Phosphaadamantanes as ligands for palladium catalyzed cross-coupling chemistry: Library synthesis, characterization, and screening in the Suzuki coupling of alkyl halides and tosylates containing β-hydrogens with boronic acids and alkylboranes

Article abstract of DOI:10.1021/jo048875+

A 15-member library of phosphaadamantane ligands has been prepared via P-arylation of 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phosphaadamantane. Screening of this tertiary phosphine collection has allowed for the rapid determination of the most suitable ligand, specifically 1,3,5,7-tetramethyl-6-(2,4- dimethoxyphenyl)-2,4,8-trioxa-6-phosphaadamantane, for facilitating Suzuki-type couplings of alkyl halides or tosylates containing β-hydrogens with either boronic acids or alkylboranes.

Full text of DOI:10.1021/jo048875+

P h osp h a a d a m a n ta n es a s Liga n d s for P a lla d iu m Ca ta lyzed
Cr oss-Cou p lin g Ch em istr y: Libr a r y Syn th esis, Ch a r a cter iza tion ,
a n d Scr een in g in th e Su zu k i Cou p lin g of Alk yl Ha lid es a n d
Tosyla tes Con ta in in g â-Hyd r ogen s w ith Bor on ic Acid s a n d
Alk ylbor a n es
Tim Brenstrum,† David A. Gerristma,† George M. Adjabeng,† Christopher S. Frampton,‡
J ames Britten,† Alan J . Robertson,§ J ames McNulty,† and Alfredo Capretta*,†
Department of Chemistry, McMaster University, Hamilton, Ontario, Canada L8S 4M1,
Bruker-Nonius B.V., Oostsingel 209, 2612 HL Delft, The Netherlands, and Cytec Canada Inc.,
P.O. Box 240, Niagara Falls, Ontario, Canada L2E 6T4
capretta@mcmaster.ca
Received J uly 2, 2004
A 15-member library of phosphaadamantane ligands has been prepared via P-arylation of 1,3,5,7-
tetramethyl-2,4,8-trioxa-6-phosphaadamantane. Screening of this tertiary phosphine collection has
allowed for the rapid determination of the most suitable ligand, specifically 1,3,5,7-tetramethyl-
6-(2,4-dimethoxyphenyl)-2,4,8-trioxa-6-phosphaadamantane, for facilitating Suzuki-type couplings
of alkyl halides or tosylates containing â-hydrogens with either boronic acids or alkylboranes.
Organopalladium cross-coupling reactions are among
the most useful and reliable methods for carbon-carbon
bond formation.1 The renewed interest in this chemistry
has been driven, to a great extent, by the development
of synthetic protocols employing sterically demanding,
electron-rich phosphine ligands.2 Utilization of catalytic
systems incorporating these bulky phosphines has al-
lowed for the successful coupling of even the least-
reactive partners in the Suzuki,3 Stille,4 Sonogashira,5
aryl amination,6 and ketone arylation7 reactions among
others. A recent addition to the organopalladium family
of reactions involves the Suzuki-type couplings of alkyl
halides or tosylates containing â-hydrogens with either
boronic acids or alkylboranes. While aryl and alkenyl
halides have been routinely used in the Suzuki reaction,
halides bonded to sp3-hybridized carbons have been
generally overlooked due to the slower rate of oxidative
addition of alkyl halides to palladium and their propen-
sity to undergo â-hydride elimination rather than the
desired coupling reaction. Fu has shown8 that the ap-
plication of palladium catalyst systems utilizing bulky
alkylphosphines allows for the Suzuki coupling of alkyl-
halides with a variety of boronic acids and alkylboranes
with little concomitant elimination product.
