Palladium-Catalyzed Amination of Aryl Triflates

Article abstract of DOI:10.1021/jo961915s

The conversion of aryl triflates to the corresponding aniline derivatives was accomplished in moderate to good yield using a catalyst consisting of the combination of palladium acetate (2 mol %) and either BINAP or Tol-BINAP. In contrast to the corresponding palladium-catalyzed amination of aryl bromides and iodides, electronically neutral aryl triflates gave higher yields of arylamines than did electron deficient aryl triflates, presumably due to the increased rate of base-promoted triflate cleavage in electron deficient substrates.

Full text of DOI:10.1021/jo961915s

1
264
J . Org. Chem. 1997, 62, 1264-1267
P a lla d iu m -Ca ta lyzed Am in a tion of Ar yl Tr ifla tes
J ohn P. Wolfe and Stephen L. Buchwald*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Received October 9, 1996X
The conversion of aryl triflates to the corresponding aniline derivatives was accomplished in
moderate to good yield using a catalyst consisting of the combination of palladium acetate (2 mol
%) and either BINAP or Tol-BINAP. In contrast to the corresponding palladium-catalyzed amination
of aryl bromides and iodides, electronically neutral aryl triflates gave higher yields of arylamines
than did electron deficient aryl triflates, presumably due to the increased rate of base-promoted
triflate cleavage in electron deficient substrates.
Several recent reports have detailed the palladium-
phosphines have been shown to promote reactions which
failed when monodentate phosphines were employed.
Furthermore, Heck arylations using aryl triflates have
been shown to proceed in nonpolar solvents such as
catalyzed conversion of aryl bromides and iodides to
1
aniline derivatives under mild conditions. In many
instances, systems which employed tri-o-tolylphosphine
as ligand were quite efficient, although the most general
catalysts were those which employ chelating bis(phos-
phines) such as 2,2′-bis(diphenylphosphino)-1,1′-binaph-
6
toluene when chelating phosphines were employed. In
light of our and Hartwig’s1h recent success with chelating
phosphines in the amination of aryl bromides, we inves-
thyl (BINAP).1
e,f,h
2
tigated the use of a combination of Pd(OAc) and BINAP
We felt that the extension of the aryl
or Tol-BINAP to catalyze the coupling of aryl triflates
with amines (eqn 1). We found that the reaction of 4-tert-
butylphenyl triflate with N-methyl piperazine employing
amination process to the conversion of aryl triflates into
aromatic amines would significantly enhance the utility
of this methodology due to the wide availability of
phenolic intermediates. Herein we report the first pal-
ladium-catalyzed method for the conversion of aryl tri-
flates to anilines. Key to the success of this transforma-
tion was the use of the chelating bis(phosphine) ligands
BINAP or 2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl
2
a mixture of Pd(OAc) /BINAP (2 mol % Pd) and NaOtBu
(1.4 eq) in toluene at 80 °C for 3 h gave the N-
arylpiperazine in 73% yield. The main side product of
the reaction was 4-tert-butylphenol resulting from nu-
cleophilic cleavage of the triflate, although a small
amount of 4-tert-butylbenzene resulting from the reduc-
tion of the aryl triflate was also detected.
(
Tol-BINAP).2
Our early attempts to couple aryl triflates with amines
2 3 3
which employed catalytic amounts of Pd (dba) /P(o-tolyl)
and a stoichiometric amount of NaOtBu in toluene (the
conditions used to couple amines with aryl bromides)
were unsuccessful. This protocol gave only phenol prod-
ucts resulting from attack at the electrophilic sulfur
center by sodium tert-butoxide.3 Attempts to promote
coupling by inclusion of halide additives4 such as LiCl
As is evident (Table 1), the best yields of coupled
products were obtained with electronically neutral or
electron rich aryl triflates such as 2,4-dimethylphenyl
triflate, 4-tert-butylphenyl triflate, and 4-methoxyphenyl
