P(i-BuNCH2CH2)3N: An effective ligand in the palladium-catalyzed amination of aryl bromides and iodides

Article abstract of DOI:10.1021/jo0205309

It is shown that the bicyclic triaminophosphine P(i-BuNCH₂CH₂)₃N serves as an effective ligand for the palladium-catalyzed amination of a wide array of aryl bromides and iodides. Other bicyclic or acyclic triaminophosphines, even those of similar basicity and/or bulk, were inferior.

Full text of DOI:10.1021/jo0205309

P (i-Bu NCH2CH2)3N: An Effective Liga n d in th e
P a lla d iu m -Ca ta lyzed Am in a tion of Ar yl Br om id es a n d Iod id es
Sameer Urgaonkar, M. Nagarajan, and J . G. Verkade*
Department of Chemistry, Gilman Hall, Iowa State University, Ames, Iowa 50011
jverkade@iastate.edu
Received August 9, 2002
It is shown that the bicyclic triaminophosphine P(i-BuNCH2CH2)3N serves as an effective ligand
for the palladium-catalyzed amination of a wide array of aryl bromides and iodides. Other bicyclic
or acyclic triaminophosphines, even those of similar basicity and/or bulk, were inferior.
In tr od u ction
exhibit improved catalytic activity in this type of trans-
formation. Although room-temperature amination reac-
tions are known,8 the range of substrate combinations
that can be employed at this temperature are rather
limited, whereas reactions performed at 80 °C or higher
accommodate a wide variety of substrates.
Palladium-catalyzed amination reactions are funda-
mentally important organic transformations that have
received tremendous attention over the past few years.1
Elegant work by Hartwig,2 Buchwald,3 and others4 has
led to significant improvements in amination methodol-
ogy since its discovery by Migita and co-workers in 1983.5
Most of the reported methods employ electron-rich phos-
phine ligands,6 possessing either a ferrocene7 or a biphen-
yl backbone,8 or bulky nucleophilic N-heterocyclic car-
benes (sometimes referred to as “phosphine mimics”).4a,c,9
Chelating phosphines such as 1,1′-bis(diphenylphosphi-
no)ferrocene (DPPF)2a and 2,2′-bis(diphenylphosphino)-
1,1′-binaphthyl (BINAP)3b,10 have been demonstrated to
Although triaminophosphines, and particularly P(N-
Me2)3, have often been used to ligate transition metals,
to the best of our knowledge there have been no reports
of the use of such ligands in Pd-catalyzed amination
chemistry. This may be partly due to the diminished
electron-donating capability of acyclic triaminophos-
phines compared with trialkylphosphines, as was re-
cently rationalized by Woollins.11 The reduced Lewis
basicity of triaminophosphines is believed to arise from
differences in the geometries of their nitrogens. X-ray
crystal structures of free tris(dialkylamino)phosphines
and their transition metal complexes12,13 reveal that
phosphorus bears two nearly planar nitrogens and one
pyramidal nitrogen. While the two planar nitrogens are
capable of donating electron density to phosphorus via
their unhybridized lone pairs (which are roughly per-
pendicular to the phosphorus lone pair) the pyramidal
nitrogen simply acts as an electron-withdrawing atom
since its more sp3-hybridized lone pair is oriented anti
to the phosphorus lone pair.
(1) (a) Tsuji, J . Palladium Reagents and Catalysts: Innovations in
Organic synthesis; J ohn Wiley & Sons: Chichester, England, 1995. For
a general review of palladium-catalyzed aryl aminations, see: (b) Wolfe,
J . P. Wagaw, S.; Marcoux, J .-F.; Buchwald, S. L. Acc. Chem. Res. 1998,
31, 805. (c) Hartwig, J . F. Acc. Chem. Res. 1998, 31, 805. (d) Hartwig,
J . F. Angew. Chem., Int. Ed. 1998, 37, 2046.
(2) (a) Driver, M. S.; Hartwig, J . F. J . Am. Chem. Soc. 1996, 118,
7217. (b) Hamann, B. C.; Hartwig, J . F. J . Am. Chem. Soc. 1998, 120,
7369. Also see ref 9.
(3) (a) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 1348. (b) Wolfe, J . P.; Wagaw, S.; Buchwald,
S. L. J . Am. Chem. Soc. 1996, 118, 7215. (c) Ali, M. H.; Buchwald, S.
L. J . Org. Chem. 2001, 66, 2560. (d) Wolfe, J . P.; Buchwald, S. L.
Angew. Chem., Int. Ed. 1999, 38, 2413. (e) Wolfe, J . P.; Singer, R. A.;
Yang, B. H.; Buchwald, S. L. J . Am. Chem. Soc. 1999, 121, 9550.