Overall, however, a review of the current chemical
literature reveals that while certain phosphines acceler-
ate a particular reaction, the same phosphine may have
little effect on a different palladium-catalyzed cross-
coupling. Although some phosphines show a greater
versatility than others, a ligand that can successfully be
employed in all organopalladium coupling reactions has
yet to be described. In our lab, for example, catalyst
systems incorporating 1,3,5,7-tetramethyl-2,4,8-trioxa-
6-phenyl-6-phosphaadamantane (Figure 1, 2) have al-
lowed for effective Suzuki cross-coupling of a variety of
† McMaster University.
‡ Bruker-Nonius.
§ Cytec Canada Inc.
(1) Metal-Catalyzed Cross Coupling Reactions; Diederich, F., Stang,
P., Eds.; Wiley-VCH: New York, 1998.
(2) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176-
4211.
(3) Littke, A. F.; Dai, C.; Fu, G. C. J . Am. Chem Soc. 2000, 122,
4020-4028. Yin, J .; Rainka, M. P.; Zhang, X.; Buchwald, S. L. J . Am.
Chem. Soc. 2002, 124, 1162-1163.
(4) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1999, 38, 2411-
2413.
(5) Tykwinski, R. R. Angew. Chem., Int. Ed. 2003, 42, 1566-1568.
Hundertmark, T.; Littke, A. F.; Buchwald, L. S.; Fu, G. C. Org. Let.
2000, 2, 1729-1731. Bohm, V. P. W.; Herrmann, W. A. Eur. J . Org.
Chem. 2000, 22, 3679-3681. Gelman, D.; Buchwald, S. L. Angew.
Chem., Int. Ed. 2003, 42, 5993-5996. Pal, M.; Parasuraman, K.; Gupta,
S.; Yeleswarapu, K. R. Synlett 2002, 14, 1976-1982. Fukuyama, T.;
Shinmen, M.; Nishitani, S.; Sato, M.; Ryu, I. Org. Lett. 2002, 4, 1691-
1694. Me´ry, D.; Heuze, K.; Astruc, D. Chem. Commun. 2003, 1934-
1935.
(6) Reddy, N. P.; Tanaka, M. Tetrahedron Lett. 1997, 38, 4807-4810.
Also see: Wolfe, J . P.; Buchwald, S. L. Angew. Chem., Int. Ed. 1999,
38, 2413-2416. Kataoka, N.; Shelby, Q.; Stambuli, J . P.; Hartwig, J .
F. J . Org. Chem. 2002, 67, 5553-5566.
(8) (a) Netherton, M. R.; Dai, C.; Neuschutz, K.; Fu, G. C. J . Am.
Chem Soc. 2001, 123, 10099-10100. (b) Kirchhoff, J . H.; Netherton,
M. R.; Hills, I. D.; Fu, G. C. J . Am. Chem Soc. 2002, 124, 13662-
13663. (c) Kirchhoff, J . H.; Dai, C.; Fu, G. C. Angew. Chem., Int. Ed.
2002, 41, 1945-1947. (d) Netherton, M. R.; Fu, G. C. Angew. Chem.,
Int. Ed. 2002, 41, 3910-3912. (e) Hills, I. D.; Netherton, M. R.; Fu, G.
C. Angew. Chem., Int. Ed. 2003, 42, 5749-5752. (f) Zhou, J .; Fu, G. C.
J . Am. Chem. Soc. 2004, 126, 1340-1341. For analogous Stille cross-
couplings see: Menzel, K.; Fu, G. C. J . Am. Chem. Soc. 2003, 125,
3718-3719. For analogous Negishi reactions see: Wiskur, S. L.; Korte,
A.; Fu, G. C. J . Am. Chem. Soc. 2004, 126, 82-83. For analogous
Hiyama reactions see: Lee, J .-Y.; Fu, G. C. J . Am. Chem. Soc. 2003,
125, 5616-5617.
