demonstrated their effectiveness as ligands for several palladium-catalyzed transformations, including allylic substitution.1 Asymmetric allylic alkylation, commonly known as AAA, is a very useful synthetic tool that tolerates a wide variety of substrates and results in the stereoselective formation of a new carbon-carbon bond; this transformation is of particular importance, as its products are useful intermediates in the synthesis of chiral *To whom correspondence should be addressed. E-mail: sattar@ csufresno.edu. (1) (a) McManus, H. A.; Guiry, P. J. Chem. Rev. 2004, 104, 4151– 4202. (b) Willms, H.; Frank, W.; Ganter, C. Organometallics 2009, 28 (10), 3049–3058. (c) Malone, Y. M.; Guiry, P. J. J. Organomet. Chem. 2000, 603, 110–115. (d) Jin, M.-J.; Takale, V. B.; Sarkar, M. S.; Kim, Y.-M. Chem. Commun. 2006, 663–664. (e) Togni, A.; Hayashi, T., Ferrocenes: Homogeneous Catalysis, Organic Synthesis, Materials Science; VCH: Weinheim, 1995. (f) Togni, A.; Halterman, R. L. Metallocenes, Vol. 2; Wiley-VCH: Weinheim, 1998. (g) Stepnicka, P. Ferrocenes: Ligands, Materials, and Biomolecules; John Wiley & Sons, Ltd: Chichester, 2008. (h) Colacot, T. J. Chem. Rev. 2003, 103, 3101–3118. (i) Sutcliffe, O. B.; Bryce, M. R. Tetrahedron: Asymmetry 2003, 14, 2297–2325. (j) Arrayas, R. G.; Adrio, J.; Carretero, J. C. Angew. Chem., Int. Ed. 2006, 45, 7674– 7715. (2) (a) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395– 422. (b) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley: New York, 1994. (c) Trost, B. M.; Schroeder, G. M. Chem.;Eur. J. 2005, 11, 174–184. (d) Graening, T.; Schmalz, H.-G. Angew. Chem., Int. Ed. 2003, 42, 2580–2584. (e) Trost, B. M. Chem. Pharm. Bull. 2002, 50, 1–14. (f) Trost, B. M.; Tang, W. J. Am. Chem. Soc. 2005, 127, 14785–14803. (3) (a) Helmchen, G. J. Organomet. Chem. 1999, 576, 203–214. (b) Trost, B. M. Chem. Rev. 2003, 103, 2921–2943. (c) Trost, B. M. J. Org. Chem. 2004, 69, 5813–5837. (d) Lange, D. A.; Goldfuss, B. Beilstein J. Org. Chem. 2007, 3 (36), 1–9. (e) Park, H.-J.; Han, J. W.; Seo, H.; Jang, H.-Y.; Chung, Y. K.; Suh, J. J. Mol. Catal. A: Chem. 2001, 174, 151–157. (f) Lee, J. H.; Son, S. U.; Chung, Y. K. Tetrahedron: Asymmetry 2003, 14, 2109–2113. pubs.acs.org/Organometallics
Published on Web 11/16/2010
Chart 1. P-N Ligands Prepared and Examined in This Study
drugs and other biologically important compounds.2 Chiral ligands with both P and N donor atoms are particularly suitable for this reaction scheme because of their electronic influence; that is, nucleophilic substitution generally occurs at the allylic terminus trans to phosphorus, the ligand’s stronger π-acceptor.3 These mechanistic considerations coupled with our knowledge of Kagan’s method4 of preparing enantiomerically pure, planar chiral ortho-substituted ferrocenecarboxaldehydes provided inspiration for our ligand design efforts. At the outset, the goal of this study was to build ligands that contained both planar and central chirality with the latter coming from L-amino acids, available inexpensively through the “chiral pool”. The (Sp)-2-(diphenylphosphino)ferrocenecarboxaldehyde ((Sp)-dppFcCHO) unit could be prepared using Kagan’s method and would provide the requisite planar chirality and some additional steric bulk. Herein we report the synthesis of three new ferrocenylimine ligands (Chart 1): two L-amino acid ester ferrocenylimines, (Sp,Sc)-1 and (Sp,Sc)-2, and a third ((Sp,Sc)-3), which was also prepared from the (Sp)-dppFcCHO scaffold and (S)-(-)-R-methylbenzylamine. The alkylation of 1,3-diphenyl2-propenyl acetate with dimethyl malonate has served as the model reaction for our catalytic studies (Scheme 1). (4) Riant, O.; Samuel, O.; Flessner, T.; Taudien, S.; Kagan, H. B. J. Org. Chem. 1997, 62, 6733–6745. r 2010 American Chemical Society
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Scheme 1. Model Reaction for Catalytic Studies
Results and Discussion Preparation of L-Amino Acid Ferrocenylimine Ligands ((Sp,Sc)-1,2). L-Phenylalanine and L-alanine were first esterified using a well-established technique by which free amino acids are converted into their corresponding methyl ester HCl salts.5 Though relatively simple to prepare, these compounds are also inexpensive and commercially available. After their preparation, the HCl salts were deprotonated to yield their free amines. While tertiary organic bases such as triethylamine have been widely used for such purposes, they were not sufficient in this case.6 Instead, activated zinc dust was used to irreversibly deprotonate the HCl salts, followed by the subsequent condensation reactions between these amino acid methyl esters and the previously prepared (Sp)-dppFcCHO (Scheme 2).7 As we began to assess the performance of these ferrocenyl-amino acid ester ligands (Table 1), we also began to speculate that the ester portion of the molecule was interfering with the proper formation of the active precatalyst (i.e., the oxygen atom(s) of the ligand were themselves acting as donor atoms, thus preventing the desired P-N coordination). In addition to low catalyst