New functionalised ditertiary phosphines via phosphorus based Mannich condensation reactions

Article abstract of DOI:10.1016/S0040-4039(03)01273-5

The one-step synthesis of a family of functionalised ditertiary aminophosphines are described including the X-ray crystal structure of 4-{(Ph₂PCH₂)₂N}C₆H₄CO ₂H.

Full text of DOI:10.1016/S0040-4039(03)01273-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5255–5257
New functionalised ditertiary phosphines via phosphorus based
Mannich condensation reactions
Sean E. Durran, Mark R. J. Elsegood, Neil Hawkins, Martin B. Smith* and Salem Talib
Department of Chemistry, Loughborough University, Loughborough, Leics, LE11 3TU, UK
Received 3 April 2003; revised 5 May 2003; accepted 16 May 2003
Abstract—The one-step synthesis of a family of functionalised ditertiary aminophosphines are described including the X-ray
crystal structure of 4-{(Ph2PCH2)2N}C6H4CO2H. © 2003 Elsevier Science Ltd. All rights reserved.
Ditertiary phosphines (including chiral variants) are
valuable synthetic tools widely used in coordination
chemistry and homogeneous catalysis.1 Many ditertiary
phosphines have been reported to date, some pertinent
examples include NUPHOS (R=Me, Ph), DPPF, (R)-
BINAP and DPPP (Chart 1).1,2 Of these, DPPP
[DPPP=1,3-(diphenylphosphino)propane] is the sim-
plest and comprises a C3-connectivity between two
-PPh2 groups.2b In the course of ongoing studies in our
group we required a suitable ditertiary phosphine bear-
ing backbone functionality, that would enable potential
grafting onto polymeric supports. Whilst there is some
literature precedence for such compounds, their func-
tional groups3 or syntheses4–6 (multistep, moderate
yields and/or require prior generation of a reactive
phosphide intermediate) were inappropriate. Recent
work by ourselves,7,8 and others9 have shown phospho-
rus based Mannich transformations to be extremely
useful in accessing new ‘hybrid’ ligands. This synthetic
procedure is versatile and offers many advantages over
more classical routes, e.g. nucleophilic substitutions
using primary/secondary phosphides, palladium
catalysed P–C couplings and free radical additions.
Herein we describe a simple high yielding one-step
method for the synthesis of new functionalised diter-
tiary phosphines derived from cheap commercially
available starting materials.
1. Results and discussion
Using a similar procedure to that recently developed for
preparing novel aminocarboxylic acid tertiary phosphi-
nes,7 reaction of two equivalents of Ph2PCH2OH [read-
ily preformed from equimolar amounts of (CH2O)n and
Ph2PH] with the appropriate stoichiometry of 4-func-
tionalised aminoaryl precursor in refluxing methanol
gave the condensed ligands 4-{(Ph2PCH2)2N}C6H4X
1a–h in good to high yields (Eq. (1), Table 1).†,‡ As
demonstrated by the synthesis of 1a–h, this simple
Chart 1.
Keywords: amines; carboxylic acids and derivatives; Mannich reactions; phosphines.
* Corresponding author. Tel.: +44 (0)1509 222553; fax: +44 (0)1509 223925; e-mail: m.b.smith@lboro.ac.uk
† A typical synthesis is illustrated here for 1c. To the solids Ph2PCH2OH (1.007 g, 4.66 mmol) and 4-H2NC6H4CH2CO2H (0.352 g, 23.29 mmol)
was added oxygen-free CH3OH (10 ml). The yellow solution was refluxed under a nitrogen atmosphere for 4 h. The solvent was evaporated to
dryness under reduced pressure to afford 1c. Yield: 1.135 g, 89%.
‡ All new compounds gave satisfactory microanalytical and spectroscopic results.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01273-5

