Synthesis and use of α-aminophosphine oxides and N,N-bis(phosphinoylmethyl)amines - A study on the related ring platinum complexes

Accepted Manuscript

Synthesis and use of α-aminophosphine oxides and N,N-bis(phosphinoyl-

methyl)amines – A study on the related ring platinum complexes

Erika Bálint, Anna Tripolszky, Erzsébet Jablonkai, Konstantin Karaghiosoff, Mátyás

Czugler, Zoltán Mucsi, László Kollár, Péter Pongrácz, György Keglevich

PII:

S0022-328X(15)30200-X

10.1016/j.jorganchem.2015.10.029

JOM 19286

DOI:

Reference:

To appear in: Journal of Organometallic Chemistry

Received Date: 11 September 2015

Revised Date: 16 October 2015

Accepted Date: 23 October 2015

Please cite this article as: E. Bálint, A. Tripolszky, E. Jablonkai, K. Karaghiosoff, M. Czugler, Z.

Mucsi, L. Kollár, P. Pongrácz, G. Keglevich, Synthesis and use of α-aminophosphine oxides and

N,N-bis(phosphinoyl-methyl)amines – A study on the related ring platinum complexes, Journal of

Organometallic Chemistry (2015), doi: 10.1016/j.jorganchem.2015.10.029.

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ACCEPTED MANUSCRIPT

Synthesis and use of α-aminophosphine oxides and N,N-bis(phosphinoyl-

methyl)amines – A study on the related ring platinum complexes

Erika Bálint,¹Anna Tripolszky,²Erzsébet Jablonkai,²Konstantin Karaghiosoff,³

Mátyás Czugler,¹Zoltán Mucsi,²László Kollár,^4,5Péter Pongrácz,^4,5György

Keglevich^2,*

¹MTA-BME Research Group for Organic Chemical Technology, 1521 Budapest, Hungary

²Department of Organic Chemistry and Technology, Budapest University of Technology and

Economics, 1521 Budapest, Hungary

³Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377

München, Germany

⁴Department of Inorganic Chemistry, University of Pécs and Szentágothai Research Center,

7624 Pécs, Hungary

⁵MTA-PTE Research Group for Selective Chemical Syntheses, H-7624 Pécs, Ifjúság u. 6.,

Hungary

ABSTRACT

The Kabachnik–Fields condensation was extended using secondary phosphine oxides, such as

dibenzylphosphine oxide and bis(4-methylphenyl)phosphine oxide as the P-reactant in

reaction with formaldehyde and different primary amines. Besides the α-aminophosphine

oxides, the corresponding bisproducts, N,N-bis(phosphinoylmethyl)amines were also

synthesized under appropriate conditions. The bis(phosphinoyl)amines were then converted to

ring platinum complexes after double deoxygenation. The substituent dependence of the

energetics of the complexation reaction using bidentate P-ligands, and the stereostructure of a

few complexes were evaluated by B3LYP/6-31G(d,p) calculations using the effective core

potential (ECP) basis set (SDD). The crystal structure of a few ring Pt species was studied by

X-ray analysis. Catalytic activity of the complexes synthesized was investigated in

hydroformylation.

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Keywords:

Kabachnik–Fields reaction; α-aminophosphine oxides, N,N-bis(phosphinoylmethyl)amines;

Bidentate P-ligand, Ring platinum complex; Hydroformylation.

1. Introduction

α-Aminophosphonates and related derivatives, such as α-aminophosphine oxides are

structural analogues of α-amino acids. Due to their versatile bioactivity, they have attracted

much attention [1-3].

One of the most convenient and widespread methods for the synthesis of

α-aminophosphonates is the Kabachik–Fields (phospha-Mannich) reaction which is based on

the condensation of an amine, an aldehyde or ketone and a >P(O)H species, such as dialkyl

phosphite or secondary phosphine oxide [4-7]. Usually, the reactions are carried out in the

presence of a catalyst and solvent [2,8–13]. However, it was found that, especially under

solvent-free conditions, there is no need for a catalyst [14,15]. The efficiency could be further

increased by the application of the microwave (MW) technique [16–19].

There are only a few examples in the literature for the synthesis of α-aminophosphine

oxides. Petrov and co-workers synthesized (phenylaminomethyl)-dibenzylphosphine oxide in

the condensation of aniline, paraformaldehyde and diphenylphosphine oxide [20]. The

reaction was carried out at 150 °C for 9 h and the yield was 73%. The (phenylaminomethyl)-

dibenzylphosphine oxide was also prepared via (hydroxymethyl)phosphine oxide [21].

Cherkasov and his research group applied the Kabachnik-Fields reaction to obtain

(butylaminomethyl)-di(p-tolyl)phosphine oxide [22]. The condensation was carried out in

benzene.

As a modification, the double Kabachnik–Fields reaction was also elaborated starting from

primary amines or amino acid derivatives to make available bis(phosphonomethyl)- or

bis(phosphinoylmethyl)amines [23–29]. The latter species were also synthesized via a

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methylene insertion reaction into

a

P–N bond followed by oxidation [30].

Bis(phosphinoylmethyl)amines may be potential bisphosphine ligands after double

deoxygenation. There are a few examples for such bidentate P-ligands synthesized by the

condensation of amines, paraformaldehyde and diphenylphosphine [31–33]. These

bisphosphines were applied successfully in the synthesis of transition metal complexes [34–

37]. A number of Pt, Ru and Au complexes show significant anticancer activity [38,39]. The

transition metal complexes incorporating P-ligands may also be used as catalyst in

hydroformylations [40–44].

We have developed a catalyst-free MW-assisted method for the synthesis of

N,N-bis(diphenylphosphinoylmethyl)amines that were converted to ring platinum complexes

after double deoxygenation [25–27]. In this paper, new N-(phosphinoylmethyl)- and N,N-

bis(phosphinoylmethyl)amines, as well as the related bidentate P-ligands and ring platinum

complexes are described. The latter complexes were tested as catalysts in the

hydroformylation of styrene.

2. Results and discussion

2.1. Synthesis of dibenzyl- and di(p-tolyl)phosphine oxides

First, the secondary phosphine oxides (1 and 2) used as P-reagents in the three component

condensations were synthesized by the Grignard reaction of diethyl phosphite applying

benzyl- or p-tolylmagnesium bromide (Scheme 1). Two equivalents of the Grignard reagent

were added to the diethyl ether solution of diethyl phosphite at 0 °C, and the mixture was

stirred at 25 °C for 1.5 h. Then, the mixture was hydrolyzed with 10% HCl solution, and the

aqueous phase was extracted with diethyl ether. After purification of the crude product so

obtained by column chromatography, the secondary phosphine oxides (1 and 2) were obtained

in yields of 84-86%. The dibenzyl- and isomeric di(p-tolyl)phosphine oxide (1 and 2) are

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known compounds [45,46]. The above synthesis elaborated by us represents a simple and

attractive approach.

Scheme 1.

2.2. Microwave-assisted synthesis of (aminomethyl)dibenzyl- or di(p-tolyl)phosphine oxides

and N,N-bis(dibenzyl- or di(p-tolyl)phosphinoylmethyl)amines

In the first approach, the Kabachnik–Fields reaction of primary amines, such as n-propyl-,

n-butyl-, cyclohexyl-, benzyl-, 4-methoxy-benzylamine, aniline or 4-methoxyaniline was

studied with paraformaldehyde and dibenzylphosphine oxide (1) at 100 °C for 1 h under MW

conditions (Scheme 2). The condensations were carried out without any catalyst in acetonitrile

as the solvent to overcome the heterogeneity of the reaction mixture. The solvent and the

water formed were removed in vacuum, and the crude products so obtained were passed

through a 1 cm silica layer using ethyl acetate as the eluent. After evaporating the solvent in

vacuum, the (aminomethyl-)dibenzylphosphine oxides (3a-g) were obtained in yields of 94–

98% in a pure form.

In the next round, the primary amines (n-butyl-, cyclohexyl-, benzyl-amine and aniline)

were reacted with paraformaldehyde and di(p-tolyl)phosphine oxide (2) in a similar way

described above. After an irradiation of 1 h at 100 °C, the corresponding products (4b-d and

4f) were isolated in 94–98% yields.

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Scheme 2.

