Phosphine-alkene ligand-mediated alkyl-alkyl and alkyl-halide elimination processes from palladium(ii)

Article abstract of DOI:10.1039/c2cc35623f

N-Diphenylphosphino-7-aza-benzobicyclo[2.2.1]hept-2-ene (2) behaves as a chelating phosphine-alkene ligand for Pd⁰ and Pd^II, promoting direct alkyl-alkyl and indirect alkyl-halide reductive elimination reactions due to the stabilisation of the resulting bis(phosphine-alkene)Pd ⁰ complex.

Full text of DOI:10.1039/c2cc35623f

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COMMUNICATION
Phosphine–alkene ligand-mediated alkyl–alkyl and alkyl–halide
elimination processes from palladium(II)w
Luke Tuxworth,ab Lise Baiget, Andreas Phanopoulos, Owen J. Metters,
ab
b
b
b
ab
b
ab
Andrei S. Batsanov, Mark A. Fox, Judith A. K. Howard and Philip W. Dyer*
Received 2nd August 2012, Accepted 31st August 2012
DOI: 10.1039/c2cc35623f
II
N-Diphenylphosphino-7-aza-benzobicyclo[2.2.1]hept-2-ene (2)
0
behaves as a chelating phosphine–alkene ligand for Pd and
elimination from Pd , we sought to explore the efficacy of a
chelating phosphine–alkene (P–alkene) framework combining
II
Pd , promoting direct alkyl–alkyl and indirect alkyl–halide
a weakly basic R
1
3
P moiety with a strongly p-accepting alkene
To this end, we describe here our use of a strained
2–14
reductive elimination reactions due to the stabilisation of the
0
resulting bis(phosphine–alkene)Pd complex.
unit.
bicyclic 7-aza-norbornene motif to maximise Pd-to-alkene
p-retrodonation through relief of ring strain.
2
The ligand N-Ph P-7-aza-benzobicyclo[2.2.1]hept-2-ene (2) was
Palladium-mediated catalytic transformations are at the heart
of contemporary synthetic organic chemistry, enabling the
prepared in 69% yield from 7-aza-benzobicyclo[2.2.1]hept-2-
ene (1), via a straightforward nucleophilic substitution strategy,
1
,2
controlled formation of C–C and C–heteroatom bonds.
1
5,16
Scheme 1.
3
w Compound 2 presents a single resonance by
31 1
Manipulation of these reactions necessitates a detailed under-
standing of the overall reaction trajectory and each step involved
in the catalytic cycle, e.g. oxidative addition, transmetallation,
insertion, and reductive elimination. In particular, establishing
factors that control reductive elimination from palladium is
crucial, since it is often this step that leads to final product
formation, via either a direct (four-coordinate) or indirect (three-
1
1
P{ H} NMR spectroscopy, d P{ H} 41.6 ppm, typical of an
aminophosphine. The barrier to inversion at nitrogen in
1
7
compound 2 has been determined computationally (B3LYP/
–
1
–1
6
-31G*) to be low, B3 kcal mol (cf. 16 kcal mol computed
for amine 1), permitting 2 to adopt the necessary conforma-
2
tion for k -P,C P–alkene metal chelation. The magnitude of
1
3,4
JSe–P (792 Hz) for the phosphine–selenide 2ꢀSe confirms that
coordinate) transition state. Rates of reductive elimination are
intimately linked to the nature of the coupling partners and to
the palladium’s ancillary ligands, with both steric and electronic
1
7
the phosphorus donor moiety of 2 is weakly basic. w
To probe the ability of P–alkene 2 to enhance reductive
II
elimination from Pd , its reaction with PdMe and PdCl(Me)
5
factors playing a significant contribution in each case. Much
2
fragments has been explored. Treating a toluene solution of
effort has been devoted to studying the impact of a variety
of monodentate phosphine and bidentate diphosphine metal
scaffolds; both their s-donor character and chelate bite angle
PdMe (tmeda) with one equivalent of compound 2 cleanly affords
2
2
cis-[PdMe (k -P,C-2)] (3), which exhibits a single resonance
2
3
1
1
6–9
(
d P{ H} 81.2 ppm), consistent with P–Pd binding. Coordination
having been found to impact directly on elimination rates.
of the olefinic moiety is reflected in a shift to lower frequency of
the alkene carbon resonance (2: d 144.3 ppm; 3: d 119.2 ppm).
Complex 3 is thermally unstable in solution and over 5 days at
r.t. smoothly evolves to afford half an equivalent of the mono-
Recently, efforts have begun to focus on the use of heteroditopic
chelate ligands to increase control and further promote elimina-
tion. For example, a phosphine bearing a pendant electron
deficient alkene has been shown to favour reductive elimination
over a competing b-hydride elimination reaction pathway in
0
2
31
1
metallic Pd complex [Pd(k -P,C-2)
2
] (4) (d P{ H} 82.3 ppm)
1
10,11
and ethane (d H 0.82 (s) ppm) as the only organic product,
according to H and P NMR spectroscopy, accompanied by
Negishi cross-couplings.
The system’s selectivity was attributed
1
31
to the presence of the strongly p-accepting alkene moiety.
Since it is now well established that weakly trans influencing,
poorly-donating/electron-accepting phosphines favour reductive
the precipitation of elemental palladium (Scheme 2).z By
comparison, complete thermolysis of [PdMe (dmpe)] is only
2
1
8,19
achieved upon heating at 90 1C for 1 week,
highlighting
a
Centre for Sustainable Chemical Processes, Department of
Chemistry, Durham University, South Road, Durham, DH1 3LE,
UK. E-mail: p.w.dyer@durham.ac.uk; Fax: +44 (0)191 334 2150;
Tel: +44 (0)191 384 4737
Department of Chemistry, Durham University, South Road, Durham,
DH1 3LE, UK
b
w Electronic supplementary information (ESI) available: Experimental
details and characterization data, including crystallographic data for 3
and 4; computational studies. CCDC 894607 and 894608. For ESI and
crystallographic data in CIF or other electronic format see DOI:
Scheme 1 Conditions: (i) Ph PCl, NEt
2
3
, CH
2
Cl
2
, ꢁ30 1C to r.t., 12 h,
10.1039/c2cc35623f
69%; (ii) Se, CDCl , r.t., 15 min, 100%.
3
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Chem. Commun., 2012, 48, 10413–10415 10413

