Electrophilic routes to tertiary adamantyl and diamantyl phosphonium salts

Article abstract of DOI:10.1055/s-0030-1260303

In highly nonpolar media both 1-adamantyl and 1-diamantyl triflates are sufficiently stable to react with nucleophiles in a controlled manner. Several tertiary phosphonium triflate salts with a single adamantyl or diamantyl residue were prepared directly

Full text of DOI:10.1055/s-0030-1260303

LETTER
2351
Electrophilic Routes to Tertiary Adamantyl and Diamantyl Phosphonium
Salts
E
lectrophi
a
lic Routes
t
s
o Tertiary
o
A
damantyl
t
a
nd Di
h
amantyl Phos
a
phonium Salts Prabagar,1 Andrew R. Cowley, John M. Brown*
Chemistry Research Laboratory, 12 Mansfield Rd., Oxford OX1 3TA, UK
Received 16 May 2011
In appreciation of the scientific contributions of Alfredo Ricci, with warm regards
phosphines through the route made practical by Beller and
co-workers, and one that is widely used. The direct elec-
trophilic phosphinylation of adamantane (PCl3, AlCl3,
then LiAlH4) provides access to the precursors Ad2PX
Abstract: In highly nonpolar media both 1-adamantyl and 1-dia-
mantyl triflates are sufficiently stable to react with nucleophiles in
a controlled manner. Several tertiary phosphonium triflate salts with
a single adamantyl or diamantyl residue were prepared directly in
this way, starting with the secondary phosphine. Three compounds (X = H, Cl).11
with the 1-phosphodiamantane structure were characterised by X-
ray.
(b)
MgBr
(a)
Key words: ligands, phosphorus, electrophilic addition, adamant-
ly, diamantyl
Pt-Bu2
P
t-Bu
(d)
We report a simple method for C–P bond synthesis that in-
troduces a 1-adamantyl group under mild conditions using
the highly reactive 1-adamantyl triflate as electrophile.
(c)
+
P
PCl2
MgCl
Cl
The method has been further extended to 1-diamantyl tri-
flate, making phosphines derived from higher diamon-
doids readily accessible.
Scheme 1 Existing synthetic routes to tri-tertiary 1-adamantyl
phosphines; ref. 9. Reagents and conditions: (a) ClP-t-Bu2, LiBr, CuI
(cat.), Et2O, 0 °C; (b) same as (a) with Cl2P-t-Bu; ref. 10; (c) n-hep-
tane, heat; (d) Me3CLi.
Beginning with the application of tri-tert-butylphos-
phine,2 the use of very bulky ligands has played an impor-
tant and sustained role in palladium catalysis. Their
involvement reduces the coordination number of palladi-
um in catalytic intermediates and promotes monoligated
species.3 By tuning the electronic and steric properties of
the ligand, catalytic reactivity is markedly altered and
may give access to otherwise inaccessible reaction path-
ways.4
1-Adamantyl triflate has been known since 1980, and is
isolable.12 It’s stability is remarkable, since tertiary sul-
fonates are highly reactive, and tertiary triflates otherwise
unknown. For example, tert-butyl tosylate has been pre-
pared and reacted in situ, but never characterised.13 The
rigid bridging environment of the 1-adamantyl moiety
clearly confers stability to the triflate derivative, since the
stability of the 1-adamantyl cation is closer to an uncon-
strained tertiary than to a secondary carbocation.14
1-Adamantyl (Ad)-based phosphine ligands can possess
distinct reactivity from their tert-butyl analogues.5 At
present many phosphines with AdPR2 and Ad2PR struc-
tures are known and have been applied in catalysis, but
Ad3P is not.6 QM analysis of the structure of Ad3P con-
firms the presence of a high level of steric strain.7 The
chemistry employed in synthesis of tert-butyl and 1-ada-
mantyl phosphines is generally distinct (Scheme 1). For t-
Bu3P, tert-butyllithium or the corresponding Grignard re-
agent are employed in a one-step or two-step synthesis
starting from PCl3.8 A synthesis of Ad-t-Bu2P involves
copper-promoted reaction between t-Bu2PCl and Ad-
MgCl; Ad2-t-BuP can be synthesised similarly.9 An earli-
er route to the latter requires two sequential nucleophilic
steps.10 AdPCl2 is reacted first with AdMgCl, and then
with t-BuLi to form the desired ligand. In general howev-
er, there is a more attractive route to bis-1-adamantyl
1-Adamantyl triflate (2) was synthesised from bromide 1
as shown in Scheme 2, and characterised by 1H NMR and
13C NMR in CDCl3, where the triflate is moderately stable
on the time scale of analysis.12a The most useful and dis-
tinctive feature is the low-field C1 signal at d = 104.0
ppm. For preparative purposes, the triflate did not need to
be isolated. The reaction solution in 2,2-dimethylbutane
was stirred for three hours at 0 °C, and then filtered from
AgBr by cannula under argon to provide a solution pure
enough for preparative purposes. In the first experiments,
neat HPPh2 was added by syringe, the reaction mixture
was allowed to warm to room temperature and stirred for
two hours. Washing the precipitate with EtOAc and dry-
ing gave the pure phosphonium salt 3 as a white solid in
94% yield [mp 248–250 °C (2.5 millimolar scale)], char-
1
acterised by H NMR, 13C NMR and 31P NMR, and
HRMS. A portion was oxidised to the corresponding P-
SYNLETT 2011, No. 16, pp 2351–2354
Advanced online publication: 13.09.2011
DOI: 10.1055/s-0030-1260303; Art ID: S04311ST
1
3
.0
9
.2
0
1
1
oxide 4,15 with basic H2O2 in 67% yield.16
© Georg Thieme Verlag Stuttgart · New York