The double Kabachnik–Fields condensation was also investigated. In these cases, the

primary amines were reacted with two equivalents of the paraformaldehyde and two

equivalents of the dibenzyl- (1) or di(p-tolyl)phosphine oxide (2) under MW conditions

(Scheme 3). The reactions were performed in acetonitrile, at 100 °C for 1 h, without any

catalyst in a similar way, as the condensations discussed above. Except for the condensation

of aniline, the N,N-bis(phosphinoylmethyl)amines (5a-e and 6b-d) were obtained in yields of

94–98%.

Scheme 3.

The outcome of the double Kabachnik–Fields reaction of aniline, paraformaldehyde and

phosphine oxides 1 and 2 was somewhat different, as besides the expected bisproduct (5f or

6f), the mono-adduct (3f or 4f) and a by-product, hydroxymethylphosphine oxide 7 or 8 were

also formed. In the reaction of aniline with two equivalents of paraformaldehyde and

dibenzylphosphine oxide (1), the product composition was 6% of bisadduct (5f) {δ_P(CDCl₃)

41.3, [M + H]⁺_found= 578.2381, C₃₆H₃₈NO₂P₂requires 578.2372}, 63% of monoadduct (3f),

and 31% of hydroxymethyldibenzylphosphine oxide

7

{δ_P(CDCl₃) 44.0,

[M + H]⁺_found= 261.1048, C₁₅H₁₈O₂P requires 261.1039}. Using di(p-tolyl)phosphine oxide

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(2) as the P-reagent, 60% of bisproduct (6f) {δ_P(CDCl₃) 27.8, [M + H]⁺_found= 578.2373,

C₃₆H₃₈NO₂P₂requires 578.2372}, 23% of mono derivative (4f) and 17% of by-product (8) {δ_P

(CDCl₃) 31.5, [M + H]⁺_found= 261.1044, C₁₅H₁₈O₂P requires 261.1039} were formed.

2.3. Utilization of bis(phosphinoylmethyl)amines as precursors for bidentate P-ligands

The bis(phosphinoylmethyl)amines (5 and 6) were utilized as precursors for bidentate

P-ligands in the synthesis of transition metal complexes. First, the double deoxygenation of

N,N-bis(phosphinoylmethyl)benzylamines 5 and 6 was investigated. In our earlier studies

[26,27], the deoxygenation of similar N,N-bis(diphenylphosphinoylmethyl)amines was carried

out using phenylsilane in benzene at 80 °C for 3 days. Under these conditions, the

deoxygenations were not complete. Recently, a better method was elaborated for the

deoxygenation of phosphine oxides in our research group. According to this, phenylsilane was

used under MW irradiation in the absence of any solvent [47]. This method has now been

applied to the reduction of bis(phosphinoylmethyl)amines 5 and 6. First, the reduction of

bis(di-p-tolyl-phosphinoylmethyl)benzylamine 6d was optimized at 120 °C under different

conditions (Scheme 4, Table 1). After a 1 h reaction time, the deoxygenation was not

complete, and 27% of phosphine-phosphine oxide 9 and 27% of bisphosphine 11d were

formed (Table 1/Entry 1). Prolonging the irradiation to 2 h, the conversion was almost

complete (95%) (Table 1/Entry 2). The best result was obtained after 2.5 h (Table 1/Entry 3).

To see the effect of the solvent, the reaction was also carried out in toluene. It was found that

the conversion decreased to 87%, and only 74% of bisphosphine 11d was formed (Table

1/Entry 4). A comparative thermal experiment was also carried out, and it was experienced

that after 2.5 h, the reaction mixture contained only 30% of bisphosphine 11d (Table 1/Entry

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5). The 40% lower conversion of the thermal control experiment refers to the role of MW

irradiation.

Scheme 4.

Table 1

Deoxygenation of bis(phosphine oxide) 6d under different conditions.

Composition (%)

Entry

Mode of heating

Solvent

t (h)

6d

46

5

9

11d

27

MW

ꢀ

–

1

27

15

0

1

2

3

4

5

–

2

80

–

toluene

–

2.5

0

100

74

13

40

13

30

Phosphine-phosphine oxide 9 and bisphosphine 11d were identified by ³¹P NMR (9: δ_P(CDCl₃)

–29.4 and 29.5; 11d: δ_P(CDCl₃) –30.4).

Based on the above experiences, the deoxygenation of bis(phosphine oxides) 5b-d and 6b-

d was carried out at 120 °C for 2.5 h under solvent-free MW-assisted conditions (Scheme 5).

Scheme 5.

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The air sensitive bisphosphines (10b-d and 11b-d) so formed were reacted further

immediately with dichlorodibenzonitrile platinum to furnish the ring platinum(II) complexes

12b-d and 13b-d in yields of 52-75%, and in a purity of ca. 99% (Scheme 6).

Scheme 6.

The bis(phosphinomethyl)amines 10d and 11d were also converted to the corresponding

bis(phosphine boranes) (14d or 15d) by reaction with an excess of dimethyl sulfide borane

(Scheme 7). The complexations were performed in toluene at 25 °C. After column

chromatography, the borane complexes 14d or 15d were obtained in yields of 60/69%. The

phosphine boranes can be regarded as the precursors of the corresponding phosphines, as the

P(III)-ligand can be liberated from them on treatment with secondary amines in an aromatic

solvent [48].

Scheme 7.

All compounds synthesized (3a-g, 4b-d, 4f, 5a-g, 6b-d, 6f, 7, 8, 12b-d, 13b-d, 14d and

15d) were characterized by ³¹P, ¹³C and ¹H NMR, as well as mass spectral data.

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2.4. Theoretical calculations

All computations, energy calculations, geometry optimizations and subsequent frequency

analyses were carried out using B3LYP/6-31G(d,p) for CHNP and B3LYP/SDD(MWB60) for

Pt including effective core potential (ECP) [49–51], applying the Gaussian09 program

package (G09) [52]. The method and basis sets were chosen for the characterization of the

compounds in agreement with studies published earlier [53].

2.4.1. Stability of the Pt-complexes

The geometry around the Pt²⁺ion is square planar, where the two phosphorus atoms bind

from one side in cis configuration, while the two chlorines from the opposite side also in cis

configuration. The energetics of the complexation process (16 → 17) are influenced

significantly by Z and moderately by Y. If Z is an alkyl type substituent, like benzyl group

(Table 2/Entries 1–7), the electron density on the P atom is much larger, resulting

complexation enthalpies of 157–167 kJ mol^–1, while aryl substituents (Table 2/Entries 8–11),

decrease the electron density, decreasing the benefit of the process by 44–54 kJ mol^–1. As

expected, the 4-MeC₆H₄group (Table 2/Entries 12–15) has a somewhat more positive effect

on the complexation, as compared to the phenyl case. According to this study, Y has much

less effect on the complexation process. Here, one can also find analogous differences

between the alkyl and aryl type of substituents, but the effect is less significant. N-alkyl

substituents resulted in somewhat higher complexation enthalpies, while in the case of aryl

groups the enthalpy values were significantly lower. A small decrease in the enthalpies may

be observed that may be due to the smaller extent of flexibility of the N-aryl substituents.

Flexible N-propyl and butyl groups may be accommodated without any sterical repulsion with

the closer P-benzyl substituents (Table 2/Entries 1 and 2). However, the N-phenyl substituent

results in a steric repulsion due to its orientation caused by the intensive conjugation with the

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nitrogen atom (Table 2/Entry 5). Slightly more negative enthalpy values can be observed for

the 4-MeC₆H₄and 4-MeOC₆H₄derivatives that may be the consequence of the smaller extent

of conjugation in these cases (Table 2/Entries 6 and 7). Cyclohexyl and benzyl groups

exhibited ∆H values that are close to the value obtained for the butyl or propyl groups (Table

2/Entries 3 and 4), however, due to the lower entropy values (∆∆S = –17.0 and –16.7 J mol^–1

K^–1, as compared to the Bu case), the final ∆G is less negative, consequently the driving force

is somewhat less. These entropy deviations can be attributed to the limited flexibility of these

N-functional groups in the course of the complexation process.