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S. E. Durran et al. / Tetrahedron Letters 44 (2003) 5255–5257
Table 1. Selected data for compounds 1–3a
method is extremely reliable and tolerant to a range of
different functional groups (CO2H, COMe, OH, Br, I,
CHꢀCH2) with no significant diminishment in yield.
The procedure also works well when a 4-functionalised
aminobenzyl substrate is used (Eq. (2) for the synthesis
of 2) or when either 2- or 3-functionalised aminoaryls
(Eq. (3)) are employed. The yields for 1–3 are unopti-
mised and in the range 50–90% with eight examples
exceeding 70% (Table 1). Occasionally small amounts
of 4-{Ph2PCH2N(H)}C6H4X were detected (by NMR)
indicating that reactions initially proceed through a
singly substituted intermediate. The 31P{1H} NMR
data (Table 1) confirm single phosphorus species at ca.
l(P) −27 ppm indicating, in all cases, that the 4-sub-
stituent exerts a negligible effect on the 31P chemical
shift (c.f. parent diphosphine 1a).10 Moreover the 31P
NMR resonances are some 10 ppm upfield with respect
to either 4-{Ph2PCH2N(H)}C6H4X7 or DPPP and 20
ppm upfield with respect to Ph2PCH2OH [l(P) −9.9
ppm (CDCl3)].8 Compounds 1–3 are freely soluble in
CH2Cl2 and THF, the acids 1b, 1c and 2 are also
soluble in methanol but show little evidence for solubil-
ity in water or weakly basic media. Furthermore 1b–1h
and 2 undergo clean derivatisation (and are thereby
protected) when treated with either BH3·THF, H2O2, S8
or [PdCl2(COD)] (COD=cycloocta-1,5-diene).
Compound Reaction Yield (%)
time (h)
31P NMRb
l(P) (ppm) Solvent
1a
1b
1c
1d
1e
1f
18
5.5
4
48
4
79 (67)c
77
89
52
90
−27.2
−27.0
−26.7
−26.7
−27.5
−27.6
−27.1
−27.1
−28.4
−25.7
−26.8
CDCl3
CDCl3/CH3OH
C6D6/(CH3)2SO
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
4
74
1g
1h
2
3a
3b
18
4
76
77
53
86
4
18d
18
73
CDCl3
a Reactions performed in CH3OH unless otherwise stated.
b All 31P{1H} NMR spectra recorded at 36.2 or 101.3 MHz.
c Taken from Ref. 10.
d In CH3OH/C7H8.
An X-ray structure (1)§ of 1b confirms that the overall
geometry of the ditertiary phosphine comprises 4-
disubstituted (Ph2PCH2)2N- and -CO2H groups.¶ The
(1)
(2)
§ Crystal data for 1b: C33H29NO2P2, Mw=533.51; triclinic, space group P-1, a=9.9541(7), b=11.1783(8), c=13.3554(10) A, h=70.891(2),
,
b=80.274(2), k=86.866(2)°, U=1383.99(17) A , Dcalcd=1.280 g cm−3, u(Mo-Ka)=0.71073 A, Z=2, v=0.188 mm−1, T=150(2) K, wR2=0.0932
for all 6269 unique data, R1=0.0341 for 5479 reflections with F2>2|(F2). Crystallographic data (excluding structure factors) for the structure
in this paper has been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 206873. Copies
of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44(0)-1223-336033 or
e-mail: deposit@ccdc.ac.uk].
3
,
,
¶
,
Selected bond lengths (A) and angles (°): P(1)ꢁC(1) 1.8827(13), P(1)ꢁC(10) 1.8317(13), P(1)ꢁC(16) 1.8311(13), C(1)ꢁN(1) 1.4632(16), N(1)ꢁC(2)
1.4633(16), C(2)ꢁP(2) 1.8803(13), P(2)ꢁC(22) 1.8369(14), P(2)ꢁC(28) 1.8293(14), C(9)ꢁO(1) 1.3208(16), C(9)ꢁO(2) 1.2273(16). C(1)ꢁP(1)ꢁC(10)
97.95(6), C(1)ꢁP(1)ꢁC(16) 101.73(6), C(10)ꢁP(1)ꢁC(16) 102.39(6), P(1)ꢁC(1)ꢁN(1) 112.21(9), C(1)ꢁN(1)ꢁC(2) 115.42(10), N(1)ꢁC(2)ꢁP(2)
113.11(9), C(2)ꢁP(2)ꢁC(22) 99.07(6), C(2)ꢁP(2)ꢁC(28) 100.68(6), C(22)ꢁP(2)ꢁC(28) 102.32(6).

S. E. Durran et al. / Tetrahedron Letters 44 (2003) 5255–5257
5257
(3)
Figure 1. X-Ray structure of compound 1b showing (i) the molecular structure and (ii) the intermolecular carboxylate head-to-tail
H-bonding motif giving rise to dimer pairs.
Ph2P- groups adopt an anti configuration with respect to
each other. Strong H-bonding, via the carboxylate
groups, is also evident and links molecules into head-to-
tail dimer pairs through hydrogen bonding [O(1)···O(2A)
2.670(1) A, H(1)···O(2A) 1.85(2) A; O(1)ꢁH(1)···O(2A)
171(2)°].
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,
,
In conclusion, we have developed a facile procedure for
the synthesis of new modified ditertiary phosphines
bearing various functional groups. This synthetic route
is extremely practical with reactions generally complete
within a few hours in refluxing CH3OH. In addition to
the short reaction times this method obviates the prepa-
ration of reactive intermediates, uses cheap and commer-
cially available starting materials, requires no purification
steps nor any stringent need for performing reactions
under a rigorously controlled oxygen free atmosphere.
Current efforts are directed towards ‘tagging’ these
molecules onto polymeric (including dendrimeric) sup-
ports, exploring their co-ordination behaviour and poten-
tial utility in catalysis.
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2002, 43, 1299–1301.
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J. W. J. Chem. Soc., Dalton Trans. 2000, 2771–2778.
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Acknowledgements
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We should like to thank The Leverhulme Trust and
EPSRC for funding.