Phosphinite ligand effects in palladium(II)-catalysed cycloisomerisation of 1,6-dienes: Bicyclo[3.2.0]heptanyl diphosphinite (B[3.2.0]DPO) ligands exhibit flexible bite angles, an effect derived from conformational changes (exo- or endo-envelope) in the b

Article abstract of DOI:10.1002/adsc.200600346

Changes in bidentate ligand structure significantly affect catalytic activity in mono-cationic Pd(II)-catalysed 1,6-diene cycloisomerisation processes to give cyclopentene products. A bicyclo-[3.2.0]heptanyl diphosphinite ligand (B[3.2.0]DPO, 3) is the fi

Full text of DOI:10.1002/adsc.200600346

FULL PAPERS
DOI: 10.1002/adsc.200600346
Phosphinite Ligand Effects in Palladium(II)-Catalysed Cycloiso-
merisation of 1,6-Dienes: Bicyclo
C
ACHTREUNG
Derived from Conformational Changes (exo- or endo-Envelope)
in the Bicyclic Ligand Scaffold
Ian J. S. Fairlamb,a,* Stephanie Grant,a Simona Tommasi,a,b Jason M. Lynam,a
Marco Bandini,b Hao Dong,c Zhenyang Lin,c and Adrian C. Whitwooda
a
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK
Fax : (+44)-1904-432-515; e-mail: ijsf1@york.ac.uk
Dipartimento di Chimica “G. Ciamician”, Via Selmi 2, 40126, Bologna, Italy
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong
b
c
Kong, Peopleꢀs Republic of China
Received: July 12, 2006; Accepted: September 13, 2006
Abstract: Changes in bidentate ligand structure sig- sumed to be a cationic Pd(II) hydride species. DFT
nificantly affect catalytic activity in mono-cationic calculations support a change in bite angle on the
Pd(II)-catalysed 1,6-diene cycloisomerisation pro- cationic Pd(II) hydride species from circa 908 (cis) to
cesses to give cyclopentene products. A bicyclo- 1708 (trans); in the latter geometry an agostic inter-
ACHTREUNG[3.2.0]heptanyl diphosphinite ligand (BACHTRE[UNG 3.2.0]DPO, action of the C4 endo hydrogen of the bicyclic ring-
3) is the first phosphorus-based bidentate ligand ca- system with Pd(II) stabilises the cationic metal
pable of promoting regioselective 1,6-diene cycloiso- centre. This unique ligand property could be exploit-
merisation. Trace quantities of water are essential for ed in other transition metal catalysed processes.
catalytic activity, as is the precise order of mixing of
1,6-diene, Pd(II) pro-catalyst and additives. Confor-
mational changes in the ligand backbone seem to be Keywords: anion effects; C C bond formation; cycli-
important in stabilising the active catalyst species, as- zation; isomerization; palladium
ꢀ
Introduction
commonly five-membered ring systems (2a–c) (1’ is
occasionally seen as a side-product).
The transition metal-catalysed cycloisomerisation of
Several transition metals are known to promote
1,6-dienes (1!2a–c) is a powerful, atom-economic 1,6-diene cycloisomerisation (Ti,[2] Rh,[3] Ru,[4] Ni,[5]
and environmentally benign method for the efficient Pd[6]), and in the majority of reports, individual cata-
synthesis of carbo- and heterocyclic compounds lyst systems have been developed permitting regiose-
(Scheme 1);[1] the resultant cyclised products are most lective cycloisomerisation for one of the regioisomeric
products 2a–c. In terms of synthetic utility, GagnØ and
co-workers have studied [(triphos)Pt(II)]+ carbophilic
Lewis acid catalysts which cycloisomerise structurally
diverse 1,6-diene substrates to give terpenoid natural
products
and
related
derivatives
[triphos=
CH3C
AHCTREUNG
cycloisomerisation processes have begun to emerge as
potentially valuable synthetic strategies. Specifically,
chiral Pd[8] or Ni[9] catalysts have been reported. For
the former,
(CH3CN)2PdCl2/2 AgBF /
a
catalyst system consisting of
4 A(R,R)-4,4’-dibenzylbisoxazo-
CTHREUNG
Scheme 1. Products from 1,6-diene cycloisomerisation.
line or (ꢀ)-sparteine, gave promising enantiomeric
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Ian J. S. Fairlamb et al.
FULL PAPERS
Figure 1. Phosphinite ligands for 1,6-diene cycloisomerisation.
excesses (ees) up to 60% for 2b (37% for 2a), al- this full paper our comprehensive studies on the cy-
though conversions and regioselectivities remained cloisomerisation activity of 4a–d are reported. The
low (2a:2b, 1:1.1). In order to utilise Pd(II) catalysts/ importance of the bicyclo
ACHTREUNG
procatalysts in asymmetric 1,6-diene cycloisomerisa- elaborated upon, revealing that BAHCTREUNG
tion processes, it is essential that the regioselectivity ceptional ligand for this reaction. DFT calculations,
be controlled, in essence this is a mandatory require- NMR spectroscopic and X-ray diffraction studies pro-
ment. It was speculated that it ought to be possible to vide evidence that BACHTRE[UNG 3.2.0]DPO ligands are flexible
utilise readily available chiral phosphine or phosphin- enough to allow changes in bite angle around the
ite ligands to promote a regio- and enantioselective metal centre, which could be important in stabilisa-
process. We have screened many commercially avail- tion of the active catalyst species, thought to be a cat-
able chiral bidentate phosphine ligands, e.g., Trost ionic Pd(II) hydride.
modular ligands 5a and 5b,[10] Manniphos 6,[11] SpirOP
7[12] and DIOPO 8, as well as non-chiral ligands 9–11,
in combination with catalytic Pd(II) (neutral or cat- Results and Discussion
ionic), for the cycloisomerisation of 1, which generally
exhibited poor catalytic activity. The unique bidentate In an initial benchmark reaction a catalytic amount of
phosphinite ligand 3 (B
[3.2.0]DPO),[13] containing a [(B
ACHRTUNEG ACHTREU[GN 3.2.0]DPO)PdCl2] (5 mol%) was added to either
bicyclo[3.2.0]heptanyl skeleton and two phosphinite an anhydrous or reagent-grade DCE solution contain-
ACHTREUNG
donors at C3 and C6 in an endo-orientation, in combi- ing dimethyl diallylmalonate 1 at 40, 60 and 808C.
nation with monocationic Pd(II) (as 4), was then However, under these conditions negligible cycloiso-
shown to promote the regioselective cycloisomerisa- merisation was observed after 48 h; note that procata-
tion of 1 to give 2b (>90% isomer selectivity) lysts, e.g., (RCN)2PdCl2 (where R=t-butyl, methyl or
(Figure 1).[14] Remarkable effects on the regioselectiv- phenyl), developed by Lloyd-Jones and co-workers,
ity were broadly seen with BAr’4, BF4, OTf and SbF6 are particularly active under identical reaction condi-
anions. The best combination of catalytic activity and tions.[6b] There are several other Pd(II) procatalysts
regioselectivity was found for the non-coordinating reported for this reaction where a cationic Pd(II) spe-
BAr’4 anion (Ar’=bis-3,5-trifluoromethylphenyl). In cies is believed to be important.[1c,6c] The above cycloi-
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G
[3.2.0]DPO)Pd]2+[X]22ꢀ} at
[3.2.0]DPO)PdCl2] and {[(BACHTREUNG
Ligand Effects in Palladium(II)-Catalysed Cycloisomerisation of 1,6-Dienes
Table 1. Anion effects in Pd(II)-catalysed cycloisomerisation
FULL PAPERS
of 1!2a–c.[a]
the catalyst/substrate concentrations employed in
these experiments. Such phenomena are apparent
with other cationic Pd(II) catalysts/procatalysts;[8] one
would anticipate a less striking outcome to that ob-
served, on both catalytic activity and selectivity, on
comparison of the neutral, +1 and +2 cationic spe-
cies.
