Triple C-H activation of 1,5-bis(di-tert-butylphosphino)-2-(S)-dimethylaminopentane on ruthenium gives a chiral carbene complex

Article abstract of DOI:10.1039/b208325f

This communication reports the preparation of a novel trans-chelating diphosphine, 1,5-bis(di-tert-butylphosphino)-2-(S)-dimethylaminopentane, that undergoes triple C-H activation in reaction with [RuCl₂(p-cymene)]₂ to give a chiral square-pyramidal 16-electron carbene complex of ruthenium.

Full text of DOI:10.1039/b208325f

Triple C–H activation of
1,5-bis(di-tert-butylphosphino)-2-(S)-dimethylaminopentane on
ruthenium gives a chiral carbene complex†
Vladimir F. Kuznetsov,a Alan J. Loughb and Dmitry G. Gusev*a
a Wilfrid Laurier University, Department of Chemistry, Waterloo, Ontario N2L 3C5, Canada.
E-mail: dgoussev@wlu.ca; Fax: +1 (519) 746-0677; Tel: +1 (519) 884-1970
b University of Toronto, Department of Chemistry, X-Ray laboratory, Toronto, Ontario M5S 3H6, Canada.
E-mail: alough@chem.utoronto.ca
Received (in Purdue, IN, USA) 28th August 2002, Accepted 8th September 2002
First published as an Advance Article on the web 24th September 2002
This communication reports the preparation of a novel
trans-chelating diphosphine, 1,5-bis(di-tert-butylphos-
phino)-2-(S)-dimethylaminopentane, that undergoes triple
C–H activation in reaction with [RuCl2(p-cymene)]2 to give
a chiral square-pyramidal 16-electron carbene complex of
ruthenium.
2-(S)-dimethylaminopentane hydrochloride, and (e) the hydro-
chloride was reacted with LiPBut2 to give 1.
Treating [RuCl2(p-cymene)]2 with 1 in boiling tert-butanol in
the presence of triethylamine afforded the carbene complex 2
shown in Scheme 4, isolated in 79% yield as air-sensitive thin
red needles soluble in common organic solvents.§ Formation of
2 apparently involved the expected trans coordination of the
two bulky PBut2 groups to ruthenium and cyclometalation of the
ligand backbone. Unexpectedly, the cyclometalated species did
not undergo b-hydrogen elimination in the fashion observed for
1,5-bis(di-tert-butylphosphino)pentane,3 but afforded the car-
bene product 2 by dehydrogenation of a methylamino group.
Complex 2 was characterized by elemental analysis and
NMR spectroscopy. Important NMR features of 2 include the
carbene NCH shifts: d 11.97 (1H) and 246.9 (13C), and the AB
Cis-chelating diphosphine ligands are ubiquitous; many of them
are chiral and have found important applications as catalysts for
enantioselective organic transformations. In contrast, very few
trans-chelating diphosphines (so-called ‘pincer’ ligands) are
known1 and their chiral forms are restricted to the derivatives of
1,3-bis(diphosphinomethyl)benzene A and B shown in Scheme
1.2
Pincer ligands possessing a C5 aliphatic spacer between the
phosphorus atoms may contain one or two stereogenic centers
in positions adjacent to the metalated carbon of the complex
(structure C in Scheme 1) and thus offer interesting structural
alternatives to the ligands with aromatic backbone. In order to
test the feasibility of this approach, we decided to prepare
1,5-bis(di-tert-butylphosphino)-2-(S)-dimethylaminopentane
(1) and investigate its reaction with [RuCl2(p-cymene)]2. We
have recently reported dehydrogenation of 1,5-bis(di-tert-
butylphosphino)pentane on ruthenium that afforded the olefin
2
system in the phosphorus spectrum, exhibiting a large JPP
coupling of 257 Hz. The solid state structure of 2 was
established by single crystal X-ray diffraction.¶ An ORTEP plot
of the molecule is shown in Fig. 1 and selected bond distances
and angles are listed in the figure caption. The coordination
environment of the ruthenium center in 2 approximates a square
pyramid with the carbene moiety occupying the apical position.