(7) Culkin, D. A.; Hartwig, J . F. Acc. Chem. Res. 2003, 36, 234-
245. Viciu, M. S.; Kelly, R. A., III; Stevens, E. D.; Naud, F.; Studer,
M.; Nolan, S. P. Org. Lett. 2003, 5, 1479-1482. Fox, J . M.; Huang, X.;
Chieffi, A.; Buchwald, S. L. J . Am. Chem. Soc. 2000, 122, 1360-1370.
10.1021/jo048875+ CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/30/2004
J . Org. Chem. 2004, 69, 7635-7639
7635

Brenstrum et al.
TABLE 1. Scr een in g th e P h osp h a a d a m a n ta n e Libr a r y
F IGURE 1. Phosphaadamantane.
aryl halides and boronic acids under mild conditions.9
This same ligand can also be used for solid-phase Suzuki
couplings involving immobilized reaction partners.10 In
addition, an air-stable palladium complex of this phen-
ylphosphaadamantane ligand has been shown to be an
effective, versatile catalyst for use in the Suzuki and
Sonogashira reactions and the R-arylation of ketones.11
However, attempts to use the ligand in Suzuki couplings
of alkyl halides containing â-hydrogens with alkylboranes
have met with less than satisfactory results.
Our search for a “one-size-fits-all” ligand has, therefore,
evolved into the following combinatorial approach. With
the phosphaadamantanes, the parent, secondary system
(Figure 1, 1) affords the opportunity for introduction of
variable aryl or alkyl moieties at the phosphorus. Each
new tertiary phosphine thus generated has different
electronic and steric properties. Parallel screening of the
phosphaadamantane library quickly establishes the su-
perior ligand to be used for the optimization of the
particular reaction. The present paper illustrates the
successful application of this new approach and describes
the synthesis, characterization, and parallel screening of
a collection of tertiary phosphaadamantanes in the
Suzuki coupling of alkyl systems containing â-hydrogens.
Resu lts a n d Discu ssion
Ligands 5-15 (Table 1)12 are prepared via derivitiza-
tion of the parent secondary phosphaadamantane13
(1,3,5,7-tetramethyl-2,4,8-trioxa-6-phosphaadaman-
tane, Figure 1, 1), using previously developed protocols.
Treatment of 1 with an equivalent or slight excess of the
appropriate aryl halide in the presence of Pd(PPh3)4 and
potassium carbonate in xylenes affords the tertiary
phosphines in good to excellent yields. The compounds
were fully characterized with 1H, 13C, and 31P NMR as
well as MS. In addition, each of the derivatized phos-
phaadamantanes was air-stable and many crystallized
to allow for X-ray structure determination.14
With the phosphaadamantane library in hand, our
attention was turned to the parallel screening of the
ligands for their effectiveness in Suzuki cross-coupling
involving alkyl halides possessing â-hydrogens. Ligands
(9) Adjabeng, G.; Brenstrum, T.; Wilson, J .; Frampton, C.; Robert-
son, A.; Hillhouse, J .; McNulty, J .; Capretta, A. Org. Lett. 2003, 5, 953-
955.
(10) Ohnmacht, S. A.; Brenstrum, T.; Bleicher, K. H.; McNulty, J .;
Capretta, A. Tetrahedron Lett. 2004, 45, 5661-5663.
(11) Adjabeng, G.; Brenstrum, T.; Frampton, C. S.; Robertson, A.
J .; Hillhouse, J .; McNulty, J .; Capretta, A. J . Org. Chem. 2004, 69,
5082-5086.
a
b
PA ) phosphaadamantane. Percent coupled product and
percent elimination product determined by GC/MS.
(12) Preparation of ligands 2, 3, and 4 is described in ref 9.
(13) Epstein, M.; Buckler, S. A. J . Am. Chem. Soc. 1961, 83, 3279-
3282.
were tested for their ability to affect the coupling of
1-bromododecane and phenylboronic acid in the presence
of Pd(OAc)2 and potassium tert-butoxide in dioxane at
room temperature. The reactions were carried out in
parallel then subjected to GC/MS analysis to determine
(14) Details regarding the crystal structure of ligands 4 (deposition
number 246300), 5 (deposition number 246301), 6 (deposition number
246304), 11 (deposition number 246302), and 15 (deposition number
246303) may be obtained from the Cambridge Crystallographic Data
Centre.