The order of mixing of reagents appears to be im-
portant. If the metal salt was added first to [(B-
AHCTREUNG
Entry
Additive
Reaction time [hours]
4
24
1
2
3
4
5
6
7
-
100/0/0/0
5/0/14/46[b]
46/0/54/0
90/0/10/0
90/0/10/0
0/0/5/53[d]
18/9/30/6[e]
98/1/2/0
8/0/5/57[c]
0/0/95/5
63/0/37/0
72/0/27/1
-
AgOTf [5 mol%]
NaBAr’4 [5 mol%]
AgBF4 [5 mol%]
AgSbF6 [5 mol%]
AgOTf [10 mol%]
NaBAr’4 [10 mol%]
-
AHCTREUNG
[a]
Reaction conditions (reaction as given in Scheme 1): 1
reactions were sluggish. After some experimentation,
it was found that 1 should be dissolved first in DCE
in a vial and then transferred to the reaction vessel,
(c=0.236M), [(BACHTRE[UGN 3.2.0]DPO)PdCl2] (5 mol%), DCE,
608C; Ratio of 1/2a/2b/2c was determined by 1H NMR
spectroscopy.
and then [(BCAHTRE[UNG 3.2.0]DPO)PdCl2] added, followed im-
[b]
[c]
[d]
[e]
Isomerised 1’ (35%) detected.
Isomerised 1’ (30%) detected.
Isomerised 1’ (37%) detected.
Isomerised 1’ (42%) detected.
mediately by the metal salt (under N2 atmosphere).
The reaction was then heated to 608C. A very slight
colour change is observed from a pale yellow to a
brighter yellow on addition of the metal salt; the pre-
cipitation of AgCl is apparent (solutions appear
somerisation reaction was conducted using one equiv- cloudy where NaCl is formed).
alent of either AgOTf, AgBF4, AgSbF6 and NaBAr’4, We next investigated the evolution of products 2b
[3.2.0]DPO)PdCl2], in DCE at and 2c, mediated by the [(B[3.2.0]DPO)PdCl2]/
NaBAr’4 (1:1, 5 mol%) catalyst system in reagent
with respect to [(B
A
ACHTREUNG
608C (Table 1).
Pronounced anion effects are seen in Table 1. The grade DCE at 608C, which is shown in Figure 2. Sig-
exo-methylenecyclopentene kinetic product 2a was nificantly, the kinetic profile exhibits the absence of
not detected for any of the additives investigated at an induction period (the reaction is slowed signifi-
608C (2a is seen in small quantities at 408C).[14] In the cantly in anhydrous DCE, purity >99.9%; conducted
presence of the OTf anion, cyclopentenyl product 2b in a dry-box at O2 levels <1 ppm). Prolonged reaction
is isomerised to 2c after 24 h (entry 2). Isomerisation to 72 h shows negligible isomerisation of 2b to 2c (re-
1
of 1 to 1’ was found for the OTf anion, which is most mains at ~95:5; as shown by H NMR spectroscopy).
likely initiated by the presence of triflic acid, a The selective formation of 2b is seen up to ~50%
common side-product formed from reaction of adven- conversion (4 h) and it is at this point that isomerisa-
titious H2O and [LnPd]
+A[OTf]ꢀ, which could also iso- tion to 2c becomes noticeable. Analysis of the reac-
CHTREUNG
merise 2b to 2c.[1c] The best combination of selectivity tion kinetics reveals that the consumption of 1 follows
and activity was established with the BAr’4 anion, pseudo first-order behaviour,
which after 24 h gave predominately 2b (95% selec- 10ꢀ5 sꢀ1 (see later for discussion).
k
obs =(3.90ꢁ0.15)”
tivity; entry 3). In terms of selectivity, the more coor-
dinating BF4 anion produces 2b exclusively, at the ex- the
Changing the solvent from DCE to CH3CN under
optimum conditions, namely [(B-
pense of higher conversion (entry 4). Only after 72 h
ACHTREU[GN 3.2.0]DPO)PdCl2]/NaBAr’4 (1:1, 5 mol%) at 608C,
is the more thermodynamically stable symmetrical resulted in a decrease in cycloisomerisation rate (6%
product 2c observed (AgBF4, 608C, 72 h; 1/2b/2c, 26/ conversion to 2b, 100% selectivity after 4 h). Compet-
73/1). For the SbF6 anion catalytic activity is compara- itive CH3CN coordination for monocationic Pd(II)
ble with the BF4 anion, although a trace quantity of presumably accounts for this finding.
2c is detected after 24 h (entry 5). Running reactions
Heating 2a, independently prepared by cycloiso-
(cod)Cl]n in i-PrOH at
[3.2.0]DPO)PdCl2] in DCE at 608C result- reflux, 89% 2a by H NMR spectroscopy (containing
ed in higher catalytic activity (entries 6 and 7). For ~11% in the presence of [(B-
2b),[4a]
the former OTf anion, the reaction was complete [3.2.0]DPO)PdCl2]/NaBAr’4 (1:1, 5 mol%) at 608C re-
with two equivalents of AgOTf or NaBAr’4 with re- merisation of 1 using [RuAHCTREUNG
1
spect to [(BACHTREUNG
AHCTREUNG
after 4 h (entry 6); for the latter BAr’4 anion, only sults in cycloisomerisation to the stable thermody-
18% of 1 remained after 4 h and a mixture of prod- namic products 2b and 2c (Table 2). The exo-methyl-
ucts 2a–c (entry 7). Extensive isomerisation of 1 to 1’ enecyclopentene 2a was isomerised to both 2b and 2c.
was seen for both cases. Crucially, it appears that We also assessed whether [(B
halide redistribution[15] is absent in this catalyst [BAr’4]ꢀ could catalyse the cycloisomerisation of 1
system, e.g., the monocationic species [(B- after isomerising 2a to 2b and 2c. Indeed, this proved
ACHTREUNG
[3.2.0]DPO)PdCl]+[X]ꢀ is not in equilibrium with [(B- to be a highly reactive catalyst system, and 2 h after
[3.2.0]DPO)PdCl]+-
ACHTREUNG
AHCTREUNG
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Ian J. S. Fairlamb et al.
