Synthesis of a chiral macrocyclic tetraphosphine -1,9-di-R,R(and S,S)-α-methylbenzyl-3,7,11,15-tetramesityl-1,9-diaza-3,7,11,15-(RSSR)-tetraphosphacyclohexadecane

Article abstract of DOI:10.1016/j.mencom.2008.03.008

Two enantiomers of the title compound containing six chiral atoms have been synthesised via stereoselective covalent self-assembly of two diphosphinopropane, four formaldehyde and two primary amine molecules.

Full text of DOI:10.1016/j.mencom.2008.03.008

Mendeleev
Communications
Mendeleev Commun., 2008, 18, 80–81
Synthesis of a chiral macrocyclic tetraphosphine –
1,9-di-R,R(and S,S)- -methylbenzyl-3,7,11,15-tetramesityl-
1,9-diaza-3,7,11,15-(RSSR)-tetraphosphacyclohexadecane
Roman N. Naumov,*a Andrey A. Karasik,a Kirill B. Kanunnikov,a Artem V. Kozlov,a
Shamil K. Latypov,a Konstantin V. Domasevitch,b Evamarie Hey-Hawkinsc and Oleg G. Sinyashina
a A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy
of Sciences, 420088 Kazan, Russian Federation. Fax: +7 843 273 2253; e-mail: naumov@iopc.knc.ru
b Kiev National University, 01033 Kiev, Ukraine. Fax: +38 044 296 2467; e-mail: dk@univ.kiev.ua
c Institüt für Anorganische Chemie der Universität Leipzig, D-04103 Leipzig, Germany.
Fax: +49 341 973 9319; e-mail: hey@rz.uni-leipzig.de
DOI: 10.1016/j.mencom.2008.03.008
Two enantiomers of the title compound containing six chiral atoms have been synthesised via stereoselective covalent self-
assembly of two diphosphinopropane, four formaldehyde and two primary amine molecules.
Chiral macrocyclic species are important selective molecular
C(34)
C(30)
recognition participants and asymmetric catalysts.1,2 The number
C(16)
C(29)
C(17)
of the chiral macrocyclic phosphines, as well as their applica-
tions in catalysis, are limited only by several examples.3,4
C(33)
C(15)
C(14)
C(13)
C(28)
C(27)
C(31)
C(60)
C(55)
C(42)
C(12)
C(18)
An insufficient attention is explained by difficulties in the
preparation of macrocyclic phosphines (template reactions5 or
high dilution conditions3,6) and the separation of stereoisomers.7
The stereoselective formation of a single isomer of 1,9-di-
benzyl-3,7,11,15-tetramesityl-1,9-diaza-3,7,11,15-(RSSR)-tetra-
phosphacyclohexadecane has been revealed.8 The high-yield
synthesis of the macrocyclic compound has been explained in
terms of a self-assembly process.8,9
C(56)
C(32)
C(35)
C(61)
C(11)
P(2)
P(1)
C(2)
N(1)
C(37)
C(9)
C(8)
C(1)
C(5)
C(38)
C(57)
C(58)
C(59)
C(54)
P(4)
C(10)
C(36)
C(39)
C(6)
C(3)
C(4)
C(41)
C(7)
C(19)
C(22)
N(2)
P(3)
C(51)
C(46)
C(20)
C(43)
C(40)
C(45)
C(50)
C(53)
C(21)
C(26)
C(25)
C(62)
C(44)
C(24)
C(49)
C(48)
Here, we report the synthesis of optically active 1,9-diaza-
C(52)
3,7,11,15-tetraphosphacyclohexadecanes 1s and 1r.
Figure 1 X-ray crystal structure of macrocycle 1s.
The reaction of a diastereomeric mixture of 1,3-bis(mesityl-
phosphino)propane,8,10 formaldehyde (30% in H2O) and (S)- or
(R)- -methylbenzylamine proceeded stereoselectively giving
only one isomer of desired chiral macrocycles 1s and 1r in a
good yield.†
the formation of chiral 1,9-diaza-3,7,11,15-tetraphosphacyclo-
hexadecanes 1s and 1r. The investigation of the structural
peculiarities conditioned by a presence in 1s and 1r of six chiral
atoms was carried out by NMR correlations (1H–1H COSY,
1H–13C HSQC, 1H–13C HMBC).
The structure of 1s was determined by X-ray analysis.‡ The
configurations of four phosphorus atoms correspond to the
RSSR-stereoisomer of desired di-1,9-(S,S)- -methylbenzyl-
3,7,11,15-tetramesityl-1,9-diaza-3,7,11,15-tetraphosphacyclo-
hexadecane. The macrocycle conformation is similar to that
described for 1,9-dibenzyl-3,7,11,15-tetramesityl-1,9-diaza-
3,7,11,15-(RSSR)-tetraphosphacyclohexadecane.8
Mes
4 CH2O,
2(R or S)-H2NCH(Me)Ph
PH
2
PH
Ph
*
Mes
Mes
*
P
N
Me
Mes
Ph
P
*
*
*
P
Mes
N
P
The presence of chiral units at the nitrogen atoms in 1s leads
to some distortion of a 16-membered ring and the whole macro-
molecule of 1s is asymmetrical.
