Sequential electrophilic P-C bond formation in metal-coordinated chlorophosphines

Article abstract of DOI:10.1039/c5dt01281c

In the presence of chloride abstractors, metal-coordinated chlorophosphines undergo facile room-temperature electrophilic substitution reactions with unsaturated organic substrates, leading to P-C bond formation. This methodology can be applied sequential

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Sequential Electrophilic P–C Bond Formation in Metal-Coordinated
Chlorophosphines
Arumugam Jayaraman, Tyler V. Jacob, Jeff Bisskey, Brian T. Sterenberg*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
substrates, and that metal coordination indeed enhances
electrophilicity.11 In this communication, we demonstrate that
50 this reactivity is general for chlorophosphines and can be applied
sequentially, and thus has wide applicability to phosphine
synthesis.
In the presence of chloride abstractors, metal-coordinated
chlorophosphines undergo facile room-temperature
electrophilic substitution reactions with unsaturated organic
substrates, leading to P–C bond formation. This methodology
10 can be applied sequentially two or three times, stepwise or in
one-pot reactions, to form phosphines with three different
substituents. The reactions are rapid and high-yielding, and
can be applied to a wide range of organic substrates, making
them valuable tools for P–C bond formation.
We first examined PPh2Cl, as the PPh2 unit is ubiquitous in
phosphine ligands, and new methods to add this group to organic
55 substrates are potentially valuable. The chlorophosphine complex
[W(CO)5{PPh2Cl}] (1)12 did not react with 1 equiv of AlCl3.
However, addition of 4 or more equiv led to a color change and
the disappearance of 1 in the 31P{1H} NMR spectrum, but no
detectable signal for a phosphenium ion, suggesting that an
60 equilibrium mixture between 1 and a phosphenium complex or an
AlCl3 adduct is being formed. The reactivity of this solution
towards a range of organic substrates has been tested. Two
illustrative examples are described here. Addition of ferrocene
resulted in immediate formation of the diphenyl ferrocenyl
65 phosphine complex 2, in a high yield (83%) (Scheme 1). This
rapid reactivity at room temperature demonstrates the increased
15 Tertiary phosphines, including unsymmetrical phosphines, find
widespread use as ligands for transition metal catalysis,1 and as
organic catalysts2 due to the tunability of their electronic and
steric properties.3 Phosphorus–carbon bond formation is an
essential step in the synthesis of tertiary phosphines, and the
20 development of new P–C bond forming reactions has been
identified as an important goal for the future advancement of
organometallic chemistry.4 The most commonly used P–C bond
forming methods involve the reaction of strong carbon-based
nucleophiles, typically organolithium or Grignard reagents, with
25 phosphorus electrophiles, usually chlorophosphines.5 Despite
their wide application, these methods have limitations, including
availability and cost of organometallic reagents or their
precursors,
a
lack of functional group tolerance,6 and
uncontrolled multiple substitutions on di- or trichloro
30 phosphines.5 One strategy for avoiding strong organic
nucleophiles is to increase the electrophilicity of the phosphorus
reagent via halide abstraction, leading to Friedel-Crafts-like
electrophilic substitution reactions. Although these reactions have
been known for a long time,7 they are not as widely used, likely
35 because they require high temperatures and are often slow and
low-yielding.8 We reasoned that the electrophilicity of the
phosphenium intermediate in these reactions might be enhanced
by coordination to an electron-poor metal. Previous researchers
have shown that metal coordinated phosphenium ions are
40 strongly electrophilic,9 however, application of these complexes
to P–C bond formation is very limited.10 In two previous papers,
we described two methods to enhance electrophilicity of metal
coordinated chlorophosphirenes: chloride abstraction with AlCl3
to form phoshirenyl cation complexes, and with silver triflate to
45 form phosphirene triflate complexes. We showed that W(CO)5
coordinated phosphirenyl cations and phosphirenyl triflates
undergo facile P–C bond forming reactions with a range of
Scheme 1. Electrophilic substitution reactions of tungsten-coordinated
chlorodiphenylphosphine. Reagents and conditions: CH2Cl2, RT, (i)
70 AlCl3, 4 equiv, Ferrocene, 2 equiv; (ii) AgOSO2CF3, 1.2 equiv, 2h; (iii)
Ferrocene, 2 equiv; (iv) anisole, 10 equiv, 12h. [W] = W(CO)5.
electrophilicity of the metal-coordinated phosphorus center, as
the comparable reaction with metal-free PPh2Cl required 24h at
105 °C to achieve 59% yield.13 Ferrocene also reacts with 1 in the
75 presence of 1 equiv of AlCl3, however, the reaction is much
slower, requiring 48h to go to completion. To probe the lower
reactivity limit, the reaction with the weakly activated substrate
anisole was attempted, but led to reversion to the precursor,
suggesting that anisole is interacting with AlCl3. These
80 observations suggest that AlCl3 does not abstract Cl, but interacts
with it, enhancing its leaving group ability. A similar mechanism
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DOI: 10.1039/C5DT01281C
has been described in a related chlorophosphirane system.14 The
limited functional group tolerance of the AlCl3 methodology led
complex 8 (Scheme 2). Compound 8 can then be converted to
allyl phenyl phosphine triflate complex 9 via addition of