FULL PAPERS
Figure 2. A: Kinetic profile for the cycloisomerisation of dimethyl diallylmalonate 1[38] by [(B
NaBAr’4 (5 mol%), DCE, 608C; monitored by H NMR spectroscopy (400 MHz); [1] at t0 =0.245M. Key: &, 1,6-diene 1;
A
1
&
,
*
endocyclic product 2b; , cyclopentenyl product 2c. B: Pseudo first-order kinetics for loss of 1,6-diene 1 {kobs =(3.90ꢁ0.15)”
10ꢀ5 sꢀ1}.
1
addition of 1 (26 h) complete consumption was found, methyl proton resonances in the H NMR spectrum,
affording a mixture of 2a–c, in favour of 2b. After a although it appeared that a mixture of diastereoiso-
further 24 h (50 h), 2a had disappeared, isomerised to meric products had been formed, ca. 1:1:2.5
2b; note that the proportion of 2c remains constant. (Scheme 2).
In a separate experiment, heating 2b exhibited slow
A crystal from this reaction was selected for study
isomerisation to 2c over 24 h. As for 2a, the addition by X-ray diffraction, which confirmed that spirodilac-
of 1 resulted in rapid cycloisomerisation, affording ini- tonisation had taken place to afford 12 (Figure 3).
tially 2a, in addition to 2b and small quantities of 2c The stereochemical course of the reaction may lead
after 2 h (26 h). After a further 24 h (50 h) the ratio to the formation of three diastereoisomers; the rela-
of 2b:2c was 93:7.
tive orientation of the substituents on the spiro-fused
lactones may be defined as symmetrical-syn, unsym-
metrical and symmetrical-anti.[17] The X-ray structure
confirms the stereochemistry as the symmetrical-syn
diastereoisomer, which occupies an unusual higher
Anion Effects
There is a possibility that cycloisomerisation of 1
could be promoted by a strong Lewis acid such as
SbF5 derived from HSbF6 {formed by reaction of [(B-
+A[SbF6]ꢀ and H2O}. Mechanistically,
ACHTREUNG[3.2.0]DPO)PdCl] CHTREUGN
it would seem plausible that six-membered ring prod-
ucts ought to be formed under such Lewis acid cataly-
sis, if a selective process could be identified.[16] Of
note is the finding that reactions mediated by catalytic
quantities of SbF5 did not promote cycloisomerisation.
Instead, some isomerisation of 1,6-diene 1!1’ occur-
red, in addition to a second more dominant reaction
pathway; the resultant product(s) from the latter reac-
tion showed loss of the alkenyl proton and ester Scheme 2. Reaction of 1 with catalytic SbF5.
Table 2. Further isomerisation of 2a and 2b by monocationic Pd(II).[a]
Cyclic product
Reaction time [hours]
0
2
4
24
26
50
2a
2b
0/89/11/0
0/0/97/3
0/63/18/19
0/0/95/5
0/59/19/22
0/0/95/5
0/24/36/40
0/091/9
1 equiv. of 1,6-diene 1 added
0/15/54/31
0/5/88/7
0/0/66/34
0/0/93/7
[a]
Reaction conditions: Cycloisomerisation product 2a or 2b (c=0.245M), [(BCATHRE[UNG 3.2.0]DPO)PdCl2] (5 mol%), NaBAr’4 (5
mol%), DCE, 608C; after 24 h 1 equiv. of 1 with respect to 2a or 2b was added to the reaction mixture; Ratio of 1/2a/2b/
1
2c was determined by H NMR spectroscopy.
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Ligand Effects in Palladium(II)-Catalysed Cycloisomerisation of 1,6-Dienes
FULL PAPERS
then followed by a more classical cyclisation process
(alkene protonation/carboxylate trapping of the resul-
tant carbocation).
Substrate Scope
Several 1,6-dienes were effectively cycloisomerised
with the [(BACTHER[UNG 3.2.0]DPO)PdCl2]/NaBAr’4 (5 mol%)
catalyst system (Table 3), which was generally effec-
tive providing that the 1,6-diene possessed a carbon
tether. Diethyl diallylmalonate 14 gave the cyclopen-
tenyl product 15 in>99% yield, in similar selectivity
to 2b (entries 1 and 2). Selective cycloisomerisations
Figure 3. X-ray crystal structure of spirocycle 12.
order symmetry space group, P43212.[18] 1H NMR spec- were also recorded for the pro-spirobicyclic 1,6-dienes
troscopic analysis of the crystals, in comparison with 16 and 18, to give spirobicycles 17 and 19 in >99%
the 1H NMR spectrum of the crude material, con- and 45% yields, respectively (entries 3 and 4). Disap-
firmed that this was the major diastereoisomer; the pointingly, substitution of the alkenyl moiety of 1, as
minor diastereoisomers seen in the crude reaction in 20 and 22, resulted in a dramatic loss of catalytic
mixture are thus the symmetrical-anti and unsymmet- activity (entries 5 and 6).
rical compounds.[18] The formation of 12 can be ra-
tionalised through consideration of the mechanism
provided in Scheme 3. Addition of SbF5 to the termi- Effect of Ligand Backbone
nal alkene generates secondary carbocation inter-
mediate I, which could potentially be trapped by the Given that the reaction conditions would be condu-
tethered alkene, however O-attack is evidently prefer- cive to the formation of HCl vide supra, we were
red to give II. Loss of MeX (e.g., X=Cl) affords cy- keen to test whether elimination of the bicyclic back-
cloadduct III which can then react with a proton to bone occurred in [(BCATHER[UNG 3.2.0]DPO)PdCl2] (or the mono-
generate the initial lactone product 13, which re- cationic species derived from reaction with MX) in
enters the cycle once more to give spirocycle 12. It is DCE. For certain types of phosphinites, oxygen proto-
highly likely that SbF5 also reacts with DCE to give nation leads to facile elimination to generate the so-
HCl amongst other products, but HCl is produced called[20] POPd dimer complex 24 (Figure 4). Indeed
from DCE on prolonged heating at 608C in the pres- we[14] and other groups[21] have observed deleterious
ence of trace quantities of H2O.[19] The super-acid degradation pathways for several monophosphinite li-
HSbF5OH could also be formed under the reaction gands in CH2Cl2, CHCl3 and DCE, and although it
conditions, which hydrolyses the esters first, which is does occur for certain bidentate and multidentate
Scheme 3. Mechanism to account for the formation of spirocycle 12.
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Ian J. S. Fairlamb et al.
FULL PAPERS
Table 3. Substrate scope for 1,6-diene cycloisomerisation reactions mediated by [(B
DCE at 608C for 24 h.[a]
ACHTREU[NG 3.2.0]DPO)PdCl2]/NaBAr’4 (5 mol%) in
Entry
1
1,6-Diene
Cycloisomerisation product
Yield [%][b]
94
Selectivity [%][c]
95
1
2b
2
3
14
16
15
17
>99
>99
93
76
4
5
18
19
45
66
20
22
21
23
4[d]
8[d]
>99
>99
6
[a]
1
Reactions were monitored by either H NMR spectroscopy, GC and/or GC/MS (where appropriate).
Yields are after purification by column chromatography.
[b]
[c]
Selectivity determined by 1H NMR spectroscopy of the crude reaction material. The regioisomeric cyclopentenyl products
cannot be separated by chromatography.