7636 J . Org. Chem., Vol. 69, No. 22, 2004

Phosphaadamantanes
TABLE 2. Su zu k i Cou p lin g of Alk yl Ha lid es a n d
Bor on ic Acid s
the relative amounts of coupled product (1-dodecylben-
zene) and the byproduct from elimination (1-dodecene).
The results appear in Table 1. Ligands containing aryl
moieties substituted with electron-donating groups per-
formed better than the unsubstituted phenylphosphaad-
amantane (2) and alkyl-substituted system (3). As ex-
pected, the 4-acetylphenyl system (15) gave only small
amounts of the desired coupled product while the 2-py-
ridinyl system did marginally better. The best results
were obtained with the methoxyphenyl-containing phos-
phaadamantanes with the ortho- (5) and para-substituted
systems (7) facilitating the coupling in 71% and 64%,
respectively. Introduction of a second methoxy group
provided the best ligand of the series 8 providing a 96%
yield of the desired coupled product with the remainder
being the product from elimination. Contrasting the
effectiveness of 5 and 7 with 8, it is clear that both OMe
substituents are required for optimal efficiency. Attempts
to prepare the trimethoxy analogue with two ortho and
one para substituent have not been successful to date. A
few additional points are worth noting. Phosphaadaman-
tane 8 contains the same o-methoxy substitutuent con-
tained in Buchwald’s latest ligand.15 The methoxy group
seems to have the correct steric and electronic properties
needed for the reaction since neither the o-benzyloxy
moiety of 12 nor the dimethylamino substituents of 9,
10, and 11 perform nearly as well.
Optimization of the reaction parameters revealed Pd-
(OAc)2 to be the best palladium source and potassium
tert-butoxide to be the best base. While both toluene and
benzene could be used as solvent, dioxane consistently
gave the superior coupling yields while minimizing the
elimination products. Finally, a slight excess of ligand
with respect to palladium was determined to be neces-
sary. With the conditions in hand, a variety of alkyl
bromides and chlorides were coupled to a series of boronic
acids and the results appear in Table 2. Use of ligand 8
allowed for the Suzuki coupling of 1-bromododecane to
electron-neutral (entries 1 and 2), more sterically de-
manding (entry 2), and electron-rich (entry 3) aryl boronic
acids in excellent yields with minimal elimination prod-
ucts. Not surprisingly, entry 7 revealed that the catalytic
species was more selective for the C-Br bond over the
C-Cl allowing for the 95% yield of 1-(5-chloropentyl)-4-
methoxybenzene. Limited success was achieved in the
coupling of secondary alkyl bromides. Using 5 equiv of
cyclohexyl bromide (relative to p-methoxyphenylboronic
acid), 44% coupling could be obtained (entry 6). Under
the reaction conditions used, rapid â-hydride elimination
gave substantial amounts of cyclohexene. Alkyl boronic
acids could also be used with butylboronic acid coupling
to 1-bromododecane with moderate success (entry 5).
Monitoring via GC/MS, however, revealed that cross-
coupling, â-hydride elimination, and boronic acid decom-
position were all occurring at similar rates and as a result
only 54% of the desired product could be obtained. The
alkyl chlorides required elevated temperatures and re-
sulted in modest yields of coupled products (entries 8 and
9).
a
b
Isolated yield and average of two runs. Reaction carried out
at 90 °C.