Table 2

Computed absolute and relative enthalpy (∆H in kJ mol^–1), Gibbs free energy

(∆G in kJ mol^–1), and entropy values (∆S in J mol^–1K^–1) for the 16 → 17 complexation using

B3LYP/6-31G(d,p) for CHNP and B3LYP/SDD(MWB60) for Pt including effective core

potential (ECP)

Absolute values (16 → 17)

Entry

Z

Y

∆H

∆G

∆S

1

2

3

4

5

Bn

ⁿPr

ⁿBu

^cHex

Bn

Ph

80.0

82.6

65.6

65.9

87.6

88.8

95.4

71.9

70.8

71.0

85.4

82.8

56.9

74.3

59.5

–163.7

–166.5

–160.9

–166.7

–157.1

–159.8

–161.0

–113.0

–112.4

–114.5

–114.9

–126.7

–138.3

–135.1

–131.1

–187.5

–191.1

–180.5

–186.3

–183.2

–186.3

–189.4

–134.4

–133.5

–135.6

–140.4

–144.6

–155.3

–157.3

–148.8

6

7

Bn

4-MeC₆H₄

4-MeOC₆H₄

^cHex

8

9

Ph

10

11

12

13

14

15

4-MeC₆H₄

4-MeOC₆H₄

ⁿBu

4-MeC₆H₄

^cHex

Bn

Ph

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2.4.2. Stereostructure of the ring Pt-complexes

Stereostructures of the N-butyl and N-cyclohexyl P,P-tetrabenzyl ring Pt complexes (12b

and 12c, respectively), and that of the N-cyclohexyl P,P-tetratolyl derivative (13c) were

calculated by the B3LYP/6-31G(d,p) method. The optimized structures are shown in Fig. 1,

while selected bond lengths, bond angles and torsion angles were collected in Table S1

(Supplementary material). It can be seen clearly that the N-substituent may cause a steric

interaction with the two closer P-benzyl groups. The N-butyl complex (12b) strives to form a

mirror symmetry structure. This is logical, as the calculations represent isotropic environment

conditions, thus the ensuing models can hardly have different “left” or “right” side molecules.

However, the N-cyclohexyl derivative (12c) somewhat breaks this symmetry due to the

asymmetrical arrangement. The central six membered hetero ring exhibits a distorted chair

conformation in its lowest energy conformer. Noteworthy, that a significant structural

difference can be observed between 12c and 13c. The six-membered hetero ring with four

sterically demanding aryl groups on the two phosphorus atoms (13c) adopts a chair-like

conformation. At the same time, the P-benzyl species (12c) takes up a half-chair

conformation. The steric hindrance between the benzyl groups and the N substituent is

significant.

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Fig. 1. Computed lowest energy 3D structure of N,N-[bis(dibenzylphosphinomethyl)-

butylamine]dichloroplatinum(II)

cyclohexylamine]dichloroplatinum(II)

(12b),

(12c)

N,N-[bis(dibenzylphosphinomethyl)-

and N,N-[bis(ditolylphosphinomethyl)-

cyclohexylamine]dichloroplatinum(II) (13c)

2.5 An X-ray study

The X-ray study on the crystals of the similar six-membered Pt complexes 12b, 12c and

13c revealed that all these substances crystallized with the DMSO solvent as main

component, and also additionally with other trace or co-solvents as well. Most important is

that the structures give information on the geometry and shape of the central P-heterocyclic

ring (Figs. 2-4). Apart from the two C atoms and the two P atoms coordinating to the central

Pt atom, the N atom bearing a cyclohexyl or an n-butyl group also plays a role. The Pt serves

as a square-planar coordination center for the P atoms and the two Cl atoms. The central ring

is of a distorted half-chair like shape with the N atom sitting invariably on the flap. This

distortion may also depend on the varying solvent content of the crystals. The Pt-centred

three-atom P-Pt-P plane portion of the square-planar coordination lends certain rigidity to this

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shape. A study of similar cationic and zwitterionic X(CH₂P)₂Pt< six-membered heterocyclic

rings (where X = B, Si or C) revealed a variety of the ring shape, as well as possible pathways

for benzene C–H activation and ligand exchange processes [54]. Inspection of closely related

crystal structures reveals the similarity of the -N(CH₂P)₂Pt< six-membered heterocyclic rings

to each other [55-57], and also to those seen in Figs. 2–4 (12b, 12c and 13c). The earlier

described ring Pt complexes incorporate cyclohexyl-, phenyl- or trisubstituted phenyl

substituents on the P atom and methyl-, phenyl- or isophthalic acid groups on the N atom [55-

57]. The corresponding bidentate P-ligands were prepared by a different approach, and were

reacted with dichloro(1,5-cyclooctadiene)platinum(II).

Fig. 2. Atomic displacement plot of N,N-[bis(dibenzylphosphinomethyl)-butylamine]-

dichloroplatinum(II) (12b) DMSO 1:1 solvate with atomic numbering

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Fig. 3. Atomic displacement plot of N,N-[bis(dibenzylphosphinomethyl)-cyclohexylamine]-

dichloroplatinum(II) (12c) with atomic numbering

Fig. 4. Atomic displacement plot of N,N-[bis(ditolylphosphinomethyl)- cyclohexylamine]-

dichloroplatinum(II) (13c) with atomic numbering

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A more detailed analysis of the central ring shape components revealed that the immediate

coordination environment of the metal ion is such that the Pt cation is always offset to nearly

the same extent from the least-squares (LSQ) plane of its four ligating atoms (c.f.

Supplementary material, Table S2). It is also visible that the Pt cations are disposed on the

opposite side of this plane to the tertiary N atom, except structure 13c. The N atom in 12b and

in 12c appears to be almost equally, by 0.36-0.41 Å distant from the LSQ plane of the two Cl

and two P atoms, while in 13c, the N atom is on the same side as the Pt and much less distant.

Fig. S1 (Supplementary material) shows the difference between the conformations of these

more or less half-chair form heterocyclic rings. As the hetero ring shapes are similar in 12b

and 12c, only one of them is compared against the heterocyclic ring of 13c. The side view

shows that these heterocyclic rings have visibly different ring shapes.

As is apparent from Fig. S2 (Supplementary material), comparing the least-squares fit of

the six atoms of the hetero ring of the theoretical model of 12c with that of the experimental

one, both the central ring and the coordination around Pt, and even the spatial position of the

N-cyclohexyl substituent agree rather well. Even some benzyl side wings coincide quite close.

Comparison of the angular values in Table S1 and S3 (Supplementary material) shows

that bond angle values agree within the usual significance criteria. This also applies for the

torsion angles of 12b and 12c, indicating that both rings in both models agree well, and

represent closely the flattened half chair-like forms. This is not quite so for 13c, as the 6-

membered heterocycle, in this case, shows significant deviations of the theoretical vs. the

experimental model. The solid state structures are affected by various effects such as the

presence of solvent molecules, the neighbouring host molecules, and the appearance of

disordered atomic positions at different loci in the studied crystals. The saturated heterocyclic

rings may change their shape easily between the chair and half-chair forms, while the pendant

aromatic wings are also able to exert a certain extent of motility. It is also obvious that the

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appearance of the n-butyl group disorder in 12b, as well as the varying extents of solvent

disorders in the crystals of 12c and also 13c may bear some relevance to the interplay of the

global molecular shapes and their energetics.

A good agreement was observed for the shape of the metalla-heterocycles 12b and 12c

obtained by theoretical calculations and single crystal X-ray analysis. However, for species

13c, the conformation obtained by the two methods mentioned were significantly different.

This may be the consequence of the different phases of the samples investigated. The data

listed in Table S1 (Supplementary material) are related to molecules in the gas phase, while

those shown in Table S3 (Supplementary material), came not only simply from solid phase

experiments, but even from crystals of associated host and solvent molecules.

2.6. Hydroformylation of styrene in the presence of the synthesized Pt(II)-complexes (12b-d,

13b-d)

The ‘pre-formed’ PtCl₂L₂-type complexes 12b-d and 13b-d containing ligands 10b-d and

11b-d, respectively, were tested as catalyst precursors in the hydroformylation of styrene. The

catalysts formed in situ from 12b-d or 13b-d and tin(II)chloride were used at 80 bar [syngas;

p(CO) = p(H₂) = 40 bar]. In addition to the branched and linear formyl regioisomers

(2-arylpropanal (A) and 3-arylpropanal (B), respectively), ethylbenzene (C) as hydrogenation

by-product was also formed (Scheme 8). The results are show in Table 3 and Table S4

(Supplementary material).