(4) (a) Huang, J .; Grasa, G. A.; Nolan, S. P. Org. Lett. 1999, 1, 1307.
(b) Herrmann, W. A.; Kocher, C. Angew. Chem., Int. Ed. Engl. 1997,
36, 2163. (c) Grasa, G. A.; Viciu, M. S.; Huang, J .; Nolan, S. P. J . Org.
Chem. 2001, 66, 7729. (d) Bei, X.; Uno, T.; Norris, J .; Turner, H. W.;
Weinberg, W. H.; Guram, A. S. Organometallics 1999, 18, 1840. (e)
Artamkina, G. A.; Ivushkin, V. A.; Beletskaya, P. Russ. J . Org. Chem.
1970, 35, 1797. (f) Bolm, C.; Hildebrand, J . P. J . Org. Chem. 2000, 65,
169. (g) Li, R.; He, M. Y.; DeShong, P.; Clark, C. G. J . Am. Chem. Soc.
2000, 122, 7600.
(5) Kosugi, M.; Kameyama, M.; Migita, T. Chem. Lett. 1983, 927.
(6) (a) Nishiyama, M.; Yamamoto, T.; Koie, Y. Tetrahedron Lett.
1998, 39, 617. (b) Hartwig, J . F.; Kawatsura, M.; Hauck, S. I.;
Shaughnessy, K, H.; Alcazar-Roman, L. M. J . Org. Chem. 1999, 64,
5575.
(7) (a) Marcoux, J .-F.; Wagaw, S.; Buchwald, S. L. J . Org. Chem.
1997, 62, 1568. (b) Hamann, B. C.; Hartwig, J . F. J . Am. Chem. Soc.
1998, 120, 7369.
(8) Wolfe, J . P.; Tomori, H.; Sadighi, J . P.; Yin, J .; Buchwald, S. L.
J . Org. Chem. 2000, 65, 1158. See also ref 4d and references therein.
(9) Stauffer, S. R.; Lee, S.; Stambuli, J . P.; Hauck, S. I.; Hartwig, J .
F. Org. Lett. 2000, 2, 1423.
As part of our own effort to understand and exploit the
stereoelectronic properties of tris(dialkylamino)phos-
phines, we reasoned that by rendering the backbone of
the triaminophosphine quite rigid in a bicyclic framework
in which all three nitrogens would be geometrically and
conformationally very similar14 to the two planar elec-
(11) (a) Clarke, M. L.; Cole-Hamilton, D. J .; Slawin, A. M. Z.;
Woollins, J . D. Chem. Commun. 2000, 2065. (b) Clarke, M. L.; Cole-
Hamilton, D. J .; Woollins, J . D. J . Chem. Soc., Dalton Trans. 2001,
2721.
(12) (a) Molloy, K. G.; Petersen, J . L. J . Am. Chem. Soc. 1995, 117,
7696. (b) Xi, S. K.; Schmidt, H.; Lensink, C.; Kim, S.; Wintergrass, D.;
Daniels, L. M.; J acobson, R. A.; Verkade, J . G. Inorg. Chem. 1990, 29,
2214. (c) Socol, S. M.; J acobson, R. A.; Verkade, J . G. Inorg. Chem.
1984, 23, 88. (d) Romming, C.; Songstad, J . Acta Chem. Scand., Ser. A
1980, 34, 365. (e) Romming, C.; Songstad, J . Acta Chem. Scand., Ser.
A 1979, 33, 187.
(13) For a discussion of the electronic structure of tris(dialkylamino)-
phosphines, see: Cowley, A. H.; Lattman, M.; Stricklen, P. M.; Verkade,
J . G. Inorg. Chem. 1982, 21, 543.
(10) Wolfe, J . P.; Buchwald, S. L. J . Org. Chem. 2000, 65, 1144.
