Rhodium(I)-catalysed conjugate phosphination of cyclic α,β- unsaturated ketones with silylphosphines as masked phosphinides

Article abstract of DOI:10.1039/b706137d

Nucleophile-activation of the phosphorus(iii)-silicon linkage in silylphosphines generates a nucleophilic phosphorus(iii) equivalent thereby allowing for a rhodium-catalysed conjugate phosphination of β-substituted α,β-unsaturated acceptors. The Royal Soc

Full text of DOI:10.1039/b706137d

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Rhodium(I)-catalysed conjugate phosphination of cyclic a,b-unsaturated
ketones with silylphosphines as masked phosphinides{
Verena T. Trepohl and Martin Oestreich*
Received (in Cambridge, UK) 24th April 2007, Accepted 22nd May 2007
First published as an Advance Article on the web 11th June 2007
DOI: 10.1039/b706137d
Nucleophile-activation of the phosphorus(III)–silicon linkage in
silylphosphines generates a nucleophilic phosphorus(III) equiva-
lent thereby allowing for a rhodium-catalysed conjugate
phosphination of b-substituted a,b-unsaturated acceptors.
Transition metal-catalysed addition of element–element bonds,
that is linkages between the heavier main group elements, across
unsaturated carbon–carbon bond systems is certainly an emerging
area in synthetic organic chemistry.1 Activation of the inter-
element linkage2 is supposed to occur by oxidative addition of the
transition metal into the element–element bond3 or by nucleophile-
induced, heterolytic fission of the element–element bond followed
by transmetalation to the transition metal.4 Within the latter mode
of action, we recently accomplished the rhodium-catalysed
conjugate silyl transfer to cyclic a,b-unsaturated acceptors using
a silicon–boron linkage in form of a silylboronic ester as the source
of nucleophilic silicon.4 We currently believe that, in basic aqueous
media, a hydroxy-rhodium(I) species nucleophilically attacks at
boron thereby facilitating transmetalation of silicon from boron to
rhodium with concomitant release of a borate.5 Based on this
putative mechanism, we reasoned that this strategy might be
extended to further rhodium-catalysed conjugate addition pro-
cesses involving nucleophile-induced cleavage of element–element
bonds (Scheme 1).
Scheme 1 Working hypothesis: postulated catalytic cycle.
b-unsubstituted acceptors such as ethyl acrylate and acrylonitrile.
Apart from this isolated report,8 examples of conjugate carbon–
phosphorus(III) bond formation of b-substituted a,b-unsaturated
carbonyl compounds are relatively scarce. An uncatalysed 1,4-
addition of A9 and a related fluoride-mediated process again using
Activation of the phosphorus(III)–silicon linkage in silylpho-
sphines A6 and subsequent conjugate phosphination of a,b-unsa-
turated carbonyl compounds E seemed as a reasonable system to
verify this hypothesis (Scheme 1). We therefore proposed that the
catalysis will begin with coordination of A to the RhI–OH catalyst5
(A A B), in which silicon is prone to intramolecular attack by the
nucleophile, Lewis basic oxygen (shown) or hydroxide after depro-
tonation (not shown) (B A D). The phosphorus–silicon bond
fission at B via a hypervalent silicon species is directly generating a
phosphinide at rhodium(I) along with silane C.7 The unsaturated
substrate E is then captured by D (not shown), and conjugate
transfer of phosphorus(III) provides intermediate F (E A F), which
liberates the active catalyst upon hydrolysis (F A G).
A
10 are the sole efforts towards this objective. An excellent article
by Enders et al.11 recently summarised the different techniques
available for conjugate phosphorus(III) as well as phosphorus(V)
transfer, including direct 1,4-addition of lithium phosphinides to
b-substituted acceptors.12 In this regard, the 1,4-addition of borane-
protected phosphines also attracted interest.13 Knochel et al.
described a general potassium tert-butoxide-catalysed addition of
phosphines to functionalised terminal alkenes.14
In this communication, we report a rhodium-catalysed 1,4-
addition of in situ-generated, diaryl- as well as dialkylsubstituted
phosphinides to cyclic a,b-unsaturated ketones. This mild carbon–
phosphorus(III) bond forming reaction complements the existing
techniques for the preparation of functionalised phosphines.