CO/H₂

PhCH CH₂

PhCH(CHO)CH₃+ PhCH₂CH₂CHO + PhCH₂CH₃

A

B

C

Scheme 8.

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In order to achieve catalytic systems of good performance, tin(II)chloride has to be used in

twofold excess. The addition of only one equivalent of tin(II)chloride resulted in a catalyst of

negligible activity both at 40 °C and 100 °C reaction temperature. The key lies in

N-coordination to tin, i.e., the tertiary nitrogen is coordinated to tin(II)chloride, and therefore,

no formation of trichlorostannato ligand, resulting in catalytically active Pt(ligand)Cl(SnCl₃)

complex, can be observed in the presence of one equivalent of tin(II)chloride only (Table

3/Entries 3,4; 5,6). The deleterious effect of a tertiary nitrogen, embedded either in the ligand

or used as an amine additive in the catalytic system, has been reported [58,59]. The ‘second’

equivalent of tin(II)chloride is inserted into Pt-Cl bond forming the Pt-SnCl₃moiety which

can be considered as a precondition of the catalytic activity. It is worth noting that using a

higher Sn to Pt ratio (e.g. 5/1), the catalytic activity could not be increased, or in some cases

even lower conversions were obtained (Table 3/Entries 6, 7 or 15, 18).

The two types of complexes, i.e., the bis(dibenzylphosphino) derivatives (12b-d) with the

more basic phosphorus(III) donor atoms and the less basic bis(di(p-tolylphosphino)

derivatives (13b-d) differ substantially in catalytic activity. The basic bis(trialkylphosphine)-

type ligands (12b-12d) form complexes of lower activity (compare for instance Table

3/Entries 6 and 15, as well as 9 and 20).

The formation of the aldehydes (A and B) was preferred in all cases. Higher

chemoselectivities (up to 88%) were obtained at lower temperature. Typically,

chemoselectivities fall in the range of 70-80% at 100 °C. For instance, the use of complex 13c

as a catalyst precursor resulted in 88% and 73-76% chemoselectivities at 40 °C and 100 °C,

respectively (Table 3/Entries 14 and 15-17).

The temperature has a pronounced effect also on regioselectivity. The formation of

branched aldehyde (A) predominated in all cases, however, much higher regioselectivities

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towards isomer A were obtained at 40 °C (typically about 80%, Table 3/Entries 1, 4, 8, 14)

than at 100 °C (typically about 60%, see for instance Table 3/Entries 15–17 or 20, 21).

Table 3

The hydroformylation of styrene in the presence of catalysts formed in situ from precursors

12b-d or 13b-d and tin(II) chloride.^a

Entry Complex Temp. (°C)

Pt/Sn

R. time (h) Conv. (%)

R_c^b(%)

R_br^c(%)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

40

100

40

1:2

1:1

1:2

1:1

1:2

1:5

1:2

1:5

1:2

24

3

24

3

24

3

24

3

6

8

24

3

6

73

72

n.d.

82

n.d.

74

79

81

70

87

75

72

75

88

73

74

76

88

87

74

79

82

65

n.d.

76

n.d.

61

62

79

65

75

64

63

78

62

63

65

76

61

56

12b

12c

12d

13b

13c

13d

32

<1

18

1

40

100

40

100

40

100

40

100

40

50

46

21

52

31

42

85

98

13

55

98

47

22

72

79

98

3

24

72

2

40

100

3

A: 2-phenylpropanal, B: 3-phenylpropanal, C: ethylbenzene.

^aReaction conditions: Pt/styrene = 1/200, p(CO) = p(H₂) = 40 bar, 1 mmol of styrene, solvent:

5 mL of toluene. (n.d.= not determined)

b

Chemoselectivity towards aldehydes (A, B). [(moles of A + moles of B)/(moles of A +

moles of B + moles of C) × 100].

^cRegioselectivity towards branched aldehyde (A). [moles of A/(moles of A + moles of B) ×

100].

In

summary,

eleven

new

α-aminophosphine oxides

and

eight

new

N,N-bis(phosphinoylmethyl)amines were synthesized by the Kabachnik-Fields reaction. The

latter species were utilized in the preparation of ring platinum complexes after double

ACCEPTED MANUSCRIPT

deoxygenation. The dependence of the enthalpy gain of the complexation of the bidentate P-

ligands on the nature of the N-substituents, and the structure of the Pt complexes was

calculated using B3LYP/6-31G(d,p) for CHNP and B3LYP/SDD(MWB60) for Pt including

effective core potential (ECP). Besides this, the crystal structures of three Pt complexes were

solved by X-ray investigation. The complexes were tested as novel catalyst in the

hydroformylation of styrene.

Experimental

General (instruments)

1

The ³¹P, ¹³C, H NMR spectra were taken in CDCl₃solution on a Bruker AV-300 or

DRX-500 spectrometer operating at 121.5, 75.5 and 300 or 202.4, 125.7 and 500 MHz,

respectively. Chemical shifts are downfield relative to 85% H₃PO₄and TMS. The couplings

are given in Hz. Mass spectrometric measurements were performed using a Q-TOF Premier

mass spectrometer in positive electrospray mode and a Shimadzu LCMS-ITTOF mass

spectrometer. The reactions were carried out in a 300 W CEM Discover focused microwave

reactor equipped with a pressure controller applying 20–80 W under isothermal conditions.

General procedure for the preparation of dibenzyl- and di(p-tolyl)phosphine oxides

The Grignard reagent formed from 0.97 g (40.0 mmol) of magnesium and 40 mmol of

alkyl or aryl halide (benzyl bromide: 4.8 mL, 4-bromotoluene: 6.8 g) in 50 mL of diethyl

ether was added dropwise to 1.7 mL (13.0 mmol) of diethyl phosphite in 10 mL of diethyl

ether at 0 °C. The resulting mixture was stirred at 25 °C for 1.5 hours. Then, the mixture was

hydrolyzed with 10 mL of water and 50 mL of 10% HCl solution, and the aqueous phase was

extracted with 2x60 mL of diethyl ether. The combined organic phases were dried (Na₂SO₄).

Evaporation of the solvent left a residue that was purified by column chromatography using

ACCEPTED MANUSCRIPT

silica gel, 1% methanol in dichloromethane as the eluent to give products 1 and 2 as white

crystals.

Dibenzylphosphine oxide (1)

Yield: 84%; white crystals; mp.: 109–110 °C, mp. [45]: 106–107 °C; ³¹P NMR (CDCl₃) δ_P

(CDCl₃) 36.2, δ_P(CDCl₃) [45] 35.5; [M+H]⁺_found= 231.0937, C₁₄H₁₆OP requires 231.0933.

Di(p-tolyl)phosphine oxide (2)

Yield: 86%; white crystals; mp.: 98–99 °C, mp. [46]: 95–96 °C; ³¹P NMR (CDCl₃) δ_P

(CDCl₃) 20.7, δ_P(CDCl₃) [46] 21.2; [M+H]⁺_found= 231.0920, C₁₄H₁₆OP requires 231.0933.

General procedure for the synthesis of (aminomethyl)dibenzyl- or di(p-tolyl)phosphine oxides

A mixture of 0.85 mmol amine (n-propylamine: 0.07 mL, n-butylamine: 0.08 mL,

cyclohexylamine: 0.10 mL, benzylamine: 0.09 mL, 4-methoxybenzylamine: 0.11 mL, aniline:

0.08 mL or 4-methoxyaniline: 0.11 g), 0.026 g (0.85 mmol) of paraformaldehyde, and

0.85 mmol of the secondary phosphine oxide (dibenzylphosphine oxide: 0.20 g or

di(p-tolyl)phosphine oxide: 0.20 g) and 1.5 mL of acetonitrile was heated at 100 °C in a

closed vial in a CEM Discover Microwave reactor equipped with a pressure controller for 1 h.