Suzuki coupling of alkyl halides and tosylates with alkyl
boranes. The requisiste alkyl boranes were easily ac-
cessed via hydroboration of the appropriate alkene with
9-borabicyclo[3.3.1]nonane (9-BBN). The coupling of alkyl
bromides with alkyl-9-BBN derivatives (entries 1, 2, 3,
and 4 of Table 3) progressed smoothly and in good yields
at room temperature in THF with Pd(OAc)2 as the
palladium source and K3PO4‚H2O as base. The reaction
conditions were compatible with a variety of functional
groups including alkenes, esters, and nitriles. Slightly
different conditions were required for the coupling of
alkyl tosylates, with dioxane, NaOH, and a temperature
of 50 °C proving optimal (entries 5, 6, 7, and 8 in Table
3). The conditions were mild enough to tolerate ketone
and ester functionalities, although the yields for these
The dimethoxyphenylphosphaadamantane ligand 8
was shown to be equally effective in facilitating the
(15) Walker, S. D.; Barder, T. E.; Martinelli, J . R.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2004, 43, 1871-1876.
J . Org. Chem, Vol. 69, No. 22, 2004 7637

Brenstrum et al.
TABLE 3. Su zu k i Cou p lin g of Alk yl Ha lid es or
Tosyla tes w ith Alk ylbor a n es
distinct advantages. Ligand 8 is air-stable, crystalline,
easy to prepared, and is easily handled. Furthermore, the
approach involving the screening of a ligand library has
allowed for the rapid determination of the most suitable
ligand for a particular reaction. Applications of this
approach to other palladium-promoted cross-coupling
reactions are currently under investigation.
Exp er im en ta l Section
For each of the coupling protocols described, a general
procedure is provided as well as one specific example. All other
experimental procedures are available in the Supporting
Information.
Gen er a l P r oced u r e for th e Ar yla tion of 1,3,5,7-Tet-
r a m eth yl-2,4,8-tr ioxa -6-p h osp h a a d a m a n ta n e. The aryl
bromide (9.26 mmol), 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phos-
phaadamantane (1, 2.0 g, 9.26 mmol), Pd(PPh3)4 (321 mg, 0.28
mmol), and potassium carbonate (3.8 g, 27.8 mmol) are stirred
in xylenes (50 mL) under an argon atmosphere and heated at
110 °C for 20 h. The mixture is diluted with diethyl ether (20
mL) and filtered through a plug of silica (2 cm × 2 cm), and
the solvent is removed at reduced pressure. Flash chromatog-
raphy (using 20% diethyl ether/hexanes) allows for the isola-
tion of the pure tertiary phosphine ligand. 1,3,5,7-Tetr am eth yl-
6-(2-m e t h o x y p h e n y l)-2,4,8-t r io x a -6-p h o s p h a a d a m -
a n ta n e (Ta ble 1, En tr y 5): synthesized as per the general
procedure with 2-bromoanisole (865 mg, 9.26 mmol). Flash
chromatography with 20% diethyl ether/hexanes afforded the
title compound (2.365 g, 79%) as white needles, mp 167-170
°C. 1Η NMR (CDCl3, 300 MHz) δ 1.23 (3H, d, J ) 12.0 Hz),
1.33 (3H, s), 1.35 (3H, s), 1.39 (1H, dd, J ) 13.4, 1.4 Hz), 1.45
(3H, d, J ) 12.6 Hz), 1.78 (1H, d, J ) 13.4 Hz), 1.86 (1H, dd,
J ) 25.3, 13.1 Hz), 2.03 (1H, dd, J ) 13.1, 7.4 Hz), 3.78 (3H,
s), 6.82 (1H, dd, J ) 8.2, 4.6 Hz), 6.91 (1H, t, J ) 7.5 Hz), 7.2
(1H, ddd, J ) 8.2, 7.5, 0.9 Hz), 8.02 (1H, dd, J ) 7.5, 0.9 Hz);
13C NMR (CDCl3, 75 MHz) δ 26.8 (d, J ) 18.9 Hz), 27.9 (s),
28.0 (d, J ) 21.2 Hz), 28.1 (s), 36.8 (d, J ) 1.8 Hz), 46.0 (d, J
) 18.9 Hz), 55.5 (s), 73.1 (d, J ) 22.4 Hz), 73.9 (d, J ) 8.8 Hz),
96.2, 96.8 (s), 110.5 (d, J ) 2.0 Hz), 121.0 (s), 122.1 (d, J )
27.9 Hz), 130.8 (s), 134.1 (d, J ) 3.6 Hz), 134.1 (d, J ) 16.9
Hz); 31P NMR (CDCl3, 81 MHz) δ -41.3; EIMS m/z (RI%) 322
(19), 222 (100), 207 (37), 179 (19), 138 (17), 85 (17), 43 (67).
