Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2013 Dec 24.
Published in final edited form as: J Organomet Chem. 2011 Dec 16;704:10.1016/j.jorganchem.2011.11.038. doi: 10.1016/j.jorganchem.2011.11.038

Palladacycles: Effective Catalysts for a Multicomponent Reaction with Allylpalladium(II)-Intermediates

Atsushi Shiota 1, Helena C Malinakova 1,*
PMCID: PMC3871172  NIHMSID: NIHMS355140  PMID: 24371362

Abstract

Palladium(II) complexes with an auxiliary bidentate ligand featuring one C-Pd bond and a Pd-N-donor bond (palladacycles) have been shown to afford improved yields of homoallylic amines from a three-component coupling of boronic acids, allenes and imines in comparison to the yields of homoallylic amines achieved with the originally reported catalyst (Pd(OAc)2/P(t-Bu)3), thus extending the scope of the reaction. 31P NMR monitoring studies indicate that distinct intermediates featuring Pd-P bonds originate in the reactions catalyzed by either Pd(OAc)2/P(t-Bu)3 or the pallada(II)cycle/P(t-Bu)3 systems, suggesting that the role of the pallada(II)cycles is more complex than just precatalysts. The importance of an additional phosphine ligand in the reactions catalyzed the pallada(II)cycles was established, and its role in the catalytic cycle has been proposed. Insights into the nature of the reactive intermediates that limit the performance of the originally reported catalytic systems has been gained.

Keywords: palladacycles, cyclopalladation, allylpalladium complex, three-component coupling reaction, catalytic intermediate

1. Introduction

Since the first reports on the isolation of cyclopalladated complexes [1], sometimes called palladacycles featuring bidentate ligands with a general structure C-X (X = N, P, S etc), numerous studies assessing the performance of these palladium(II) complexes as catalysts in traditional palladium-catalyzed reactions, including Heck reactions and cross-coupling protocols were published [2]. Extensive discussions of different mechanistic possibilities [3] appear to converge on the notion that palladacycles operate as precatalysts that give rise to low concentrations of palladium(0), rather than engaging in catalytic cycles with Pd(II)/Pd(IV) intermediates [4]. Recently, novel palladium-catalyzed reactions under oxidative conditions have been shown to involve palladacycles as key intermediates. In these protocols, substrates undergo cyclopalladation yielding pallada(II)cycles, which are then oxidized to Pd(IV) complexes poised to release functionalized substrates via a reductive elimination [5].

In contrast, palladium-catalyzed reactions in which cyclopalladated ligands in pallada(II)cycles function as true auxiliary ligands throughout the catalytic cycle remain rare [6]. A catalytic asymmetric aza-Cope reaction described by Overman represents an example of such a process [6a]. Grigg has employed a Pd(II) catalyst bearing a cyclopalladated auxiliary ligand to catalyze an annulation reactions involving an intramolecular allylation of aldehydes and ketones [6b]. Szabo pioneered the application of (PCP) palladium(II) pincer complexes in allylations of aldehydes and imines with trifluoro(allyl)borates [6c].

Herein, we report that pallada(II)cycles featuring C-X (X = Nsp2 or Nsp3) chelates effectively catalyze a three-component coupling reaction of boronic acids I, allenes II and imines III yielding highly substituted homoallylic amines IV (Fig. 1) recently described [7] by the author’s laboratory. The structure-activity relationship for the auxiliary C-X ligand in the catalysts have been surveyed, and the optimum pallada(II)cycle catalyst provided improved yields of homoallylic amines IV in comparison to the previously reported palladium catalyst (Pd(OAc)2) in reactions featuring heteroatom-substituted boronic acids I. The importance of additional phosphine ligand in the reactions catalyzed the pallada(II)cycles was established, and its role in the catalytic cycle has been proposed. Mechanistic experiments utilizing 31P NMR monitoring suggested that the pallada(II)cycle-based catalysts did not give rise to intermediates common with the reactions catalyzed by Pd(OAc)2. Furthermore, the 31P NMR monitoring provided insights into the nature of the reactive intermediates limiting the scope of the originally reported catalytic system.

Fig. 1.

Fig. 1

Open in a new tab

General overview of the pallada(II)-cycle-catalyzed three-component coupling

2. Results and discussion

The original report from our laboratories on the preparation of homoallylic amines IV via palladium catalyzed three-component coupling identified Pd(OAc)2/P(t-Bu)3 (Pd : P = 1 : 1) as the catalyst of choice [7a]. The allylpalladium(II) complex V, existing as equilibrium between complexes Va and Vb (path (b) in Fig. 2) and arising via a sequential B to Pd transmetalation, allene migratory insertion and a second transmetalation (path (a) in Figure 2) was proposed as the key intermediate. Complex V then reacts with imine (path (c) in Fig. 2) giving rise to a η1-bonded allylpalladium(II) complex involved in the nucleophilic allyl transfer providing the homoallylic amine (path (d) in Fig. 2) [7,8]. A complete catalytic cycle for the reactions catalyzed by Pd(OAc)2 including the product release step (path (e) in Fig. 2) is shown in Fig. 2.

Fig. 2.

Fig. 2

Open in a new tab

Catalytic cycle proposed for reactions catalyzed by Pd(OAc)2

Aiming to identify more robust and broader-scope palladium(II) catalysts for this reaction, we set out to explore the performance of cyclopalladated Pd(II) dimers bearing C-X (X = N, S, P) chelates. We reasoned that allylpalladium(II) complexes VI existing as equilibrium between complexes VIa and VIb and closely analogous to the originally proposed nucleophilic allylpalladium(II) intermediates V would arise from the cyclopalladated complexes by a shorter sequence of B to Pd transmetalation (path (a) in Fig. 3) and allene migratory insertion (path (b) in Fig. 3). A subsequent complexation of the imine to form complex VII (path (c) in Fig. 3) and the nucleophilic allyl transfer would deliver the homoallylic amines in a manner analogous to the catalytic cycle shown in Fig. 2. However, it will have to be ascertained by experimentation whether the pallada(II)cyclic catalyst is capable of mediating the nucleophilic allyl transfer, since the only relevant precedents involve a rather specific intramolecular 5-exo-trig cyclization event reported by Grigg [6b], and a nucleophilic allyl transfer from a Pd(II) complex bearing a tricoordinate pincer ligand [6c] that effectively forces the requisite η1-bonding [8, 9] of the allyl fragment.

Fig. 3.