The acetonitrile and the water formed were removed in vacuum. The crude product so

obtained was passed through a 1 cm silica gel layer using ethyl acetate. After evaporation of

the solvent, the products (3a-g, 4b-d and 4f) were obtained as crystals. The following

products were thus prepared:

ACCEPTED MANUSCRIPT

(Propylaminomethyl)dibenzylphosphine oxide (3a)

31

Yield: 96% (0.25 g) of compound 3a as white crystals. Mp: 80-82 °C; P NMR (CDCl₃)

δ 44.0; ¹³C NMR (CDCl₃) δ 11.6 (CH₃), 22.9 (CH₃CH₂), 34.3 (d, ¹J_CP= 60.0, P(O)CH₂), 45.2

1

3

(d, J_CP= 79.2, NHCH₂P), 53.7 (d, J_CP= 14.4, CH₃CH₂CH₂NH), 126.9 (d, J_CP= 2.8, C₄),

128.8 (d, J_CP= 2.4, C₃), 129.7 (d, ³J_CP= 5.1, C₂), 131.9 (d, ²J_CP= 7.0, C₁); ¹H NMR (CDCl₃)

δ 0.90 (t, J_HH= 7.4, 3H, CH₃), 1.41–1.50 (m, 2H, CH₃CH₂), 1.65 (s, 1H, NH), 2.54 (t, J_HH

=

1

7.1, 2H, CH₃CH₂CH₂NH), 2.73 (d, J_PH= 7.8, 2H, NHCH₂P), 3.10–3.25 (m, 4H, P(O)CH₂),

7.23–7.35 (m, 10H, ArH); [M+H]⁺_found= 302.1676, C₁₈H₂₅NOP requires 302.1668.

(Butylaminomethyl)dibenzylphosphine oxide (3b)

Yield: 97% (0.26 g) of compound 3b as slightly yellow crystals. Mp: 75–76 °C; ³¹P NMR

13

(CDCl₃) δ 44.6; C NMR (CDCl₃) δ 13.7 (CH₃), 20.0 (CH₃CH₂), 31.6 (CH₃CH₂CH₂), 34.1

1

3

(d, J_CP= 60.0, P(O)CH₂), 45.0 (d, J_CP= 79.1, NHCH₂P), 51.3 (d, J_CP= 14.3,

CH₃(CH₂)₂CH₂NH), 126.7 (d, J_CP= 2.8, C₄), 128.5 (d, J_CP= 2.4, C₃), 129.5 (d, ³J_CP= 5.1, C₂),

131.7 (d, ²J_CP= 7.1, C₁); ¹H NMR (CDCl₃) δ 0.90 (t, J_HH= 7.2, 3H, CH₃), 1.25–1.48 (m, 4H,

1

CH₃CH₂CH₂), 1.47 (s, 1H, NH), 2.56 (t, J_HH= 6.6, 2H, CH₃(CH₂)₂CH₂NH), 2.74 (d, J_PH

=

7.7, 2H, NHCH₂P), 3.07–3.28 (m, 4H, P(O)CH₂), 7.23–7.36 (m, 10H, ArH); [M+H]⁺

found

316.1832, C₁₉H₂₇NOP requires 316.1825.

(Cyclohexylaminomethyl)dibenzylphosphine oxide (3c)

Yield: 95% (0.28 g) of compound 3c as white crystals. Mp: 125–126 °C; ³¹P NMR

1

(CDCl₃) δ 44.4; ¹³C NMR (CDCl₃) δ 24.8 (C₃), 26.0 (C₄), 33.2 (C₂), 34.3 (d, J_CP= 60.1,

P(O)CH₂), 42.5 (d, ¹J_CP= 79.5, NHCH₂P), 58.5 (d, ³J_CP= 13.7, C₁), 126.9 (d, J_CP= 2.9, C_4’),

128.8 (d, J_CP= 2.4, C_3’), 129.7 (d, ³J_CP= 5.1, C_2’), 132.0 (d, ²J_CP= 7.0, C_1’); ¹H NMR (CDCl₃)

δ 0.95–1.10 (m, 2H, C₂H_ax.), 1.11–1.29 (m, 3H, C₄H_ax.,C₃H_ax.), 1.53–1.63 (m, 2H, C₂H_eq.),

ACCEPTED MANUSCRIPT

1.64–1.75 (m, 3H, C₄H_eq., C₃H_eq.), 1.81 (s, 1H, NH), 2.22–2.34 (m, 1H, C₁H), 2.75 (d, ¹J_HP

=

1

8.3, 2H, NHCH₂P), 3.17 (pt, J_HP=14.8, 4H, P(O)CH₂), 7.22–7.36 (m, 10H, ArH);

[M+H]⁺_found= 342.1989, C₂₁H₂₉NOP requires 342.1981.

(Benzylaminomethyl)dibenzylphosphine oxide (3d)

Yield: 98% (0.29 g) of compound 3d as white crystals. Mp: 119–121 °C; ³¹P NMR

1

(CDCl₃) δ 43.8; ¹³C NMR (CDCl₃) δ 34.3 (d, J_CP= 60.2, P(O)CH₂), 44.4 (d, J_CP= 78.9,

NHCH₂P), 55.5 (d, ³J_CP= 15.2, CH₂NH), 126.9 (d, J_CP= 2.8, C_4’), 127.3 (C₄), 128.4 (d, J_CP

=

3

2

2.5, C_3’), 128.79 (C₃)*, 128.82 (C₂)*, 129.7 (d, J_CP= 5.1, C_2’), 131.8 (d, J_CP= 7.1, C_1’),

1

139.2 (C₁), *may be reversed; H NMR (CDCl₃) δ 1.82 (s, 1H, NH), 2.74 (d, ¹J_HP=7.8, 2H,

1

NHCH₂P), 3.15 (pt, J_HP=14.7, 4H, P(O)CH₂), 3.75 (s, 2H, CH₂NH), 7.19–7.32 (m, 15H,

ArH); [M+H]⁺_found= 350.1677, C₂₂H₂₅NOP requires 350.1668.

(4-Methoxybenzylaminomethyl)dibenzylphosphine oxide (3e)

Yield: 95% (0.31 g) of compound 3e as white crystals. Mp: 103–105; ³¹P NMR (CDCl₃) δ

13

1

43.9; C NMR (CDCl₃) δ 34.3 (d, J_CP= 60.2, P(O)CH₂), 44.2 (d, J_CP= 79.1, NHCH₂P),

54.9 (d, ³J_CP= 15.4, CH₂NH), 55.3 (OCH₃), 113.8 (C₂), 126.9 (d, J_CP= 2.8, C_4’), 128.8 (d, J_CP

3

2

= 2.3, C_3’), 129.6 (d, J_CP= 4.6, C_2’), 129.7 (C₃), 131.3 (C₁), 131.8 (d, J_CP= 7.0, C_1’), 158.9

(C₄); ¹H NMR (CDCl₃) δ 1.73 (s, 1H, NH), 2.72 (d, ¹J_HP= 7.8, 2H, NHCH₂P), 3.14 (pt, ¹J_HP

=

14.4, 4H, P(O)CH₂), 3.69 (s, 2H, CH₂NH), 3.81 (s, 3H, OCH₃), 6.86 (d, J_HH=8.4, 2H, C₃H),

7.17–7.32 (m, 12H, ArH); [M+H]⁺_found= 380,1782, C₂₃H₂₇NO₂P requires 380,1774.

(Phenylaminomethyl)dibenzylphosphine oxide (3f)

Yield: 94% (0.27 g) of compound 3f as white crystals. Mp: 159–161 °C; Mp[30]: 158-

31

13

1

159; P NMR (CDCl₃) δ 42.9; C NMR (CDCl₃) δ 34.7 (d, J_CP= 60.4, P(O)CH₂), 39.9 (d,

ACCEPTED MANUSCRIPT

¹J_CP= 75.1, NHCH₂P), 113.5 (C₂), 118.8 (C₄), 127.2 (d, J_CP= 2.9, C_4’), 129.0 (d, J_CP= 2.4,

C_3’), 129.3 (C₃), 129.7 (d, ³J_CP= 5.2, C_2’), 131.3 (d, ²J_CP= 7.1, C_1’), 147.6 (d, ³J_CP= 10.6, C₁);

¹H NMR (CDCl₃) δ 2.17 (s, 1H, NH), 3.33–3.14 (m, 6H, CH₂), 6.57 (d, J_HH= 7.8, 2H, C₂H),

6.78 (t, J_HH= 7.0, 1H, C₄H), 7.18 (t, J_HH= 8.0, 2H, C₃H), 7.23–7.38 (m, 10H, ArH);

[M+H]⁺_found= 336.1516, C₂₁H₂₃NOP requires 336.1512.