2352
J. Prabagar et al.
LETTER
3
without isolation on a 1.2-millimolar scale and led to the
isolation of the desired phosphonium salt 11 in 92% yield
(mp 272–274 °C). The structure was confirmed by oxida-
tion to the corresponding phosphine oxide 12, which was
recrystallised from CHCl3 for X-ray analysis
[Figure 2(A)]. Since the 1-diamantyl cation is in very rap-
id equilibrium with the less favoured 4-isomer,23 this X-
ray formally rules out an alternative structure for the phos-
phonium salt.
+
4
2
1
(b)
(a)
H
OTf–
PR2
Br
OTf
3 R = Ph
5 R = c-C6H11
6 R = t-Bu
1
2
(c)
R = Ph
O
PPh2
4
Scheme 2 1-Adamantylphosphonium salts. Reagents and conditi-
ons: (a) AgOTf, neohexane, 3 h, 0 °C; (b) HPR2, r.t., 2 h; (c) 30%
H2O2, t-BuOK, CH2Cl2, r.t., 14 h.
It proved possible to synthesise more bulky 1-diamantyl
phosphines by using the same protocol. Using HPCy2 on
a 2-millimolar scale, the phosphonium salt 13 was pre-
pared in 88% yield (mp >278 °C). In this case the 13C
NMR spectrum showed diastereotopic splitting for both
possible sites (C12, C13), as indicated in Scheme 3. The
salt could be directly recrystallised to X-ray quality from
CH2Cl2, and the structure is shown in Figure 2(B). Final-
ly, the C–P coupling reaction was carried out using HP-t-
Bu2 and the product 14 was obtained in 69% yield. Again,
crystals of X-ray quality were formed by direct crystalli-
sation from CH2Cl2, and the structure is shown in
Figure 2(C).24 Additional strain in the all-tertiary phos-
phonium salt is expressed in elongation of the P–C bonds
by ca. 0.05 Å compared to the less bulky analogue 13.25,26
Encouraged by this result, related experiments with
HPCy2 and HP-t-Bu2 were carried out, and the tertiary
phosphonium salts 5 and 6 were isolated in 73% and 63%
yield, respectively, and characterised as before. The syn-
thesis constitutes a simple route to 1-adamantyl phosphine
ligands, since phosphonium salts can be employed direct-
ly in Pd-catalysed reactions.17 In 5, where the ligand is
novel, the 13C NMR shows that cyclohexyl carbons adja-
cent to the C–P bond are diastereotopic, with 0.8 ppm sep-
aration.
The success in these syntheses encouraged their applica-
tion to a more bulky diamondoid framework. Diamantane
is readily accessible from rearrangement of BINOR-S, it-
self a dimer of norbornadiene,18 and may be brominated
specifically at the radial position to give monobromide
7.19 Despite this ease of precursor access, there are only
two relevant reports of C–P synthesis to date. Olah and
co-workers demonstrated the electrophilic phosphonyla-
tion of diamantane with PCl3/AlCl3, and isolated the phos-
phonic dichloride 8 (Figure 1).20 More recently, Schreiner
and co-workers have shown that phosphonylation of 1-
bromodiamantane gave the disubstituted product 9
(Figure 1) in good yield.21 This was converted into a range
of simple derivatives. The lack of further examples may
be due to the relative difficulty of access to 1-diamantyl
lithium or magnesium derivatives.22
+
H
(b)
OTf–
(a)
PR2
Br
OTf
(c)
R = Ph
7
10
11 R = Ph
13 R = c-C6H11
14 R = t-Bu
9
OTf–
14
13
10
1
8
7
12
11
H
O
P+
PPh2
13'
12'
6
5
2
13
3
4
12,12'
13,13'
12
diastereotopic C's
Scheme 3 Synthesis of 1-diamantyl phosphonium salts. Reagents
and conditions: (a) AgOTf, neohexane, 1.5 h, 0 °C; (b) HPR2, neo-
hexane, r.t., 2 h; (c) 30% H2O2, t-BuOK, CH2Cl2, r.t., 14 h.