Silylphosphines 1–3 used in this study were accessed in high
yields according to a reported procedure (left, Scheme 2).15 The
related preparation of 4–5 bearing an aryl group at silicon failed
though; quantitative formation of the corresponding disilane
indicated a lithium–chlorine exchange at silicon. Reversal of the
nucleophilicity and electrophilicity of the reaction partners
produced these silylphosphines in good yields as well (right,
Scheme 2).
While we were examining the above-discussed strategy, Hayashi
et al. disclosed a rhodium-catalysed phosphination of carbon–
carbon triple bonds using A.8 This fine investigation also includes
examples of conjugate phosphorus(III) transfer yet limited to
Organisch-Chemisches Institut, Westfa¨lische Wilhelms-Universita¨t,
Corrensstrasse 40, D-48149 Mu¨nster, Germany.
E-mail: martin.oestreich@uni-muenster.de; Fax: +49 (0)251 83-36501;
Tel: +49 (0)251 83-33271
{ Electronic supplementary information (ESI) available: Characterisation
data as well as 1H, 13C and 31P NMR spectra of all new compounds. See
DOI: 10.1039/b706137d
3300 | Chem. Commun., 2007, 3300–3302
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Scheme 2 Preparation of silylphosphines used in this survey.
Scheme 3 Identification of both the rhodium(I) catalyst and the essential
base for the phosphinyl transfer.
Scheme 4 Synthesis of b-phosphinyl and b-phosphinoyl cyclic ketones
(see Table 1 for details).
In the light of the mechanistic analogy of rhodium-catalysed
conjugate silyl and phosphinyl transfer,4 we chose to start
with cationic rhodium(I) complex [(dppp)Rh(cod)]ClO4/dppp
(5.0 mol%).16 We had previously observed that the presence of
strongly coordinating counterions hamper product formation. In
experimental error (Scheme 4 and Table 1, entries 1–6). We also
targeted the formation of a carbon–phosphorus bond using the
novel silylphosphines 3b, 4b and 5c, which would release a dialkyl-
rather than a diarylphosphinyl moiety. Under standard conditions,
the cyclic b-dicyclohexylphosphinyl ketones were formed in
excellent yields yet isolation of these oxygen-sensitive phosphines
by flash chromatography proved difficult. We therefore decided
to directly oxidise the intermediate trivalent phosphine, which
afforded b-dicyclohexylphosphinoyl ketones 12b–14b (Scheme 4,
Table 1, entries 7–12). The corresponding b-di-tert-butylphos-
phinoyl ketones 12c–14c were produced in moderate yields
following the identical reaction sequence (Table 1, entries 13–15).
If the phosphines are desired, purification on larger scale by
Kugelrohr distillation is also possible.
2
fact, weakly or non-coordinating anions (X2 = BF42, ClO4 as
well as OTf2) were critical for success. This is in agreement with
the above-mentioned report by Hayashi et al.,8 in which chloride-
bridged [Rh(cod)Cl]2 required stoichiometric addition of AgOTf
in order to generate a catalytically active cationic rhodium(I)
catalyst. We were then pleased to find that our catalyst promoted
the conjugate phosphination of 6 using conventional silylphos-
phine 1a under reaction conditions identical to those of the silyl
transfer4 (6 A 9a, Scheme 3).
