Microwave-assisted synthesis of α-aminophosphine oxides

Article abstract of DOI:10.1080/10426507.2018.1541898

Aminophosphine oxides and bis(phosphinoylmethyl)amines were synthesized by the microwave (MW)-assisted Kabachnik-Fields reaction of primary amines, paraformaldehyde and secondary phosphine oxides. The bisphosphines obtained after deoxygenation of the bis(phosphinoymethyl)amine derivatives were utilized in the synthesis of cyclic transition metal complexes.

Full text of DOI:10.1080/10426507.2018.1541898

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: https://www.tandfonline.com/loi/gpss20
Microwave-assisted synthesis of α-
aminophosphine oxides
Anna Tripolszky, Erika Bálint & György Keglevich
To cite this article: Anna Tripolszky, Erika Bálint & György Keglevich (2019): Microwave-assisted
synthesis of α-aminophosphine oxides, Phosphorus, Sulfur, and Silicon and the Related Elements,
DOI: 10.1080/10426507.2018.1541898
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2018.1541898
Microwave-assisted synthesis of a-aminophosphine oxides
Anna Tripolszky, Erika Bálint, and György Keglevich
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary
ABSTRACT
ARTICLE HISTORY
Received 1 October 2018
Accepted 24 October 2018
Aminophosphine oxides and bis(phosphinoylmethyl)amines were synthesized by the microwave
(MW)-assisted Kabachnik-Fields reaction of primary amines, paraformaldehyde and secondary
phosphine oxides. The bisphosphines obtained after deoxygenation of the bis(phosphinoymethyl)-
amine derivatives were utilized in the synthesis of cyclic transition metal complexes.
KEYWORDS
Kabachnik–Fields reaction;
microwave; a-aminophos-
phine oxides; transition
metal complexes
GRAPHICAL ABSTRACT
Introduction
Kabachnik-Fields reaction of secondary
phosphine oxides
a-Aminophosphine oxides as potential precursors of a-ami-
nophosphine ligands have attracted much attention. a--
Aminophosphines are of considerable importance in the
synthesis of P(III)-transition metal complexes.1 One of the
most convenient and widespread methods for the synthesis
of a-aminophosphine oxides is the Kabachik-Fields, or so
called phospha-Mannich reaction.2–4 This reaction 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. In case of the double
Kabachnik-Fields condensations, the primary amines are
reacted with two equivalents of aldehyde and two equiva-
lents of the P-component. Since the discovery of the reac-
tion, most of the papers were on cases utilizing dialkyl
phosphites.5 However, there are only a few examples with
secondary phosphine oxides. In this work, our recent results
are summarized on the synthesis of novel aminophos-
phine oxides.6
In the first approach, the phospha-Mannich reaction of
various primary amines (propyl-, butyl-, cyclohexyl … ,
benzyl- or 4-methoxy-benzylamine, as well as aniline or 4-
methoxyaniline) was studied with paraformaldehyde and
dibenzyl- (1), diphenyl- (2) or bis(4-methylphenyl)-phos-
phine oxide (3) at 100 °C under MW conditions in the
absence of any catalyst (Scheme 2). The condensations were
performed in acetonitrile due to the heterogeneity of the
reaction mixtures. After an irradiation of 1 h, the (amino-
methyl)phosphine oxides (4a-f, 5a-f and 6a-f) were obtained
in excellent yields (94–98%).
Double Kabachnik-Fields reaction of secondary
phosphine oxides
The synthesis of bis(phosphinoylmethyl)amines (7b-d, 8b-d
and 9b-d) was also studied by the double Kabachnik-Fields
reaction of primary amines, two equivalents of paraformalde-
hyde and two equivalents of the > P(O)H species (dibenzyl- (1),
diphenyl- (2) or bis(4-methylphenyl)-phosphine oxide (3)
(Scheme 3). The condensations were performed without any
catalyst, and the corresponding bis(phosphinoylmethyl)amines
(7b-d, 8b-d and 9b-d) were obtained in yields of 88–98%.
Results and discussion
Synthesis of secondary phosphine oxides by
Grignard reaction
As the first step of our work, the secondary phosphine
oxides (dibenzyl- (1), diphenyl- (2) and bis(4-methylphe-
nyl)phosphine oxide (3)) were prepared from diethyl phos-
phite by reaction with Grignard reagent, such as alkyl- or
arylmagnesium bromide (Scheme 1).7 After purification of
the crude product, the secondary phosphine oxides were
obtained in yields of 84–86%.
Kabachnik-Fields reaction of
(aminomethyl)dibenzylphosphine oxide
The synthesis of nonsymmetric N,N-bis(phosphinoylme-
thyl)amines (10b-d) was carried out by the condensation of
CONTACT Anna Tripolszky
tripolszky.anna@mail.bme.hu
ß 2019 Taylor & Francis Group, LLC