The two trans coordinated P atoms and the mutually trans Cl
and C3 atoms define the basal plane of the pyramid. The Ru–C7
and Ru–C3 bond distances of 1.868(4) and 2.143(4) Å,
respectively, are within the normal range for Fischer carbene
complex
RuHCl[But2PCH2CH2((E)-CH = CH)CH2PBut2]
(Scheme 2, left).3 From 1, we anticipated formation of olefin
complexes shown in Scheme 2.
Preparation of 1 was accomplished in five steps‡ as shown in
Scheme 3 and involved (a) methylation of
conversion of N, N-dimethyl-( )-glutamic acid to the corre-
L
-glutamic acid, (b)
L
sponding dimethyl ester, which (c) afforded 2-(S)-dimethylami-
nopentane-1,5-diol upon reduction with LiAlH4. In the
following two steps, the diol was (d) converted to 1,5-dichloro-
Scheme 1
Scheme 3
Scheme 2
† Electronic supplementary information (ESI) available: NMR data for the
products in Scheme 3. See http://www.rsc.org/suppdata/cc/b2/b208325f/
Scheme 4
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CHEM. COMMUN., 2002, 2432–2433
This journal is © The Royal Society of Chemistry 2002

Hg). Yield: 20.5 g (63%). (c) N,N-Dimethyl-(L)-glutamic acid dimethyl
ester (20.35 g, 100.15 mmol) was added dropwise over ca. 15 min to a
stirred suspension of LiAlH4 (7.2 g, 189.7 mmol) in THF (300 mL) at 280
°C. Stirring continued at room temperature for 1 h and then under reflux
overnight. The resulting suspension was cooled in an ice bath and carefully
treated with water (10 mL) added dropwise and then with 15% NaOH (5
mL). The mixture was stirred at room temperature for 30 min then heated to
reflux and filtered while hot. The solid was washed with hot THF (3 3 40
mL), the combined filtrate was evaporated and dried under vacuum at 100
°C to give 2-(S)-dimethylaminopentane-1,5-diol (14.3 g, 97%) as a
colorless oil. (d) SOCl2 (26.2 g, 220 mmol) was added dropwise to a
solution of 2-(S)-dimethylaminopentane-1,5-diol (10.41 g, 70.71 mmol) in
40 mL of CH2Cl2 at 280 °C. Stirring continued at room temperature for 1
h and then under reflux for 0.5 h. The resulting solution was evaporated and
dried under vacuum at 100 °C. The oily residue was triturated with abs.
Et2O (40 mL) to give 1,5-dichloro-2-(S)-dimethylaminopentane hydro-
chloride as a white solid, which was filtered, washed with abs. Et2O (3 3 20
mL) and dried under vacuum. Yield: 15.32 g (98 %). Deprotonation of the
hydrochloride was not carried out because of the spontaneous formation of
2-chloromethyl-1,1-dimethylpyrrolidinium chloride. (e) All manipulations
were carried out under argon. A stirred suspension of 1,5-dichloro-2-(S)-
dimethylaminopentane hydrochloride (4.97 g, 22.53 mmol) in THF (30 mL)
was treated at 280 °C with a solution of LiPBut2 (12.0 g, 78.87 mmol, in 30
mL of THF) added dropwise over ca. 15 min. Stirring continued at room
temperature for 1 h and then under reflux for 0.5 h. The mixture was
evaporated to ca. 30 mL, diluted with hexane (30 mL) and washed with
deoxygenated water (3 3 8 mL). The organic phase was dried over K2CO3,
filtered and evaporated. The residue was distilled under vacuum of an oil
pump. Three fractions boiling in the intervals 32–37, 135–145, and 145–152
°C were collected. According to 31P NMR, the first fraction was HPBut2
(4.61 g), the second was a mixture of 1 and (But2P)2. The third was
spectroscopically pure 1 (pale yellow pyrophoric oil) (6.28 g, 69%).