In a series of control experiments, we were able to show that
both a cationic rhodium(I) catalyst and a base are essential for
achieving conversion. These findings corroborate that this
transformation is not simply base-catalysed but might require
the base to form a nucleophile, at least in equilibrium, for the
assumed transmetalation step (vide supra) (B A D, Scheme 1).17
Silylphosphines A are likely to coordinate to and thereby stabilise
the catalyst (A A B, Scheme 1). The presence of an additional
phosphine ligand (dppp) might therefore be superfluous. However,
when using phosphine-free [Rh(cod)2]BF4 (5.0 mol%) instead of
[(dppp)Rh(cod)]ClO4/dppp (5.0 mol%), phosphinyl transfer from
1a to 6 proceeded at markedly lower reaction rate affording 9a
in poor yield (Scheme 3). Similar results were obtained for other
reagent–substrate combinations. We also note here that conversion
In summary, silylphosphines served as protected phosphinides
in conjugate carbon–phosphorus bond formation catalysed by a
cationic rhodium(I) complex. Extension of this methodology to
Table 1 Conjugate phosphinyl transfer form silylphosphines 1–5 to
a,b-unsaturated acceptors 6–8 followed by oxidation{
Yielda Phosphine Yielda
Entry Si–PR2 Acceptor Phosphine (%)
oxide
(%)
1
2
3
4
5
6
7
8
1a
1a
1a
2a
2a
2a
3b
3b
3b
4b
4b
4b
5c
5c
5c
6 (n = 1) 9a
7 (n = 2) 10a
8 (n = 3) 11a
6 (n = 1) 9a
7 (n = 2) 10a
8 (n = 3) 11a
91
77
91
80
65
79
—
—
—
—
—
—
—
—
—
12a
13a
14a
12a
13a
14a
12b
13b
14b
12b
13b
14b
12c
13c
14c
88
73
89
72
60
76
79
87
92
64
84
89
48
55
58
is not dependent on the counter anion (X2 = BF42, ClO4 or
2
6 (n = 1)
7 (n = 2)
8 (n = 3)
6 (n = 1)
7 (n = 2)
8 (n = 3)
6 (n = 1)
7 (n = 2)
8 (n = 3)
—
—
—
—
—
—
—
—
—
OTf2) present in the reaction mixture (Scheme 3).5
After identification of the suitable catalyst, we continued
employing further acceptors 7 and 8 and tested phosphinide
sources. Isolated yields were invariably high with 1a (77–91%)
performing slightly better than 2a (65–80%) (Scheme 4, Table 1,
entries 1–6). Diarylsubstituted 9a–11a were not sensitive toward
oxidation during purification; subsequent treatment with hydrogen
peroxide prior to flash chromatography gave the corresponding
phosphine oxides 12a–14a in the same yields within the
9
10
11
12
13
14
15
a
Isolated yield of analytically pure product after flash
chromatography.
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(36). The combined organic phases were dried (MgSO4) and the volatiles
removed under reduced pressure. Purification by flash column chromato-
graphy on silica gel (ethyl acetate) provided the phosphine oxides 12a–14a,
12b–14b and 12c–14c. All compounds gave satisfactory characterisation
data (ESI{).
acyclic acceptors as well as elucidation of the mechanism of action,
transmetalation (RhI–PR2) or oxidative addition (RhIII–PR2)
reaction pathway, are the current focus of our investigations.
The research was supported by the International Research
Training Group Mu¨nster–Nagoya (GRK 1143) (predoctoral
fellowship to V. T. T., 2007–2009) and the Aventis Foundation
(Karl Winnacker fellowship to M. O., 2006–2008). Generous
donation of chemicals from Wacker AG (Burghausen/Germany) is
gratefully acknowledged.
1 (a) I. Beletskaya and C. Moberg, Chem. Rev., 2006, 106, 2320–2354; (b)
M. Suginome and Y. Ito, Chem. Rev., 2000, 100, 3221–3256.
2 K. Tamao and S. Yamaguchi, J. Organomet. Chem., 2000, 611,
3–4.
3 L.-B. Han and M. Tanaka, Chem. Commun., 1999, 395–402.
4 C. Walter, G. Auer and M. Oestreich, Angew. Chem., Int. Ed., 2006, 45,
5675–5677.
5 For an excellent summary of rhodium(I)-catalysed conjugate addition
reactions of carbon–element bonds, see: K. Yoshida and T. Hayashi, in
Modern Rhodium-Catalyzed Organic Reactions, ed. P. A. Evans, Wiley-
VCH, Weinheim, 2005, pp. 55–77.
6 G. Fritz and P. Scheer, Chem. Rev., 2000, 100, 3341–3401.
7 After a single catalytic turnover, coordination of A to rhodium(I) in
intermediate F followed by transmetalation to afford D is also
conceivable. Intermolecular attack of hydroxide at silicon in B cannot
be ruled out.
8 M. Hayashi, Y. Matsuura and Y. Watanabe, J. Org. Chem., 2006, 71,
9248–9251.
9 C. Couret, J. Escudie, J. Satge, N. T. Anh and G. Soussan,
J. Organomet. Chem., 1975, 91, 11–30.
10 M. Hayashi, Y. Matsuura and Y. Watanabe, Tetrahedron Lett., 2004,
45, 9167–9169.
11 D. Enders, A. Saint-Dizier, M.-I. Lannou and A. Lenzen, Eur. J. Org.
Chem., 2006, 29–49.
12 (a) G. Knu¨hl, P. Sennhenn and G. Helmchen, J. Chem. Soc., Chem.