*
Me
Mes
1s,r
The asymmetry of macrocycles 1r and 1s is also seen in 1H, 13
C
Scheme 1
and 31P NMR spectra (two sets of signals). The 2D 1H–13C HMBC
NMR spectrum of 1r indicates that the atoms of both non-equiva-
lent parts of the macromolecule are covalently bonded through
methylene chains. Hence, the spectral signals were attributed to
P*(S)CH2NC*(S)CH2P*(S) (A) and P*(R)CH2NC*(S)CH2P*(R)
(A') parts of the molecules. An equivalence of PCH2 fragments
in each subunit (A or A') is due to the fast exchange between
twisted conformations with simultaneous inversion of nitrogen
configuration. The chemical shift of the methyl group of CH*Me
on side A' is strongly downfield shifted ( d1H 0.43 ppm and
The 31P NMR spectroscopic monitoring of the reaction
mixture showed that the concentration of 1s grew from 30%
towards to all products after 1 h, since the beginning of the
reaction, to 47% in 24 h. Pure 1s was obtained in 73% yield,
possibly, due to the relatively fast equilibrium between inter-
mediates and products of the reaction.
Compounds 1s and 1r are air-stable and readily soluble in
1
organic solvents (CHCl3, CH2Cl2, C6H6 and toluene). 31P, H
and 13C NMR spectroscopic data and elemental analysis confirm
– 80 –
© 2008 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2008, 18, 80–81
d13C 8.68 ppm) relative to Me on side A. An opposite is
This work was supported by the Volkswagen Foundation
(I/82 020), the Russian Foundation for Basic Research (project
no. 06-03-32754-a and 05-03-32558-a), the President of the
Russian Federation (grant for the support of leading scientific
schools no. 5148.2006.3). R. N. Naumov aknowledges the Inter-
national Postgraduate Program (DAAD) and Staatsministerium
für Wissenschaft und Kunst (SMWK) for the research grants.
Sh. K. Latypov acknowledges the Russian Science Support
Foundation for a doctoral grant. This investigation was carried
out at the NMR department of the Federal Collective Spectral
Analysis Center for Physical and Chemical Investigations of
Structure, Properties and Composition of Matter and Materials
(CKP SAC) and Federal CKP for Physical and Chemical
Investigations of Matter and Materials (FCKP PCI) (state contracts
nos. 02.451.11.7036 and 02.451.11.7019 of the Russian Federation
Ministry of Education and Science).
observed for other nuclei [e.g., o-Ph (1H) and ipso-Ph (13C)].
Such a low field shift of C*HMeA' is due to a close vicinity with
phosphorus lone pair at P(R)P(R) side, while on the P(S)P(S)
side the similar effects for nuclei of C*PhA are seen. This
hypothesis is supported by the chemical shift calculations for
simple model systems, and an inspection of X-ray and MM
minimised structures.§
Thus, the structure asymmetry for 1s and 1r was established by
NMR correlations (1H–1H COSY, 1H–13C HSQC, 1H–13C HMBC)
in a solution.§,11
†
All manipulations were carried out with standard high-vacuum and
dry-nitrogen techniques. The NMR experiments were carried out with
an Avance 600 (Bruker) specrtometer. 31P NMR (242.97 MHz), external
85% H3PO4; 1H NMR (600.13 MHz), internal solvent; 13C NMR
(150.90 MHz), internal solvent. The melting points were determined on a
Boetius apparatus and are uncorrected. Specific rotation was determined
on a Perkin–Elmer Model 341 polarimeter at 589 nm. Bis(mesityl-
phosphino)propane was synthesised according the method described
previously.8,10
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(RSSR)-tetraphosphacyclohexadecane 1s. A solution of (S)- -methyl-
benzylamine (0.25 g, 2.0 mmol) in 5 ml of benzene was slowly added
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1
(74%), mp 148–150 °C. 31P NMR (C6D6) d: –41.91, –41.75. H NMR
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3
(C6D6, d 7.15) d: 1.06 (d, 3H, MeA, JHH 6.8 Hz), 1.49 (d, 3H, MeA',
3JHH 7.0 Hz), 1.80–2.50 (m, 12H, PCH2CH2CH2P(A + A')), 2.08 (s, 6H,
p-MeA or A'), 2.09 (s, 6H, p-MeA or A'), 2.55 (s, 12H, o-MeA or A'), 2.61
(partly covered by o-MeA', P–CH2A'–N), 2.64 (s, 12H, o-MeA or A'), 3.03
(dd, 2H, P–CHA2 –N, 2JHH 12.8 Hz, 2JHP 10.0 Hz), 4.01 (d, 2H, P–CHA2 –N,
2
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2JHH 12.8 Hz), 4.09 (d, 2H, P–CH2A'–N, JHH 13.0 Hz), 4.72 (m, 1H,
2
C*HA'), 4.80 (m, 1H, C*HA), 6.75 (s, 8H, m-H in Mes), 6.98 (dd, 1H,
p-HA', 3JHH 7.4 Hz, 3JHH 7.4 Hz), 7.05 (dd, 2H, m-HA' in Ph, 3JHH 7.4 Hz,
3JHH 7.4 Hz), 7.12–7.20 (o-HA' and p-HA overlapped with the C6D6), 7.29
(dd, 2H, m-HA in Ph, 3JHH 7.5 Hz, 3JHH 7.5 Hz), 7.49 (d, o-H, 3JHH 7.5 Hz).