activity, palladium black was observed in many of the reaction mixtures, indicating that a redox reaction could also be taking place in preference to the desired Pd-catalyzed transformation. To confirm our suspicions, samples of ligands (Sp,Sc)-1 and -2 in combination with different palladium species were prepared, and their 31 P{1H} NMR spectra were collected; several distinct signals were present in each spectrum, indicating that one coordination mode was not predominant. There are many plausible “interference scenarios” here, but we decided not to pursue a rigorous determination of the source. Instead we reasoned that a slight ligand modification may provide some insight into the source of the interference, while also rendering a viable ligand for the system under analysis. Preparation of a Third, Modified Ferrocenylimine Ligand ((Sp,Sc)-3). The third ligand, (Sp,Sc)-3, was prepared using enantiomerically pure (S)-R-methylbenzylamine, with the latter being easily resolved from its racemate using L-(þ)(5) (a) Li, J.; Sha, Y. Molecules 2008, 13, 1111–1119. (b) Otera, J.; Nishikido, J. Esterification: Methods, Reactions, and Applications, 2nd ed.; Wiley-VCH: Weinheim, 2010; p 386. (6) (a) Jones, J. The Chemical Synthesis of Peptides; Clarendon Press: Oxford, 1991. (b) Gutte, B. Peptides: Synthesis, Structures, and Applications; Academic Press: San Diego, 1995. (7) Ananda, K.; Suresh Babu, V. V. J. Pept. Res. 2001, 57, 223–226. (8) (a) Ohta, T.; Sasayama, H.; Nakajima, O.; Kurahashi, N.; Fujii, T.; Furukawa, I. Tetrahedron: Asymmetry 2003, 14, 537–542. (b) Pignataro, L.; Lynikaite, B.; Colombo, R.; Carboni, S.; Krupicka, M.; Piarulli, U.; Gennari, C. Chem. Commun. 2009, 3539–3541. (c) Dell'Anna, M. M.; Mastrorilli, P.; Nobile, C. F.; Suranna, G. P. J. Mol. Catal. A: Chem. 2003, 201, 131–135. (9) Ault, A. J. Chem. Educ. 1965, 42, 269.
Scheme 2. Preparation of Ligands (Sp,Sc)-1-3
tartaric acid9 and is therefore quite inexpensive. This amine was condensed with (Sp)-dppFcCHO in toluene with the aid of a Dean-Stark trap to yield the corresponding ferrocenylimine, (Sp,Sc)-3 (Scheme 2). This ligand is to be very similar in structure to the other two ((Sp,Sc)-1,2) in the sense that it contains both planar and central chirality. The apparently troublesome ester group was simply replaced with a phenyl group, and the results of the catalytic studies performed with ligand (Sp,Sc)-3 indicate that it is an excellent chiral ligand for this model reaction. Table 1 summarizes the catalytic studies performed using (Sp,Sc)-3 (both in situ and with the isolated precatalyst (4)). Preparation of [Pd(η3-C3H5)((Sp,Sc)-3)]BF4 (4). Complex 4 was prepared by stirring the corresponding ligand ((Sp,Sc)-3) with di-μ-chlorobis[(η3-C3H5)palladium(II)] in methylene chloride. After solvent removal, anion exchange of the cationic complex was accomplished in acetone with a slight excess of NaBF4. Crystallography-grade crystals of this complex were obtained by layering a concentrated acetone solution of 4 with hexanes. Catalytic Studies. The substrates used in this reaction were standard ones; 1,3-diphenyl-2-propenyl acetate was the allylic substrate, and the nucleophile was generated from dimethyl malonate. The palladium precursor was an allylpalladium chloride dimer, di-μ-chlorobis[(η3-C3H5)palladium(II)]. Though their mode of action is not always easy to interpret, the virtues of using metal acetate additives in combination with a base such as N,O-bis(trimethylsilyl)acetamide have been documented by Trost and co-workers.10 In an attempt to optimize the AAA reaction conditions (10) Trost, B. M.; Bunt, R. C. J. Am. Chem. Soc. 1998, 120, 70–79.
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Table 1. Selected Results for the AAA Using Ligands (Sp,Sc)-1-3 and 4 a
entry
L*
solvent
additive
temp (°C)
time (h)
convb (%)
% eec (config)d
1 2 3 4 5 6 7 8 9 10
(Sp,Sc)-1 (Sp,Sc)-2 (Sp,Sc)-3 (Sp,Sc)-3 (Sp,Sc)-3 (Sp,Sc)-3 (Sp,Sc)-3 (Sp,Sc)-3 4e 4
THF THF toluene toluene THF THF CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2
NaOAc NaOAc KOAc NaOAc KOAc NaOAc KOAc NaOAc KOAc NaOAc
25 25 25 25 25 25 25 25 25 25
20 20 20 20 20 20 20 20 20 20
21 32 99 99 98 92 92 95 99 99
53 (R) 55 (R) 94 (R) 91 (R) 94 (R) 94 (R) 92 (R) 93 (R) 93 (R) 90 (R)
a For entries 1-8, 2.5 mol % [Pd(η3-C3H5)Cl]2, 5 mol % L*, 3 equiv of dimethyl malonate, 3 equiv of BSA, and a catalytic amount of additive were used. For entries 9 and 10, 5 mol % 4 was used. b % conversion determined by 1H NMR. c % ee was determined by chiral HPLC; Chiralcel OD-H column, 99:1 hexane-IPA, flow = 0.5 mL/min. d Wherein the chiral HPLC analysis parameters designated in footnote b were equal, absolute configuration was determined by comparison of the product elution order with samples reported in the literature.1d,8a-8c e Catalytic studies summarized in entries 9 and 10 were performed with 4, which was formed from (Sp,Sc)-3 and di-μ-chlorobis[(η3-C3H5)palladium(II)], and isolated after anion exchange with NaBF4. Studies were not carried out in toluene or THF because of the relative insolubility of 4 in those solvents.