Fig. 3

Open in a new tab

Intermediates proposed for reactions catalyzed by (C-X)Pd(II) palladacycles

Thus, the reaction of boronic acid 1a, allene 2 and imine 3a catalyzed by cyclopalladated dimer A (10 mol% Pd) under conditions (1a : 2 : 3, 2 : 5 : 1 mol equiv, THF, 40 °C, 16 h) otherwise optimized for the Pd(OAc)2/P(t-Bu)3 catalyst was investigated (Scheme 1). In all cases, a single diastereomer of the amine 4a, identical to the diastereomer obtained under the originally reported conditions and assigned as anti [7a], was obtained in the experiments reported in Scheme 1 and Table 1 (vide infra). Unexpectedly, the addition of a phosphine ligand was required in order to achieve optimum performance of the catalyst. The most sterically demanding phosphines P(t-Bu)3 and PPh(t-Bu)2 delivered as HP(t-Bu)3BF4 and HPPh(t-Bu)2BF4 afforded the best yields of amine 4a (76% and 73%, respectively), in comparison to P(o-Tol)3 (18%) and PPh3 (44%) ligands (Scheme 1). Notably, the yield of amine 4a obtained with the cyclopalladated catalyst A (76%) was indeed higher than the yield ever achieved with the originally reported Pd(OAc)2/P(t-Bu)3 catalyst (61%) [7a]. The reaction mixtures with catalyst A did not show apparent signs (color change or precipitation) of the formation of Pd(0) noted in the Pd(OAc)2-catalyzed reactions, although an aryl-aryl coupling side reaction was detected in both systems.

Scheme. 1.

Scheme. 1

Open in a new tab

Optimization of conditions for the reaction catalyzed by the pallada(II)cycle

a Cond. A: 1a : 2 : 3a = 2 : 5 : 1 (mol equiv.), THF, 40 °C, 16 h, 10 mol% Pd as complex A, L (PR3) (10 mol%), CsF (4 equiv). Cond. B: same as Cond. A except 10 mol% Pd as Pd(OAc)2, HP(t-Bu3)BF4 (10 mol%)

Table 1.

Comparison of the performance of different pallada(II)cycles as catalysts

graphic file with name nihms355140t1.jpg
entry catalyst yield of 4a (%)
1 Pd(OAc)2 61
2 A 76
3 B 61
4 C 21
5 D 55
6 E 67 (3.1)b
7 F 50
8 G 58
9 H 56 (2.0)b
10 I 34
11 J 16
12 K 29
13 L 20 (0)
Open in a new tab
a

Cond. 1a : 2 : 3a, 2 : 5 : 1 (mol equiv), THF, 40 °C, 24 h, Pd catalyst (10 mol%), HP(t-Bu)3BF4 (10 mol%), CsF (4 equiv).

b

Enantiomeric excess (%) measured by chiral phase HPLC.

Next, the performance of a series of cyclopalladated dimer complexes B-L (Fig. 4) as catalysts for the preparation of amine 4a under the conditions optimized with the pallada(II)cycle A was evaluated (Table 1). In general, cyclopalladated complexes A-H [10] possessing the C-N chelate in the auxiliary ligands proved to be viable catalysts affording amine 4a in yields higher than 50% (entries 2, 3 and 5–9, Table 1). However, none of the complexes performed better than complex A or the originally reported Pd(OAc)2. Interestingly, a rigid cyclopalladated 1,10-phenanthroline ligand in the palladacycle C provided only poor yields of the homoallylic amine (entry 4, Table 1). Comparison of the yields achieved with complexes A vs. B and D vs. E suggests that an increased steric bulk around the heteroatom favors the desired reaction course, possibly due to favoring the η1-bonding of the allyl fragment to the palladium center in intermediates VI (entries 2, 3, 5 and 6, Fig. 3). No significant differences in the performance of cyclopalladated complexes featuring an sp2-hybridized N-donor (A-F, Fig. 4) and sp3-hybridized N-donor atom (G and H, Fig. 4) were observed. Furthermore, cyclopalladated complexes that differed in the nature of the C-Pd bond, featuring the Pd bonded to either the sp2- or sp3-hybridized carbons (B and F, Fig. 4) afforded similar yields 61% and 50%, respectively, of the homoallylic amine 4a (entries 3 and 7, Table 1).

Fig. 4.

Fig. 4

Open in a new tab

Cyclopalladated complexes

Notably, catalysts bearing P-heteroatom and S-heteroatom I-L [11] capable of back-bonding via the d-orbitals and thus diminishing the electron density at the Pd(II) center in η1-bonded allylpalladium(II) intermediate VII (Fig. 2) afforded low yields of the amine 4a (entries 10–13, Table 1). The lack of catalytic activity of complex K is significant in terms of considering the reactive species involved in the catalytic cycle of reactions catalyzed by Pd(OAc)2/P(t-Bu)3 system, since under the reaction conditions, palladation of the phosphine ligand giving rise to a four-membered cyclopalladated ligand present in the complex K should be facile [11c].

An attempt to realize asymmetry transfer from chiral nonracemic cyclopalladated complexes E, H and L disappointingly did not afford enantiomerically enriched product 4a (entries 6, 9 and 13, Table 1).

Catalysis with complex A under the optimized conditions (Scheme 1, Table 1) was then employed in the three-component coupling reactions of selected boronic acids 1a-g bearing heteroatom-containing substituents (methoxy, methylcarbonyl, cyano, fluoro, chloro) and the methyl group in the para position. Indeed catalyst A afforded amines 4a-e bearing methoxy, cyano, fluoro and methylcarbonyl groups in the boronic acid substituents in yields moderately improved (8–34%) in comparison to the results with the originally reported Pd(OAc)2 catalyst, thus extending the scope of the three-component coupling reactions [7]. Some of the boronic acids selected for these experiments afforded particularly low yields of the corresponding amines 4c-e in reactions catalyzed by Pd(OAc)2/P(t-Bu)3 (entries 5, 7 and 9, Table 2). However, substituents that exert relatively the least significant electronic effects on the aromatic ring (e.g. Me and Cl) did not seem to differentiate the performance of the two types of catalysts (compare entries 11 and 12, and 13 and 14, Table 2). Using boronic acids bearing p-methyl and p-chloro substituents the corresponding amines 4f and 4g were obtained in comparable yields using either cyclopalladated catalyst A or the originally reported Pd(OAc)2 (entries 11–14, Table 2).

Table 2.

Survey of the reaction scope with substituted boronic acids

graphic file with name nihms355140t2.jpg
entr substrate 1
(R)		 catalyst prdt
4		 yield
(%)
1 4-MeOOCC6H4- Pd(OAc)2 4a 61
2 A 76
(+15)
3 4-MeOC6H4- Pd(OAc)2 4b 48
4 A 64
(+16)
5 4-MeCOC6H4- Pd(OAc)2 4c 43
6 A 77
(+34)
7 4-CNC6H4- Pd(OAc)2 4d 30
8 A 54
(+24)
9 4-FC6H4- Pd(OAc)2 4e 29
10 A 37
(+8)
11 4-ClC4H4- Pd(OAc)2 4f 54
12 A 56
(+2)
13 4-MeC6H4- Pd(OAc)2 4g 56
14 A 58
(+2)
Open in a new tab
a

Cond. 1a : 2 : 3a, 2 : 5 : 1 (mol equiv), THF, 40 °C, 16 h, Pd catalyst (10 mol%), HP(t-Bu)3BF4 (10 mol%), CsF (4 equiv).