10.1021/jo0205309 CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/24/2002
452
J . Org. Chem. 2003, 68, 452-459

P(i-BuNCH2CH2)3N
TABLE 1. Scr een in g of Tr ia m in op h osp h in e Liga n d s for
th e Rea ction Sh ow n in Eq 1a
tron-donating nitrogens in tris(dialkylamino)phosphines,
we could significantly enhance the basicity of such
phosphines and thus facilitate oxidative addition to the
metal. Furthermore, the electronic and steric influences
in such ligands could be easily tailored by introducing
suitable organic substituents at each PN3 nitrogen to
impart the desired steric bulk which could assist in the
reductive elimination step. In addition to these advan-
tages possessed by pro-azaphosphatranes of types 1a -
6a , such bicyclic systems also feature the potential for
entry ligand yield (%)b entry
ligand
yield (%)b
1
2
3
4
5
1a
2a
3a
4a
5a
15
5
0
97
30
6
7
8
9
6a
0
P(NMe2)3
P(NEt2)3
P[N(i-Bu)2]3
10c
11c
15c
a
Control experiments show that either in the absence of a Pd
source or in the absence of the bicyclic triaminophosphine ligand
4, no reaction was observed. b Isolated yields (average of two runs).
c 15% of hydrodehalogenated arene was isolated.
bulky bicyclic triaminophosphines 3a and 4a were em-
ployed in this reaction. Although ligand 3a was not
effective, it was gratifying to find that, with 4a (a
colorless liquid), the desired amination product was
isolated in 97% yield (Table 1, entry 4). Interestingly,
further increases in ligand steric hindrance (5a and 6a )
proved ineffective (Table 1, entries 5 and 6). The inef-
ficiency of ligand 3a might be due to the fact that it does
not provide sufficient steric bulk since the Me groups on
the i-Pr substituents are turned outward and away when
the Pd is coordinated to phosphorus, a conformation that
is also present in the solid-state structure of the free
ligand and its protonated form.14 Although 5a could be
assumed to be at least as efficient as 4a , if not more so,
it appears that, after a point achieved in 4a , additional
steric hindrance becomes detrimental to catalyst activity.
Thus, 4a presumably possesses a unique balance of
stereoelectronic influences that optimize activity of the
catalyst system. As expected, the relatively electron-poor
acyclic triaminophosphine ligands P(NR2)3 (R ) Me, Et,
i-Bu) gave very poor yields with incomplete conversion
(Table 1, entries 7-9).
The best results were obtained in aminations per-
formed at 80 °C in toluene using NaO-t-Bu19 as a base
and a catalyst system generated in situ from 2 mol %
Pd(OAc)2 and 4 mol % of 4a . With optimized conditions
in hand, the scope of this catalytic process was examined
with various aryl bromides and iodides, and the results
are summarized in Tables 2 and 3, respectively. As seen
in Table 2, the Pd/4a catalyst system efficiently catalyzed
the cross-coupling reaction of electronically diverse aryl
bromides with a variety of amines. Thus, electron-poor
(e.g., 4-bromobenzonitrile), electron-neutral (e.g., 4-tert-
butylbromobenzene), and electron-rich (e.g., 4-bromoani-
sole) aryl bromides coupled smoothly with various anilines
(primary and secondary) to afford the N-arylated prod-
ucts in excellent yields (Table 2, entries 3, 7, 8, 17, and
18). Secondary cyclic amines were also efficiently ary-
lated. For example, morpholine and pyrrolidine reacted
with 4-bromobenzonitrile to give the desired products in
high yields (Table 2, entries 1 and 2). Similarly, piperi-
dine coupled with 4-tert-butylbromobenzene and 4-bro-
moanisole in good to excellent yields (Table 2, entries 9
and 19). It may be noted that the piperidine coupling
reaction gave a large amount of reduced side products
with a very active Pd/BINAP catalyst system.10
basicity enhancement via transannulation of the bridge-
head nitrogen’s lone pair to the phosphorus as in 1b-
6b15 some of which we recently showed possess pKa
values of approximately 33 in acetonitrile.16 Compounds
of type 1 have proven to be exceedingly useful nonionic
bases and catalysts for a variety of useful transformations
during the last 10 years.17 Herein we show that com-
mercially available 4a is an excellent ligand in the
palladium-catalyzed aminations of aryl bromides and
iodides.
Resu lts a n d Discu ssion
For our optimization studies, we selected the Pd(OAc)2/
L-catalyzed amination of 4-bromobenzonitrile with 2-eth-
ylaniline in toluene as a model reaction (reaction 1).