Scheme 3. Presumed Catalytic Cycle for AAA Using Ligand (Sp,Sc)-3
for this system, two different metal acetate additives and three different solvents were evaluated. Studies were performed with the catalyst being formed in situ (entries 1-8, Table 1) and with the isolated catalyst 4 (entries 9 and 10, Table 1). The presumed transition states that correspond to the catalyst formed using ligand (Sp,Sc)-3 are shown in Scheme 3 and may help to explain the origins of chiral induction for this catalytic transformation.3a As noted above, it is well established that in this catalytic system substitution of the π-allylic terminus generally occurs trans to phosphorus; deracemization of the allylic acetate may therefore occur as the stabilized π-allyl-metal intermediate undergoes increased substitution at the electronically differentiated allylic terminus. The molecular structure of the precatalyst (4) shows the significant steric bulk that ligand (Sp,Sc)-3 imparts to the
allylic system. This structure, taken in concert with the presumed transition states drawn in Scheme 3, demonstrates the destabilization of the exo transition state because of the proximity of the allylic substrate’s phenyl groups to the bulky elements of the chiral ligand. In this context, the proposed path to chiral induction is consistent with experimental findings and the formation of product mixtures that are composed largely of the R product isomer. Structural Features of (Sp,Sc)-1,2. The solid-state molecular structures of (Sp,Sc)-1 and (Sp,Sc)-2 and selected geometric parameters for each are shown in Figures 1 and 2, respectively. One characteristic of ferrocenyl ligands that makes them useful for catalysis is their rigidity, which can be evaluated by examining the dihedral angle between the Cp least-squares planes for a given ferrocenyl backbone (i.e., the tilt angle for ferrocene). The ferrocenyl scaffolds for
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Figure 1. Molecular structure of (Sp,Sc)-1. Thermal ellipsoids are shown at 50% probability, and selected geometric parameters are reported in Table 2.
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Figure 2. Molecular structure of (Sp,Sc)-2. Thermal ellipsoids are shown at 50% probability, and selected geometric parameters are reported in Table 2.
Table 2. Selected Geometric Parameters for (Sp,Sc)-1,2 (Sp,Sc)-1
(Sp,Sc)-2 Bond Lengths (A˚)
P(1)-C(13) P(1)-C(1) P(1)-C(7) N(1)-C(23) O(1)-C(26)
1.817(3) 1.833(3) 1.842(3) 1.271(3) 1.202(4)
P(1)-C(3) P(1)-C(18) P(1)-C(12) N(1)-C(1) O(1)-C(32)
1.8216(14) 1.8373(14) 1.8377(15) 1.2697(17) 1.1990(18)
C(2)-C(3)-P(1) C(3)-C(2)-C(1) N(1)-C(1)-C(2) C(1)-N(1)-C(31)
124.74(10) 124.58(12) 122.36(12) 115.18(12)
C(1)-C(2)-C(3)-P(1) N(1)-C(1)-C(2)-C(6) C(31)-N(1)-C(1)-C(2)
-4.3(2) 13.3(2) 176.27(12)
Bond Angles (deg) C(14)-C(13)-P(1) C(23)-C(14)-C(13) N(1)-C(23)-C(14) C(23)-N(1)-C(24)
124.6(2) 124.4(3) 122.6(3) 115.4(3) Torsion Angles (deg)
P(1)-C(13)-C(14)-C(23) C(15)-C(14)-C(23)-N(1) C(24)-N(1)-C(23)-C(14)
8.6(4) 3.5(5) -176.4(3)
molecular structures (Sp,Sc)-1 and (Sp,Sc)-2 are quite rigid, with tilt angles (2.2° and 2.1°, respectively) that are comparable to similar compounds reported in the literature.11 Structural Features of Ligand 3 and Its Precatalyst Complex (4). The solid-state molecular structures of (Sp,Sc)-3 and its cationic precatalyst complex, [Pd(η3-C3H5)((Sp,Sc)-3)]BF4 (4), are shown in Figures 3 and 4, respectively. Significant conformational changes are expected for ligand (Sp,Sc)-3 as it approaches palladium’s coordination sphere, and they can be observed by comparing several sets of dihedral angles between these structures. The change in the dihedral angle C(11)-N(1)-C(12)-C(14) in going from the free ligand (-147.90(10)o) to the Pd complex (120.1(2)o) is indicative of the rotation of the phenyl and R-methyl groups of the imine substituent about the N(1)-C(12) axis, while the change in the N(1)-C(12)-C(14)-C(15) dihedral angle (-97.79(13)o for the free ligand; -59.2(3)o for the bound ligand) suggests a rotation of that substituent’s phenyl group about the C(12)C(14) axis. These are the most apparent conformational (11) (a) Thimmaiah, M.; Luck, R. L.; Fang, S. J. Organomet. Chem. 2007, 692, 1956–1962. (b) Mateus, N.; Routaboul, L.; Daran, J.-C.; Manoury, E. J. Organomet. Chem. 2006, 691, 2297–2310. (c) Stepnicka, P.; Cisarova, I. Inorg. Chem. 2006, 45, 8785–8798.
changes, although similar ring plane rotations are seen for the diphenylphosphino substituent. The efficient π-conjugation that extends beyond the cyclopentadienyl ring system can be observed by examining the dihedral angles for C(1)-C(2)-C(11)-N(1) (171.92(11)o). Bond angles of 162.68(9)o for P(1)-Pd(1)-C(20) and 169.39° for N(1)-Pd(1)-C(22) correspond to the pseudosquare-planar configuration that is expected and observed for palladium complex 4. Additionally, the Pd-P (2.2685(5) A˚) and Pd-N (2.125(2) A˚) distances for 4 are within expected ranges for such compounds.1b,11c The C(22)-Pd(1)C(20) bond angle (67.60(11)o) for the η3-(C3H5)-π-allyl ligand is also comparable to other values reported for similar Pd-L-π-allyl complexes.12 The electronic differentiation referred to earlier between the P and N donor atoms of this and other P-N ligands bound to palladium reveals itself also in the solid-state structures of such complexes.12b,13 (12) (a) Lamac, M.; Tauchman, J.; Cisarova, I.; Stepnicka, P. Organometallics 2007, 26, 5042–5049. (b) Minato, M.; Kaneko, T.; Masauji, S.; Ito, T. J. Organomet. Chem. 2006, 691, 2483–2488. (13) (a) Brown, J. M.; Hulmes, D. I.; Guiry, P. J. Tetrahedron 1994, 50, 4493. (b) Matt, P. v.; Loiseleur, O.; Koch, G.; Pfaltz, A. Tetrahedron: Asymmetry 1994, 5, 573.