To assess the possibility that complex A serves as a precatalyst ultimately giving rise to intermediates identical to those formed in reactions catalyzed by the Pd(OAc)2/P(t-Bu)3 system, 31P NMR monitoring experiments were performed. Two reaction mixtures consisting of the boronic acid 1a (2 mol equiv), allene 2 (5 mol equiv) and imine 3a (1 mol equiv), HP(t-Bu)3PBF4 (1 mol equiv), CsF (4 mol equiv) [12] and either Pd(OAc)2 (1 mol equiv) or the cyclopalladated complex A (1 mol equiv) dissolved in THF-d8 were prepared inside NMR tubes at room temperature. For each reaction system, 31P NMR spectra were recorded 16 times over the course of 1 hour (Fig. 5).

Fig. 5.

Fig. 5

Open in a new tab

31P NMR monitoring experiments

After the initial 10 minutes, spectral traces recorded for the reaction mediated by Pd(OAc)2 revealed two signals at 84.8 ppm and at −9.2 ppm, that could be assigned to Pd(0)L2 complex (84.8 ppm) [13] and to a four-membered cyclometalated P-chelated palladacycle (−9.2 ppm) analogous to the structure of the complex K (Fig. 4), particularly since and in situ cyclometalation of P(t-Bu)3 ligand is expected to be facile under the reaction conditions [14]. However, since we have shown that complex K was not an active catalyst for the three-component coupling reaction (entry 12, Table 1), a complex giving rise to the −9.2 ppm 31P NMR signal might represent a stable species formed in a high concentration accompanied by a low concentration of an undetected high-energy catalytically active intermediate [15]. Notably, 31P NMR monitoring of the reaction mediated by the cyclopalladated catalyst A revealed the presence of different intermediates. Thus, a signal for a free P(t-Bu)3 ligand (63.4 ppm) [16], along with a signal at 50.9 ppm that was gradually increasing over 40 minutes time period, were detected (Fig. 5). The signal at 50.9 ppm likely indicates the presence of a Pd(II) intermediate with a single phosphine ligand present in the coordination sphere along with one more organic ligand, e.g. possibly the proposed intermediates VI or VII (Fig. 3) or their precursors. Although these experiments could not identify the structures of the catalytically active intermediates, the results suggest that distinct catalytic intermediates operate in reactions catalyzed by the cyclopalladated calyst A in contrast to the reaction catalyzed by Pd(OAc)2, thus underlying the unique catalytic potential and function of the palladacycles in this synthetic process.

In summary, experiments described above yielded the following observations regarding the differences between the reactions catalyzed by Pd(OAc)2 and by the (C-N) Pd(II) palladacycles. Unexpectedly, the presence of an additional phosphine ligand was required to achieve an optimum performance of the (C-N)Pd(II) palladacycles. Best results were obtained with palladacycles featuring nitrogen as the heteroatom in the auxiliary ligand sphere and particularly those possessing an increased steric bulk about the heteroatom (N). As anticipated based on the initial mechanistic proposals (Fig. 2 and Fig. 3), reactions catalyzed by the palladacycles proved to be tolerant of a broader range of substituted boronic acids affording improved yields of functionalized homoallylic amines 4a-g (Table 2). Finally, distinct intermediates featuring Pd-bonded phosphorus ligands were detected in reactions catalyzed by either the Pd(OAc)2 or the (C-N)Pd(II) palladacycles via 31P NMR monitoring. The chemical shift of the 31P NMR signal detected in the reactions catalyzed by Pd(OAc)2 appear to suggest the formation of a cyclometalated complex analogous to the complex K (Fig. 4).

The fact that the cyclopalladated catalyst A appears to better tolerate substitution with groups significantly effecting the electron density in the aromatic ring of the boronic acid component and consequently a broader range of the rates of B to Pd transmetalation steps, correlates with the fewer number of transmetalation steps needed to assemble the proposed key allylpalladium(II) intermediate VI (paths (a, b) in Fig. 3) bearing the cyclometalated auxiliary ligand than the intermediate V (path (a) in Fig. 2).

To rationalize the initially unexpected need for additional phoshine ligands in reactions catalyzed by the cyclopalladated catalyst A it must be considered that the phosphine ligand may play a critical role in one or more of the four phases of the catalytic cycle of the reactions catalyzed by the (C-N)Pd(II) palladacycle A (Fig. 6), including (i) bridge splitting of the original dimer of catalyst A (path (a) in Fig. 6); (ii) assembly of the allyl fragment via transmetalation and migratory insertion (paths (a, b) in Fig. 6); (iii) equilibrium between the η3 and η1-bonded complexes VIa and VIb and VII (path (c) in Fig. 6); (iv) nucleophilic allyl transfer (path (d) in Fig. 6) and finally the (v) catalyst regeneration with concomitant product release (path (e) in Fig. 6). Thus, a revised catalytic cycle for reactions catalyzed by the (C-N) Pd(II) palladacycle along with the H(t-Bu)3PBF4 has been proposed (Fig. 6).

Fig. 6.

Fig. 6

Open in a new tab

Catalytic cycle for reactions catalyzed by complex A with P(t-Bu)3 ligand

In order to understand the role of the phosphine ligand in the bridge splitting of the complex A, control experiments involving 31P NMR monitoring of reaction systems consisting of the cyclopalladated complex A and HP(t-Bu)3BF4 along with either N,N-diisopropylethyl amine, pyridine or CsF, or both CsF and ArB(OH)2 were performed. N,N-diisopropylethyl amine, pyridine and CsF are known to release free P(t-Bu)3 from its tetrafluoroborate salt [12]. Evidence for the release of the free phosphine was indeed obtained in the presence of N,N-diisopropylethyl amine, pyridine and CsF (for 31P NMR data see the Supporting Information). However, the bridge splitting of complex A was only detected in the presence of either pyridine or both CsF and boronic acid ArB(OH)2 and not in the presence of only CsF and HP(t-Bu)3BF4 (for 31P NMR data see Supporting Information). Thus, the phosphine ligand does not play a critical role in the initinal bridge splitting step of the catalytic cycle (Fig. 6).

A component of the reaction mixture, likely the aryl boronic acid ensures the bridge-splitting of complex A, and permits the formation of a complex with the Pd(II)-bonded phosphine (50.9 ppm signal, trace b, Fig. 5).

The formation of an allyl ligand on Pd(II) centers via migratory insertion of allenes into aryl-Pd(II) bonds (path (b), Fig. 6) both in the presence of absence of auxiliary phosphine lignads has been described in the literature [17, 18], including complexes bearing cyclometalated (C-N) ligands [6b, 18]. Thus, the formation of the allyl palladium(II) intermediate VI via allene migratory insertion is unlikely to constitute the step in which the presence of the phosphine ligand is critical.

However, computational data revealed that in order for the nucleophilic allyl transfer (path (d), Fig. 6) to become feasible, the allyl ligand has to be bonded in the η1 mode [6d, 9]. These findings are further supported by the facile nucleophilic allyl trasfer from the (PCP)Pd(II) pincer complexes reported by Szabo [6c], in which a single coordination site remains available for the bonding of the allyl fragment. In the absence of a phosphine ligand in the reaction described herein, only weak donor ligands L (allene, imine and THF solvent) are present to shift the position of the equilibrium between the η3- and η1-bonded complexes VIb and VIa and VII in favor of the complex VII that must be formed in order for the nucleophilic allyl transfer to occur via a closed transition state, as indicated by the anti-stereochemistry consistently obtained in the homoallylic amine products.