Cl
P
O
PCl2
In summary, a method for forming a single C–P bond to a
tertiary ring-bridging position is demonstrated, by ex-
ploiting access to highly reactive electrophiles. This is ex-
emplified here by the synthesis of tertiary 1-adamantyl
and 1-diamantyl phosphines. The reactions described
have been carried out on a small scale (2.5 mmol) allow-
ing rapid and convenient access to quantities suitable for
ligand screening protocols. We note that Takeuchi and co-
workers have prepared hexane solutions containing 55
mmoles of triflate (2).27 The method described should be
more general, provided that the bridgehead reaction site
can accommodate a carbocation of reasonable stability.
Experimental details for all phosphonium salts are includ-
ed; see Supporting Information.28
O
8
9
Figure 1
The reaction of 1-diamantyl bromide (7) with AgOTf in
2,2,-dimethylbutane was examined as above. AgBr was
precipitated more rapidly than in the 1-adamantyl case,
and the triflate 10 was formed as colourless crystals when
the solvent was removed at 0 °C after cannula filtration.
The solution stability was lower, albeit sufficient for spec-
tral analysis although impurities were evident. The 13C
NMR spectrum showed nine distinct high-field signals as
well as C1 at d = 109.9 ppm and CF3 at d = 118.7 ppm
(JCF = 317 Hz). The reaction with HPPh2 was carried out
Synlett 2011, No. 16, 2351–2354 © Thieme Stuttgart · New York

LETTER
Electrophilic Routes to Tertiary Adamantyl and Diamantyl Phosphonium Salts
2353
Almena, J.; Beller, M. Adv. Synth. Catal. 2006, 348, 1255.
(d) For an earlier work, see: Goerlich, J. R.; Schmutzler, R.
Phosphorus, Sulfur Silicon Relat. Elem. 1995, 102, 211.
(12) (a) Takeuchi, K.; Moriyama, T.; Kinoshita, T.; Tachino, H.;
Okamoto, K. Chem. Lett. 1980, 9, 1385. (b) Takeuchi, K.;
Ikai, K.; Shibata, T.; Tsugeno, A. J. Org. Chem. 1988, 53,
2852.
(13) (a) Kim, J. G.; Jang, D. O. Synlett 2007, 2501.
(b) Hoffmann, H. M. R. J. Chem. Soc. 1965, 6748.
(14) (a) Arnett, E. M.; Hofelich, T. C. J. Am. Chem. Soc. 1983,
105, 2889. (b) Abboud, J.-L. M.; Castano, O.; Della, E. W.;
Herreros, M.; Mueller, P.; Notario, R.; Rossier, J.-C. J. Am.
Chem. Soc. 1997, 119, 2262.
(15) (a) Gillespie, D. G.; Walker, B. J. J. Chem. Soc., Perkin
Trans. 1 1983, 1689. (b) For the phosphine, see: Rossi, R.
A.; Palacios, S. M.; Santiago, A. N. J. Org. Chem. 1982, 47,
4654.
(16) An early experiment under more forcing conditions [(1),
Cy2PH, AcOH, 120 °C)] failed to produce the desired
phosphine.
(17) Netherton, M. R.; Fu, G. C. Org. Lett. 2001, 3, 4295.
(18) (a) Courtney, T.; Johnston, D. E.; McKervey, M. A.;
Rooney, J. J. J. Chem. Soc., Perkin Trans. 1 1972, 2691.
(b) Gund, T. M.; Osawa, E.; Williams, V. Z. Jr.; Schleyer, P.
von R.. J. Org. Chem. 1974, 39, 2979.
Figure 2 Three X-ray structures of phosphodiamantanes; A: 12; B:
13; C: 14; crystallographic numbering. ORTEP-3 diagrams are shown
with ellipsoids at 40% probability. Key data: 12: R = 0.0353, wR =
0.0408; 13: R = 0.0410, wR = 0.0479; 14: R = 0.0517, wR = 0.0622.