Commun., 1995, 1845–1846; (b) T. Minami, Y. Okada, T. Otaguro,
S. Tawaraya, T. Furuichi and T. Okauchi, Tetrahedron: Asymmetry,
1995, 6, 2469–2474; (c) J. F. G. Jansen and B. L. Feringa, Tetrahedron:
Asymmetry, 1990, 1, 719–720.
13 (a) T. Imamoto, T. Oshiki, T. Onozawa, T. Kusumoto and K. Sato,
J. Am. Chem. Soc., 1990, 112, 5244–5252; (b) P. Pellon, C. Le Goaster
and L. Toupet, Tetrahedron Lett., 1996, 37, 4713–4716; (c) M. Le´autey,
G. Castelot-Deliencourt, P. Jubault, X. Pannecoucke and J.-C. Quirion,
Tetrahedron Lett., 2002, 43, 9237–9240; (d) B. Join, O. Delacroix and
A.-C. Gaumont, Synlett, 2005, 1881–1884.
14 T. Bunlaksananusorn and P. Knochel, Tetrahedron Lett., 2002, 43,
5817–5819.
15 M. Hayashi, Y. Matsuura and Y. Watanabe, Tetrahedron Lett., 2004,
45, 1409–1411.
16 K. Tani, T. Yamagata, S. Otsuka, H. Kumobayashi and S. Akutagawa,
Org. Synth., 1989, 67, 33–43.
17 It is interesting to note that a mechanism involving oxidative addition
and reductive elimination was postulated for the related phosphination
of alkynes.8 We believe though that the need for the presence of a base
supports a transmetalation pathway.
Notes and references
{ General procedure for the preparation of silylphosphines 4b and 5c: To a
large excess (y10 equiv.) of freshly cut lithium wire (previously activated
with Me3SiCl) in THF (30 mL), dimethylphenylsilyl chloride (4.40 g,
25.8 mmol, 1.00 equiv.) was added in one portion at room temperature
under argon atmosphere. The reaction mixture was maintained at 213 uC
for 18 h (dark red coloration indicated formation of dimethylphenylsi-
lyllithium). The mixture was allowed to warm to 0 uC and stirred for an
additional hour under sonication. In order to separate the dimethylphe-
nylsilyllithium solution from unreacted lithium metal, the supernatant was
transferred to a dropping funnel connected to a Schlenk flask via a double-
ended cannula. The Schlenk flask was then charged with the chlorodialkyl-
phosphine (25.8 mmol, 1.00 equiv.) and n-hexane (60 mL) before the
anionic lithium species was added slowly over a period of 2 h at 0 uC. The
addition was accompanied by a color change and precipitation of LiCl.
The reaction mixture was allowed to warm to room temperature and
maintained at this temperature for an additional 2 h. After evaporation of
the solvents, the residue was purified via Kugelrohr distillation. The title
compounds gave satisfactory characterisation data (ESI{).General proce-
dure for the rhodium-catalysed 1,4-addition of a,b-unsaturated cyclic
ketones: Under an argon atmosphere, a Schlenk tube equipped with a
magnetic stirring bar was charged with the a,b-unsaturated cyclic acceptor
6–8 (1.0 equiv.) dissolved in deoxygenated 1,4-dioxane–H2O = 10 : 1
(y0.5 M based on substrate). After addition of [(dppp)Rh(cod)]ClO4
(5.0 mol%) and dppp (5.0 mol%) or [Rh(cod)2]X (5.0 mol%), Et3N
(1.0 equiv.) and silylphosphine 1–5 (2.5 equiv.) were successively added.
The reaction mixture was maintained at 60 uC for 2 days. Depending on
the oxygen-sensitivity of the phosphorus(III) intermediate, one of the
following procedures was applied: Method A (R = Ph): A small portion of
silica gel was added after cooling to room temperature and the solvents
were evaporated under reduced pressure. The residue was subjected to
flash column chromatography on silica gel (cyclohexane–ethyl acetate =
5 : 1) affording the b-phosphinyl ketones 9a–11a. Method B (R = Ph, Cy
and t-Bu): The reaction mixture was cooled to room temperature and
directly oxidised with H2O2 (30%, 2.0 equiv.). After additional stirring for
4 h, H2O and aqueous FeSO4 (0.5 M) were added. The organic layer was
separated and the aqueous phase extracted with tert-butyl methyl ether
3302 | Chem. Commun., 2007, 3300–3302
This journal is ß The Royal Society of Chemistry 2007