Thus, the role of the additional phoshine ligand in the reactions catalyzed by complex A could be rationalized by the involvement of both the phosphine ligand (L) and the imine in a series of ligand exchange equilibriums featuring the allylpalladium(II) intermediates VI and VII, ultimately providing the optimum concentration of the η1-bonded allylpalladium(II) complex VII necessary for the nucleophilic allyl transfer [6d, 9] (Fig. 6).1

Finally, the product release along with catalyst regeneration likely involves transmetalation transferring the aryl group from B to Pd(II) (path (e), Fig. 6). This step must be favored by an electron deficient Pd(II) center, and therefore the presence of a phosphine donor is not likely to be critical for the release of the homoallylic amine IV.

The 31P NMR monitoring data described in Fig. 5, trace (a) provide additional insights into the nature of the reactive intermediates involved in the reactions catalyzed by Pd(OAc)2/HP(t-Bu)3BF4. The signal detected at −9.2 ppm suggests that a cyclometalation of the P(t-Bu)3 ligand might be occurring ultimately giving rise to an allylpalladium(II) complex VIII (Fig. 7) [11c]. We observed that an analogous cyclopalladated complex K (Fig. 4) did not prove to be an active catalyst for synthesis of amine 4a (vide supra). Thus, the in situ cyclopalladation of the phosphine ligand might be diminishing the concentration of the catalytically active Pd(II) species, and be responsible for the limitations in the performance of the Pd(OAc)2/HP(t-Bu)3BF4 catalytic systems discussed herein.

Fig. 7.

Fig. 7

Open in a new tab

A proposed intermediate limiting the effectiveness of the Pd(OAc)2 catalyst

3. Conclusions

A new application of pallada(II)cycles featuring a cyclopalladated auxiliary ligand with N-donor atom as catalysts in a three-component coupling reaction for the synthesis of highly substituted homoallylic amines has been described. The optimum pallada(II)cycle afforded improved yields of the homoallylic amines in comparison to the catalytic system based on Pd(OAc)2, in particular in reactions utilizing electronically differentiated boronic acids bearing MeO, COOMe, COMe, CN and F substituents. A brief structure-activity survey indicated that the structure of the cyclopalladated auxiliary ligand controlled the catalyst reactivity, and distinct reactive intermediates were detected in the reaction catalyzed by Pd(OAc)2 and the optimum pallada(II)cycle A. The presence of the nitrogen heteroatom and steric bulk in the cyclopalladated ligands were identified as the structural features critical for the optimum reactivity of the palladacyclic catalyst. Furthermore, the need for a phosphine ligand in reactions catalyzed by the pallada(II)cycles was established, and its role in the catalytic cycle of the three-component coupling reaction was proposed. 31P NMR studies provided insights into the structures of the intermediates operating in the reaction catalyzed by Pd(OAc)2/HP(t-Bu)3BF4, revealing that an in situ cyclopalladation of the phosphine ligand is likely limiting the performance of the originally reported catalytic system.

4. Experimental section

4.1 General Methods

Unless otherwise indicated, all NMR data were collected at room temperature in CDCl3 with internal CHCl3 as the reference (δ 7.26 ppm for 1H and 77.00 ppm for 13C) and internal (present in a sealed capillary inserted into the NMR tube) H3PO4 (δ 0 ppm) as the reference for 31P NMR. IR spectra were measured as thin films on salt (NaCl) plates. MS were measured under electrospray ionization (ES+) conditions. HPLC was recorded with Shimadzu SCL-10A system equipped with CHIRALCEL OD column. Analytical thin-layer chromatography (TLC) was carried out on commercial Merck silica gel 60 plates, 0.25 µm thickness, with fluorescent indicator (F-254) or stained with aqueous KMnO4 solution. Column chromatography was performed with 40–63 µm silica gel (Sorbent). Tetrahydrofuran (THF) was freshly distilled from sodium/benzophenone. Methylene chloride, toluene, acetonitrile, and DMF were kept over 3Å (8–12 mesh) molecular sieves. Benzene was distilled from CaH2 and kept over 3Å (8–12 mesh) molecular sieves under an atmosphere of dry argon; other solvents were used as received. Unless otherwise specified, all reactions were carried out under an atmosphere of dry argon in oven-dried (at least 6 h at 140 °C) glassware. p-Methoxyphenylboronic acid and p-chlorophenylboronic acid were purchased from Sigma-Aldrich, purified by recrystallization from water, and dried under vacuum for at least 16 h. 1,2-nonadiene [19] and (E)-N-benzylidene-4-methoxyaniline [20] were prepared according to modified literature procedures. Pd complexes A-L [10,11] were prepared according to indicated literature procedure. Other materials were used as received from commercial suppliers.

4.2 General protocol for the preparation of homoallylic amines

Homoallylic amines were prepared according to a modified literature procedure [7a]. A solution of 1,2-nonadiene 2 (1.25 mmol, 5.0 equiv) in dry THF (3.0 ml) was injected into a vessel containing the solid reagents including (E)-N-benzylidene-4-methoxyaniline 3a (0.25 mmol 1.0 equiv), boronic acid 1a-g (0.50 mmol, 2.0 equiv), palladium acetate (0.025 mmol, 0.1 equiv) or palladium complex A-L (0.0125 mol, 0.05 equiv), phosphine ligand, tri-t-butylphosphonium tetrafluoroborate, triphenylphosphine, or tri-o-tolylphosphine (0.025 mmol, 0.10 equiv) and CsF (1.00 mmol, 4.0 equiv). The reaction mixture was then stirred at 40 °C under argon for 24 h. Water (20 ml) was added, and the mixture was extracted with ether (4 × 20 ml). Organic extracts were dried (MgSO4), and the solvents were removed under reduced pressure to afford the crude products that were separated by flash chromatography over silica eluting with EtOAc/Hexanes mixtures to yield pure amines as yellow oils.

4.3 Application of the general protocol to the experiments described in Scheme 1

The following protocol was applied to experiments described in Scheme 1. Treatment of 1,2-nonadiene 2 (0.155 g, 1.25 mmol, 5.0 equiv), (E)-N-benzylidene-4-methoxyaniline 3a (0.053 g, 0.25 mmol 1.0 equiv), p-methoxycarbonylphenylboronic acid 1a (0.090 g, 0.50 mmol, 2.0 equiv), either palladium acetate (0.006 g, 0.025 mmol, 0.1 equiv) or palladium complex A (0.009 g, 0.0125 mol, 0.05 equiv), and one of the following phosphine ligands, tri-t-butylphosphonium tetrafluoroborate (0.0073 g, 0.025 mmol, 0.10 equiv), triphenyl phosphine (0.0066 g, 0.025 mmol, 0.10 equiv), tri-o-tolylphosphine (0.0076 g, 0.025 mmol, 0.10 equiv), or phenyl-(di-t-butyl)phosphonium tetrafluoroborate (0.0078 g, 0.025 mmol, 0.10 equiv), and CsF (0.151g, 1.00 mmol, 4.0 equiv) according to the general procedure described above followed by flash chromatography over silica eluting with EtOAc/Hexanes (1:20) afforded 4a as a yellow oil.