§ Synthesis of 2: all manipulations were carried out under argon. A stirred
mixture of 1 (825 mg, 2.04 mmol), [RuCl2(p-cymene)]2 (0.57 g, 0.93
mmol), and Et3N (0.4 g, 3.96 mmol) in 10 mL of t-BuOH was refluxed for
12 h. After evaporation, the residue was extracted with Et2O (20 mL) and
filtered. The filtrate was diluted with hexane (10 mL) and evaporated to ca.
10 mL. The precipitated dark-red solid was separated and re-dissolved in
ether (16 mL). The solution was diluted with isooctane (16 mL), passed
through basic alumina (30 3 20 mm) and eluted with isooctane (8 mL). The
combined eluate was evaporated to ca. 8 mL. Spectroscopically pure 2
crystallized upon standing and was separated by decantation, washed with
hexane (2 3 4 mL) and dried under vacuum. Yield: 0.79 g (79%). Anal.
Calc. for C23H48ClNP2Ru: C, 51.43; H, 9.01; N, 2.61. Found: C, 51.61; H,
Fig. 1 Partial structure of 2 with ellipsoids set at the 30% probability level.
Most of the hydrogen atoms and methyl groups are omitted for clarity. Key
parameters (Å, deg): Ru–C3 2.143(4), Ru–C7 1.868(4), C7–N 1.317(5),
C2–N 1.469(5), C6–N 1.468(5), Ru–Cl 2.467(1), Ru–P1 2.332(1), Ru–P2
2.345(1), P1–Ru–P2 160.31(4), C3–Ru–Cl 173.16(11), C3–Ru–C7
76.20(16), C7–Ru–Cl 110.53(12), N–C7–Ru 122.6(3), C7–Ru–P1
86.24(12), C7–Ru–P2 100.87(12).
and alkyl-ruthenium species. The short C7–N distance of
1.317(5) Å and the planarity of the N–C2–C6–C7 four-atom
fragment indicate strong p-bonding between C7 and the
nitrogen atom and a significant double-bond character of the
C7–N bond.
The molecule of 2 has three chiral centers. The C2 center was
present in 1 and retained its configuration, whereas C3 and Ru
became chiral upon formation of the complex. The (R)-C3, (L)-
Ru stereochemistry is explicitly defined by the (R)-configura-
tion of C2 and the trans arrangement of the PBut2 groups.
1
Indeed, H, 13C and 31P NMR spectra of 2 have demonstrated
that in solution the complex exists as single epimer. Solutions of
20
2 rotate plane-polarized light ([a]D + 876.2°, c = 0.24,
toluene), providing conclusive evidence that formation of the
complex occurred without racemization.
In summary, this work has successfully demonstrated that
new types of diphosphine ‘pincer’ ligands with chiral centers in
the aliphatic backbone can be developed. The methodology
applied to the synthesis of 1 can be easily extended toward
preparation of diaryl- and dialkylphosphino analogues of 1 e.g.,
1,5-bis(diphenylphosphino)-2-(S)-dimethylaminopentane. The
availability of the phosphorus and nitrogen donor centers and
multiple C–H activation pathways in 1 open several possibilities
for addition of this type of ligand to transition metals, promising
an intriguing structural diversity of the products. The use of 1
and its analogues in organometallic chemistry can lead to novel
chiral metal complexes of interest for fundamental and catalytic
research.
2
9.11; N, 2.67%. 31P{1H} NMR (C6D6): d 77.5, 82.8 (d, JPP = 257 Hz).