Initial reactions with 1a and 2a as ligands were disap-
pointing, providing only a trace amount of N-arylated
product (Table 1, entries 1 and 2). Since ligand steric
hindrance can improve catalytic performance,18 the more
(14) An X-ray structural study of 3a showed that the bonding
environment around the PN3 nitrogen is rather planar, the sum of
angles being 354.9, 356.6, and 357.5° (Wroblewski, A. E.; Pinkas, J .;
Verkade, J . G. Main Group Chem. 1995, 1, 69).
(15) See: (a) Kisanga, P.; Verkade, J . G. Tetrahedron 2001, 57, 467
and references therein. (b) Liu, X.; Verkade, J . G. Manuscript in
preparation.
(16) Kisanga, P. B.; Verkade, J , G.; Schwesinger, R. J . Org. Chem.
2000, 65, 5431.
(17) Verkade, J . G. In New Aspects of Phosphorus Chemistry II.
Top. Curr. Chem. Majoral, J . P., Ed. 2002, 233, 1.
(18) Hartwig, J . F.; Richards, S.; Baranano, D.; Paul, F. J . Am.
Chem. Soc. 1996, 118, 3626.
The Pd/4a catalyst system was also effective for
primary aliphatic amines that were branched at the R
(19) Weaker bases such as Cs2CO3, CsF, K3PO4, K2CO3, and NaOH
failed to promote coupling.
J . Org. Chem, Vol. 68, No. 2, 2003 453

Urgaonkar et al.
TABLE 2. P a lla d iu m /4a -Ca ta lyzed Am in a tion of Ar yl Br om id esa
454 J . Org. Chem., Vol. 68, No. 2, 2003

P(i-BuNCH2CH2)3N
Ta ble 2 (Con tin u ed )
a
Reaction conditions: 1.0 mmol of aryl bromide, 1.2 mmol of amine, 1.5 mmol of NaO-t-Bu, 2.0 mol % Pd/(OAc)2, 4.0 mol % 4a , 5 mL
of toluene, 80 °C, 9-15 h. Reaction times have not been minimized. Isolated yields (average of two runs). c 5.0 mol % Pd(OAc)2 was
used. 3.0 mol % Pd(OAc)2 was used.
b
d
position. For instance, cyclohexylamine reacted with
4-tert-butylbromobenzene to produce the N-arylated prod-
uct in 89% yield (Table 2, entry 10). Moreover, sterically
hindered 2-bromotoluene reacted cleanly with cyclohex-
ylamine (Table 2, entry 16). A slightly lower yield was
obtained with electron-poor 4-bromochlorobenzene (Table
2, entry 6). A catalyst loading of 5 mol % allowed the
reaction of 4-bromobenzonitrile with sec-butylamine (Table
2, entry 5). However, the reaction of long-chain primary
alkylamines such as n-hexylamine with aryl bromides
usually gave less than 50% yield of the desired product
even when greater quantities of catalyst and/or longer
reaction times were employed. The main side products
were the diarylated amine, which may be attributed to
the formation of a catalytically inactive bis(primary
amine)palladium(II) complex,20 and the hydrodehaloge-
nated arene, resulting from â-hydride elimination. Reac-
tions of acyclic secondary amines with aryl bromides also
occurred (in moderate yields) although they required the
use of 5 mol % Pd(OAc)2. Thus, 4-bromobenzonitrile and
4-tert-butylbromobenzene reacted with diisobutylamine
and diethylamine, respectively, to form the corresponding
N-aryl product (Table 2, entries 4 and 11, respectively).
Steric hindrance on either coupling partner was well
tolerated, often giving the desired product in almost
quantitative yield. For example, mono and di-ortho-
substituted aryl bromides reacted with 2-aminobiphenyl
to give excellent yields of the desired product (Table 2,
entries 12 and 13). Particularly noteworthy is the reac-
tion of 2-bromomesitylene with 2,6-dimethylaniline, which
afforded the tetra-ortho-substituted arylamine product
in 99% isolated yield (Table 2, entry 15). With DPEphos
(bis[2-(diphenylphosphino)phenyl] ether), rac-BINAP, or
(20) Widenhoefer, R. A.; Buchwald, S. L. Organometallics 1996, 15,
3534.
J . Org. Chem, Vol. 68, No. 2, 2003 455

Urgaonkar et al.