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Thiesen et al. Table 3. Selected Geometric Parameters for (Sp,Sc)-3 and [Pd(η3C3H5)((Sp,Sc)-3)]BF4 (4) Coordination Parameters for 4 Bond Lengths (A˚) Pd(1)-P(1) Pd(1)-N(1) Pd(1)-C(22) Pd(1)-C(21A) Pd(1)-C(20)
Bond Angles (deg) (continued)
2.2685(5) 2.125(2) 2.108(2) 2.155(4) 2.240(3)
Bond Angles (deg)
P(1)-Pd(1)-N(1) P(1)-Pd(1)-C(22) N(1)-Pd(1)-C(20) C(22)-Pd(1)-C(20) C(1)-P(1)-Pd(1)
93.50(6) 97.11(8) 101.84(10) 67.60(11) 105.35(7)
Torsion Angles (deg)
P(1)-Pd(1)-C(20) 162.68(9) Pd(1)-P(1)-C(29)-C(30) -5.55(19) N(1)-Pd(1)-C(22) 169.39(8) Pd(1)-N(1)-C(12)-C(14) -66.01(19) Comparison of Free and Coordinated Ligand (Sp,Sc)-3
4
Bond Lengths (A˚)
Figure 3. Molecular structure of (Sp,Sc)-3. Thermal ellipsoids are shown at 50% probability and selected geometric parameters are reported in Table 3.
P(1)-C(1) N(1)-C(11)
1.8149(11) 1.2782(14)
1.793(2) 1.279(3)
Bond Angles (deg) C(1)-P(1)-C(23) N(1)-C(11)-C(2) C(11)-N(1)-C(12) N(1)-C(12)-C(14) N(1)-C(12)-C(13)
102.44(5) 121.89(10) 116.01(9) 109.09(9) 108.58(10)
106.66(10) 126.9(2) 119.4(2) 108.80(18) 115.73(19)
Torsion Angles (deg) P(1)-C(1)-C(2)-C(11) C(12)-N(1)-C(11)-C(2) C(11)-N(1)-C(12)-C(14) C(11)-N(1)-C(12)-C(13) N(1)-C(12)-C(14)-C-15)
Figure 4. Molecular structure of [Pd(η3-C3H5)((Sp,Sc)-3)]BF4 (4). Thermal ellipsoids are shown at 50% probability, and selected geometric parameters for this figure are reported in Table 3.
The Pd-C distances for complex 4 are as follows: Pd(1)-C(22) (trans to N) = 2.108(2) A˚ and Pd(1)-C(20) (trans to P) = 2.240(3) A˚. These bond lengths are expected for such a complex and indicate that this system is under trans influence, which further reinforces the assertions made concerning the chiral induction that was observed in the catalytic studies described above. CD Studies. Because the X-ray crystallographic data collected for this study allowed for the stereochemistry of (Sp,Sc)-1-3 to be determined definitively, it seemed appropriate to also obtain chiroptical data for these compounds. This was a unique opportunity to expand the very limited library of CD data available for this useful class of compounds (14) (a) Barisic, L.; Dropucic, M.; Rapic, V.; Pritzkow, H.; Kirin, S. I.; Metzler-Nolte, N. Chem. Commun. 2004, 2004–2005. (b) Kirin, S. I.; Kraatz, H.-B.; Metzler-Nolte, N. Chem. Soc. Rev. 2006, 35, 348–354. (c) Barisic, L.; Cakic, M.; Mahmoud, K. A.; Liu, Y.-n.; Kraatz, H.-B.; Pritzkow, H.; Kirin, S. I.; Metzler-Nolte, N. Chem.;Eur. J. 2006, 12, 4965–4980.
9.75(16) -175.13(9) -147.90(10) 87.61(12) -97.79(13)
13.2(3) -178.3(2) 120.1(2) 6.1(3) -59.2(3)
while establishing a correlation between the stereochemical configuration of (Sp,Sc)-1-3 and their characteristic Cotton effects (CEs). It should be noted that a significant amount of CD data does exist for the axially chiral 1,n0 -disubstituted ferrocenes,1g,14 especially for peptide conjugates of this type. However, much less CD data is available for the 1,2-disubstituted planar chiral ferrocenes, and except for one such study,11c these literature accounts do not contain comparative CD data for ligands and their corresponding metal-L* complexes. The d-d-type transitions that are characteristic of ferrocene apply also to most disubstituted analogues (e.g., (Sp,Sc)1-3) and constitute the necessary chromophore that, in concert with the chirality of these compounds, gives rise to their CD spectra.15 Two inverse CEs at or around 350 and 475 nm, respectively, have been shown to exist for enantiomeric and pseudoenantiomeric planar chiral 1,2-disubstituted ferrocenes. Additional elements of central chirality, if they exist, are less susceptible to a straightforward CD analysis, and the examination of (Sp,Sc)-1-3 will also exclude attempts at assigning specific artifacts in the CD spectra to substituent central chirality. As compounds (Sp,Sc)-1-3 are structurally very similar, it was expected that their CD spectra would also be quite (15) (a) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; John Wiley & Sons: New York, 1994. (b) Hayashi, T.; Takaya, M.; Fukushima, M.; Kagotani, M.; Nagashima, N.; Hamada, Y.; Matsumoto, A.; Kawakami, S.; Konishi, M.; Yamamoto, K.; Kumada, M. Bull. Chem. Soc. Jpn. 1980, 53, 1138–1151. (c) Janowska, I.; Zakrzewski, J. Tetrahedron: Asymmetry 2003, 14, 3271–3273. (d) Schlogl, K.; Walser, M. Monatsh. Chem. 1969, 100, 1515–1539.