4.4 Application of the general protocol to the experiments described in Table 1

The following protocol was applied to experiments described in Table 1. Treatment of a series of palladium complexes A-L (0.012 mmol, 0.10 equiv of Pd), 1,2-nonadiene 2 (0.155 g, 1.25 mmol, 5.0 equiv), (E)-N-benzylidene-4-methoxyaniline 3a (0.053 g, 0.25 mmol 1.0 equiv), p-methoxycarbonylphenylboronic acid 1a (0.090 g, 0.50 mmol, 2.0 equiv), tri-t-butylphosphonium tetrafluoroborate (0.0073 g, 0.025 mmol, 0.10 equiv), and CsF (0.151g, 1.00 mmol, 4.0 equiv) according to the general procedure described above followed by flash chromatography over silica eluting with EtOAc/Hexanes (1:20) afforded 4a as a yellow oil. The amounts of palladium complexes used were as following:

  • Catalyst A (9.4 mg) afforded amine 4a (90 mg, 76 %)

  • Catalyst B (8.0 mg) afforded amine 4a (72 mg, 61 %)

  • Catalyst C (8.6 mg) afforded amine 4a (25 mg, 21 %)

  • Catalyst D (7.8 mg) afforded amine 4a (65 mg, 55 %)

  • Catalyst E (8.8 mg) afforded amine 4a (79 mg, 67 %, 3.1 % ee)

  • Catalyst F (7.7 mg) afforded amine 4a (59 mg, 50 %)

  • Catalyst G (8.1 mg) afforded amine 4a (68 mg, 58 %)

  • Catalyst H (7.8 mg) afforded amine 4a (66 mg, 56 %, 2.0 % ee)

  • Catalyst I (11.0 mg) afforded amine 4a (40 mg, 34 %)

  • Catalyst J (11.8 mg) afforded amine 4a (19 mg, 16 %)

  • Catalyst K (8.0 mg) afforded amine 4a (34 mg, 29 %)

  • Catalyst L (9.0 mg) afforded amine 4a (24 mg, 20 %, no significant % ee observed)

HPLC was recorded with Shimadzu SCL-10A system equipped with CHIRALCEL OD column, eluting with 1% isopropanol in hexane.

4.5 Preparation and complete characterization of homoallylic amines 4a-g (Table 2)

4.5.1 General protocol

Homoallylic amines were prepared according to the general protocol described in section 4.2.

4.5. 2 N-p-methoxyphenyl-2-(1-hexyl)-3-(p-methoxycarbonylphenyl)-1-(phenyl)-3-butenamine (4a)

Treatment of p-methoxycarbonylphenylboronic acid 1a (0.090 g, 0.50 mmol, 2.0 equiv) according to the general procedure described above followed by flash chromatography over silica eluting with EtOAc/Hexanes (1:20) afforded 4a (0.072 g, 61 % with Pd(OAc)2 and 0.090 g, 76 % with A) as a yellow oil.

Analytical data for 4a: Rf = 0.22 (EtOAc/Hexane= 1/10); 1H NMR (400 MHz) δ 7.93 (d, J = 8.0 Hz, 2 H), 7.31-7.16 (m, 7 H), 6.61 (d, J = 12.0 Hz, 2 H), 6.39 (d, J = 12.0 Hz, 2 H), 5.43 (s, 1 H), 5.29 (s, 1 H), 4.14 (s br, 1 H), 4.07 (d, J = 8.0 Hz, 1 H), 3.92 (s, 3 H), 3.67 (s, 3 H), 2.80 (q, J = 8.0 Hz, 1 H), 1.33-1.11 (m, 10 H), 0.82 (t, J = 8.0 Hz, 3 H); 13C NMR (125 MHz) δ 166.9, 151.9, 149.6, 147.1, 147.0, 145.1, 142.8, 141.5, 129.6 (2 carbons), 129.0, 128.3 (2 carbons), 127.6 (2 carbons), 127.3 (2 carbons), 127.1, 117.6, 114.7 (2 carbons), 114.6 (2 carbons), 62.1, 55.7, 53.2, 52.1, 31.7, 30.3, 29.2, 27.4, 22.6, 14.1; IR (neat, cm−1) 3402 (w br), 1718 (s), 1607 (m) ; HRMS (ES+) C31H38NO3, calcd M + H+ = 472.2852, found 472.2821.

4.5.3 N-p-methoxyphenyl-2-(1-hexyl)-3-(p-methoxyphenyl)-1-(phenyl)-3-butenamine (4b)

Treatment of p-methoxyphenylboronic acid 1b (0.076 g, 0.50 mmol, 2.0 equiv) according to the general procedure described above followed by flash chromatography over silica eluting with EtOAc/Hexanes (1:30) afforded 4b (0.053 g, 48 % with Pd(OAc)2 and 0.071 g, 64 % with A) as a yellow oil.

Analytical data for 4b: Rf = 0.20 (EtOAc/Hexane= 1/20); 1H NMR (400 MHz) δ 7.34 (d, J = 4.0 Hz, 2 H), 7.28-7.24 (m, 3 H), 7.20 (d, J = 8.0 Hz, 2 H), 6.84 (d, J = 8.0 Hz, 2 H), 6.61 (d, J = 8.0 Hz, 2 H), 6.38 (d, J = 8.0 Hz, 2 H), 5.32 (s, 1 H), 5.16 (s, 1 H), 4.06 (d, J = 12.0 Hz, 1 H), 3.81 (s, 3 H), 3.66 (s, 3 H), 2.72 (q, J = 8.0 Hz, 1 H), 1.28-1.10 (m, 10 H), 0.81 (t, J = 8.0 Hz, 3 H);13C NMR (125 MHz) δ 159.0, 151.8, 149.59, 143.3, 141.8, 134.59, 128.3 (2 carbons), 128.2 (2 carbons), 127.7 (2 carbons), 127.0, 115.5, 114.6 (2 carbons), 114.5 (2 carbons), 113.7 (2 carbons), 62.5, 55.7, 55.3, 31.66, 30.57, 29.2, 27.3, 22.6, 14.1; IR 3398 (w br), 1510 (s), 1242 (s); HRMS (ES+) C30H38NO2, calcd M + H+ = 444.2903, found 444.2896.

4.5.4 N-p-methoxyphenyl-2-(1-hexyl)-3-(p-acetylphenyl)-1-(phenyl)-3-butenamine (4c)

Treatment of p-acetylphenylboronic acid 1c (0.082 g, 0.50 mmol, 2.0 equiv) according to the general procedure described above followed by flash chromatography over silica eluting with EtOAc/Hexanes (1:30) afforded 4c (0.049 g, 43 % with Pd(OAc)2 and 0.088 g, 77 % with A) as a yellow oil.