[d]
These numbers represent% conversion. We were unable to fully characterise these cyclic products, given the low conver-
sions (separation of 20 from 21, and 22 from 23, was not possible – identical Rf values). However, new alkenic signals,
consistent with structures 21 and 23 were observed by H and 13C NMR spectroscopy (the position of the trisubstituted
1
alkene can be explained by the mechanism shown in Scheme 8; see later).
25 exhibits no cycloisomerisation activity, complex 26,
formed in situ by reaction of 25 with NaBAr’4, isomer-
izes 1 to 1’ only.
We went on to investigate modifications to the
backbone structure of the bicyclic skeleton. Novel
ligand 28 was prepared from the known diol com-
pound 27[14] in 85% yield using standard conditions
(Scheme 4). This ligand reacts quantitatively with
Figure 4. POPd dimer complex 24.
(CH3CN)2PdCl2 in CH2Cl2 to give complex 29. Com-
plex 29 in CDCl3 solution exhibits a pair of doublets
(P1 at d=103.67, P2 at d=106.83, DdPP =3.16); a
[(B- lower difference in chemical shift for the two phos-
phosphinites,[22]
the
crystallization
of
A
environments
compared
to
[(B-
AHCTREUNG
2
AHCTREUNG
of 5 mol% NaBAr’4 promoted cycloisomerisation, tallised from CDCl3, which allowed the X-ray crystal
producing products 2a–c (entry 2). The result high- structure to be determined (Scheme 4). Interestingly,
lights the importance of the ligand backbone. Further- there is a difference in the bite angle in 29 when com-
ꢀ
ꢀ
more, we were able to evaluate the neutral and cat- pared with [(B
ionic Pd(II) complexes 25 and 26 containing two P2=94.01(2)8; for [(B
monophosphinite ligands (Figure 5). Whilst complex P2=95.99(2)8}.[14]
ACHTREU[GN 3.2.0]DPO)PdCl2] {for 29, P1 Pd
ꢀ
ꢀ
AHCTRE[UNG 3.2.0]DPO)PdCl2], P1 Pd
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Ligand Effects in Palladium(II)-Catalysed Cycloisomerisation of 1,6-Dienes
FULL PAPERS
Table 4. Catalytic activity of POPd dimer complex 24 in the
cycloisomerisation of 1.[a]
Solution and Solid-State Behaviour of the Cationic
Pd(II) Phosphinite Complexes
Entry
Additive
-
1
2a
2b
2c
To gain an insight into the solution behaviour of the
1
2
>99
15
-
26
-
31
-
15
monocationic
(solv)Cl]+[X]ꢀ (4a–d), 31P NMR spectroscopic studies
were carried out. Firstly, to a CDCl3 solution of [(B-
complexes
[(BACHTRE[UGN 3.2.0]DPO)Pd-
[b]
NaBAr’4
AHCTREUNG
[a]
Reagents and conditions: identical to Table 1.
Isomerised 1’ (13%) detected.
[b]
AHCTREU[GN 3.2.0]DPO)PdCl2] was added AgBF4 (1 equiv.) at
258C (c=100 mM);[23] the 31P NMR spectrum of this
reaction exhibited two broad signals (Figure 6).
At ꢀ208C these peaks sharpen to give two strong
doublets (P1 at d=105.90, P2 at d=99.01, DdPP =
2
6.89, JPP =49.7 Hz). At ꢀ508C, another minor species
becomes resolved (P1 at d=103.37; P2 at d=91.28,
2
DdPP =12.09, JPP =55.7 Hz). Given the absence of a
donor solvent (e.g., acetonitrile or methanol), and the
small difference in chemical shift, the major species
appears to be the Pd(II) dimer complex 30a with two
bridging chlorides, which is in equilibrium with the
monomeric complex 4a. To confirm this hypothesis an
identical experiment was performed in a mixture of
CDCl3/CD3CN (4:1, v/v) (Figure 7). The 31P NMR
Figure 5. Monophosphinites containing the bicycloCAHTRE[UNG 3.2.0]-
heptane ring.
Complex 29 in the presence of NaBAr’4 mediates spectra of [(BACHTERU[NG 3.2.0]DPO)PdCl2] in CDCl3 (spectrum
1,6-diene cycloisomerisation in DCE at 608C, albeit A) and in CDCl3/CD3CN (spectrum B) are shown for
slowly. After 4 h, the conversion to 2b was 10% (2a comparison (a small solvent-induced shift, ca. 1 ppm,
and 2c not observed). After 24 h, the conversion rises is seen in spectrum B). On addition of AgBF4
to 43%, with the isomer selectivity remaining>99%. (1 equiv.) to this solution, two new species are formed
To summarise this section, a very subtle modification at d=103.98 and d=91.88, appearing as doublets
2
to the ligand structure has a pronounced effect on the (DdPP =12.1; JPP =54.4 Hz) (spectrum C). The similar
rate of the cycloisomerisation reaction; other modifi- chemical shift and spin-spin coupling constant of the
cations in the bicyclic structure would similarly be ex- minor species observed at ꢀ508C in Figure 6, con-
pected to exert dramatic effects on the reaction rate firms that this is most likely the monomeric complex
and potentially product selectivity.
[(BACHRTENU[G 3.2.0]DPO)PdACHERT(UNG CD3CN)Cl] CHTREUNG
+A[BF4]ꢀ 4a. The obser-
Scheme 4. Synthesis of a brominated variant of [(BACHTERU[NG 3.2.0]DPO)PdCl2].
Adv. Synth. Catal. 2006, 348, 2515 – 2530
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Figure 6. Variable temperature 31P NMR spectra of [(B-
ACHTREUNG[3.2.0]DPO)PdCl2]/AgBF4 (1:1) in CDCl3 (202 MHz, in
CDCl3); solv.=CDCl3 or H2O (reversible on re-warming the
solution).
Figure 8. X-ray crystal structure of 30b. Top: complex with
phenyl groups on phosphorus removed, and 2”OTf and 2”
CHCl3 omitted for clarity. Bottom: Asymmetric unit with
OTf and CHCl3 omitted for clarity. Thermal ellipsoids at
ꢀ
ꢀ
50% probability level. Bond angles (8): O(1) P(1) Pd
ꢀ
ꢀ
ꢀ
ꢀ
119.58(11), O(2) P(2) Pd 115.55(11), P(1) Pd Cl(1)
ꢀ
ꢀ
ꢀ
ꢀ
93.81(3), P(2) Pd Cl(1) 169.60(4), P(2) Pd P(1) 90.10(4);
Bond lengths (Š): O(1) P(1) 1.587(3), O(2) P(2) 1.581(3),
P(1) Pd 2.259(10), P(2) Pd 2.232(10), Pd Cl(1) 2.410(9),
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Pd Cl(1) 2.393(10).