2
A. TRIPOLSZKY ET AL.
Scheme 1. Synthesis of secondary phosphine oxides by Grignard reaction.
Scheme 2. Kabachnik-Fields reaction of primary amines, paraformaldehyde and secondary phosphine oxides.
Scheme 3. Synthesis of bis(phospinoylmethyl)amines.
Scheme 4. Kabachnik-Fields reaction of (aminomethyl)dibenzylphosphine oxide.
(aminomethyl)dibenzylphosphine oxides (4b-d) with one dichlorodibenzonitrile palladium(II) (Scheme 5) to furnish
equivalent of paraformaldehyde and diphenylphosphine cyclic transition metal complexes (13b-d, 14b-d, 15b-d and
oxide (2) (Scheme 4). The reactions were performed in
16b-d) in yields of 40–75%.
acetonitrile at 100 °C for 70 min under MW conditions, and
The catalytic activity of the platinum(II) complexes (13b-
the corresponding nonsymmetric bis(phosphine oxides) d and 14b-d) was also investigated (Table 1). Because of its
(10b-d) were isolated in yields of 94–97%.
industrial significance, our model reaction was the hydrofor-
mylation of styrene. The catalysts formed in situ from
bis(dibenzylphosphino) (13b-d) and bis(di(p-tolylphosphino)
derivatives (14b-d) and tin(II)chloride were used at 100 °C.
The catalytic activity of 13b-d or 14b-d was different.
Applying the bis(dibenzylphosphino) derivatives (13b-d), the
hydroformylation was not complete, only a moderate con-
version (32–52%) was achieved (Table 1/Entry 1–3).
However, in case of the bis(di(p-tolylphosphino) derivatives
Sythesis of cyclic platinum and palladium complexes
We wished to study the utilization of the bis(phosphinoyl-
methyl)amines (7b-d, 8b-d and 9b-d) mentioned above,
therefore, the bis(dibenzylphosphinoylmethyl)amines (7b-d)
and bis(di-p-tolylphosphinoylmethyl)amines (9b-d) were
subjected to double deoxygenation applying phenylsilane.
The bisphosphines obtained (11b-d and 12b-d) were reacted (14b-d), the conversion was almost complete after 3-8 h
with dichlorodibenzonitrile platinum(II) or (Table 1/Entry 4-6). Our complexes (13b-d and 14b-d)

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
Scheme 5. Synthesis of cyclic platinum and palladium complexes.
Table 1. Testing our complexes in the hydroformylation of styrene.
a
b
Entry
Z
Y
t [h]
Conv. [%]
Rc [%]
Rbr [%]
1
2
3
4
5
6
Bn
nBu
cHex
Bn
3
3
3
8
6
3
32
50
52
98
98
98
72
74
70
75
74
79
65
61
65
63
63
56
4-MeC6H4
nBu
cHex
Bn
aChemoselectivity towards aldehydes (A, B). [(moles of A + moles of B)/(moles of A + moles of B + moles of C) × 100].
bRegioselectivity towards branched aldehyde (A). [moles of A/(moles of A + moles of B) × 100].
induced good chemoselectivity. Among the two main hydroformylation of styrene, where the Pt(II) complexes syn-
products, always the branched chain aldehyde (A) was
formed in somewhat larger proportion. The Pt(II) complexes
containing p-tolyl groups on the phosphorus atoms proved
to be more efficient, than the complexes incorporating
benzyl groups.
thesized showed high chemoselectivity and an unusual
regioselectivity.
Acknowledgments
The project was supported by the Hungarian Research Development
and Innovation Fund (FK123961 and K119202). The authors thank for
Prof. László Kollár and Dr. Péter Pongrácz to testing the platina com-
plexes synthesized in the hydroformylation of styrene.
Conclusions
(Aminomethyl)phosphine oxides (4b-d, 5b-d and 6b-d), symmet-
ric and nonsymmetric bis(phosphinoylmethyl)amines (7b-d, 8b-
d, 9b-d and 10b-d) were prepared by the single or double
Kabachnik-Fields reactions of primary amines, paraformaldehyde
and secondary phosphine oxides (1-3). Exploiting the advantages
of the MW technique, the reactions were carried out without
any catalyst.
After double deoxygenation, the bis(phosphinoylmethyl)-
amines (7b-d, 9b-d) were utilized as phosphine ligands in the
synthesis of platinum and palladium complexes (13b-d, 14b-
d, 15b-d and 16b-d). The catalytic activity of the platinum
complexes (13b-d and 14b-d) was tested in the
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