(4-Methoxyanilinomethyl)dibenzylphosphine oxide (3g)

Yield: 95% (0.29 g) of compound 3g as slightly yellow crystals. Mp: 141–143 °C; ³¹P

13

1

NMR (CDCl₃) δ 43.0; C NMR (CDCl₃) δ 34.6 (d, J_CP= 60.4, P(O)CH₂), 40.9 (d, J_CP

=

75.7, NHCH₂P), 55.7 (OCH₃), 114.8 (C₂)*, 114.9 (C₃)*, 127.2 (d, J_CP= 2.9, C_4’), 129.0 (d,

3

2

3

J_CP= 2.4, C_3’), 129.7 (d, J_CP= 5.2, C_2’), 131.4 (d, J_CP=7.1, C_1’), 141.7 (d, J_CP= 11.4, C₁),

153.0 (C₄), *may be reversed; ¹H NMR (CDCl₃) δ 2.00 (s, 1H, NH), 3.13–3.33 (m, 6H, CH₂),

3.75 (s, 3H, OCH₃), 6.54 (d, 2H, J_HH= 8.7, C₂H)*, 6.78 (d, 2H, J_HH= 8.8, C₃H)*, 7.22–7.38

(m, 10H, ArH), *may be reversed; [M+H]⁺_found= 366,1615, C₂₂H₂₅NO₂P requires 366,1617.

(Butylaminomethyl)di(p-tolyl)phosphine oxide (4b)

Yield: 96% (0.26g) of compound 4b as slightly yellow oil. ³¹P NMR (CDCl₃) δ 29.7;

13

δ[32] (C₆D₆) 42.0; C NMR (CDCl₃) δ 13.9 (CH₃CH₂), 20.2 (CH₃CH₂), 21.5 (C₄CH₃) 31.7

1

3

(CH₃CH₂CH₂), 49.5 (d, J_CP= 80.5, P(O)CH₂), 51.4 (d, J_CP= 13.4, CH₃(CH₂)₂CH₂NH),

128.9 (d, ¹J_CP= 99.9, C₁), 129.3 (d, ²J_CP= 12.0, C₂), 131.1 (d, ³J_CP= 9.5, C₃), 142.2 (d, J_CP

=

1

2.7, C₄); H NMR (CDCl₃) δ 0.87 (t, J_HH= 7.2, 3H, CH₃CH₂), 1.22–1.35 (m, 2H,

CH₃CH₂CH₂), 1.37–1.49 (m, 2H, CH₃CH₂CH₂), 1.45 (s, 1H, NH), 2.40 (s, 6H, C₄CH₃), 2.67

(t, J_HH= 7.0, 2H, CH₃(CH₂)₂CH₂NH), 3.43 (d, ¹J_HP= 8.0, 2H, NHCH₂P), 7.27 (d, ³J_HP= 5.6,

2

4H, C₃H), 7.68 (dd, J_HP= 11.1, J_HP= 8.1, 4H, C₂H); [M+H]⁺

= 316.1828, C₁₉H₂₇NOP

found

requires 316.1825.

ACCEPTED MANUSCRIPT

(Cyclohexylaminomethyl)di(p-tolyl)phosphine oxide (4c)

Yield: 98% (0.28 g) of compound 4c as slightly yellow oil. ³¹P NMR (CDCl₃) δ 29.6; ¹³C

1

NMR (CDCl₃) δ 21.5 (CH₃), 22.5 (C₃), 26.7 (C₄), 31.6 (C₂), 49.5 (d, J_CP= 80.5, P(O)CH₂),

51.7 (d, ³J_CP= 13.3, C₁), 128.9 (d, ¹J_CP= 99.9, C_1’), 129.2 (d, ²J_CP= 12.0, C_2’), 131.1 (d, ³J_CP

1

= 9.6, C_3’), 142.2 (d, J_CP= 2.7, C_4’); H NMR (CDCl₃) δ 0.83–0.89 (m, 3H, C₄H_ax.,C₃H_ax.),

1.19–1.30 (m, 5H, C₂H_ax., C₄H_eq., C₃H_eq), 1.37–1.49 (m, 2H, C₂H_eq.), 1.75 (s, 1H, NH), 2.39

(s, 6H, CH₃), 2.66 (t, ³J_HP= 7.1, 1H, C₁H), 3.43 (d, ¹J_HP= 7.8, 2H, NHCH₂P), 7.22–7.31 (m,

2

14H, C_3’), 7.67 (d, J_HP= 11.1, J_HP= 8.1, 4H, C₂H); [M+H]⁺

= 342.1987, C₂₁H₂₉NOP

found

requires 342.1981.

(Benzylaminomethyl)di(p-tolyl)phosphine oxide (4d)

Yield: 95% (0.28 g) of compound 4d as slightly yellow crystals. Mp: 115–117 °C; ³¹P

13

1

NMR (CDCl₃) δ 29.9; C NMR (CDCl₃) δ 21.5 (C₄CH₃), 48.3 (d, J_CP= 81.2, P(O)CH₂),

55.1 (d, ¹J_CP= 14.3, CH₂NHCH₂P), 127.1 (C₄), 128.2 (C₂), 128.3 (C₃), 128.8 (d, ¹J_CP= 100.4,

C_1’), 129.3 (d, ²J_CP= 12.0, C_2’), 131.1 (d, ³J_CP= 9.6, C_3’), 139.2 (C₁), 142.3 (d, J_CP= 2.8, C_4’);

¹H NMR (CDCl₃) δ 2.00 (s, 1H, NH), 2.40 (s, 6H, CH₃), 3.39 (d, ¹J_HP=8.0, 2H, NHCH₂P),

2

3.87 (s, 2H, CH₂NH), 7.22–7.34 (m, 9H, ArH, C₃H), 7.65 (dd, J_HP= 11.1, J_HP= 8.1, 4H,

C₂H); [M+H]⁺_found= 350.1669, C₂₂H₂₅NOP requires 350.1668.

(Phenylaminomethyl)di(p-tolyl)phosphine oxide (4f)

Yield: 94% (0.27 g) of compound 3f as yellow crystals. Mp: 139–141 °C; ³¹P NMR

(CDCl₃) δ 30.1; ¹³C NMR (CDCl₃) δ 21.6 (CH₃), 43.9 (d, ¹J_CP= 78.8, P(O)CH₂), 113.4 (C₂),

118.5 (C₄), 127.9 (d, ¹J_CP= 102.8, C_1’), 129.2 (C₃) 129.5 (d, ²J_CP= 12.3, C_2’), 131.1 (d, ³J_CP

9.9, C_3’), 142.9 (d, J_CP= 2.8, C_4’), 147.7 (d, ³J_CP= 11.2, C₁); ¹H NMR (CDCl₃) δ 2.39 (s, 6H,

=

ACCEPTED MANUSCRIPT

CH₃), 3.88 (d, J_PH= 9.0, 2H, P(O)CH₂), 3.99 (s, 1H, NH), 6.65 (d, J_HH= 8.3, 2H, C₂H), 6.74

(t, J_HH= 7.1, 1H, C₄H), 7.16 (t, J_HH= 7.7, 2H, C₃H), 7.24–7.31 (m, 4H, C_3’H), 7.66 (dd, ²J_HP

= 11.4, J_HP= 8.0, 4H, C_2’H); [M+H]⁺_found= 336.1507, C₂₁H₂₃NOP requires 336.1512.