In CDCl3, in the presence and absence of acetoni-
trile, similar spectra were seen for the reaction of [(B-
AHCTRE[UNG 3.2.0]DPO)PdCl2] with AgOTf (1 equiv.). From the
CDCl3 solution crystallised the dicationic Pd(II)
dimer complex 30b, after several weeks at 258C in the
absence of acetonitrile (Figure 8).[24] The key bond
angles and bond lengths are given in Figure 8, howev-
Figure 7. 31P NMR spectra of [(B
(1:1) (c=12 mM, 202 MHz):
[3.2.0]DPO)PdCl2] CDCl3;
ACHTRE[UGN 3.2.0]DPO)PdCl2]/AgBF4
spectrum
spectrum
A=[(B-
B=[(B-
ꢀ ꢀ
er note that a narrow P M P’ bite angle is observed
G
in
(90.18), which is significantly different to the bite
[3.2.0]DPO)PdCl2] (95.98).[14] Crys-
angle found in [(BACHTREUNG
ACHTREUNG
ACHTREUNG
tals of 30b dissolve in CDCl3, giving rise to two broad
phosphorus signals at d=98.88 and d=105.78; the
chemical shifts confirm that this is a dimer in CDCl3
solution.
ACHTREUNG
&
&
Key:
major monomeric species 4a;
minor monomeric
species 4a’.
The 31P NMR spectra from the reaction of [(B-
AHCTRE[UGN 3.2.0]DPO)PdCl2] with NaBAr’4 (1 equiv.) in CDCl3
vation of a minor species at d=102.1 and d=90.3 alone were complex. At low temperature, several spe-
(DdPP =11.8; unresolved) is likely to be the isomeric cies were observed. Superior spectra were obtained
form of the major complex species (see later for dis- from the reaction of [(BACHTREUNG
cussion).
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Ligand Effects in Palladium(II)-Catalysed Cycloisomerisation of 1,6-Dienes
FULL PAPERS
nating solvent (e.g., CD3CN), the monomeric Pd(II)
complexes 4a and 4b are observed exclusively, even at
258C. At lower temperature the major and minor iso-
mers of the monomeric species are detected. The sit-
uation is different for non-coordinating anions (e.g.,
BAr’4); in CDCl3 a dynamic process is apparent,
which on cooling revealed a large number of different
species. On addition of CD3CN, a rapid equilibrium
between dimeric and monomeric Pd(II) species was
observed, which on cooling showed the predominant
appearance of the dimeric Pd(II) species 30d, as well
as the major isomer of the monomeric Pd(II) complex
4d. The proposed equilibrium is depicted in
Scheme 5; the isomeric forms are shown as 4 and 4’.
Figure 9. Variable temperature 31P NMR spectra of [(B-
[3.2.0]DPO)PdCl2]/NaBAr’4 (1:1) in CDCl3/CD3CN (4:1)
ACHTREUNG
On the Conformation of the Bicyclic Ring
&
*
(c=12 mM, 202 MHz). Key: dimeric species 30d; mono-
meric species 4d.
Although the variable temperature 31P NMR experi-
ments did not reveal different conformers in solution
(Figure 9). At 258C, two pairs of broad signals were at low temperature, direct evidence for the existence
observed; a major species at d=104.1 and d=99.3 of the higher energy exo-envelope conformation in
and minor species at d=103.7 (overlapping with d= the bicycloACHTRE[UGN 3.2.0]heptane skeleton was revealed in the
104.1) and d=92.3 (Figure 9). The major species formation of a unique Pd(0) dimeric complex [Pd2(B-
cleanly resolves to give a pair of doublets at lower
ACHRTEUNG[3.2.0]DPO)3], containing three bridging BACHTRENUG
temperatures (2JPP =54.5 Hz at ꢀ508C). The minor ligands, prepared by reaction of Pd
2ACHTREUNG
species resolves to a certain extent, although not
BACHTRE[UNG 3.2.0]DPO (ca. 3 equivs. per Pd), which was charac-
cleanly, the chemical shifts of which point to this terized principally by X-ray diffraction studies
being [(B[3.2.0]DPO)Pd(solv)Cl]
N
G
CHTREUNG
only isomer detected). Halving the concentration re- can adopt both endo and exo-envelope conformations.
sults in complex 4d becoming the major species in so-
lution. Attempts to crystallise the monocationic com-
plexes
[(B
G
(solv)Cl]+[X]ꢀ
(solv=
CH3CN, MeOH or CHCl3, X=BF4, OTf or BAr’4)
have been unsuccessful.
From these NMR spectroscopic studies we are able
conclude that coordinating anions in CDCl3, e.g., BF4
or OTf, favour formation of the dimeric Pd(II) com-
Figure 10. First example of BACHTER[UNG 3.2.0]DPO showing an exo-en-
plexes 30a and 30b. In the presence of added coordi- velope conformation.
Scheme 5.
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Theoretical Studies
The dynamic behaviour of the monocationic com-
plexes in solution, and the identification of the exo-
envelope conformation in [Pd2(BACHTRE[UNG 3.2.0]DPO)3] in the
solid-state, led us to consider further the potential for
conformational change in the bicyclic backbone. With
the results provided above and given that such ring-
flips are well documented for the bicyclo-
ACHTREUNG
[3.2.0]heptane ring system, this is conceivable.[26] The
equilibria are complicated by the ligand containing
two phosphinite environments in the cyclobutyl and
cyclopentyl rings, which means that the chloride
ligand may be cis or trans with respect to the C3 and
C6 phosphinite groups leading to the two different
isomeric forms. The relative stability of the proposed
structures (I and II) shown in Scheme 6 were thus
Figure 11. Relative energies of the monocationic Pd(II)
complexes.
two R groups associated with the phosphorus atom
ꢀ
cis to it. In the T-shaped A1 structure, the smaller Cl
ꢀ ꢀ
Pd P Me dihedral angle is 49.48, while in A2 the
ꢀ
ꢀ ꢀ
smaller Cl Pd P Me dihedral angle is 20.28.
Based on the relative energies calculated for the
three structural isomers, we believe that the major
and minor species observed on cooling a CDCl3 solu-
tion of the mono-cationic complexes 4a–d should be
related to the A1 and A2 structures, respectively. The
A3 structure is too high in energy to be in equilibrium
Scheme 6. The endo-to-exo envelope ring-flip.
studied. Several structural isomers for the model cat- with other structural isomers at temperatures below
ionic complex [{Me2PO(bicycloheptyl)OPMe2}PdCl]+ 08C (Scheme 7).
were calculated (optimised) with the aid of density
functional theory calculations at the B3LYP level.