Analytical data for 4c: Rf = 0.26 (EtOAc/Hexane= 1/8); 1H NMR (400 MHz) δ 7.88 (d, J = 8.0 Hz, 2 H), 7.35 (d, J = 8.0 Hz, 2 H), 7.30-7.28 (m, 4 H), 7.21 (t, J = 8.0 Hz, 1 H), 6.65 (d, J = 8.0 Hz, 2 H), 6.41 (d, J = 8.0 Hz, 2 H), 5.47 (s, 1 H), 5.34 (s, 1 H), 4.17 (s br, 1 H), 4.10 (d, J = 8.0 Hz, 1 H), 3.69 (s, 3 H), 2.84 (q, J = 8.0 Hz, 1 H), 2.62 (s, 3 H), 1.37-1.15 (m, 10 H), 0.83 (t, J = 8.0 Hz, 3 H); 13C NMR (125 MHz) δ 197.8, 151.9, 149.5, 147.1, 142.8, 141.5, 128.4 (2 carbons), 128.3 (2 carbons), 127.6 (2 carbons), 127.5 (2 carbons), 127.1 (2 carbons), 117.7, 114.7, 114.6, 62.1, 55.7, 53.2, 31.7, 30.3, 29.2, 27.4, 26.6, 22.6, 14.1; IR (neat, cm−1) 3398 (w br), 1682 (m), 1602 (m) ; HRMS (ES+) C31H38NO2, calcd M + H+ = 456.2903, found 456.2875.

4.5.5 N-p-methoxyphenyl-2-(1-hexyl)-3-(p-cyanophenyl)-1-(phenyl)-3-butenamine (4d)

Treatment of p-cyanophenylboronic acid 1d (0.074 g, 0.50 mmol, 2.0 equiv) according to the general procedure described above followed by flash chromatography over silica eluting with EtOAc/Hexanes (1:30) afforded 4d (0.034 g, 30 % with Pd(OAc)2 and 0.062 g, 54 % with A) as a yellow oil.

Analytical data for 4d: Rf = 0.20 (EtOAc/Hexane= 1/10); 1H NMR (400 MHz) δ 7.52 (d, J = 8.0 Hz, 2 H), 7.29 (d, J = 8.0 Hz, 2 H), 7.24 -7.21 (m, 3 H), 7.16 (d, J = 8.0 Hz, 2 H), 6.63 (d, J = 8.0 Hz, 2 H), 6.37 (d, J = 12.0 Hz, 2 H), 5.43 (s, 1 H), 5.34 (s, 1 H), 4.09 (d, J = 8.0 Hz, 1 H), 4.07 (s br. 1 H), 3.67 (s, 3 H), 2.83 (q, J = 8.0 Hz, 1 H), 1.37-1.15 (m, 10 H), 0.83 (t, J = 8.0 Hz, 3 H); 13C NMR (125 MHz) δ 152.0, 149.0, 158.5, 147.1, 142.1, 141.2, 132.0 (2 carbons), 128.3 (2 carbons), 127.9 (2 carbons), 127.5 (2 carbons), 127.2, 118.9, 118.3, 114.7 (2 carbons), 114.6 (2 carbons), 110.9, 61.6, 55.7, 53.0, 31.6, 30.8, 28.9, 27.4, 22.6, 14.1; IR (neat, cm−1) 3402 (w br), 2225 (m), 1512 (s), 1238 (s); HRMS (ES+) C30H35N2O, calcd M + H+ = 439.2749, found 439.2740.

4.5.6 N-p-methoxyphenyl-2-(1-hexyl)-3-(p-fluorophenyl)-1-(phenyl)-3-butenamine (4e)

Treatment of p-fluorophenylboronic acid 1e (0.070 g, 0.50 mmol, 2.0 equiv) according to the general procedure described above followed by flash chromatography over silica eluting with EtOAc/Hexanes (1:40) afforded 4e (0.031 g, 29 % with Pd(OAc)2 and 0.040 g, 37 % with A) as a yellow oil.

Analytical data for 4e: Rf = 0.29 (EtOAc/Hexane= 1/20); 1H NMR (400 MHz) δ 7.31 (d, J = 4.0 Hz, 2 H), 7.26 (d, J = 8.0 Hz, 2 H), 7.21 -7.17 (m, 3 H), 6.96 (t, J = 8.0 Hz, 2 H), 6.61 (d, J = 12.0 Hz, 2 H), 6.39 (d, J = 12.0 Hz, 2 H), 5.33 (s, 1 H), 5.22 (s, 1 H), 4.18 (s br. 1 H), 4.03 (d, J = 8.0 Hz, 1 H), 3.67 (s, 3 H), 2.73 (q, J = 8.0 Hz, 1 H), 1.29-1.11 (m, 10 H), 0.82 (t, J = 8.0 Hz, 3 H); 13C NMR (125 MHz) δ 162.7 (d, J13C-19F = 245 Hz), 151.9, 149.3, 143.0, 141.6, 138.1, 129.0, 128.9, 128.3 (2 carbons), 127.7 (2 carbons), 127.0, 116.8, 115.2, 115.0, 114.7 (2 carbons), 114.5 (2 carbons), 62.0, 55.7, 53.6, 31.7, 30.5, 29.2, 27.4, 22.6, 14.1; IR(neat, cm−1) 3404 (w br), 1510 (s), 1238 (s); HRMS (ES+) C29H35FNO, calcd M + H+ = 432.2703, found 432.2697.

4.5. 7 N-p-methoxyphenyl-2-(1-hexyl)-3-(p-chlorophenyl)-1-(phenyl)-3-butenamine (4f)

Treatment of p-chlorophenylboronic acid 1f (0.078 g, 0.50 mmol, 2.0 equiv) according to the general procedure described above followed by flash chromatography over silica eluting with EtOAc/Hexanes (1:40) afforded 4f (0.061 g, 54 % with Pd(OAc)2 and 0.063 g, 56 % with A) as a yellow oil.

Analytical data for 4f: Rf = 0.30 (EtOAc/Hexane= 1/20); 1H NMR (400 MHz) δ 7.34 -7.27 (m, J = 4.0 Hz, 5 H), 7.23 (d, J = 4.0 Hz, 2 H), 7.20 (d, J = 8.0 Hz, 2 H), 6.65 (d, J = 8.0 Hz, 2 H), 6.40 (d, J = 8.0 Hz, 2 H), 5.38 (s, 1 H), 5.26 (s, 1 H), 4.18 (s br. 1 H), 4.06 (d, J = 8.0 Hz, 1 H), 3.69 (s, 3 H), 2.76 (q, J = 8.0 Hz, 1 H), 1.33-1.14 (m, 10 H), 0.85 (t, J = 8.0 Hz, 3 H); 13C NMR (125 MHz) δ 151.9, 149.2, 142.9, 141.5, 140.5, 133.2, 128.7 (2 carbons), 128.4 (2 carbons), 128.3 (2 carbons), 127.6 (2 carbons), 127.0, 117.0, 114.7 (2 carbons), 114.6 (2 carbons), 62.0, 55.7, 53.5, 31.7, 30.0, 29.0, 27.7, 22.6, 14.1; IR (neat, cm−1) 3404 (w br), 1510 (s), 1238 (s) ; HRMS (ES+) C29H35ClNO, calcd M + H+ = 448.2407, found 448.2386.