TABLE 3. P a lla d iu m /4a -ca ta lyzed Am in a tion of Ar yl Iod id esa
a
Reaction conditions: 1.0 mmol of aryl iodide, 1.2 mmol of amine, 1.5 mmol of NaO-t-Bu, 2.0 mol % of Pd(OAc)2, 4.0 mol % of ligand
4a , 5 mL of toluene, 80 °C, 9-12 h. Reaction times have not been minimized. Isolated yields (average of two runs). c 10% of
b
hydrodehalogenated arene was isolated. 2.0 mol % of Pd2(dba)3 was used instead of Pd(OAc)2. e 4.0 mol % of Pd(OAc)2 was employed.
d
456 J . Org. Chem., Vol. 68, No. 2, 2003

P(i-BuNCH2CH2)3N
TABLE 4. Am in a tion of Ar yl Br om id es Usin g P d /4a a t Low Ca ta lyst Loa d in ga
a
b
0.5 mol % Pd(OAc)2; 1 mol % ligand 4a . Isolated yields.
DPPF as a ligand,21 the analogous reaction involving
2-bromo-m-xylene and 2,6-diisopropylaniline required
much higher catalyst loading (5 mol % Pd) and a reaction
temperature of 100 °C (20 °C higher than that reported
in the present work).
Our protocol was equally effective for aryl bromides
possessing substituents at various positions (Table 2,
entries 21-24). The reaction of an heteroaryl bromide
with morpholine also proceeded well (Table 2, entry 25).
Next, we investigated amination reactions of exten-
sively used and easy obtainable aryl iodides (Table 3).
With the Pd(OAc)2/4a catalyst system, electronically
neutral aryl iodides readily combined with anilines (Table
3, entries 1, 5, and 7) and secondary cyclic amines (Table
3, entries 2 and 6). Slightly lower yields of arylamines
were achieved with electron-deficient aryl iodides (Table
3, entry 3) owing to formation of reduced arene side
products. Electron-rich aryl iodides were also suitable
substrates (Table 3, entries 10 and 11). Although Pd-
(OAc)2 was used as a palladium source for most reactions,
reactions of electron-rich aryl iodides usually proceeded
well when Pd2(dba)3 was employed (Table 3, compare
entries 8 and 9). The reaction of aryl iodides with primary
aliphatic amines and acyclic secondary amines did not
(21) Sadighi, J . P.; Harris, M. C.; Buchwald, S. L. Tetrahedron Lett.
1998, 39, 5327.
J . Org. Chem, Vol. 68, No. 2, 2003 457

Urgaonkar et al.
proceed to completion even with higher catalyst loading
(5 mol % Pd) and longer reaction times. However,
cyclohexylamine did react with aryl iodides although in
moderate yields (Table 3, entries 12-15) when a slightly
higher catalyst loading (4 mol % Pd) was employed to
permit the reaction to go to completion. In general (as
can be seen from Tables 2 and 3) aryl iodides provided
lower yields of the arylamine product compared with
their bromide counterparts, the former being more prone
to â-hydride elimination leading to formation of hydro-
dehalogenation product.
the possibility for augmented basicity of the phosphorus
arising from transannular bonding between the bridge-
head nitrogen and the phosphorus atom. Both of these
basicity-enhancing stereoelectronic influences are lacking
in acyclic triaminophosphines, which we have shown
behave poorly under our reaction conditions. Finally, we
believe that the comparatively very low price of ligand
4a , compared with other phosphine ligands usually
employed in amination reactions, enhances its appeal.
An exploration of aryl chloride aminations using our
approach is underway.
We also carried out amination reactions at a low
catalyst loading (0.5 mol % Pd, Table 4),22 and most of
these reactions were complete in <22 h. The sterically
hindered arylamine in entry 1 was formed in excellent
yield (94%). Secondary cyclic amines were generally also
efficiently arylated, often giving improved results over
those obtained using either Pd/BINAP or Buchwald’s
catalyst sytem. For example, the reaction of 1-bromo-4-
tert-butylbenzene with piperidine using 0.5 mol % Pd/
4a afforded the desired product in 92% yield while
Buchwald’s catalyst system utilizing (o-biphenyl)PCy2 as
a ligand with 0.5 mol % Pd gave an 86% yield.8 Similarly,
the aforementioned substrate and morpholine were
coupled in 99% isolated yield using 0.5 mol % Pd/4a while
the Pd/BINAP catalyst system gave a 93% yield when
the reaction was run neat.10 Additionally, N-methyl-
aniline, which is often a problematic substrate for the
Pd/BINAP catalyst system, was also cleanly arylated
(Table 4).
