First titanium-catalyzed 1,4-hydrophosphination of 1,3-dienes

Article abstract of DOI:10.1002/chem.200901863

"Chemical Equation Presented" Titanium complexes outshine other catalysts: Titanium complexes have been found to catalyze 1,4-hydrophosphination of dienes, which is thought to proceed through an allyl intermediate (see scheme). Unprecedented regioselectivities (1,4- vs. 1,2-) are reached by using [TiCp₂(PMe₃)₂] or a titanocene complex bearing a pendant phosphine tether as catalysts.

Full text of DOI:10.1002/chem.200901863

DOI: 10.1002/chem.200901863
First Titanium-Catalyzed 1,4-Hydrophosphination of 1,3-Dienes
Arnaud Perrier, Virginie Comte, Claude Moꢀse, and Pierre Le Gendre*[a]
Tertiary phosphines are useful compounds widely em-
ployed as synthetic reagents in organic synthesis and as li-
gands for transition-metal complexes in organometallic cat-
alysis. These compounds can be readily prepared by nucleo-
philic substitution using either phosphide anions or halo-
geno phoshines. A cleaner route to these compounds in-
phosphines react in a similar way with titanocene. On the
basis of this analogy and of our preliminary results on hy-
drosilylation,[15] we decided to examine the hydrophosphina-
tion of dienes using titanium-based catalysts. In an initial ex-
periment, we carried out the reaction with isoprene and di-
phenylphosphine as substrates and [TiCp2ACHTNUGTRENUNG(PMe3)2] as a pre-
À
À
volves the addition of a P H bond to an unsaturated C C
bond. This reaction, so-called hydrophosphination,[1] can be
achieved under strong basic conditions[2] or radical activa-
tion.[3] Recently, metal-catalyzed hydrophosphination was
revealed to be an attractive method that generally offers
better control over regio- and stereoselectivity. In 1990,
Pringle and Smith described the platinum-catalyzed hydro-
phosphination of acrylonitrile.[4] Ten years later, Marks and
Douglass described the lanthanide-mediated intramolecular
hydrophosphination of unactivated alkenes.[5] Since these
pioneering works, the range of precatalysts for intra- and in-
termolecular hydrophosphination was extended to other
metals such as nickel,[6] palladium,[7] rhodium,[8] cobalt,[9] or
ruthenium.[10] Surprisingly, only one result using an early
transition metal has been described,[11,12] although their use
for the closely related hydroamination reaction has been
known for a long time and clearly offers significant bene-
fits.[13] Among these are the low cost of the metals, their low
toxicity, and their eco-compatibility. Herein, we report the
first regioselective 1,4-hydrophosphination of dienes using
titanocene derivatives.
catalyst. The titanium species was first briefly heated at
908C with diphenylphosphine, resulting in a color change
from brown to dark green. The flask was then cooled down
to room temperature and isoprene was added dropwise. The
reaction mixture was further stirred at 908C and monitored
by GC analysis. To our delight, no remaining diphenylphos-
phine was detected after only three hours. NMR analysis of
the products obtained after sulfidation confirmed that the
hydrophosphination of isoprene occurred leading almost ex-
clusively to the (3-methyl-but-2-enyl)diphenylthiophosphine
(1a), which corresponds to the 1,4-tail-addition product
(Scheme 1). Thus, for the first time, a titanium-based com-
Scheme 1. Titanium-catalyzed hydrophosphination of isoprene.
In 1998, Harrod et al. published an article dealing with
the heterodehydrocoupling of phosphines and silanes cata-
lyzed by titanium complexes.[14] He noticed that silanes and
plex is revealed to be a remarkably efficient catalyst for the
hydrophosphination of isoprene and outshines other cata-
lysts in term of regioselectivity.[16,17]
The difficulty in handling trimethylphosphine and the air-
[a] A. Perrier, Dr. V. Comte, Prof. C. Moꢀse, Prof. P. Le Gendre
Institut de Chimie Molꢁculaire de l’Universitꢁ de Bourgogne
ICMUB-UMR CNRS 5260
sensitive [TiCp
other titanium(II) species to promote the reaction (Table 1).