HRMS molecular weight for C17H23O4P calcd 322.1334, obsd
322.1324.
Gen er a l P r oced u r e for Su zu k i Cou p lin gs of Alk yl
Ha lid es a n d Ar yl Bor on ic Acid s. A reaction vessel con-
taining Pd(OAc)2 (4%, 9.0 mg, 0.04 mmol), 1,3,5,7-tetramethyl-
6-(2,4-dimethoxyphenyl)-2,4,8-trioxa-6-phosphaadamantane
(ligand 8, 4%, 11.7 mg, 0.04 mmol), potassium tert-butoxide
(337 mg, 3.0 mmol), and boronic acid (1.0 mmol) was sealed
with a rubber septum and its contents placed under an argon
atmosphere. Toluene (dry, degassed, 1.5 mL) and the alkyl
bromide (1.2 to 5.0 mmol as indicated) were added via a
syringe. The flask was stirred at room temperature and the
reaction was monitored via TLC (5% EtOAc in hexane). Once
the reaction was judged as completed, the toluene was diluted
with diethyl ether (10 mL) and washed with distilled water (1
× 10 mL) and brine (1 × 10 mL). The organic solution was
concentrated under reduced pressure and the residue purified
via flash silica gel chromatography (5% ethyl acetate in
hexane). 1-Dod ecylben zen e (Ta ble 2, En tr y 1): synthesized
as per the general procedure above with 1-bromododecane
(299.1 mg, 288.1 µL, 1.2 mmol) and phenylboronic acid (121.9
mg, 1.0 mmol). After 26 h the reaction was stopped. Chroma-
tography resulted in a 97% yield of 1-dodecylbenzene (239.0
mg, 97 mmol). 1H NMR (CDCl3, 300 MHz) δ 0.94 (3H, m), 1.32
(18H, br m), 1.67 (2H, m), 2.65 (2H, t, J ) 7.18 Hz), 7.21-
7.32 (5H, m); 13C NMR (CDCl3, 75 MHz) δ 14.2, 22.8, 29.4,
29.5, 29.6, 29.7, 29.8, 29.8, 29.8, 31.7, 32.1, 36.1, 125.6, 127.3,
a
b
Isolated yield and average of two runs. 4% Pd(OAc)2, 5%
ligand 8, 1.2 equiv of K3PO4‚H2O, THF, rt, 24 h. c 4% Pd(OAc)2,
16% ligand 8, 1.2 equiv NaOH, dioxane, 50 °C, 24 h. 10%
d
Pd(OAc)2, 20% ligand 8, 1.1 equiv CsOH‚H2O, dioxane, 90 °C, 48
e
h. 10% Pd(OAc)2, 20% ligand 8, 1.1 equiv KOH, dioxane, 90 °C,
48 h.
were moderate. For the alkyl chlorides more vigorous
conditions were required, with a temperature of 90 °C
and CsOH‚H2O generally affording excellent results
(entries 9-13, Table 3). At these temperatures, cataly-
stand ligand decomposition became an issue and, there-
fore, higher catalyst loading was deemed necessary.