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Figure 5. CD spectra for compounds (Sp,Sc)-1-3 and 4.
Figure 6. UV/vis spectra for compounds (Sp,Sc)-3 and 4.
similar. As shown in Figure 5, all three compounds exhibit a positive CE at about 475 nm (474-476 nm) and a negative CE at about 360 nm (358-362 nm), both of which correspond to the planar chiral configuration of these compounds as S. Stepnicka and co-workers reported on the synthesis, CD, and X-ray crystallographic characterization of (Sp)-2-(diphenylphosphino)-1-vinylferrocene,11c which is a close analogue to the ferrocenylimines we have reported. While the lower wavelength CE is less pronounced for Stepnicka’s planar chiral vinylferrocene, a positive CE is seen to exist at about 475 nm, which is indicative of its S planar chirality. Surprisingly, the CD spectrum for a Pd complex of Stepnicka’s vinylferrocene ligand contained what appeared to be inverse CEs as compared to those present in the spectrum of the free ligand; because the coordination of this ligand to palladium did not correspond to an inversion of the stereochemistry of the ligand, these inversions were attributed to shifts in the UV bands of the ligand upon coordination to palladium. The CD data for (Sp,Sc)-3 and 4, shown in Figure 5, respectively, and the
UV/vis spectra shown in Figure 6 fully corrobororate Stepnicka’s observations. These CD spectra contain very similar but opposite CEs, and their UV spectra seem to indicate a shift in absorption of (Sp,Sc)-3 upon coordination to palladium.
Conclusion Both the precatalyst formed in situ from (Sp,Sc)-3 and di-μchlorobis[(η3-C3H5)palladium(II)] and the isolated precatalyst (4) demonstrated high activity (92-99% conversion) and enantioselectivity (90-94% ee) when applied to the AAA reaction. Crystal structures were obtained for all three ligands ((Sp,Sc)-1-3) synthesized and screened in this study. In addition, a crystal structure was obtained for the cationic palladium complex (4) that was prepared from the best performing ligand, (Sp,Sc)-3, and di-μ-chlorobis[(η3-C3H5)palladium(II)]; following anion exchange, [Pd(η3-C3H5)(Sp,Sc)-3]BF4 (4) was obtained in good yields and excellent purity.
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Experimental Section General Procedures. The preparations of (Sp)-dppFcCHO,4 [Pd(η3-C3H5)Cl]2,16 and 1,3-diphenyl-2-propenyl acetate17 were carried out according to established literature procedures. Toluene and THF were distilled over sodium/benzophenone, and methylene chloride was stored over molecular sieves and distilled over phosphorus pentoxide prior to use. All syntheses and catalytic reactions were performed under argon unless otherwise noted. 1H NMR, 13C NMR, and 31P NMR spectra were recorded using either a Bruker DRX-400 MHz spectrometer or a Varian400 MHz spectrometer. Chemical shifts for 31P NMR were referenced to an external 85% aqueous H3PO4 standard. IR data were collected on a Nicolet Avatar 320 FT-IR spectrometer, and CD spectra were recorded on a JASCO J-815 CD spectrometer. UV/vis data were collected on an HP 8452A diode array spectrophotometer. (Sp,Sc)-2-(Diphenylphosphino)-[(2-methoxy-1-methyl-2-oxoethyl)iminomethyl]ferrocene ((Sp,Sc)-1). To an oven-dried 25 mL flask was added 0.147 g (1.05 mmol) of L-alanine-OMe 3 HCl and 0.137 g (2.10 mmol) of activated zinc dust. Dry CH2Cl2 (15 mL) was added to the flask, and the reaction mixture was stirred for 30 min before being filtered through Celite into an oven-dried 25 mL flask containing 0.398 g (1.00 mmol) of (Sp)-dppFcCHO. Activated 4 A˚ molecular sieves (5 g) were added to the flask, and the stirred mixture was refluxed overnight. The reaction mixture was filtered over Celite, transferred to a 60 mL separatory funnel, and washed (3 10 mL) with deionized water. The CH2Cl2 layer was then transferred to an Erlenmeyer flask and dried over anhydrous sodium sulfate (Na2SO4). The solvent was removed under reduced pressure, and a crude red oil remained; 0.358 g, 84%. Red-orange crystals of (Sp,Sc)-1 were obtained after recrystallization of the crude product from hot heptane. 1 H NMR (CDCl3), δ: 1.45 (d, 3H, CH3, J = 6.9 Hz); 3.63 (s, 3H, OCH3); 3.90 (m, 1H, C5H3) 4.02 (q, 1H, NCH, J = 6.9 Hz); 4.09 (s, 5H, C5H5); 4.54 (m, 1H, C5H3); 5.20 (m, 1H, C5H3); 7.12-7.58 (m, 10H, PPh2); 8.48 (d, 1H, CHdN, JP-H = 3.0 Hz). 