4.5.8 N-p-methoxyphenyl-2-(1-hexyl)-3-(p-tolyl)-1-(phenyl)-3-butenamine (4g)

Treatment of p-tolylboronic acid 1g (0.068 g, 0.50 mmol, 2.0 equiv) according to the general procedure described above followed by flash chromatography over silica eluting with EtOAc/Hexanes (1:40) afforded 4g (0.060 g, 56 % with Pd(OAc)2 and 0.062 g, 58 % with A) as a yellow oil.

Analytical data for 4g: Rf = 0.28 (EtOAc/Hexane= 1/20); 1H NMR (400 MHz) δ 7.38 (d, J = 8.0 Hz, 2 H), 7.29 (t, J = 8.0 Hz, 2 H), 7.21 (t, J = 8.0 Hz, 1 H), 7.18 (d, J = 8.0 Hz, 2 H), 7.13 (d, J = 8.0 Hz, 2 H), 6.62 (d, J = 8.0 Hz, 2 H), 6.38 (d, J = 8.0 Hz, 2 H), 5.37 (s, 1 H), 5.19 (s, 1 H), 4.23 (s br. 1 H), 4.05 (d, J = 8.0 Hz, 2 H), 3.67 (s, 3 H), 2.75 (q, J = 4.0 Hz, 1 H), 2.36 (s, 3 H), 1.32 -1.11 (m, 10 H), 0.83 (t, J = 8.0 Hz, 3 H); 13C NMR (125MHz) δ 151.8, 150.1, 143.4, 141.9, 139.3, 137.12, 129.0 (2 carbons), 128.3 (2 carbons), 127.8 (2 carbons), 127.2 (2 carbons), 127.0, 116.0, 114.6 (2 carbons), 114.5 (2 carbons), 62.6, 55.7, 53.5, 31.7, 30.5, 29.2, 27.3, 22.6, 21.1, 14.1; IR (neat, cm−1) 3400 (w br), 1510 (s), 1238 (s); HRMS (ES+) C30H38NO, calcd M + H+ = 428.2953, found 428.2916.

Supplementary Material

01

Acknowledgement

This work was supported in part by the Office of Science of the U.S. Department of Energy (DE-FG02-06ER15792) and the National Institutes of Health Kansas University Chemical Methodologies and Library Development Center of Excellence (NIH0063950 P50).

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Appendix A. Supplementary material

Full page 1H NMR and 13C NMR spectra for compounds 4a-g and detailed description of the 31P NMR monitoring experiments discussed in the text, as well as the description of additional control experiments.

1

Nucleophilic allyl transfer from an η1-bonded (PCP)(allyl)Pd(II) pincer complex observed in situ by 1H NMR to aldehydes and imines was examined by DFT calculations, see [6d] and references cited therein.