1H{31P} NMR (C6D6): d 0.51 (m, 1H), 0.83–1.10 (m, 2H), 1.13, 1.25, 1.30,
1.38 (s, 4 3 9H, CH3), 1.52 (m, 2H), 1.81 (dt, JHH = 6, 18 Hz, 1H), 2.24
(s, 3H, N-CH3), 2.57 (dd, JHH = 6, 11 Hz, 1H), 3.27 (s, 1H, CH–N), 11.97
(s, 1H, NCH). 13C{1H} NMR (C6D6): d 21.1 (dd, JCP = 1.3, 19.1 Hz, CH2),
26.3 (d, JCP = 18.5 Hz, CH2), 28.7 (dd, JCP = 1.4, 4.7 Hz, CH3), 29.2 (dd,
JCP = 1.1, 5.1 Hz, CH3), 30.4 (dd, JCP = 1.1, 4.3 Hz, CH3), 31.2 (dd, JCP
= 1, 4.7 Hz, CH3), 33.4 (dd, JCP = 3.9, 7.2 Hz, CMe3), 34.3 (dd, JCP = 2.3,
11.3 Hz, CH2), 34.7 (dd, JCP = 2.2, 5.4 Hz, CMe3), 35.2 (dd, JCP = 1.9, 9.9
Hz, CMe3), 36.3 (dd, JCP = 4.5, 9 Hz, CMe3), 39.7 (d, JCP = 1.3 Hz, CH3),
50.5 (t, 2JCP = 2.3 Hz, CH), 76.3 (dd, JCP = 2.7, 10.5 Hz, CH), 246.9 (dd,
2JCP = 9.3, 10.3 Hz, NCH). [a]D20 + 876.20 (c = 0.24, toluene).
¶ Crystal data:
C23H48ClNP2Ru, M = 537.08, orthorhombic, a =
8.4390(2), b = 14.5810(4), c = 21.9890(5), V = 2705.73(12) Å3, T = 150
K, space group P212121 (no. 19), Z = 4, m(MoKa) = 0.71073 Å, Flack
Funding from WLU, NSERC, Ontario Government and
Research Corporation is gratefully acknowledged.
parameter 20.03(4), 21334 reflections measured, 6188 unique (Rint
=
0.0768) which were used in all calculations. The final wR(F2) was 0.0840
(all data). CCDC reference number 192434. See http://www.rsc.org/
suppdata/cc/b2/b208325f/ for crystallographic data in CIF or other
electronic format.
Notes and references
‡ Synthesis of 1: (a) L-glutamic acid (25 g, 169.9 mmol), formaldehyde
(37%, 60 mL, ca. 800 mmol) and palladium on carbon (10%, 8 g) were
stirred in 200 mL of water for 48 h under H2. Then the flask was purged with
nitrogen; the mixture was heated to reflux and filtered while hot. After
1 Reviews: M. Albrecht and G. van Koten, Angew. Chem., Int. Ed., 2001,
40, 3750; A. Vigalok and D. Milstein, Acc. Chem. Res., 2001, 34, 798; C.
M. Jensen, Chem. Commun., 1999, 2443; B. Rybtchinski and D. Milstein,
Angew. Chem., Int. Ed., 1999, 38, 870; B. L. Shaw, J. Organomet. Chem.,
1980, 200, 307.
evaporation, the white solid of N,N-dimethyl-(
under vacuum at 100 °C for 8 h. Yield: 28.17 g (95%). (b) A stirred
suspension of N,N-dimethyl-( )-glutamic acid (28.0 g, 159.8 mmol) in abs.
L)-glutamic acid was dried
L
methanol (100 ml) was cooled to 280 °C and treated with SOCl2 (47.6 g,
400 mmol) added dropwise over ca. 30 min. Stirring continued at room
temperature for 1 h and then at 40 °C for 16 h. After evaporation and drying
under vacuum, the residue was stirred with 100 mL of Et2O and 50 mL of
20% K2CO3. The aqueous phase was separated and discarded. The ether
2 F. Gorla, T. Togni, L. M. Venanzi, A. Albertini and F. Lianza,
Organometallics, 1994, 13, 1607; J. M. Longmire, X. Zhang and M.
Shang, Organometallics, 1998, 17, 4374; B. S. Williams, P. Dani, M.
Lutz, A. L. Spek and G. van Koten, Helv. Chim. Acta, 2001, 84, 3519; D.
Morales-Morales, R. E. Cramer and C. M. Jensen, J. Organomet. Chem.,
2002, 654, 44.
solution was dried over Na2SO4, filtered and evaporated. N,N-dimethyl-(
L)-
glutamic acid dimethyl ester was isolated by distillation (bp 83 °C/1 mm
3 D. G. Gusev and A. J. Lough, Organometallics, 2002, 21, 2601.
CHEM. COMMUN., 2002, 2432–2433
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