General procedure for the synthesis of N,N-bis(dibenzyl- or di-p-tolylphosphinoylmethyl)amines

A mixture of 0.85 mmol amine (n-propylamine: 0.07 mL, n-butylamine: 0.08 mL,

cyclohexylamine: 0.10 mL, benzylamine: 0.09 mL, 4-methoxybenzylamine: 0.11 mL, aniline:

0.08 mL or 4-methoxyaniline: 0.11 g), 0.05 g (1.7 mmol) of paraformaldehyde, and 1.7 mmol

of the secondary phosphine oxide (dibenzylphosphine oxide: 0.40 g or di(p-tolyl)phosphine

oxide: 0.40 g) and 2.5 mL of acetonitrile was heated at 100 °C in a closed vial in a CEM

Discover Microwave reactor equipped with a pressure controller for 1 h. The acetonitrile and

the water formed were removed in vacuum. The crude products were passed through a 1 cm

silica gel layer using ethyl acetate. After evaporation of the solvent, the products (5a-e and

6b-d) were obtained as crystals. The following products were thus prepared:

N,N-Bis(dibenzylphosphinoylmethyl)propylamine (5a)

Yield: 95% (0.44 g) of compound 5a as white crystals. Mp: 183–185 °C; ³¹P NMR

1

(CDCl₃) δ 40.4; ¹³C NMR (CDCl₃) δ 11.6 (CH₃), 19.8 (CH₃CH₂), 35.5 (d, J_CP= 60.0,

1

3

P(O)CH₂), 53.5 (dd, J_CP= 87.9, J_CP= 7.9, NCH₂P), 60.6 (d, J_CP= 6.1, CH₃CH₂CH₂N),

126.8 (d, J_CP= 2.6, C₄), 128.7 (d, J_CP= 2.0, C₃), 129.8 (d, ³J_CP= 5.3, C₂), 131.8 (d, ²J_CP= 7.3,

1

C₁); H NMR (CDCl₃) δ 0.89 (t, J_HH= 7.2, 3H, CH₃), 1.28–1.44 (m, 2H, CH₃CH₂), 2.73 (t,

1

J_HH=7.2, 2H, CH₃CH₂CH₂), 2.94 (d, J_HP= 7.4, 4H, NCH₂P), 3.02–3.30 (m, 8H, P(O)CH₂),

7.18–7.39 (m, 20H, ArH); [M+H]⁺_found= 544.2523, C₃₃H₄₀NO₂P₂requires 544.2529.

ACCEPTED MANUSCRIPT

N,N-Bis(dibenzylphosphinoylmethyl)butylamine (5b)

Yield: 96% (0.45 g) of compound 5b as white crystals. Mp: 174–176 °C; ³¹P NMR

(CDCl₃) δ 40.5; ¹³C NMR (CDCl₃) δ 14.0 (CH₃CH₂), 20.2 (CH₃CH₂), 28.9 (CH₃CH₂CH₂),

35.5 (d, ¹J_CP= 60.1, P(O)CH₂), 53.4 (dd, ¹J_CP= 87.9, ³J_CP= 7.1, NCH₂P), 58.5 (d, ³J_CP= 6.1,

CH₃(CH₂)₂CH₂N), 126.8 (d, J_CP= 2.5, C₄), 128.7 (d, J_CP= 1.8, C₃), 129.8 (d, ³J_CP= 5.2, C₂),

131.8 (d, ²J_CP= 7.3, C₁); ¹H NMR (CDCl₃) δ 0.88 (t, J_HH= 6.0, 3H, CH₃), 1.21–1.32 (m, 4H,

CH₃CH₂), 2.73 (t, J_HH=7.1, 2H, CH₃CH₂CH₂N), 2.91 (d, ¹J_HP= 4.4, 4H, NCH₂P), 3.02–3.27

(m, 8H, P(O)CH₂), 7.19–7.33 (m, 20H, ArH); [M+H]⁺_found= 558.2701, C₃₇H₃₉NO₂P₂requires

558.2691.

N,N-Bis(dibenzylphosphinoylmethyl)cyclohexylamine (5c)

Yield: 95% (0.47 g) of compound 5c as white crystals. Mp: 205–207 °C; ³¹P NMR

1

(CDCl₃) δ 40.3; ¹³C NMR (CDCl₃) δ 25.6 (C₃), 26.1 (C₄), 28.2 (C₂), 35.4 (d, J_CP= 60.3,

P(O)CH₂), 50.1 (dd, ¹J_CP= 91.0, ³J_CP= 7.6, NCH₂P), 61.9 (t, ³J_CP= 10.7, C₁), 126.7 (d, J_CP

=

3

2

1

2.5, C_4’), 128.6 (d, J_CP= 2.1, C_3’), 129.8 (d, J_CP= 5.2, C_2’), 132.0 (d, J_CP= 7.3, C_1’); H

NMR (CDCl₃) δ 0.84–1.33 (m, 5H, C₂H_ax., C₄H_ax.,C₃H_ax.), 1.55–1.77 (m, 5H, C₂H_eq., C₄H_eq.,

1

C₃H_eq.), 2.92 (d, J_HP= 4.7, 4H, NCH₂P), 2.99–3.32 (m, 9H, C₁H, P(O)CH₂), 7.19–7.33 (m,

20H, ArH); [M+H]⁺_found= 584.2835, C₃₆H₄₄NO₂P₂requires 584.2842.

N,N-Bis(dibenzylphosphinoylmethyl)benzylamine (5d)

Yield: 97% (0.49 g) of compound 5d as slightly yellow crystals. Mp: 175–177 °C; ³¹P

13

1

NMR (CDCl₃) δ 40.4; C NMR (CDCl₃) δ 35.3 (d, J_CP= 60.4, P(O)CH₂), 52.5 (dd, J_CP

=

3

87.5, J_CP= 6.9, NCH₂P), 63.6 (t, J_CP= 6.3, CH₂N), 126.7 (d, J_CP= 2.6, C_4’), 127.6 (C₄),

128.4 (C₃), 128.6 (d, J_CP= 2.1, C_3’), 129.7 (d, ³J_CP= 5.1, C_2’), 130.1 (C₂), 131.7 (d, ²J_CP= 7.3,

1

C_1’), 137.5 (C₁); H NMR (CDCl₃) δ 2.92 (d, 4H, ¹J_HP= 4.5, NCH₂P), 3.05 (pt, 8H, J_HP

=

ACCEPTED MANUSCRIPT

14,8, P(O)CH₂), 3.88 (s, 2H, CH₂N), 7.08–7.15 (m, 5H, ArH), 7.18–7.34 (m, 20H, Ar’H);

[M+H]⁺_found= 592.2535, C₃₇H₄₀NO₂P₂requires 592.2529.

N,N-Bis(dibenzylphosphinoylmethyl)-4-methoxybenzylamine (5e)

Yield: 94% (0.50 g) of compound 5e as white crystals. Mp: 128–130 °C; ³¹P NMR

13

1

(CDCl₃) δ 40.5; C NMR (CDCl₃) δ 35.4 (d, J_CP= 60.3, P(O)CH₂), 52.3 (dd, J_CP= 88.0,

³J_CP= 7.5, NCH₂P), 55.2 (OCH₃), 62.3 (t, ³J_CP= 6.7, CH₂N), 113.8 (C₃), 126.7 (d, J_CP= 2.4,

C_4’), 128.6 (d, J_CP= 1.9, C_3’), 129.6 (C₁), 129.8 (d, ³J_CP= 5.2, C_2’), 131.3 (C₂), 131.8 (d, ³J_CP

= 7.3, C_1’), 159.1 (C₄); ¹H NMR (CDCl₃) δ 2.91 (d, 4H, ¹J_HP=3.8, NCH₂P), 3.06 (pt, 8H, ¹J_HP

=14.0, P(O)CH₂), 3.80 (s, 2H, CH₂N), 3.81 (s, 3H, OCH₃), 6.82 (d, J_HH=8.1, 2H, C₃H), 7.09–

7.29 (m, 22H, ArH); [M+H]⁺_found= 622.2648, C₃₈H₄₂NO₃P₂requires 622.2640.

N,N-Bis(di-p-tolylphosphinoylmethyl)butylamine (6b)

Yield: 98% (0.46 g) of compound 6b as slightly yellow oil. ³¹P NMR (CDCl₃) δ 29.5; ¹³C

NMR (CDCl₃) δ 13.9 (CH₃CH₂), 19.9 (CH₃CH₂), 21.4 (C₄CH₃), 28.5 (CH₃CH₂CH₂), 55.9

1

3

2

(dd, J_CP= 85.1, J_CP= 7.7, NCH₂P), 58.3 (t, J_CP= 6.9, CH₃(CH₂)₂CH₂N), 128.9 (d, J_CP

=

1

3

1

11.8, C₂), 129.2 (d, J_CP= 99.9, C₁), 131.1 (d, J_CP= 9.5, C₃), 141.7 (d, J_CP= 2.8, C₄); H

NMR (CDCl₃) δ 0.73 (t, J_HH= 7.2, 3H, CH₃CH₂), 0.95–1.09 (m, 2H, CH₃CH₂), 1.16–1.29 (m,

2H, CH₃CH₂CH₂), 2.32 (s, 12H, C₄CH₃), 2.93 (t, ³J_HH=7.1, 2H, CH₃CH₂CH₂CH₂N), 3.62 (d,

3

2

¹J_HP= 5.5, 4H, NCH₂P), 7.12 (d, J_HP= 7.8, 8H, C₃H), 7.59 (dd, J_HP= 11.0, J_HP= 8.1, 8H,

C₂H); [M+H]⁺_found= 558.2680, C₃₄H₄₂NO₂P₂requires 558.2685.