13C{H} NMR (C6D6, d 128.02) d: 11.94 (s, MeA), 20.62 (s, MeA'), 20.93
3
4
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(s, p-Me), 23.85 (d, o-MeA or A' 3JPC 18.8 Hz), 23.97 (d, o-MeA or A'
, ,
3JPC 18.3 Hz), 29.40–29.90 (m, PCH2CH2CH2P), 29.60 (s, PCH2CH2CH2P),
52.36 (d, P–CH2A or A'–N, 1JPC 9.7 Hz), 52.43 (d, P–CHA2 or A'–N, 1JPC 9.2 Hz),
3
3
58.76 (t, C*HA, JPC 8.9 Hz), 59.33 (t, C*HA', JPC 8.7 Hz), 126.87 (s,
p-CA in Ph), 127.05 (s, p-CA' in Ph), 128.00–128.54 (o-C(A + A') in Ph
overlapped with C6D6), 128.59 (s, m-CA in Ph), 128.76 (s, m-CA' in Ph),
129.95 (s, m-CA or A' in Mes), 130.00 (s, m-CA or A' in Mes), 131.27 (d,
5
6
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ipso-CA or A' in Mes, JCP 20.4 Hz), 131.32 (d, ipso-CA or A' in Mes,
1
1JCP 21.4 Hz), 138.64 (s, p-CA or A' in Mes), 138.67 (s, p-CA or A' in Mes),
141.06 (s, ipso-CA' in Ph), 144.69 (d, o-CA or A' in Mes, JPC 14.2 Hz),
2
144.75 (d, o-CA or A' in Mes, JPC 14.2 Hz), 145.45 (s, ipso-CA in Ph).
2
[a]D20 +29 (c 0.001, C6H6). Found (%): C, 75.6; H, 8.1; N, 2.9; P, 12.4.
Calc. for C62H82P4N2 (979) (%): C 76.0, H 8.4, N 2.8, P 12.6.
1r was obtained analogously. Yield 0.65 g (36%), mp 148–150 °C.
[a]D20 –29 (c 0.001, C6H6). Found (%): C, 75.8; H, 8.1; N, 2.6; P, 12.3.
Calc. for C62H82P4N2 (979) (%): C, 76.0; H, 8.4; N, 2.8; P, 12.6.
7
8
9
Phosphorus-Carbon Heterocyclic Chemistry: The Rise of a New Domain,
ed. F. Mathey, Pergamon, Amsterdam, 2001, p. 11.
‡
R. N. Naumov, A. A. Karasik, O. G. Sinyashin, P. Lönnecke and E. Hey-
Hawkins, Dalton Trans., 2004, 3, 357.
A. S. Balueva, R. M. Kuznetsov, S. N. Ignat’eva, A. A. Karasik, A. T.
Gubaydullin, I. A. Litvinov, O. G. Sinyashin, P. Lönnecke and E. Hey-
Hawkins, Dalton Trans., 2004, 3, 442.
Crystallographic data for 1s: C62H82N2P4; M = 979.18, triclinic, space
–
group P1, a = 9.6643(9), b = 12.7047(11) and c = 13.2562(11) Å, a =
= 66.297(9)°, b = 87.254(10)°, g = 74.928(10)°, V = 1436.1(3) Å3, Z = 1,
dcalc = 1.132 mg cm–3; T = 173 K, m(MoK ) = 0.170 mm–1; 13824 reflec-
tions measured, 12026 independent reflections. Final R1 = 0.0374, Rw =
= 0.0816 for 7852 reflections with I ³ 2s(I), and R1 = 0.0563, Rw = 0.0853
for all reflections.
10 A. A. Karasik, R. N. Naumov, Y. S. Spiridonova, P. Lönnecke, E. Hey-
Hawkins and O. G. Sinyashin, Z. Anorg. Allg. Chem., 2007, 633, 205.
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(c) Atta-ur-Rahman, One and Two Dimensional NMR Spectroscopy,
Elsevier, Amsterdam, 1989.
CCDC 680561 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
For details, see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2008.
§
Details of NMR experiments, as well as calculation data will be
published later in a separate paper.
Received: 26th September 2007; Com. 07/3019
– 81 –