The exchange between the chloro ligand and the
coordinated solvent ligand is expected to be a slow
Three relevant structural isomers were obtained process, allowing the detection of the two species in
from these calculations. Isomer A3 adopts a square solution at low temperature. The reason to propose
planar geometry around Pd and possesses an agostic an equilibrium involving the solvent is as follows. The
bond with an endo-disposed cyclopentyl hydrogen complexity in the structure of the diphosphinite
atom (Figure 11). The conformation of the bicyclo- ligand should give rise to some other energy mini-
heptyl moiety in this isomer is similar to that in II. mum structures. However, we do not expect larger
The relative energies indicate that A3 is unstable, al- barriers for the interchange processes among these
though containing an additional agostic bond. Struc- energy minimum structures. In other words, we
ꢀ
ꢀ
ture A3 shows longer P O and Pd P bonds in com- expect a fluxional nature of the diphosphinite ligand
parison with A1 and A2 (Figure 12). Therefore, the in solution. The observation of more than one species
instability of A3 is likely due to the structure experi- in solution from the 31P NMR spectra is unlikely due
encing strain as a result of maintaining favourable to the different conformers adopted by the diphos-
ꢀ
Pd P bonding interactions. Both A1 and A2 adopt a phinite ligand (due to high energy of A3, 12.6 kcal
T-shaped geometry around Pd, as expected for 14- molꢀ1).
electron ML3 complexes. The stability of the two
Interestingly, when Cl is replaced with H, we found
structural isomers is similar to each other. A1 is more that the A3_H structure is the most stable
stable than A2 by 3.2 kcalmolꢀ1. On examining the (Figure 12). The energy difference between A1_H
structures of A1 and A2, we believe that in A1 the re- and A2_H is smaller than that between A1 and A2.
pulsive interactions between the chloro ligand and the A hydride ligand is small and creates smaller repul-
two R groups associated with the phosphorus atom sive interactions when compared with a chloro ligand,
cis to it are smaller than the corresponding repulsive giving smaller energy difference between the two
interactions in A2. In each of the two isomers, there structures. The high stability of the A3_H structure
are two 1,4-repulsive interactions between Cl and the can be related to the strong trans-influencing property
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Ligand Effects in Palladium(II)-Catalysed Cycloisomerisation of 1,6-Dienes
FULL PAPERS
Figure 12. Calculated
structures
for
the
model
complexes
[{Me2PO(bicycloheptyl)OPMe2}PdCl]+
and
[{Me2PO(bicycloheptyl)OPMe2}PdH]+. The bond distances are given in angstroms and the bond angles in degrees (agostic
interaction shown in broken lines).
coordination unsaturation. However, contrary to what
we see for the chloro complex, we expect that the
population of the A3_H structure in solution, due to
its high intrinsic stability, should be comparable to the
other two species, making the A3_H structure poten-
tially observable in solution. At higher temperatures,
e.g., 608C, one may confidently predict that the A3/
A3_H conformer could play a role in catalysis.
Scheme 7. Equilibrium between 4 and 4’.
of the hydride ligand. The strong trans-influencing hy- On the Ligand Effects and Mechanistic Discussion
dride ligand destabilises both the A1_H and A2_H
ꢀ
structures because it significantly weakens the Pd P Monocationic Pd(II) complexes 4a–d, containing a B-
bond trans to it (Figure 12). In each of the A1 H and
ACHTRE[UNG 3.2.0]DPO ligand, promote the catalytic cycloisomer-
ꢀ
A2_H structures, the Pd P bond trans to the hydride isation of 1 to give 2a–c. The regioselectivity is influ-
ligand is longer than the other Pd P bond by more enced on changing the anion on Pd(II) (e.g., BAr’4,
ꢀ
than 0.22 Š. In the A3_H structure, the hydride BF4, OTf and SbF6), with the best selectivity found
ligand is trans to the agostic bond and has the shortest for the more bulky and non-coordinating BAr’4 anion.
distance with the metal centre in the three structures. It was determined that the neutral complex was an in-
Despite the high stability of the A3_H structure, we effective cycloisomerisation catalyst/procatalyst. In
do not expect that it is the major species in the solu- contrast, the dicationic complexes, although more
tion because the other two less stable structures active in cycloisomerisation, resulted in lower isomer
should have greater solvation energies due to their selectivity. A screen of other diphosphine and diphos-
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Ian J. S. Fairlamb et al.
FULL PAPERS
phinite ligands has revealed that B
A
Consideration of the ligand coordination and the
unique ligand for cycloisomerisation. It was possible bite angles exerted by BACHTREU[NG 3.2.0]DPO goes some way to
to eliminate other possibilities as the active catalyst explaining the poor reactivity of the other bidentate
species through testing the POPd dimer complex 24 phosphine and phosphinite ligands 7–10. Simple mo-
in the presence and absence of NaBAr’4, which lecular models of the Pd(II) complexes containing
showed poor isomer selectivity in comparison with these ligands indicate relatively small ligand bite
4d. Removal of the C3 phosphinite, as in Pd(II) angles ca. 90–1008, which are less flexible than B-
complex 25, again resulted in poor isomer selectivity.
ACHTRE[UNG 3.2.0]DPO. A small bite angle would lead to the sub-
Interestingly, modification of the ligand backbone to sequent monocationic Pd(II) complex being less
include a C2 exo-bromo substituent (e.g., in 30) ex- likely to form the Pd(II) hydride species resulting in
hibited lesser catalytic activity compared to 4a and poor catalytic activity.
4d.
The reaction kinetics showed pseudo first-order be-
31NMR spectroscopy clearly indicates that com- haviour in 1, which stands in contrast to the pseudo
plexes 4a–d are in equilibrium with the dimeric com- zero-order behaviour established for different Pd(II)
plexes 30a–d. On the other hand, the DFT calcula- catalyst systems by other groups.[6b,29] Given the com-
tions and solid-state studies support the proposal that prehensive experimental evidence supporting the in-
the BACHTREUNG[3.2.0]DPO ligands are flexible enough to allow volvement of a Pd(II) hydride as the active catalyst
changes in bite angle. The question that needs to be species,[32] the unexpected outcome in the reaction
addressed is whether this structural property is impor- order with respect to 1 allows us to propose [(B-
tant for the 1,6-diene cycloisomerisation process. On
[3.2.0]DPO)PdH]+[X]ꢀ as being the catalyst resting
ACHTREUNG
a general note, ligand bite angles can influence cata- state, which is ultimately regenerated in each turn-
lytic activity in transition metal catalysed processes over, and moreover dependent on the concentration
considerably. Indeed, Van Leuween and co-workers of 1. To probe the involvement of a Pd(II) hydride
have elegantly demonstrated that substantial changes species, Pd
in rates and selectivities are seen in hydroformylation, (Pd:L, 1:1) in DCE at 258C to give the intermediate
hydrocyanation, allylic alkylation and cross-coupling [(BC[3.2.0]DPO)Pd(0)
(h2-dba)] {P1 at d=108.1 and
2ACHRTEU(NG dba)3 was reacted with BACHTREU[GN 3.2.0]DPO
A
ACHTREUNG
reactions as a function of altering the ligand bite P2 at d=109.8 (br s), Dn1/2 =40 Hz }, which is not an
angle.[27] Relevant to our investigations are the studies active cycloisomerisation catalyst in its own right. A
reported by DuBois and co-workers who have shown solution of HBF4 (54% in Et2O, 1 equiv. with respect
that the ligand bite angle is able to control the hydric- to Pd) was added to this to generate initially [(BC-
ity of Pd(II) diphosphine complexes.[28] For a series of
[3.2.0]DPO)Pd(0)(h2-dba-H+)][BF4]ꢀ {P1 at d=108.9
ACHRTEUNG ACHTREUGN
[Pd(diphosphine)2]ACHTERU[NG BF4]2 and [Pd(diphosphine)2] com- and P2 at d=109.2 (br s); Dn1/2 =18 Hz}, which de-
plexes, it was established that Pd(II) complexes with grades to give a new species appearing as a pair of
2
small bite angles exhibit a geometry that is very close doublets {P1 at d=105.8 and P2 at d=110.4; JPP =
to square planar, while ligands with large bite angles 52.5 Hz). This species is most likely [(B-
distort the geometry from square planar to near tetra-
A
(solv)H]
T
Addition
of
1
hedral. Such a distortion towards a tetrahedral geom- (20 equivs.) to this solution resulted in some cycloiso-
etry results in stabilisation of the LUMO, resulting in merisation (ratio of 1’:2b:2c, 32:7:35), and although
a more favourable formation of a Pd(II) hydride spe- this outcome does not mirror the reaction mediated
cies. Consequently, Pd(II) diphosphine complexes by the [(BACHTER[UNG 3.2.0]DPO)PdCl2]/AgBF4 catalyst system
with large bite angles are good hydride acceptors and (entry 4, Table 1), it indicates that cycloisomerisation
poor hydride donors and, vice versa, we can predict of 1!2b and 2c is possible, as is the isomerisation 1!