13 C{1H} NMR (CDCl3), δ: 20.00 (CHCH3); 52.26 (OCH3); 67.48 (C5H3, CH); 70.12 (CHCH3); 70.62 (C5H5); 72.46 (C5H3, CH); 74.24 (C5H3, CH); 78.94 (C5H3, C-PPh2); 84.64 (C5H3, C-CdN); 128.14-129.61 (Ph and PPh2, CH); 132.26 (d, Jpc = 17 Hz, PPh2, CH); 135.29 (d, Jpc = 21 Hz, PPh2, CH); 136.89 (d, 1Jpc = 9 Hz, PPh2 Cipso); 139.58 (d, 1Jpc = 10 Hz, PPh2 Cipso); 162.61 (CHdN); 173.23 (COOCH3). 31P{1H} NMR (CDCl3), δ: -22.55 (s). IR ν(cm-1): 1736 (s) (CdO), 1634 (m) (CdN), 1433 (m), 1200 (m), 1167 (m), 1123 (m), 1107 (m), 820 (m), 742 (s), 696 (s). Mp: 172-173 °C. (Sp,Sc)-2-(Diphenylphosphino)-[(2-methoxy-2-oxo-1-(phenylmethyl)ethyl)iminomethyl]ferrocene ((Sp,Sc)-2). To an oven-dried 25 mL flask were added 0.227 g (1.05 mmol) of L-phenylalanineOMe 3 HCl and 0.137 g (2.10 mmol) of activated zinc dust. Dry CH2Cl2 (15 mL) was added to the flask, and the reaction mixture was stirred until dissolution of the white crystalline solid was complete. The mixture was then filtered through Celite into an oven-dried 25 mL flask containing 0.398 g (1.00 mmol) of (Sp)dppFcCHO. Activated 4 A˚ molecular sieves (5 g) were added to the flask, and the mixture was refluxed overnight before being filtered over Celite, transferred to a 60 mL separatory funnel, and washed (3 10 mL) with deionized water. The CH2Cl2 layer was then transferred to an Erlenmeyer flask and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure, yielding a crude red oil; 0.426 g, 87%. Orange crystals of (Sp,Sc)-2 were harvested after recrystallization of the crude product from hot heptane. 1H NMR (CDCl3), δ: 3.14 (dd, 1H, CH2, J = 9.8, 13.7 Hz); 3.31 (dd, 1H, CH2, J = 4.4, 13.7 Hz); 3.56 (s, 3H, OCH3); (16) Hayashi, T.; Yamamoto, A.; Ito, Y.; Nishioka, E.; Miura, H.; Yanagi, K. J. Am. Chem. Soc. 1989, 111, 6301–6311. (17) Leung, W.; Cosway, S.; Jones, R. H. V.; McCann, H.; Wills, M. J. Chem. Soc., Perkin Trans. 1 2001, 2588–2594.
Thiesen et al. 3.82 (m, 1H, C5H3); 3.84 (s, 5H, C5H5); 4.11 (m, 1H, C5H3); 4.46 (t, 1H, NCH, J = 2.5 Hz); 5.04 (m, 1H, C5H3); 7.10-7.52 (m, 15H, PPh2, Ph); 8.25 (d, 1H, CHdN, JP-H = 2.6 Hz). 13C{1H} NMR (CDCl3), δ: 39.64 (CH2Ph); 52.27 (OCH3); 69.71 (C5H3, CH); 70.46 (C5H5); 72.08 (C5H3, CH); 74.02 (C5H3, CH); 74.58 (CHCH2Ph); 78.93 (C5H3, C-PPh2); 84.78 (C5H3, C-CdN); 126.80-131.94 (Ph and PPh2, CH); 132.30 (d, Jpc = 18 Hz, PPh2, CH); 135.18 (d, Jpc = 21 Hz, PPh2, CH); 136.84 (d, 1Jpc = 9 Hz, PPh2 Cipso); 139.59 (d, 1Jpc = 10 Hz, PPh2 Cipso); 163.88 (CHdN); 171.99 (COOCH3). 31P{1H} NMR (CDCl3), δ: -21.99 (s). IR ν(cm-1): 1736 (s) (CdO), 1633 (m) (CdN), 1433 (m), 1199 (m), 1165 (m), 1027 (m), 1001 (m), 820 (m), 741 (s), 696 (s). Mp: 127-128 °C. (Sp,Sc)-2-(Diphenylphosphino)-[(1-phenylethyl)iminomethyl]ferrocene ((Sp,Sc)-3). To an oven-dried, 100 mL round-bottomed flask was added 0.505 g (1.27 mmol) of (Sp)-dppFcCHO. Dry toluene (50 mL) was added to the flask, and the mixture was warmed and stirred to facilitate dissolution of the solid, at which point 0.172 mL (1.33 mmol) of (S)-R-methylbenzylamine was added. The flask was then fitted with a Dean-Stark trap, and the mixture was refluxed for 1 h before toluene collection began. Approximately 35 mL of toluene was collected over the next 2 h, and the crude product was obtained as a dark red oil after the remaining solvent was removed under reduced pressure. Bright red crystals of (Sp,Sc)-3 were obtained after recrystallization of the crude product from hot petroleum ether (low boiling). 1H NMR (CDCl3), δ: 1.49 (d, 3H, CH3, J = 6.7 Hz); 3.87 (m, 1H, C5H3); 4.13 (s, 5H, C5H5); 4.40 (q, 1H, NCH, J = 6.6 Hz); 4.51 (m, 1H, C5,H3); 5.19 (m, 1H, C5,H3); 7.13-7.60 (m, 15H, PPh2, Ph); 8.50 (d, 1H, CHdN, JP-H = 2.6 Hz). 13C{1H} NMR (CDCl3), δ: 24.74 (CHCH3); 69.30 (C5H3, CH); 70.39 (CHCH3); 70.54 (C5H5); 71.90 (C5H3, CH); 73.92 (C5H3, CH); 78.37 (C5H3, C-PPh2); 85.80 (C5H3, C-CdN); 126.78-131.94 (PPh2, CH); 132.36 (d, Jpc=18 Hz, PPh2, CH); 135.27 (d, Jpc = 20 Hz, PPh2, CH); 137.30 (d, 1Jpc = 10 Hz, PPh2 Cipso); 139.75 (d, 1Jpc = 10 Hz, PPh2 Cipso); 158.64 (CHdN). 