References

  • 1.(a) Cope AC, Siekman RW. Formation of covalent bonds from Platinum or Palladium to carbon by direct substitution. J. Am. Chem. Soc. 1965;87:3272–3273. [Google Scholar]; (b) Cope AC, Friedrich EC. Electrophilic aromatic substitution reactions by Platinum(II) and Palladium(II) chlorides on N, N-dimethylbenzylamines. J. Am. Chem. Soc. 1968;90:909–913. [Google Scholar]
  • 2.(a) Chartoire A, Lesieur M, Slawin AMZ, Nolan SP, Cazin CSJ. Highly active well-defined Palladium precatalyst for the efficient amination of aryl chlorides. Organometallics. 2011;30:4432–4436. [Google Scholar]; (b) Zim D, Buchwald SL. An air and thermally stable one-component catalyst for the amination of aryl chlorides. Org. Lett. 2003;5:2413–2415. doi: 10.1021/ol034561h. [DOI] [PubMed] [Google Scholar]; (c) Dupont J, Consorti CS, Spencer J. Potential of palladacycles: more than just precatalysts. Chem. Rev. 2005;105:2527–2571. doi: 10.1021/cr030681r. [DOI] [PubMed] [Google Scholar]
  • 3.(a) Beletskaya IP, Cheprakov AV. Palladacycles in catalysis-a critical survey. J. Organomet. Chem. 2004;689:4055–4082. [Google Scholar]; (b) Louie J, Hartwig JF. A Route to Pd0 from PdII metallacycles in amination and cross-coupling chemistry. Angew. Chem. Int. Ed. Engl. 1996;35:2359–2361. [Google Scholar]; (c) Farina V. High-Turnover Palladium Catalysts in Cross-Coupling and Heck Chemistry: A Critical Overview. Adv. Synth. Catal. 2004;346:1553–1582. [Google Scholar]
  • 4.(a) Shaw BL. Speculations on new mechanisms for Heck reactions. New J. Chem. 1998;22:77–79. [Google Scholar]; (b) Shaw BL, Perera SD, Staley EA. Highly active, stable catalysts for the Heck reaction; further suggestions on the mechanism. Chem. Commun. 1998:1361–1362. [Google Scholar]
  • 5.(a) Neufeldt SR, Sanford MS. O-Acetyl oximes as transformable directing groups for Pd-catalyzed C-H bond functionalization. Org. Lett. 2010;12:532–535. doi: 10.1021/ol902720d. [DOI] [PMC free article] [PubMed] [Google Scholar]; (b) Dick AR, Hull KL, Sanford MS. A highly selective catalytic method for the oxidative functionalization of C-H bonds. J. Org. Chem. 2004;126:2300–2230. doi: 10.1021/ja031543m. [DOI] [PubMed] [Google Scholar]
  • 6.(a) Anderson CE, Overman LE. Catalytic asymmetric rearrangement of allylic trichloroacetimidates. A practical method for preparing allylic amines and congeners of high enantiomeric purity. J. Am. Chem. Soc. 2003;125:12412–12413. doi: 10.1021/ja037086r. [DOI] [PubMed] [Google Scholar]; (b) Gai X, Grigg R, Collard S, Muir JE. Palladium catalyzed intramolecular nucleophilic addition of allylic species, generated from allene, to aryl aldehydes and ketones. Chem. Commun. 2000:1765–1766. [Google Scholar]; (c) Solin N, Wallner OA, Szabo KJ. Palladium Pincer-Complex Catalyzed Allylation of Tosylimines by Potassium Trifluoro(allyl)borates. Org. Lett. 2005;7:689–691. doi: 10.1021/ol0475010. [DOI] [PubMed] [Google Scholar]; (d) Selander N, Szabo KJ. Catalysis by Palladium pincer complexes. Chem. Rev. 2011;111:2048–2076. doi: 10.1021/cr1002112. [DOI] [PubMed] [Google Scholar]
  • 7.(a) Hopkins CD, Malinakova HC. Allylpalladium umpolung in the three-component coupling synthesis of homoallylic amines. Org. Lett. 2006;8:5971–5974. doi: 10.1021/ol0624528. [DOI] [PubMed] [Google Scholar]; (b) Hopkins CD, Malinakova HC. Synthesis of unnatural alpha-amino acid derivatives via a three-component coupling method utilizing an allylpalladium umpolung. Synthesis. 2007;22:3558–3566. [Google Scholar]
  • 8.(a) Nakamura H, Iwama H, Yamamoto Y. Palladium- and Platinum-catalyzed addition of aldehydes and imines with allylstannanes. Chemoselective allylation of imines in the presence of aldehyde. J. Am. Chem. Soc. 1996;118:6641–6647. [Google Scholar]; (b) Sebelius S, Wallner OA, Szabo KJ. Palladium-catalyzed coupling of allyl acetates with aldehyde and imine electrophiles in the presence of bis(pinacolato)diboron. Org. Lett. 2003;5:3065–3068. doi: 10.1021/ol035052i. [DOI] [PubMed] [Google Scholar]; (c) Kurosawa H, Urabe A. Electrophilic substitution of structurally rigid η 1-allylpalladium complexes. Chem. Lett. 1985:1839–1840. [Google Scholar]; (d) Barczak NR, Grote RE, Jarvo ER. Catalytic umpolung allylation of aldehydes by π-allylpalladium complexes containing bidentate N-heterocyclic carbene ligands. Organometallics. 2007;26:4863–4865. [Google Scholar]
  • 9.Szabo KJ. Palladium-Catalyzed Electrophilic Allylation Reactions via Bis(allyl)palladium Complexes and Related Intermediates. Chem. Eur. J. 2004;10:5268–5275. doi: 10.1002/chem.200400261. [DOI] [PubMed] [Google Scholar]
  • 10.For the synthesis of complex A, see: Navarro-Ranninger C, Zamora F, Martinez-Cruz LA, Isea R, Masaguer JR. Synthesis and NMR structural analysis of several orthopalladated complexes of substituted benzo-imidazole, -oxazole, and –thiazole and study two polymorphic crystals. J. Organomet. Chem. 1996;518:29–36. For the synthesis of complexes B and C, see: (b) “Synthesis and characterization of a homologous series of mononuclear palladium complexes containing different cyclometalated ligands” Aiello I, Crispini A, Ghedini M, La Deda M, Barigelletti F. Inorg. Chim. Acta. 2000;308:121–128. For the synthesis of complex D, see: (c) Ohff M, Ohff A, Milstein D. Highly active Pd(II) cyclometallated imine catalysts for the Heck reaction. Chem. Commun. 1999:357–358. For the synthesis of complex E, see: (d) Hallman K, Moberg C. Palladium(II)-catalyzed oxidation of alcohols with air as reoxidant. Adv. Synth. Catal. 2001;343:260–263. For the synthesis of complex F, see: (e) Evans P, Hogg P, Grigg R, Nurnabi M, Hinsley J, Sridharan V, Suganthan S, Korn S, Simon C, Muir JE. 8-Methylquinoline palladacycles: stable and efficient catalysts for carbon-carbon bond formation. Tetrahedron. 2005;61:9696–9704. For the synthesis of complex G, see: (d) Thompson JM, Heck RF. Carbonylation reactions of ortho-palladation products of α-arylnitrogen derivatives. J. Org. Chem. 1975;40:2667–2674. For the synthesis of complex H, see: (e) Mosteiro R, Fernandez A, Vazquez-Garcia D, Lopez-Torres M, Rodriguez-Castro A, Gomez-Blanco N, Vila JM, Fernandez JJ. Cyclometallated palladium diphosphane compounds derived from the chiral ligands (S)-PhCH(Me)NMe2. Michael addition reactions to the vinylidene double bond. Eur. J. Inorg. Chem. 2011:1824–1832.
  • 11.For the synthesis of complex I, see: Hiraki K, Fuchita Y, Uchiyama T. Cyclopalladation of benzyldiphosphine by palladium (II) acetate. Inorg. Chim. Acta. 1982;69:187–190. For the synthesis of complex J, see: (b) Bohm VP, Herrman WA. Mechanism of Heck Reaction Using a Phosphapalladacycle as the Catalyst: Classical versus Palladium (IV) Intermediates. Chem. Eur. J. 2001;7:4191–4197. doi: 10.1002/1521-3765(20011001)7:19<4191::aid-chem4191>3.0.co;2-1. For the synthesis of complex K, see: (c) Wu L, Hartwig JF. Mild palladium-catalyzed selective monoarylation of nitriles. J. Am. Chem. Soc. 2005;127:15824–15832. doi: 10.1021/ja053027x. For the synthesis of complex L, see: (d) Dupont J, Gruber AS, Fonsesca GS, Monterio AL, Ebeling G, Burrow RA. Synthesis and catalytic properties of configurationally stable and non-racemic sulfur-containing palladacycles. Organometallics. 2001;20:171–176.
  • 12.The role of the CsF consists in releasing the free P(t-Bu)3 ligand from its air-stable HBF4 salt, see: Fu GC, Netherton MR. Air-stable Trialkylphosphonium salts: simple, practical, and versatile replacements for air-sensitive trialkylphosphines. Applications in stoichiometric and catalytic processes. Org. Lett. 2001;3:4295–4298. doi: 10.1021/ol016971g.
  • 13.The reported 31P NMR signal for Pd[(P(t-Bu)3]2 is 84.8 ppm, see: Mitchell EA, Baird MC. Optimization of Procedures for the Syntheses of Bis-phosphinoepalladium (0) recursors for Suzuki-Miyaura and Similar Cross-Coupling Catalysis; Identification of 3 : 1 Coordination Compounds in Catalyst Mixtures Containing Pd (0) PCy3 and/or PMeBut2. Organometallics. 2007;26:5230–5238.
  • 14.The reported 31P NMR signal for complex K (Figure 3) is −7.8 ppm, see: reference 11c.
  • 15.Wassenaar J, Jansen E, van Zeist WJ, Bickelhaupt FM, Siegler MA, Spek AL, Reek JNH. Catalyst selection based on intermediate stability measured by mass spectrometry. Nature Chemistry. 2010;2:417–421. doi: 10.1038/nchem.614. [DOI] [PubMed] [Google Scholar]
  • 16.The reported 31P NMR signal for P(t-Bu)3 is 63 ppm and for P(=O)(t-Bu)3 is −41 ppm see: Tebby JC. Handbook of Phosphorus-31 Nuclear Magnetic Resonance Data. Boca Raton: CRC Press; 1991.
  • 17.Ahmar M, Barieux JJ, Cazes B, Gore J. Carbopalladation of allenic hydrocarbons: A new way to functionalized styrenes and 1,3-butadienes. Tetrahedron. 1987;43:513–526. [Google Scholar]
  • 18.Gai X, Grigg R, Ramzan MI, Sridharan V, Collard S, Muir JE. Pyrazole and benzothiazole palladacycles: stable and efficient catalysts for carbon-carbon bond formation. Chem. Communn. 2000:2053–2054. [Google Scholar]
  • 19.Moreaou JL, Gauclemar M. Action des organomagnesiens sur les ethers-oxydes propargyliques en presence de bromure cuivreux: synthese de carbures alleniques. J. Organomet. Chem. 1976;108:159–164. [Google Scholar]
  • 20.Manhas MS, Ghosh M, Bose AK. Studies on lactams. Part 84. β-Lactams via α,β-unsaturated acid chlorides: intermediates for carbapenem antibiotics. J. Org. Chem. 1990;55:575–580. [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

01
NIHMS355140-supplement-01.doc (601KB, doc)

RESOURCES