that complexes with smaller bite angles are more 1’.[30]
likely to donate their hydride. Any variation in the
Our proposed mechanism for 1,6-diene cycloiso-
natural bite angle of the ligand will alter the hydricity merisation (Scheme 8) is similar to the Widenhoefer
of the Pd(II) hydride. Although their study focused mechanism [with cationic palladium(II) phenanthro-
on phosphines and not phosphinites, we may propose line complexes],[31] and Lloyd-Jones mechanism [with
that monocationic Pd(II) complexes 4a–d can flip be- neutral palladium(II) complexes containing nitrile li-
tween two conformational forms, allowing at least gands],[6b] and supported by our experimental findings
two bite angles. In the exo-envelope the Pd(II) hy- (Scheme 6). The catalytic cycle is dependent on the
dride species is stabilised, while a flip to the endo-en- generation of [(B
[3.2.0]DPO)PdH]+ (II) from [(B-
ACHTREUNG
velope would facilitate hydride donation. Since the re-
AHCTREUNG
actions are at elevated temperatures (608C) we would this occurs. The phosphinite ligand could undergo a
expect that there is a higher population of the exo- series of associative/dissociative processes (biden-
conformer of the ligand, enabling stabilisation of the tate!monodentate) throughout the catalytic cycle
Pd(II) hydride.
(not shown for simplicity). Hydropalladation of a
tethered alkene in 1 would form palladium alkyl
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Ligand Effects in Palladium(II)-Catalysed Cycloisomerisation of 1,6-Dienes
FULL PAPERS
Scheme 8. Plausible mechanism for cycloisomerisation of 1,6-dienes mediated by cationic Pd(II) complexes containing B-
ACHTREUNG[3.2.0]DPO ligands.
alkene intermediate IV, via initial intermediate III. for this mechanism. The formation of 2b through this
The reaction kinetics suggest that this step is slow. pathway indicates that the Pd(II) hydride moiety does
The pseudo first-order behaviour is consistent with not dissociate prior to the second hydropalladation
ꢀ
the intermolecular capture of the Pd H/insertion event (VI!VII!VIII). The very slow isomerisation
step. Monodentate coordination of the 1,6-diene 1 is of 2b to 2c indicates that 2b is also a poor ligand for
presumably reversible, with the pseudo first-order II, whereas 2a is an excellent ligand.
arising from the dependence of this equilibrium on
the concentration of 1. Intramolecular carbopallada-
tion of IV reveals palladium cyclopentylmethyl com- Conclusions
plex V which then undergoes b-hydride elimination to
form palladium methylenecyclopentane complex VI. In summary, a regioselective catalyst for 1,6-diene cy-
Loss of II provides product 2a. A second hydropalla- cloisomerisation has been identified. BACHTRE[UGN 3.2.0]DPO is
dation event in VII provides the syn tertiary palladi- clearly an exceptional ligand for this process, provid-
um cyclopentylmethyl complex VIII, from which a re- ing that a non-coordinating anion is using in combina-
gioselective b-hydride elimination process from the tion with Pd(II). In due course, our findings regarding
secondary hydrogen atom in VIII forms product 2b, the asymmetric process will be reported.
regenerating [(BACHTREUNG
[3.2.0]DPO)PdH]+ (II). Note that b-
hydride elimination cannot occur from the more sub-
stituted carbon in VIII.[6b] The formation of 2c can be
rationalised through steps IX!X. Recoordination of
II to 2a gives alkenyl Pd(II) complex IX. Hydropalla-
dation anti to the b-methyl substituent gives anti terti-
ary palladium cyclopentylmethyl complex VIII and
subsequent syn b-hydride elimination, which can then
undergo a syn b-hydride elimination to reveal 2c with
regeneration of II.
Experimental Section
General Remarks
Solvents were dried where necessary using standard proce-
dures prior to use and stored under an argon atmosphere.
Nitrogen gas was oxygen-free and was dried immediately
prior to use by passage through an 80 cm column containing
sodium hydroxide pellets and silica. Argon gas was used di-
rectly via balloon transfer or on a Schlenk line. TLC analysis
+A[BAr’4]ꢀ rap-
The finding that [(BACTHER[UGN 3.2.0]DPO)PdCl] CHTREUGN
idly isomerizes 2a to both 2b and 2c, provides support was performed routinely using Merck 5554 aluminium-
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Ian J. S. Fairlamb et al.
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backed silica plates or Macherey–Nagel polygramꢂ ALOX
N/UV254 aluminium oxide-coated plastic sheets. Com-
pounds were visualised using UV light (254 nm) and a basic
aqueous solution of potassium permanganate or acidic DNP
(dinitrophenol hydrazine). GC parameters: analysis was per-
formed using a Varian CP-3800 GC equipped with a CP-
8400 Autosampler. Separation was achieved using a DB-1
column (30 m”0.32 mm, 0.25 mm film thickness) with carrier
gas flow rate of 3 mLminꢀ1 and a temperature ramp from
508C to 2508C at 208C minꢀ1. The injection volume was
1 mL with a split ratio of 50. Mass spectrometry was carried
out using a Fisons Analytical (VG) Autospec instrument.
1H NMR spectra were recorded at 400 MHz using a JEOL
ECX 400 spectrometer or 500 MHz on a Bruker AV 500
spectrometer; 31P NMR spectra were recorded at 202 MHz
(1H decoupled). Chemical shifts are reported in parts per
million (d) downfield from an internal tetramethylsilane ref-
erence. Coupling constants (J values) are reported in Hertz
(Hz), and spin multiplicities are indicated by the following
symbols: s (singlet), d (doublet), t (triplet), q (quartet), m
(multiplet), br (broad).
Compounds 1 (prepared from dimethyl allylmalonate),
2a–c, 14–20 and 22 have been previously reported (the
NMR and MS data are in agreement with literature
data).[6b,d] Complexes 24--26 have been reported previous-
ly.[14] NaBAr’4 was prepared as described by Brookhart
et al.,[32a] taking into consideration the points made by Berg-
mann and Yakelis.[33b] AgBF4, AfOTf, AgSb6 and anhydrous
DCE were purchased from Sigma–Aldrich. Reagent grade
DCE was purchased from Alfa-Aesar.