31P{1H} NMR(CDCl3), δ: -20.72 (s). IR ν(cm-1): 1634 (m) (CdN), 1433 (m), 1250 (w), 1164 (m), 1106 (m), 1027 (m), 1000 (m), 818 (m), 736 (s), 694 (s). Mp: 125-126 °C. [Pd(η3-C3H5)((Sp,Sc)-3)]BF4 (4). To a 25 mL round-bottomed flask were added 0.023 g (0.063 mmol) of [Pd(η3-C3H5)Cl]2 and 0.063 g (0.126 mmol) of (Sp,Sc)-3, followed by 3 mL of dry CH2Cl2. This solution was stirred for 5 h, and the solvent was then removed under reduced pressure. The residue was reconstituted in 3 mL of acetone, and 0.0153 g (0.139 mmol) of NaBF4 was added. This mixture was stirred for 1 h before being filtered over Celite into a clean, dry flask. The acetone was removed under reduced pressure, and the residue that remained was reconstituted in a minimum volume of acetone and layered with hexanes. The resulting crystals were harvested on a Buchner funnel and washed with THF until the filtrate was colorless. Yield: 76% 1H NMR (CDCl3), δ: 1.70 (bs, 3H, CH3); 2.33-3.54 (v bs, 3H, π-allyl); 4.25 (s, 5H, C5H5); 4.41 (bs, 1H, C5H3); 4.48 (bs, 1H, NCH); 4.97 (bs, 1H, C5,H3); 5.35 (bs, 1H, C5,H3); 5.26 (v bs, 1H, π-allyl) 5.65 (v bs, 1H, π-allyl); 6.98-7.61 (m, 15H, PPh2, Ph); 8.75 (bs, 1H, CHdN). 13C{1H} NMR (CDCl3), δ: 21.88 (CHCH3); 72.39 (C5H5); 74.37 (CHCH3); 75.76 (C5H3, CH); 79.07 (d, Jpc = 8 Hz, C5H3, Cipso-PPh2); 80.80 (d, Jpc = 18 Hz, C5H3, C-CdN); 120.34-129.46 (PPh2, CH); 131.08; 132.04 (d, Jpc = 13 Hz, PPh2, CH); 132.32; 132.76 (d, 1Jpc = 49 Hz, PPh2 Cipso); 133.91 (d, Jpc = 14 Hz, PPh2, CH); 142.71; 169.00 (CHdN); CH of C5H3 (2) and one Cipso-PPh2 were not located. 31P{1H} NMR(CDCl3), δ: þ18.75 (br s). IR ν(cm-1): 1613 (m) (CdN), 1435 (m), 1270 (m), 1230 (w), 1173 (w), 1048 (s, b), 913 (w), 830 (m), 730 (s), 697 (s). Dec = 195 °C. Typical Procedure for the Asymmetric Allylic Alkylation of 1,3-Diphenyl-2-propenyl Acetate with Dimethyl Malonate. To an oven-dried, 10 mL round-bottomed flask were added 0.0089 g (0.024 mmol, 2.5 mol %) of [Pd(η3-C3H5)Cl]2, 0.0244 g (0.0487 mmol, 5 mol %) of (Sp,Sc)-3, and 3 mL of dry CH2Cl2. This
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Table 4. Crystal Data and Structure Refinement for (Sp,Sc)-1-3 and 4 (Sp,Sc)-1 empirical formula fw temperature wavelength cryst syst space group unit cell dimens
volume Z density (calcd) absorp coeff F(000) cryst size cryst color and habit θ range for data collection reflns collected indep reflns obsd reflns (I > 2σ(I)) max. and min. transmn goodness-of-fit on F2 final R indices [I > 2σ(I)] R indices (all data) absolute struct param largest diff peak and hole
(Sp,Sc)-2
(Sp,Sc)-3
C27H26FeNO2P 483.31 90(2) K 0.71073 A˚ orthorhombic P212121 a = 8.7544(18) A˚
C33H30FeNO2P 559.4 90(2) K 0.71073 A˚ orthorhombic P212121 a = 9.1351(3) A˚
C31H28FeNP 501.36 90(2) K 0.71073 A˚ orthorhombic P212121 a = 8.4272(3) A˚
b = 12.073(2) A˚
b = 13.2485(4) A˚
b = 12.4311(5) A˚
c = 22.141(4) A˚
c = 22.6615(7) A˚
c = 23.6623(9) A˚
2340.2(8) A˚3 4 1.372 Mg/m3 0.737 mm-1 1008 0.13 0.08 0.03 mm3 yellow needle 2.50 to 25.27°
2742.64(15) A˚3 4 1.355 Mg/m3 0.639 mm-1 1168 0.55 0.10 0.09 mm3 yellow-orange needle 2.71 to 27.94°
2478.85(16) A˚3 4 1.343 Mg/m3 0.693 mm-1 1048 0.44 0.11 0.07 mm3 orange needle 2.57 to 31.50°
C34H33BF4FeNPPd 735.64 90(2) K 0.71073 A˚ triclinic P1 a = 9.0254(2) A˚, R = 106.356(3)° b = 9.6542(3) A˚, β = 90.187(2)° c = 9.7700(3) A˚, γ = 110.903(3)° 757.95(4) A˚3 1 1.612 Mg/m3 1.175 mm-1 372 0.06 0.24 0.27 mm3 red plate 2.43 to 30.51°
21 980 4254 [R(int) = 0.0684] 3650
31 820 6567 [R(int) = 0.0294] 6235
32 735 8244 [R(int) = 0.0239] 7822
18 016 8998 [R(int) = 0.0183] 8901
0.9782 and 0.9103 1.016 R1 = 0.0339, wR2 = 0.0638 R1 = 0.0468, wR2 = 0.0681 -0.002(16) 0.359 and -0.257 e 3 A˚-3
0.9447 and 0.7200 1.034 R1 = 0.0232, wR2 = 0.0544 R1 = 0.0256, wR2 = 0.0554 0.000(8) 0.286 and -0.207 e 3 A˚-3
0.9531 and 0.7503 1.036 R1 = 0.0241, wR2 = 0.0591 R1 = 0.0266, wR2 = 0.0603 -0.009(7) 0.421 and -0.187 e 3 A˚-3
0.943 and 0.786 1.037 R1 = 0.0269, wR2 = 0.0685 R1 = 0.0272, wR2 = 0.0687 -0.010(11) 0.550 and -0.458 e 3 A˚-3