Overall, the 1,3,5,7-tetramethyl-6-(2,4-dimethoxyphen-
yl)-2,4,8-trioxa-6-phosphaadamantane ligand (8) has dem-
onstrated itself to be effective in facilitating the Suzuki-
type couplings of alkyl halides or tosylates containing
â-hydrogens with either boronic acids or alkylboranes.
In contrast to the other ligands used in these transfor-
mations, the phosphaadamantane offers a number of
7638 J . Org. Chem., Vol. 69, No. 22, 2004

Phosphaadamantanes
128.3, 143.0. EIMS m/z (RI%) 57 (13), 92 (100), 105 (12), 246.
(87); HRMS molecular weight for C18H30 calcd 246.2347, obsd
246.2353.
alkyl chloride (1.0 mmol). n -Octa d eca n e (Ta ble 3, en tr y
1): synthesized as per the general procedure above with
n-bromododecane (249 mg, 1.00 mmol) and the organoborane
(2.4 mL of a 0.50 M solution in THF; 1.2 mmol) prepared from
hydroboration of 1-hexene with 9-BBN. After 24 h, workup
followed by column chromatography (hexanes) afforded the
title compound as a white, waxy solid (236 mg, 93%). 1H NMR
(CDCl3, 300 MHz) δ 1.26 (32H, br s), 0.88 (6H, t, J ) 6.8 Hz);
13C NMR (CDCl3, 50 MHz) δ 2 × 3.1, 10 × 29.9, 2 × 29.5, 2 ×
22.8, 2 × 14.2. EIMS m/z (RI%) 254 (7), 231 (15), 117 (38), 99
(35), 85 (67), 71 (100), 57 (60); HRMS molecular weight for
Gen er a l Cr oss-Cou p lin g P r oced u r e of Alk yl Ha lid es/
Tosyla tes w ith 9-BBN Ad d u cts. For the alkyl bromide
substrates, the following procedure was employed. A reaction
vessel containing Pd(OAc)2 (9.0 mg, 0.040 mmol), 1,3,5,7-
tetramethyl-6-(2,4-dimethoxyphenyl)-2,4,8-trioxa-6-phospha-
adamantane (ligand 8, 17.6 mg, 0.050 mmol), and K3PO4‚H2O
(276 mg, 1.2 mmol) was sealed with a rubber septum and its
contents placed under an argon atmosphere. The alkyl bromide
(1.0 mmol) and organoborane (1.2 mmol) were added in turn
via syringe and the mixture stirred at the indicated temper-
ature for the indicated time. The reaction was then diluted
with Et2O, filtered through silica gel with copious washing
(Et2O), concentrated, and purified by column chromatography.
For the alkyl tosylate substrates, the above procedure was
employed but with 1,3,5,7-tetramethyl-6-(2,4-dimethoxyphen-
yl)-2,4,8-trioxa-6-phosphaadamantane (ligand 8, 56.3 mg, 0.16
mmol), NaOH (24 mg, 1.2 mmol), alkyl tosylate (1.0 mmol),
and additional dioxane (4.0 mL). For the alkyl chloride
substrates, the above procedure was employed but with Pd-
(OAc)2 (22.5 mg, 0.10 mmol), 1,3,5,7-tetramethyl-6-(2,4-
dimethoxyphenyl)-2,4,8-trioxa-6-phosphaadamantane (ligand
8, 70.4 mg, 0.20 mmol), CsOH‚H2O (184 mg, 1.1 mmol), and
C
18H38 calcd 254.2974, obsd 254.2949.
Ack n ow led gm en t. We thank Cytec Canada Inc.
and the Natural Sciences and Engineering Research
Council of Canada for financial support.
Su p p or tin g In for m a tion Ava ila ble: ORTEP and crystal-
lographic data for 8 (CIF); experimental procedures for com-
pounds shown in Table 1 (entries 6-15), Table 2 (entries 2-10)
and Table 3 (entries 2-13) and 1H NMR spectra for all
compounds described. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O048875+
J . Org. Chem, Vol. 69, No. 22, 2004 7639