At first, we simply replaced [TiCp2A(PMe3)2] by the unpro-
tected titanocene “[TiCp2]” generated in situ by adding two
2ACHTUNGTERN(NUNG PMe3)2] prompted us to scrutinize some
CTHUNGTRENNUNG
Universitꢁ de Bourgogne
9 avenue Alain Savary, BP 47870, 21078 Dijon Cedex (France)
Fax : (+33)3-80-39-60-98
AHCTUNGTRENNUNG
equivalents of nBuLi to a solution of titanocene dichloride
in toluene. Using these conditions, the hydrophosphination
of isoprene from PPh2H proceeded as fast as the hydrophos-
phination catalyzed by [TiCp2ACHTNUGTRNEUNG(PMe3)2], but led to a mixture
of 1,2- and 1,4-tail-addition products in a 1:1 ratio (Table 1,
E-mail: pierre.le-gendre@u-bourgogne.fr
Supporting information for this article (experimental procedures,
compounds characterisation data and EPR spectrum of the reaction
mixture) is available on the WWW under http://dx.doi.org/10.1002/
chem.200901863.
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Chem. Eur. J. 2010, 16, 64 – 67

COMMUNICATION
Table 1. Screening of titanium complexes for the catalytic hydrophosphi-
nation of isoprene from PPh2H.[a]
Table 2. Hydrophosphination of dienes using 10 mol% of [TiCpCl
C5H4A
(CH2)2PPh2}] (3) as precatalyst.[a]
2ACHTUNGTRENNUNG
{h5-
CTHUNGTRENNUNG
Entry
Complex
Isolated
1a/2a
yield [%]
ratio
1
2
3
4
5
N
94
92
94
97
96
50:50
51:49
47:53
98:2
CHTUNGTRENNUNG
CHTUNGTRENNUNG
E
G
97:3
Entry Diene
Product
t
Isolated 1/2
[a] Reaction conditions: Diphenylphosphine (0.21 mL, 1.25 mmol) and of
isoprene (0.5 mL, 5 mmol) were added to solution of complex
(0.124 mmol) in toluene (2 mL). The reaction mixture was stirred 2 h at
908C (full consumption of Ph2PH, followed by GC). S8 (41.6 mg,
0.163 mmol) was added to allow easier purification on silica gel. The 1/2
ratio was determined by NMR spectroscopy. [b] nBuLi (2 equiv).
[h] yield
[%]
ratio[b]
a
1
2
3
isoprene
3
5
96
92
97:3
myrcene
96:4[d]
1,3-pentadiene[c]
20 91
24 88
>98:2[e]
>98:2[e]
entry 1). Other titanocene complexes stabilized by CO or
BTMSA (BTMSA=bis(trimethylsilyl)acetylene)[18] were
used, but led in both cases to the same result (Table 1, en-
tries 2 and 3). The reaction was then performed with [Ti-
(Z)-1-phenyl-1,3-
butadiene
4
3-methyl-1,3-
pentadiene[c]
5
6
32 86
12 97
>98:2[f]
>98:2
ACHTUNGTRENNUNG ACHTUNGTRENNUGN
(iPrO)2(h2-propene)], prepared in situ from [Ti(OiPr)4].[19]
2,3-dimethyl-1,3-
butadiene
Surprisingly, the reaction under these conditions completely
lost its regioselectivity leading to a mixture of 1,2- and 1,4-
tail-addition products (1a and 2a) accompanied by the two
1,4-head-addition products ((Z)- and (E)-2-methylbut-2-
enyl)diphenylphosphine). We next envisaged the use of a
phosphine-substituted titanocene as it is evident that the
presence of the trimethylphosphine is a determining element
for the regioselectivity of the reaction. Our group is indeed
used to synthesize titanocene complexes bearing a pendant
1,3-cyclohexa-
diene
7
8
22 89
16 86
>98:2
(1R)-nopadiene
>98:2[g]