mixture was allowed to stir for 45 min, and it was subsequently added to another oven-dried, round-bottomed flask that contained 3 mL of dry CH2Cl2, 0.245 g (0.971 mmol) of 1,3diphenyl-2-propenyl acetate, 346 μL (2.92 mmol, 3 equiv) of dimethyl malonate (97%), 804 μL (2.92 mmol, 3 equiv) of 90% N,O-bis(trimethylsilyl)acetamide (BSA), and a catalytic amount of KOAc. The reaction was allowed to proceed overnight before the solvent was removed under reduced pressure. The mixture was then diluted with ether and transferred to a separatory funnel. The ether layer was washed with saturated ammonium chloride (2 10 mL), and the aqueous layer was then extracted with diethyl ether (3 10 mL). The organic layers were combined, dried over sodium sulfate (Na2SO4), and then filtered over Celite. The solvent was removed under reduced pressure, yielding the crude product as an orange oil. The mixture was further purified by flash chromatography (9:1 hexanes-ether) and analyzed by chiral HPLC and 1H NMR. Note: Where catalytic studies were performed in toluene (Table 1, entries 1, 2), gentle heating was used to facilitate the in situ formation of the precatalyst. This precatalyst solution was allowed to come to room temperature before it was added to the solution containing the substrate. Finally, where the isolated precatalyst (4) was used instead of in situ catalyst formation (Table 1, entries 9 and 10), catalytic reactions were carried out in a single flask whereby the nucleophile was generated first, followed by addition of the additive, substrate, and then 4 (5 mol %). Typical Procedure for the Determination of % ee Using Chiral HPLC. Samples were prepared at approximately 1 mg/mL in 9:1 hexanes-IPA. A Chiralcel OD-H column (250 mm 4.6 mm, 5 μm particle size) was used for these analyses, which were performed using the following instrument parameters: flow rate 0.5 mL/ min; elution method isocratic; eluent 99:1 hexane-IPA; injection volume 5 μL. The retention times for the enantiomeric products were as follows: 25.9 min (R), 28.3 min (S). X-ray Crystallography. Crystals suitable for single-crystal X-ray diffraction analysis were grown from hot heptane ((Sp,Sc)-1
4
and (Sp,Sc)-2); from hot, low boiling petroleum ether ((Sp,Sc)-3; from acetone-hexanes (4). Diffraction data were collected on a Bruker SMART Apex II using graphite-monochromatized Mo KR radiation at 90(2) K. A suitable crystal of each compound was mounted on a glass fiber with silicone grease and placed in the N2(g) cold stream provided by a CryoIndustries apparatus. Data collection was carried out with the use of Apex2 software, and data reduction was done using SAINT and corrected for absorption using SADABS.18 The structures were solved with the use of SHELXS97 and refined with SHELXL97.19 Hydrogen atoms were added geometrically and refined with a riding model. Crystal data and selected data collection and refinement parameters are presented in Table 4. CD Spectroscopy. CD samples were prepared in CH2Cl2 (Figure 5): sample 1 ((Sp,Sc)-1), c=8 mM; sample 2 ((Sp,Sc)-2), c = 7 mM; sample 3 ((Sp,Sc)-3), c = 8 mM; sample 4 (4), c = 2.5 mM. UV/vis samples were also prepared in CH2Cl2 (Figure 6): sample 1 ((Sp,Sc)-3), c = 8 mM; sample 2 (4), c = 2.5 mM.
Acknowledgment. We would like to acknowledge the following individuals for their help during this project: (a) Dr. Santanu Maitra (Department of Chemistry, CSU Fresno) for helpful discussions and for the use of the Chiralcel OD-H column; (b) Dr. Melissa Golden (Department of Chemistry, CSU Fresno) for helpful discussions; (c) Dr. Krish Krishnan (Department of Chemistry, CSU Fresno) for collecting NMR data and for providing us with access to the CD spectropolarimeter in the RIMI lab at CSU Fresno (funded by NIH grant 5P20MD002732); (d) Dr. Phil Dennison (Department of Chemistry, UC Irvine) (18) APEX2, SAINT, SADABS; Bruker AXS Inc.: Madison, WI, USA, 2009 (19) Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112.
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and Dr. James Nowick (Department of Chemistry, UC Irvine) for allowing us access to the NMR facilities at UC Irvine and for collecting NMR data; (e) Douglas Kliewer (Department of Chemistry, CSU Fresno) for his help with the operation and maintenance of the analytical instruments in our department; (f) Hamid Khaledi (University of Malaya) for his assistance with the crystal structure determination of (Sp,Sc)-3; (g) Dr. Andrew Rogerson
Thiesen et al.
(Dean, College of Science and Math, CSU Fresno) for partial financial support of this research through a FacultySponsored Student Research award. Supporting Information Available: X-ray crystallograpic data for the compounds reported here ((Sp,Sc)-1-3 and 4) are available in CIF format. This material is available free of charge via the Internet at http://pubs.acs.org.