(19) Gund, T. M.; Schleyer, P. von R..; Unruh, G. D.; Gleicher,
G. J. J. Org. Chem. 1974, 39, 2994.
(20) Olah, G. A.; Farooq, O.; Wang, Q.; Wu, A. H. J. Org. Chem.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
1990, 55, 1224.
(21) Schwertfeger, H.; Machuy, M. M.; Wurtele, C.; Dahl, J. E.
P.; Carlson, R. M. K.; Schreiner, P. R. Adv. Synth. Catal.
2010, 352, 609.
(22) Molle, G.; Bauer, P.; Dubois, J. E. J. Org. Chem. 1983, 48,
2975.
Acknowledgment
We thank the University of Jaffna for granting leave to J.P., and the
Clarendon Fund (Oxford) for an award.
(23) Olah, G. A.; Prakash, G. K. S.; Shih, J. G.; Krishnamurthy,
V. V.; Mateescu, G. D.; Liang, G.; Sipos, G.; Buss, V.;
Gund, T. M.; Schleyer, P. von R.. J. Am. Chem. Soc. 1985,
107, 2764.
(24) CCDC files 824773-824775 contain the supplementary
crystallographic data. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
(25) The related t-Bu3PH cation appears frequently in the CCDC
crystallographic database. The average C–P bond length (13
structures) is 1.863 Å; c.f. 1.883 Å in 14.
(26) Fletcher, D. A.; McMeeking, R. F.; Parkin, D. J. Chem. Inf.
Comp. Sci. 1996, 36, 746.
References and Notes
(1) Present address: Dept. of Chemistry, University of Jaffna,
Jaffna, Sri Lanka.
(2) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10; ref. 10
therein summarises earlier work..
(3) (a) Hartwig, J. F.; Paul, F. J. Am. Chem. Soc. 1995, 117,
5373. (b) Galardon, E.; Ramdeehul, S.; Brown, J. M.;
Cowley, A.; Hii, K. K.; Jutand, A. Angew. Chem. Int. Ed.
2002, 41, 1760. (c) Barrios-Landeros, F.; Carrow, B. P.;
Hartwig, J. F. J. Am. Chem. Soc. 2009, 131, 8141.
(4) See, for example: Watson, D. A.; Su, M. J.; Teverovskiy, G.;
Zhang, Y.; Garcia-Fortanet, J.; Kinzel, T.; Buchwald, S. L.
Science 2009, 325, 1661.
(5) Stambuli, J. P.; Buehl, M.; Hartwig, J. F. J. Am. Chem. Soc.
2002, 124, 9346.
(6) Despite the presumed non-existence of authentic (1-Ad)3P, it
is cited in Chemical Abstracts in four distinct patents.
(7) Wann, D. A.; Turner, A. R.; Goerlich, J. R.; Kettle, L. J.;
Schmutzler, R.; Rankin, D. W. H. Struct. Chem. 2011, 22,
263.
(8) (a) Hoffmann, H.; Schellenbeck, P. Chem. Ber. 1967, 100,
692. (b) Srivastava, R. C. J. Chem. Res., Synop. 1985, 33.
(9) Stambuli, J. P.; Stauffer, S. R.; Shaughnessy, K. H.; Hartwig,
J. F. J. Am. Chem. Soc. 2001, 123, 2677.
(27) Takeuchi, K.; Akiyama, F.; Miyazaki, T.; Kitagawa, I.;
Okamoto, K. Tetrahedron 1987, 43, 701.
(28) Experimental data:
Caution: The tertiary triflates 2 and 10 are powerful
electrophiles and should be treated with care; avoid contact.
Sample Preparation 11 and 12 via 10: Anhydrous AgOTf
(105 mg, 0.4 mmol) was added to a solution of 1-
bromodiamantane (100 mg, 0.37 mmol) in anhyd 2,2-
dimethylbutane (10 mL) at 0 °C and stirred with exclusion of
light for 1.5 h. The solution was filtered under argon by
cannula and the solvent was removed under vacuum at 0 °C
to afford 1-diamantyl triflate(10) as colourless crystals. 1H
NMR (500 MHz, CDCl3, 25 °C): d = 1.54–2.40 (m). 13
C
(10) Lavrova, E. A.; Koidan, G. N.; Marchenko, A. P.; Pinchuk,
NMR (125 MHz, CDCl3, 25 °C): d = 118.7 (q, JCF = 316.7
Hz, CF3), 109.9 (C1), 43.6 (C10), 42.9 (C2), 42.4 (C7), 37.9
(C5), 36.8 (C8), 36.4 (C6), 32.8 (C3), 32.1 (C9), 24.8 (C4).