Exp er im en ta l Section
Gen er a l Exp er im en ta l Con d ition s. All reactions were
performed under an atmosphere of argon in oven-dried glass-
ware. Toluene was collected from a solvent purification system
and stored over 4 Å molecular sieves. 1H and 13C NMR spectra
were recorded at 300 and 75.5 MHz, respectively, unless
otherwise noted. Thin-layer chromatography (TLC) was per-
formed using commercially prepared 60 mesh silica gel plates
visualized with short-wavelength UV light (254 nm). Silica
gel 60 (9385, 230-400 mesh) was used for column chroma-
tography. Melting points were determined in unsealed capil-
lary tubes and are uncorrected. The reported yields are isolated
yields and are the average of two runs. All commercially
available reagents were used as received. Ligands 1a -6a were
prepared according to our previously reported procedures15
(although ligands 1a , 3a , and 4a are commercially available
from Aldrich).
Gen er a l P r oced u r e for Am in a tin g Ar yl Br om id es a n d
Iod id es. An oven-dried Schlenk flask equipped with a mag-
netic stirring bar was charged with Pd(OAc)2 (2 mol %) and
NaO-t-Bu (1.5 mmol) inside a nitrogen-filled glovebox. The
flask was capped with a rubber septum and removed from the
glovebox. Aryl halide (1.0 mmol), amine (1.2 mmol), and
toluene (5 mL) were then successively added. The flask was
placed in an 80 °C oil bath, and the reaction mixture was
stirred until the starting material had been completely con-
sumed as judged by TLC. The mixture was cooled to room
temperature and adsorbed onto silica gel. The crude product
was purified by column chromatography. The presence of
hydrodehalogenated product in some of the preparations was
verified by TLC using authentic samples for comparison.
It appears that the catalytic system comprising Pd-
(OAc)2 and ligand 4a is the most effective catalyst
reported to date for the reaction of sterically hindered
arylbromides and anilines. Moreover, the scope of Pd/4a
catalyst system exceeds (for the examples discussed
above) or generally equals that of Pd/BINAP, Pd/(o-
biphenyl)PCy2, or Pd/(o-biphenyl)P(t-Bu)2.
Because arylamines are industrially important syn-
thetic targets, a crucial requirement for viability of an
industrial process to synthesize them using palladium
technology is ligand cost. In this regard it is worth
mentioning that 4a at $50.50/5 g is cheaper than racemic
BINAP, P(t-Bu)3 and (o-biphenyl)PCy2, or (o-biphenyl)P-
(t-Bu)2 by almost a factor of 2, 3, and 5, respectively.23
In summary, we have demonstrated that ligand 4a
functions uncommonly efficiently in amination reactions.
Various aryl bromides and iodides were readily coupled
with a range of amines, including primary and secondary
anilines, cyclic secondary amines, primary amines
branched at the R position, and (with limited success)
acyclic secondary amines. Good to excellent yields were
obtained with the vast majority of substrate combina-
tions. Several salutary features of 4a are (a) commercial
availability, (b) optimum steric effects provided by the
i-butyl groups, and (c) electron-richness of the phosphorus
arising from the donating capability of all three virtually
planar nitrogens adjacent to the phosphorus, as well as
N-(p-Cya n op h en yl)-2-eth yla n ilin e: white solid, mp 63-
1
64 °C; H NMR (300 MHz, CDCl3) δ 7.43 (d, 2H, J ) 7.9 Hz),
7.32 (d, 1H, J ) 6.7 Hz), 7.25-7.19 (m, 3H), 6.77 (d, 2H, J )
8.8 Hz), 5.90 (s, 1H), 2.59 (q, 2H, J ) 4.7 Hz), 1.20 (t, 3H, J )
6.3 Hz); 13C NMR (75.5 MHz, CDCl3) δ 149.9, 139.1, 137.5,
133.8, 129.7, 127.1, 126.1, 125.1, 120.3, 114.2, 100.5, 24.5, 14.5.
Anal. Calcd for C15H14N2: C, 81.08; H, 6.30; N, 12.61. Found:
C, 81.00; H, 6.38; N, 12.27.