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Scheme 2 Conditions: (i) toluene, r.t., >99%; (ii) toluene, r.t., 120 h,
99%.
>
the potential of ligand 2 in promoting reductive elimination
Scheme 3 Conditions: (i) toluene, r.t., >99%.
processes.
The X-ray molecular structures of complexes 3 and 4
2
the pathway from 3 to 4. Consequently, we propose that the
second equivalent of ligand 2 reacts with complex 3 to form a
five-coordinate intermediate 5, which then undergoes rapid
reductive elimination to afford 4 (Scheme 3).
(
Fig. 1)y confirm k -P,C chelation of 2. In complex 3 the
palladium centre is planar, with one site occupied by the
2
midpoint (Md) of the Z -bound C(2 )Q C(3) bond, which
is inclined by 88.31 to the coordination plane. The bond
distances to palladium fall within the range observed for
The rate of reductive elimination from complex 5 is likely to
be much greater than that from tetracoordinate complex 3
since prior reports have clearly established rate enhancements in
2
20–24
other complexes of the type cis-[PdCl
2
(Z ꢁCQC)(PR
3
)].
2
7
Consistent with moderate Pd - p*(CQC) retro-donation, the
reductive elimination with increasing coordination number.
˚
C(2)QC(3) bond in 3 (1.359(3) A) is longer than the corres-
ponding bond in an uncoordinated analogue of 2, N-BOC-
The intermediacy of a five-coordinate species here is further
supported by the observation that treating complex 3 with
2
5
˚
aza-benzonorborna-diene oxadisilole (1.315(4) A).
3
either 5 mol% of PPh or propene both lead to a significant
In complex 4, the Pd coordination geometry is distorted-tetra-
increase in the rate of reductive elimination of ethane, with
formation of 4 being complete within 7 and 30 h, respectively, at
20 1C (cf. 120 h in the absence of L-donor ligand).
hedral, with the Md-Pd–P planes of the two P–alkene ligands
2
forming an 89.11 dihedral angle. Although the Z -coordinated
˚
CQC bonds of 4 are longer (1.401(2) and 1.406(2) A) than that of
To probe the role of the alkene moiety of 2 in promoting
3
1
1
3
, as would be expected, the difference is only moderate due to the
reductive elimination from 3, the P–alkane ligand 6 (d P{ H}
38.6 ppm), possessing an aza-norbornane rather than aza-
norbornene framework, was prepared from N-BOC-7-aza-
10
26
comparatively poor p-donor character of d palladium species.
If PdMe (tmeda) is treated instead with 2 in a Pd : 2 ratio of
: 2, much faster and quantitative formation of 4 is achieved
5 h, 20 1C) consistent with rapid reductive elimination.
2
2
8
1
benzobicyclo[2.2.1]heptane. w Reaction of two equivalents of
1
(
6 with PdMe (tmeda) in toluene forms cis-[PdMe
2
2 2
(k -P-6) ] (7),
31
1
P{ H} 61.0 ppm, which isomerises cleanly to the trans-
Investigation of this reaction by variable temperature NMR
d
3
1
1
spectroscopy (VT NMR) did not reveal any intermediates on
diphosphine complex 8 (d P{ H} 59.7 ppm,) within 24 h
at 20 1C (Scheme 4); no further reaction of 8 is observed even
in the presence of excess 6 at 60 1C. Clearly k -P,C chelation is
vital in retaining the necessary cis geometry for reductive
2
elimination from 3.
Due to significant M–Cl bond polarisation the barrier to
alkyl chloride reductive elimination is much greater than that
for alkyl–alkyl elimination; consequently, to the best of our
II
14
knowledge no examples from Pd have been reported. There-
fore we were interested to probe whether P–alkene ligand 2 could
also promote alkyl halide elimination. Notably, reaction of 2
with cis-PdCl(Me)(cod) (Pd : 2 = 1 : 1) does indeed give rise to
0
Pd complex 4 (consistent with reductive elimination), which is
formed extremely rapidly (reaction complete within seconds at
ꢁ
40 1C according to VT NMR). However, 4 is obtained along
31
1
with an equimolar quantity of 9 (d P{ H} 38.1 ppm), the methyl
phosphonium chloride salt of 2, and leaving unreacted palladium
starting material. In contrast, treating cis-PdCl(Me)(cod) with
three equivalents of 2 rapidly and quantitatively affords a 1 : 1
mixture of 4 and 9 as the only products (Scheme 5).
An analogous reaction of cis-PdCl(Me)(cod) with two or
three equivalents of the P–alkane ligand 6 (B5 min, 20 1C)
1
31
affords only trans-[PdCl(Me)(k -P-6) ] (10) (d P 6.7 ppm). To
2
Fig. 1 X-ray molecular structures of 3 and 4; thermal ellipsoids at
˚
5
2
0% probability level. Selected bond distances (A) in 3: Pd–P
.2876(6), Pd–C(01) 2.068(3), Pd–C(02) 2.074(3), Pdꢀ ꢀ ꢀC(2) 2.238(2),
Pdꢀ ꢀ ꢀC(3) 2.266(2), P–N 1.732(2); in 4: Pd–P(1) 2.3440(4), Pd–P(2)
2
2
1
.3341(4), Pdꢀ ꢀ ꢀC(2) 2.1901(14), Pdꢀ ꢀ ꢀC(3) 2.1912(15), Pdꢀ ꢀ ꢀC(12)
.2095(15), Pdꢀ ꢀ ꢀC(13) 2.1916(14), P(1)–N(1) 1.7470(13), P(2)–N(2)
.7454(13).
Scheme 4 Conditions: (i) toluene, r.t., >99%; (ii) toluene, r.t.,
24 h, >99%.
1
0414 Chem. Commun., 2012, 48, 10413–10415
This journal is c The Royal Society of Chemistry 2012