2-(trimethylsilyl-
methyl)-1,3-buta-
diene
9
4
93
>98:2[h]
phosphine tether such as [TiCl2CpACHTNUTRGENNUG 4CAHTUNGTREN(NUGN CH2)2PPh2}]
{h5-C5H
10
11
12
isoprene
myrcene
16 97
20 94
22 95
98:2
97:3[i]
(3)[20] for which previous studies have shown that the PPh2
function is able to coordinate and so to stabilize the highly
reactive titanium center obtained after reduction. Thus, the
use of 3 as pre-catalyst and of two equivalents of nBuLi as
reducing agent, under reaction conditions that were other-
wise similar to those described above, led to the allylthio-
phoshine 1a in 96% yield with a regioselectivity comparable
2,3-dimethyl-1,3-
butadiene
>98:2
[a] Reaction conditions: nBuLi (1.6m in hexane, 0.155 mL, 0.248 mmol),
phosphine (1.25 mmol) and diene (5 mmol) were successively added to a
solution of 3 (58.6 mg, 0.124 mmol) in toluene (2 mL). The reaction mix-
ture was stirred at 908C until full consumption of phosphine. [b] Deter-
mined by NMR spectroscopy. [c] A mixture of diastereoisomers was
used. [d] Z/E ratio: 66:34. [e] Only the E isomer is formed. [f] Z/E ratio:
20:80. [g] Z/E ratio: 77:23. [h] Z/E ratio: 60:40. [i] Only the Z isomer is
formed.
that obtained with [TiCp
The scope of the reaction was then explored using the in-
situ-reduced form of [TiCl2Cp 4A(CH2)2PPh2}] (3) in-
{h5-C5H
stead of [TiCp2A(PMe3)2]. As highlighted in Table 2, the
2ACHTNUGTREN(NNUG PMe3)2] (Table 1, entry 5 vs. 4).
A
CHTUNGTRENNUNG
CHTUNGTRENNUNG
method proved to be successful for a wide range of dienes.
Indeed, all the hydrophosphination products were obtained
after sulfidation in high yields and excellent regioselectivi-
ties. Looking the results more in details, it appears that dis-
ubstituted 1,3-dienes or those substituted at the 1-position
required longer reaction times than 1,3-dienes substituted at
the 2-position to go to completion (Table 2, entries 3–6 vs.
entries 1, 2 and 9). Cyclic dienes such as 1,3-cyclohexadiene
underwent hydrophosphination to yield (cyclohex-2-enyl)di-
phenylthiophosphine (1g; Table 2, entry 7). The use of (1R)-
nopadiene as substrate provided a straightforward route to
the chiral allylthiophosphine 1h in good yield (Table 2,
entry 8). Interestingly, trimethylsilyl moiety did not interfere
with the reaction and the addition of PPh2H to 2-(trimethyl-
silylmethyl)-1,3-butadiene led to the allylthiophosphine 1i
with an SiMe3 group in allylic position (Table 2, entry 9).
Aware of the fact that most of the hydrophosphination reac-
tions described to date are limited to PPh2H,[1c] we attempt-
ed the titanium-catalyzed hydrophosphination with methyl-
phenylphosphine. Although the reactions were slower to
near completion, all the three dienes tested led to the 1,4-
tail-addition products with very high yields, regio-, and dia-
stereoselectivities (Table 2, entries 10, 11, and 12). In con-
trast to these results, the addition of the more basic phos-
phine PCy2H to isoprene remained unsuccessful.