N,N-Diisobu tyl-4-cya n oa n ilin e: white solid, mp 71-73
°C; 1H NMR (300 MHz, CDCl3) δ 7.43 (d, 2H, J ) 9.0 Hz),
6.61 (d, 2H, J ) 9.1 Hz), 3.21 (d, 4H, J ) 7.4 Hz), 2.14-1.98
(m, 2H), 0.92 (d, 12H, J ) 6.6 Hz); 13C NMR (75.5 MHz, CDCl3)
δ 150.9, 133.6, 121.0, 112.0, 96.6, 60.1, 26.5, 20.4. Anal. Calcd
for C15H22N2: C, 78.26; H, 9.56; N, 12.17. Found: C, 78.10; H,
10.01; N, 12.25.
1
N-(4-ter t-Bu tylp h en yl)cycloh exyla m in e: H NMR (300
MHz, CDCl3) δ 7.25-7.19 (m, 2H), 6.58-6.56 (m, 2H), 3.28-
3.21 (m, 1H), 2.05 (d, 2H, J ) 12.1 Hz), 1.80-1.65 (m, 3H),
1.41-1.15 (m, 15 H); 13C NMR (75.5 MHz, CDCl3) δ 145.2,
139.7, 126.2, 113.0, 52.1, 33.8, 31.8, 26.2, 25.2, 16.5. Anal.
Calcd for C16H25N: C, 83.11; H, 10.82; N, 6.06. Found: C,
83.21; H, 10.56; N, 5.92.
2,5-Dim eth yl-2′-p h en yld ip h en yla m in e: 1H NMR (300
MHz, CDCl3) δ 7.51-7.35 (m, 5H), 6.77 (d, 1H, J ) 2.57), 5.42
(s, 1H), 2.29 (s, 3H), 2.05 (s, 3H); 13C NMR (75.5 MHz, CDCl3)
δ 141.4, 141.2, 139.3, 136.7, 130.84, 129.5, 129.1, 128.7, 127.6,
(22) The reaction of 1-chloro-4-iodobenzene with morpholine using
the Pd/4a catalyst system (0.5 mol % Pd) gave an 85% yield of the
desired product. The general protocol for the amination of aryl iodides
using Pd/4a at such a low catalyst loading has not yet been fully scoped.
(23) Ligand 4a : $50.50 (5 g, Aldrich). Racemic BINAP: $90.60 (5
g, Aldrich). P(t-Bu)3: $148.00 (5 g, Aldrich). 2-(Di-tert-butylphosphino)-
biphenyl or 2-(dicyclohexylphosphino)biphenyl: $99.00 (2 g, Strem).
458 J . Org. Chem., Vol. 68, No. 2, 2003

P(i-BuNCH2CH2)3N
126.1, 123.1, 120.3, 120.1, 116.8, 21.4, 17.6. Anal. Calcd for
Ack n ow led gm en t. The authors are grateful to the
National Science Foundation for research support. We
also thank Dr. G. K. J naneshwara for providing a
sample of 4a .
C
20H19N: C, 87.91; H, 6.96; N, 5.13. Found: C, 87.88; H, 6.73;
N, 5.38.
2,6-Dim eth yl-2′-p h en yld ip h en yla m in e: white solid, mp
1
101-103 °C; H NMR (300 MHz, CDCl3) δ 7.63 (d, 2H, J )
7.3 Hz), 7.54 (t, 2H, J ) 6.7 Hz), 7.43 (t, 1H, J ) 7.0 Hz), 7.23
(d, 1H, J ) 6.7 Hz), 7.16-7.12 (m, 4H), 6.85 (t, 1H, J ) 7.0
Hz), 6.27 (d, 1H, J ) 8.2 Hz), 5.32 (s, 1H), 2.23 (s, 6H); 13C
NMR (75.5 MHz, CDCl3) δ 143.3, 139.7, 138.4, 136.3, 130.4,
129.6, 129.1, 128.7, 128.6, 127.7, 127.5, 126.0, 117.9, 111.7,
18.5. Anal. Calcd for C20H19N: C, 87.91; H, 6.96; N, 5.13.
Found: C, 87.79; H, 6.66; N, 5.45.
Su p p or tin g In for m a tion Ava ila ble: Spectra of previ-
ously unknown compounds and references for known com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O0205309
J . Org. Chem, Vol. 68, No. 2, 2003 459