After repeating on a 1.2-millimolar scale and cannula
filtration HPPh2 (210 mg, 196 mL, 1.12 mmol)was added and
the solution was warmed to r.t. After 2 h stirring at r.t., a
white solid precipitated. Solvent was removed and the solid
A. M. J. Gen. Chem. USSR. 1995, 64, 1393.
(11) (a) Tewari, A.; Hein, M.; Zapf, A.; Beller, M. Synthesis
2004, 935. (b) Zapf, A.; Jackstell, R.; Rataboul, F.;
Riermeier, T.; Monsees, A.; Fuhrmann, C.; Shaikh, N.;
Dingerdissen, U.; Beller, M. Chem. Commun. 2004, 38.
(c) Neumann, H.; Brennfuehrer, A.; Gross, P.; Riermeier, T.;
Synlett 2011, No. 16, 2351–2354 © Thieme Stuttgart · New York

2354
J. Prabagar et al.
LETTER
was washed with EtOAc and dried in vacuo to give 1-
diamantyldiphenylphosphonium triflate(11) as a white solid
(506 mg, 92% yield); mp 272–274 °C. 1H NMR (400 MHz,
CDCl3, 25 °C): d = 9.24 (d, 1 H, HP, JHP = 506 Hz), 8.07 (m,
4 H, H12), 7.74 (m, 2 H, H14), 7.64 (m, 4 H, H13), 2.57 (d,
JHH = 14.2 Hz, 2 H, H3), 2.17 (br m, 1 H, H4), 2.04 (br m, 3
H, H7, H9), 1.92 (br m, 2 H, H2), 1.85 (br m, 2 H, H8), 1.81
(br m, 1 H, H6), 1.77 (br m, 5 H, H10, H3, H8), 1.64 (br m,
3 H, H8, H5). 31P NMR (162 MHz, CDCl3, 25 °C): d = 3.6.
13C NMR (100 MHz, CDCl3, 25 °C): d = 134.8 (d, JCP = 2.7
Hz, C14), 134.5 (d, JCP = 9.4 Hz, C12), 130.4 (d, JCP = 12.3
Hz, C13), 114.2 (d, JCP = 78.3 Hz, C11), 42.9 (d, JCP = 37.9
Hz, C1), 37.9 (C10), 37.7 (C2), 37.6 (C6), 36.5 (C8), 36.4
(C7), 36.1 (C5), 32.7 (d, JCP = 3.8 Hz, C3), 25.2 (d, JCP = 9.7
Hz, C9), 24.6 (C4). A portion was oxidised: triflate 11 (160
mg, 0.42mmol), t-BuOK (246.8 mg, 2.2 mmol) in CH2Cl2
(20 mL), together with 30% H2O2 (1.0 mL) were stirred for
14 h. After workup and flash chromatography (EtOAc) 1-
diamantyldiphenylphosphine oxide(12) was obtained (124
mg, 76% yield); mp 261–262 °C. 1H NMR (400 MHz,
CDCl3, 25 °C): d = 7.99 (m, 4 H, H12), 7.49 (m, 6 H, H13,
H14), 3.11 (d, JHH = 12.7 Hz, 2 H, H3), 2.03 (br m, 2 H, H2),
1.91 (br m, 1 H, H4), 1.31 (br m, 1 H, H9), 1.76 (br m, 2 H,
H7), 1.70 (br m, 5 H, H5, H6, H8), 1.59 (br m, 4 H, H8,
H10), 1.43 (d, JHH = 12.9 Hz, 2 H, H3). 31P NMR (162 MHz,
CDCl3, 25 °C): d = 39.6. 13C NMR (100 MHz, CDCl3, 25
°C): d = 132.4 (d, JCP = 7.5 Hz, C12), 132.2 (d, JCP = 88.3
Hz, C11), 131.1 (d, JCP = 2.5 Hz, C14), 128.1 (d, JCP = 10.7
Hz, C13), 42.7 (d, JCP = 66.9 Hz, C1), 39.3 (C5), 38.9 (C8),
38.8 (d, JCP = 4.0 Hz, C7), 37.6 (C6), 37.5 (d, JCP = 1.4 Hz,
C2), 37.3 (C10), 34.1 (C3), 25.9 (d, JCP = 11.2 Hz, C9), 25.2
(C4). HRMS (ES+): m/z calcd for C26H29PO: 389.2034;
found: 389.2041.
Synlett 2011, No. 16, 2351–2354 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or
emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.
However, users may print, download, or email articles for individual use.