Regards to the diastereoselectivity of these reactions,
changing from isoprene to other dienes involves the possibil-
ity to obtain either E or Z diastereoisomers for the 1,4-addi-
Chem. Eur. J. 2010, 16, 64 – 67
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65

P. Le Gendre et al.
tion products 1. The Z/E selectivity was unambiguously de-
termined by NOESY NMR experiments and interestingly
proved to be dependent upon the nature of the diene. For
instance, whereas the hydrophosphination of myrcene led
preferentially to the (Z)-allylthiophosphines (entries 2 and
11), other dienes such as 1,3-pentadiene and 1-phenyl-1,3-
butadiene gave the (E)-allylthiophosphines (entries 3 and
4).
double bond of the diene, which is then inserted into the ti-
tanium–phosphorous bond. At this stage, it is reasonable to
assume that the syn p-allyl intermediate is formed as major
isomer. Then, a p/s rearrangement is initiated by the recoor-
dination of PMe3 (or of the PPh2 function on the Cp ring in
the case of 3) to the titanium center. Finally protonolysis of
the resulting h1-allyl complex with the diphenylphosphine
present in the reaction mixture leads to the 1,4-tail-addition
It is worth noting that the use of our titanium catalyst
could be extended to the addition of PPh2H to cyclic trienes
product and regenerates [TiCp
cess.
2ACHUTNGTREN(NGU PMe3)CAHUTNGTREN(NUGN PPh2)] in the pro-
and other C C multiple bonds. Thus the addition of PPh2H
31P NMR monitoring of the reaction of isoprene with
À
to 1,3,5-cycloheptatriene under similar conditions gave (3,5-
cycloheptadienyl)diphenylthiophosphine (4) in 89% yield
(Scheme 2). The hydrophosphination of styrene with diphe-
PPh2H using [TiCp2ACHTGUNTERNNU(G PMe3)2] as catalyst was conducted. The
spectra were recorded at room temperature from aliquots of
the reaction mixture on running no-lock NMR sequences.
Although the spectra clearly shows that the reaction did
occur, no other signal than those due to PPh2H, the allyl-
phosphine, and the free PMe3 could be observed. These data
strongly suggest that the reaction produces NMR-silent par-
amagnetic titanium species. The presence of TiIII species was
indeed confirmed by the observation of unidentified signals
in the EPR analysis of the reaction mixture. All the at-
tempts to trap and to characterize these species using a stoi-
chiometric amount of titanium complex led directly to the
allylphosphine in moderate yields. Taking into account that
the reaction is highly dependent on the concentration and
pKa of the phosphine, we presume that the protonolysis is
the rate-determining step of the catalytic process and that
the formation of the allyltitanium complex is reversible.
As mentioned above, the hydrophosphination of myrcene
led preferentially to (Z)-allylphosphines, whereas other
dienes led to (E)-allylphosphines. Although the opposite
configurations of the double bond in these products is sur-
prising at the first sight, it corresponds in fact to the same
relative position of the (diphenylphosphino)methyl and R
groups, which is consistent with the formation of the less
congested syn-p-allyltitanium complex as the favored inter-
mediate.
Scheme 2. Hydrophosphination of 1,3,5-cycloheptatriene from PPh2H cat-
alyzed by [TiCl2CpACHTUNGTRENNUNG 4ACHUTNTGERN(NUGN CH2)2PPh2}] (3).
{h5-C5H
nylphosphine could also be achieved. The reaction took 12 h
at 908C to near completion and led regioselectively to the
anti-Markovnikov product (PhACTHUNTRGNE(UNG CH2)2PPh2). Unfortunately,
attempts to transpose this methodology to alkynes, such as
phenylacetylene or diphenylacetylene, were ineffectual.