us to consider silver triflate as an alternative. Compound 1 reacts 40 AgOSO2CF3, and then to the allyl-anilinyl-phenyl phosphine
with silver triflate to form diphenyl phosphine triflate complex 3.
Reaction of 3 with ferrocene afforded 2, in an excellent yield
(92%). Reaction with anisole in CH2Cl2 at room temperature for
12h afforded the regiospecific para-substituted anisolyl diphenyl
complex 10 via addition of N,N-diethylaniline. Compound 10 can
also be obtained from 7 by altering the sequence of addition.
Reaction of 7 with N,N-diethylaniline leads to the para-
substituted anilinyl phenyl chloro phosphine complex 11.
5
phosphine complex 4, in 82% yield. This reaction shows that the 45 Addition of AlCl3 to 11 in the presence of allyl trimethylsilane
triflate methodology is appropriate for cases where the AlCl3 is
then leads to 10.
10 incompatible with the substrate.
Successful mono-substitution reactions led us to consider the
possibility of sequential multiple substitutions. We next explored
Compound 7 also reacts with the unactivated substrate toluene
to afford the para-substituted tolyl phenyl chloro phosphine
complex 12 (Scheme 2). This reaction demonstrates that 7 is
the reactivity of dichloro phenyl phosphine complex 50 more electrophilic than 3, and is capable of activating very
[W(CO)5{PPhCl2}] (5).15 Addition of AlCl3 to 5 resulted in a
15 color change, the disappearance of 5 in the 31P{1H} NMR
spectrum, but no detectable signal for a phosphenium ion.
Addition of activated substrates to this solution leads to
unreactive substrates. The higher reactivity can be attributed to
electronegative Cl substituent, which increases electrophilicity at
P. In the subsequent step, compound 12 was converted to the
corresponding triflate 13, and reacted with thiophene, to form the
disubstitution, regardless of stoichiometry, illustrated here in the 55 phenyl-p-tolylthienylphosphine complex 14.
reaction with N,N-diethylaniline. Addition of 1 equiv of substrate
20 and 1 equiv of AlCl3 leads to a 50:50 mixture of 5 and the
bis(N,N-diethyl anilinyl) phenyl phosphine complex 6. Addition
of 2 equiv of substrate and excess AlCl3 leads to 6 as the only
Sequential formation of two P–C bonds from 5 led us to
consider the sequential introduction of three P–C bonds to the
trichloro phosphine complex [W(CO)5{PCl3}].16 Unfortunately,
this complex was unreactive toward AlCl3, AgOSO2CF3 and all
major product. Greater control can be achieved by using silver 60 other chloride abstractors we tried. Furthermore, there was no
triflate as the chloride abstractor. Reaction of 5 with 1.2 equiv of
25 AgOSO2CF3 for 3h at room temperature selectively abstracts one
chloride and forms the chloro phenyl triflate phosphine complex
reaction with any organic substrate in the presence of AlCl3. This
suggests that the Cl substituents lack sufficient π-donation to
stabilize a transient dichloro phosphenium ion. Since amino
substituents are well-known to effectively stabilize the low-valent
65 phosphorus species through π-donation,17 we next considered the
7
(Scheme 2), which reacts with substrates to give
monosubstituted products. For example, reaction of 7 with allyl
N,N-diethylaminodichloro
phosphine
complex
[W(CO)5{P(NEt2)Cl2}] (15).18 Reaction of 15 with 1 equiv of
AlCl3 resulted in immediate formation of a red solution. Using
this solution, we have demonstrated a one-pot sequential triple P–
70 C bond formation using three different substrates (Scheme 3).
First, allyl trimethylsilane was used to add an allyl group. This
was followed by addition of indole (1.3 equiv), followed by
ferrocene (1.0 equiv), to give the indolyl allyl ferrocenyl
phosphine complex 16 in 79% yield (Scheme 3). In this reaction
75
Scheme 3. A one-pot sequential triple electrophilic substitution reaction.
Reagents and conditions: CH2Cl2, RT. (i) AlCl3, 1 equiv, 15 min; (ii) allyl
trimethylsilane, 1 equiv, 10 min; (iii) indole, 1.3 equiv; (iv) ferrocene, 1
equiv, 12h. [W] = W(CO)5.
30 Scheme 2. Sequential electrophilic substitution reactions of tungsten-
coordinated dichlorophenylphosphine. Reagents and conditions: CH2Cl2,
RT, (i) AlCl3, N,N-diethylaniline, 1 equiv; (ii) AgOSO2CF3, 1.2 equiv, 3h;
(iii) allyl trimethylsilane, 3 equiv; (iv) AgOSO2CF3, 1.2 equiv, 12h; (v)
N,N-diethylaniline, 2 equiv; (vi) N,N-diethylaniline, 2 equiv; (vii) allyl
35 trimethylsilane, 3 equiv, AlCl3, 1 equiv; (viii) toluene, 15 equiv, 36h; (ix)
AgOSO2CF3, 1.2 equiv, 2h. (x) thiophene, 2 equiv. [W] = W(CO)5.
80 sequence, the regeneration of AlCl3 as a by-product of the first
step promotes the second substitution step by abstracting
chloride, while the HCl generated in the second step promotes the
third substitution step by protonating the amino group.
Compound 16 has been characterized by X-ray crystallography,
85 and an ORTEP diagram of the structure in shown in Figure 1.
trimethylsilane leads to the allyl phenyl chloro phosphine
2
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This work was financially supported by the University of
25 Regina. We thank Bob McDonald and Mike Ferguson
(University of Alberta) for X-ray data collection.
Notes and references
Department of Chemistry and Biochemistry, University of Regina, 3737
Wascana Parkway, Regina, Saskatchewan S4S 0A2, Canada. Tel:
30 1(306)585-4106; E-mail: brian.sterenberg@uregina.ca
† Electronic Supplementary Information (ESI) available: Experimental
details and compound characterization data. A CIF file containing
crystallographic data for 16. See DOI: 10.1039/b000000x/
35
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