16 h. After this time, the mixture was passed through
Celiteꢂ under nitrogen atmosphere [washed through with
THF (50 mL)]. The solvent was removed under vacuum to
give 28 as a viscous cloudy white oil (>85% yield), which
was reacted directly with (CH3CN)2PdCl2 in the next step.
This compound was handled as the free ligand in a dry-box,
as it is air sensitive. Selected data: 31P NMR (dry and de-
gassed CDCl3, 202 Hz): d=108.42 (s) and 114.01 (s).
[3-endo-6-endo-Bis(diphenylphosphinooxy)-2-exo-
bromobicyclo
(29)
ACHTRE[UNG 3.2.0]heptanyl]palladium(II) Chloride
To a solution of 28 (182 mg, 0.31 mmol, 1 equiv.) in dry
CH2Cl2 (3.0 mL) was added via cannula transfer a solution
of (CH3CN)2PdCl2 (93 mg, 0.31 mmol, 1 equiv.) in CH2Cl2
(3 mL). The solution was allowed to stir for 2 h at 258C.
The solvent was removed under vacuum to afford a pale
yellow solid; yield: 145 mg (70%); mp 228–2298C
(decomp.); 1H NMR (CDCl3, 500 MHz): d=2.22 (1H, m,
H4exo), 2.35 (2H, m, H5 and H4endo), 2.78 (2H, m, H1 and
2
H7exo), 3.26 (1H, d, J=15.6, H7endo), 4.19 (1H, 2, H2), 4.29
2
(1H, br s, H3exo), 4.50 (1H, t, J=4.2, H6exo), 7.28 (3H, m,
Ar), 7.53 (10H, m, Ar), 7.75 (3H, m, Ar), 7.98 (4H, m, Ar);
31P NMR (CDCl3, 202 Hz): d=103.67 (d, 2J=56.6 Hz),
2
106.83 (d, J=56.6 HZ); MS (FAB): m/z=717 (M+ꢀCl, 66),
682 (M+ꢀ2Cl, 8), 573 (M+ꢀ2Cl-Pd, 7), 509 (17), 461 (27),
401 (60), 281 (37), 207 (45), 147 (100), 139 (95); anal. calcd.
for C31H29O2P2Cl2BrPd: C 48.46, H 3.88; found: C 48.74, H
4.04.
General Procedure for the Monocationic Pd(II)
Complexes
General Procedure for 1,6-Diene Cycloisomerisation
To a stirred solution of the 1,6-diene (50 mg, 0.236 mmol,
1 equiv.) in analytical reagent grade DCE (1 mL) was added
[(BACHTREUNG[3.2.0]DPO)PdCl2] (7.9 mg, 0.012 mmol, 0.05 equivs.), fol-
Detailed information concerning the characterisation of
these complexes can be found in the main text of the paper.
With magnetic stirring, a CDCl3 solution (0.5 mL), or
CDCl3/CD3CN solution (4:1, v/v), containing [(B-
lowed immediately by the appropriate metal counter ion
(0.012 mmol, 0.05 equivs.), at room temperature. The reac-
tion was heated in a preheated oil bath at the relevant tem-
perature (temperature quoted is that of the oil-bath and
monitored by an external temperature probe, ꢁ18C). An
aliquot from each reaction mixture (ca. 30–50 mL) was fil-
tered through a short silica-gel plug using CH2Cl2 (1 mL),
which was concentrated under vacuum (no further conver-
sion was detected in these analysis samples). This sample
was taken up in CDCl3 and reaction progress monitored by
1H NMR spectroscopy. On several occasions GC was em-
ployed to monitor reaction progress. Conversions by GC
AHCTREUNG
[3.2.0]DPO)PdCl2] (10 mg, 1.5”10ꢀ5 mol) was added the ap-
propriate metal salt (1.5”10ꢀ5 mol). A precipitate forms
almost immediately. The solid precipitate was allowed to
settle, and then the solution was transferred by cannula to a
NMR tube, and analysed directly by NMR spectroscopy.
The solutions were injected into an ESI-MS/MS to confirm
the molecular ions (in + mode) and anions (in ꢀ mode);
MS (ESI, + mode): m/z=636.9 (M+ꢀBAr’4, 100); identical
spectra were obtained for the dimer (doubly charged) and
monomer (singly charged) complexes.
1
were compared with those determined by H NMR spectros-
Variable Temperature 31P{1H} NMR Experiments
copy, through integration of the methyl signals of the cyclo-
isomerisation products or the methylene signals of the 1,6-
diene.
Experiments were run on a Bruker AV 500 spectrometer,
running at 202.47 MHz. Where a mixture of CDCl3/CD3CN
was used, the solvent lock was on CDCl3. A low tempera-
ture calibration was performed using neat MeOH as previ-
ously described.[33] In brief, with the sweep set to off, a
1H NMR spectrum was recorded. The difference between
the two proton signals (A and B) represents an absolute
value of Dn in Hz at a given temperature. Using the follow-
ing equation, with the appropriate values of A and B, the
actual temperature of the sample was calculated {Tcalibrated
(K)=403ꢀA·DnꢀB·(Dn)2} (A=0.059 and B=9.53”10ꢀ5 at
500 MHz).
Synthesis of Ligand 28
Under an atmosphere of argon a THF solution (10 mL) of
diol 27[14] (400.0 mg, 1.9 mmol, 1 equiv.) was cooled to 08C
and then Et3N (562 mL, 4.04 mmol, 2.1 equivs.) in THF
(2 mL) was added by cannula and allowed to stir at this tem-
perature for 0.5 h. Chlorodiphenylphosphine (740 mL,
4.04 mmol, 2.1 equivs.) was added dropwise slowly at 08C.
Et3N·HCl formed immediately (precipitate). The mixture
was allowed to warm to 258C and stirring was continued for
2528
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ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 2515 – 2530

Ligand Effects in Palladium(II)-Catalysed Cycloisomerisation of 1,6-Dienes
FULL PAPERS
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Computational Details
Density functional theory calculations at the B3LYP level
were performed to calculate the structures of the model
complexes.[34] The effective core potentials (ECPs) of Hay
and Wadt with a double-z valance basis set (LanL2DZ)
were used for Pd, Cl, and P.[35] The 6–31G basis set was used
for C, H, and O.[36] Polarization functions were also added
for C (zd =0.6), O (zd =1.154), Cl (zd =0.514), and P (zd =
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Acknowledgements
I. J. S. F. thanks the Royal Society for a University Research
Fellowshipand generous equipment grant. We thank EPSRC
for a Ph.D. studentshipto S.G., Stylacats Ltd. for CASE
funding, and Prof. S. M. Roberts for supporting this project.
Heather Fish is thanked for assistance with low temperature
NMR experiments, and Mr. B. E. Moulton for help with X-
ray crystallography. We thank the University of Bologna
(Italy) for supporting a research stay in York for S.T. We are
grateful to Prof. G. C. Lloyd-Jones (Bristol) for discussions
concerning this work.
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3
c, 22.023(4) Š, U=899.1(2) Š
T=100(2) K, l=
(Mo-Ka)=
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0.71073 Š, space group P43212, Z=4,
mACHTREUNG
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Adv. Synth. Catal. 2006, 348, 2515 – 2530