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˚
a = 10.2185(3), b = 10.6113(4), c = 19.2717(7) A, b = 104.176(14)1,
3
ꢁ1
˚
U = 2026.0(1) A , Z = 4, m = 1.00 mm , 26 057 reflections (2y r
2
6
01), Rint = 0.061, R = 0.031 on 4196 data with I Z 2s(I), wR(F ) =
.061 on all 5912 unique data. CCDC 894607. 4, C44 Pd,
0
36 2 2
H N P
M = 761.09, triclinic, space group P 1% (No. 2), a = 11.9327(6), b =
Scheme 5 Conditions: (i) toluene, r.t., >99%.
˚
1
8
2.2787(6), c = 13.2937(6) A, a = 70.057(7), b = 74.120(7), g =
1.517(7)1, U = 1757.92(7) A , Z = 2, m = 0.65 mm , 40 908
3
ꢁ1
˚
reflections (2y r 701), Rint = 0.038, R = 0.036 on 11 656 data with
2
I Z 2s(I), wR(F ) = 0.088 on all 14 631 unique data. CCDC 894608.
1
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1
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0
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Durham University and the EU (Marie Curie IE Fellowship
to LB) are gratefully acknowledged for financial support.
Johnson Matthey is thanked for the loan of palladium salts.
Dr A. M. Kenwright and Mr I. H. McKeag are thanked for
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1
31
1
z Integration of both the H and P[ H] NMR spectra was quantified
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y Bruker SMART 6000 CCD area detector, Mo-K
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˚
.71073 A), T = 120 K, Olex2 software.
0
C
24
H
1
This journal is c The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 10413–10415 10415