N,N-Bis(di-p-tolylphosphinoylmethyl)cyclohexylamine (6c)

Yield: 95% (0.47 g) of compound 6c as slightly yellow oil. ³¹P NMR (CDCl₃) δ 30.2; ¹³C

NMR (CDCl₃) δ 21.5 (CH₃), 24.6 (C₃), 25.6 (C₄), 27.7 (C₂), 51.8 (dd, ¹J_CP= 87.2, ³J_CP= 8.0,

ACCEPTED MANUSCRIPT

3

2

NCH₂P), 61.7 (t, J_CP= 5.9, C₁), 128.9 (d, J_CP= 12.0, C_2’), 129.1 (d, J_CP= 99.9, C_1’), 131.2

3

1

(d, J_CP= 9.4, C_2’), 141.6 (d, J_CP= 2.8, C_4’); H NMR (CDCl₃) δ 0.88–1.07 (m, 3H,

C₄H_ax.,C₃H_ax.), 1.20–1.35 (m, 3H, C₂H_ax.), 1.58–1.77 (m, 5H, C₂H_eq., C₄H_eq., C₃H_eq.), 2.34 (s,

12H CH₃), 3.42 (t, ³J_HP= 11.5, 1H, C₁H), 3.69 (d, ¹J_HP= 6.5, 4H, NCH₂P), 7.14 (d, ³J_HP= 6.2,

8H, C_3’H), 7.62 (dd, ²J_HP= 10.8, J_HP= 8.1, 8H, C_2’H); [M+H]⁺_found= 584.2836, C₃₆H₄₄NO₂P₂

requires 584.2842.

N,N-Bis(di-p-tolylphosphinoylmethyl)benzylamine (6d)

Yield: 94% (0.47 g) of compound 6d as slightly yellow oil. ³¹P NMR (CDCl₃) δ 30.2; ¹³C

1

3

NMR (CDCl₃) δ 21.5 (CH₃), 55.1 (dd, J_CP= 85.0, J_CP= 7.7, NCH₂P), 63.1 (t, J_CP= 7.5,

1

2

CH₂N), 127.1 (C₄), 127.9 (C₂), 128.9 (d, J_CP= 100.7, C_1’), 129.0 (d, J_CP= 12.1, C_2’), 129.8

(C₃), 131.1 (d, ³J_CP= 9.5, C_3’), 137.7 (C₁), 141.7 (d, J_CP= 2.8, C_4’); ¹H NMR (CDCl₃) δ 2.35

(s, 12H, CH₃), 3.67 (d, 4H, ¹J_HP= 6.2, NCH₂P), 4.08 (s, 2H, CH₂N), 6.88 (d, 2H, J_HH= 7.0,

2

C₂H), 7.07–7.28 (m, 11H, C_3’H, C₃H, C₄H), 7.50 (dd, J_HP= 11.0, J_HP= 8.1, 8H, C_2’H);

[M+H]⁺_found= 592.2522, C₃₇H₄₀NO₂P₂requires 592.2529.

General procedure for the synthesis of ring platinum complexes

To 0.20 mmol of the bis(>P(O)CH₂)amine 5 or 6 (5b or 6b: 0.11 g, 5c or 6c: 0.11 g or 5d

or 6d: 0.12 g) was added 0.15 mL (1.20 mmol) of phenylsilane under nitrogen. The mixture

was stirred at 120 °C in a vial in a CEM Discover Microwave reactor equipped with a

pressure controller for 2.5 h. Then the mixture was diluted by the addition of 1 mL of

degassed benzene. To the solution of phosphine 10b-d or 11b-d so obtained was added 0.10 g

(0.21 mmol) of dichlorodibenzonitrile platinum and the mixture stirred at 25 °C for overnight.

The solid crystallized from the mixture was separated by filtration to afford complex 12b-d or

13b-d after washing with pentane–acetone (8:2) and drying.

ACCEPTED MANUSCRIPT

[Bis(dibenzylphosphinomethyl)butylamine-dichloroplatinum(II) (12b)

Yield: 75% (0.12 g) of compound 12b as white powder. ³¹P NMR (d-DMSO) δ –4.6 (¹J_P-Pt

13

1

= 3400); C NMR (CDCl₃) δ 13.7 (CH₃CH₂), 20.3 (CH₃CH₂), 30.0 (d, J_CP= 37.3, PCH₂),

30.5 (CH₃CH₂CH₂), 52.0 (dd, ¹J_CP= 68.8, ³J_CP= 5.6, NCH₂P), 61.6 (CH₃(CH₂)₂CH₂N), 126.5

2

1

(C₄), 128.2 (C₃), 129.9 (C₂), 132.9 (d, J_CP= 7.3, C₁); H NMR (CDCl₃) δ 0.82-0.92 (m, 3H,

CH₃), 1.11–1.26 (m, 4H, CH₃CH₂, CH₃CH₂CH₂), 2.16 (s, 2H, CH₃CH₂CH₂CH₂N), 2.44 (s,

4H, NCH₂P), 3.01–3.14 and 3.51–3.64 (m, 8H, PCH₂), 7.15–7.35 (m, 20H, ArH); [M–

Cl]⁺_found= 754.2061, C₃₄H₄₁NP₂ClPt requires 754.2051.

[Bis(dibenzylphosphinomethyl)cyclohexylamine]dichloroplatinum(II) (12c)

Yield: 58% (0.09 g) of compound 12c as white powder. ³¹P NMR (CDCl₃) δ –6.1 (¹J_P-Pt

=

13

1

3404); C NMR (CDCl₃) δ 25.2 (C₃), 25.3 (C₄), 26.9 (C₂), 31.0 (d, J_CP= 35.7, PCH₂), 56.2

(dd, ¹J_CP= 73.8, ³J_CP= 4.9, NCH₂P), 67.2 (bs, C₁), 126.5 (C_4’), 128.2 (C_3’), 129.9 (C_2’), 133.1

1

(C_1’); H NMR (CDCl₃) δ 0.90–1.13 (m, 5H, C₂H_ax., C₄H_ax.,C₃H_ax.), 1.23–1.32 (m, 2H,

C₂H_eq.), 1.49–1.56 and 1.65–1.73 (m, 3H C₄H_eq., C₃H_eq.), 1.71 (s, 1H, C₁H), 2.58 (s, 4H,

NCH₂P), 3.03–3.14 and 3.53–3.64 (m, 8H, PCH₂), 7.15–7.38 (m, 20H, ArH); [M–Cl]⁺

780.2217, C₃₆H₄₃NP₂ClPt requires 780.2207.

=

found

[Bis(dibenzylphosphinomethyl)benzylamine]dichloroplatinum(II) (12d)

Yield: 69% (0.11 g) of compound 12d as white powder. ³¹P NMR (d-DMSO) δ –5.2 (¹J_P-Pt

13

1

3

= 3404); C NMR (CDCl₃) δ 30.7 (d, J_CP= 35.9, PCH₂), 46.8 (dd, J_CP= 55.2, J_CP= 3.2,

3

NCH₂P), 65.4 (t, J_CP= 10.9, CH₂N), 126.6 (C_4’), 127.9 (C₄), 128.4 (C_3’), 129.4 (C₃), 129.7

1

(C_2’), 130.3 (C₂), 133.3 (C_1’), 135.5 (C₁); H NMR (CDCl₃) δ 2.96–3.06 (m, 2H, CH₂N),

Article Doi

Synthesis and use of α-aminophosphine oxides and N,N-bis(phosphinoylmethyl)amines - A study on the related ring platinum complexes

DOI: 10.1016/j.jorganchem.2015.10.029

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Article abstract of DOI:10.1016/j.jorganchem.2015.10.029

Full text of DOI:10.1016/j.jorganchem.2015.10.029

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