With regard to the mechanism of the hydrophosphination
reaction, a proposed mechanism from [TiCp
substituted 1,3-dienes is reported in Scheme 3. This involves
the formation of [TiCp2A(PMe3)(PPh2)] generated from
[TiCp2A
(PMe3)2] and diphenylphosphine.[14] Once this species
formed, the labile PMe3 is displaced by the less substituted
2ACHTUNGTRNEN(UNG PMe3)2] and 2-
C
ACHTUNGTRENNUNG
CHTUNGTRENNUNG
To confirm the ability of the intermediate [TiCp
(PPh2)] to catalyze the hydrophosphination reaction, we de-
cided to generate this species using another procedure (i.e.,
addition of PPh2H to [TiCp2(H)(PMe3)] and to make use of
2ACHTUNGTRENNUNG(PMe3)-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
the resulting complex for the catalytic addition of PPh2H to
isoprene. Using these conditions, the allylthiophosphine 1a
was obtained with 90% yield. Support of the mechanism
outlined in Scheme 4 was also provided by a deuterium-la-
beling experiment. Thus, when the reaction of isoprene was
conducted in the presence of PPh2D and [TiCp2ACHTUNGTRENNUNG(PMe3)2]
(10 mol%), the allylthiophoshine was obtained with 92% of
Scheme 3. Postulated mechanism of the [TiCp
phosphination of 2-substituted 1,3-dienes.
(PMe3)2]-catalyzed hydro-
Scheme 4. 1,4-Addition of PPh2D to isoprene catalyzed by [TiCp2-
AHCTUNTGREG(NNUN PMe3)2].
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Homogeneous Catalysis
COMMUNICATION
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incorporation of deuterium at the methyl carbon atoms. The
fact that the (E)-allylthiophosphine was predominant again
gives evidence of the formation of the syn-p-allyltitanium
complex as major intermediate.
In summary, we have described here the first titanium-cat-
alyzed hydrophosphination of a wide range of dienes with
excellent yields and the best regioselectivities ever encoun-
tered for this reaction. The importance of having a coordi-
nating phosphine on the titanium toward the regioselectivity
of the hydrophosphination has been demonstrated. We have
also extended the scope of this reaction to cyclic dienes, tri-
enes and activated olefins such as styrene. Preliminary re-
sults with methylphenylphosphine are presented and open
the way of asymmetric titanium catalyzed hydrophosphina-
tion.
[11] The hydrophosphination of diphenylacetylene with PPh2H utilizing
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Experimental Section
Typical procedure for the titanium -catalyzed hydrophosphination of
dienes: in
a Schlenk tube, the titanium complex (e.g., 3; 58.6 mg,
0.124 mmol) was introduced and suspended in freshly distilled toluene
(2 mL). The mixture was cooled to À788C and then nBuLi was added
(1.6m in hexane, 0.155 mL, 0.248 mmol, 2 equiv). The brown solution was
left for 1 h at À788C. Diphenylphosphine (0.21 mL, 1.25 mmol, 10 equiv)
was added at room temperature and the solution was then warmed to
908C and slowly turned green. The solution was stirred for 10 min at
908C and cooled down to room temperature; isoprene (0.5 mL, 5 mmol,
40 equiv) was then added. The solution was then warmed again to 908C
and stirred until full consumption of diphenylphosphine was observed
(followed by GC). S8 (41.6 mg, 0.163 mmol) was added to allow easy pu-
rification of the product by silica gel chromatography (Et2O/pentane,
1:9), affording a colorless oil in 96% yield (339.6 mg, 1.12 mmol).
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Acknowledgements
Prof. Dr. Uwe Rosenthal is greatly acknowledged for a generous gift of
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[TiCp
2ACHTUNGTRENNUNG(BTMSA)]. This work was supported by the Agence Nationale de
la Recherche (ANR MetChirPhos)
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Keywords: dienes
hydrophosphination · phosphines · titanium
·
homogeneous
catalysis
·
[1] a) D. K. Wicht, D. S. Glueck in Catalytic Heterofunctionalization
(Eds.: A. Togni, H. Grꢃtzmacher), Wiley-VCH, Weinheim, 2001;
Received: July 6, 2009
Published online: November 13, 2009
Chem. Eur. J. 2010, 16, 64 – 67
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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67