triflate as substrates. In contrast to results obtained in
the amination of aryl bromides, aminations of electron-
poor aryl triflates such as 4-cyanophenyl triflate gave
significantly lower yields. The moderate yields obtained
with electron-poor aryl triflates may be due to the
enhanced leaving group ability of the electron-deficient
phenoxide which leads to an increased rate of triflate
a
NCl and/or by employing coordinating solvents4b
or Bu
4
such as THF or DMF were also unsuccessful. Addition-
ally, procedures which utilized weaker bases such as
K CO in order to prevent cleavage of the triflate moiety
2 3
generated no cross-coupled products.
5
a
In the related palladium-catalyzed carbonylation,
reduction,5b and cyanation of aryl triflates, chelating
5c
X
Abstract published in Advance ACS Abstracts, February 1, 1997.
cleavage. Addition of various halides (LiCl, LiBr, Bu
4
NBr)
(
1) (a) Kosugi, M.; Kameyama, M.; Migita, T. Chem. Lett. 1983, 927-
failed to increase the yields of these reactions and, in fact,
resulted in lower yields of coupled products when elec-
tronically neutral triflates were employed. However,
employment of Pd (dba) at high catalyst loading (5 mol
2 3
% Pd) under high-dilution conditions gave higher yields
in some cases. In most cases, use of DPPF as a ligand
9
28. (b) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 1348-1350. (c) Wolfe, J . P.; Buchwald, S. L.
J . Org. Chem. 1996, 61, 1133-1135. (d) Wolfe, J . P.; Rennels, R. A.;
Buchwald, S. L. Tetrahedron 1996, 52, 7525-7546. (e) Wolfe, J . P.;
Wagaw. S.; Buchwald, S. L. J . Am. Chem. Soc. 1996, 118, 7215-7216.
(
f) Wagaw, S.; Buchwald, S. L. J . Org. Chem. 1996, 61, 7240-1. (g)
Louie, J .; Hartwig, J . F. Tetrahedron Lett. 1995, 36, 3609-3612. (h)
Driver, M. S.; Hartwig, J . F. J . Am. Chem. Soc. 1996, 118, 7217-7218.
afforded lower yields of coupled products when Pd(OAc)
2
(2) Both BINAP and Tol-BINAP are commercially available from
Strem Chemicals Inc. The price of 1 g of Tol-BINAP is ∼1/3 the price
of 1 g of BINAP. Both enantiomers gave identical results and were
used interchangeably.
was employed as a precatalyst (2 mol % Pd catalyst
loading). However, Hartwig has found that DPPF affords
(
3) No traces of sulfonated amines were detected in the crude
reaction mixtures. Control experiments which involved the heating of
aryl triflates and amines in toluene gave no reaction, suggesting that
the amines are not responsible for cleavage of the triflate.
(5) (a) Cacchi, S.; Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron
Lett. 1986, 27, 3931-3934. (b) Cacchi, S.; Ciattini, P. G.; Morera, E.;
Ortar, G. Tetrahedron Lett. 1986, 27, 5541-5544. (c) Takagi, K.;
Sakakibara, Y. Chem. Lett. 1989, 1957-1958.
(6) Ozawa, F.; Kubo, A.; Hayashi, T. J . Am. Chem. Soc. 1991, 113,
1417-1419.
(
4) (a) Echavarren, A. M.; Stille, J . K. J . Am. Chem. Soc. 1987, 109,
478-5486. (b) Farina, V.; Krishnan, B.; Marshall, D. R.; Roth, G. P.
J . Org. Chem. 1993, 58, 5434-5444.
5
S0022-3263(96)01915-9 CCC: $14.00 © 1997 American Chemical Society

Palladium-Catalyzed Amination of Aryl Triflates
J . Org. Chem., Vol. 62, No. 5, 1997 1265
Ta ble 1. Ca ta lytic Am in a tion of Ar yl Tr ifla tes
the coupled products in good yields when a higher
catalyst loading (5 mol %) of Pd(dba) was employed at
00 °C under more dilute conditions. Additionally,
Hartwig has shown that yields for some coupling reac-
tions may be improved by slow addition of the triflate to
the reaction mixture.7 We have found that in some cases
this works well, and yields are significantly improved
inhibition of the catalytic reaction by the dba ligand.9
Solvents such as DMF, THF, and dioxane also afforded
lower yields of aminated products, presumably due to
increased solvation of Na resulting in enhanced nucleo-
philicity of the alkoxide base. Bases weaker than NaOt-
2
7
1
+
Bu such as K
2
CO
3
, Na
2 3
CO , DABCO, DBU, Proton
Sponge, Et
coupling.
3
N, Na
3
PO , and NaOH failed to promote
4
(Table 1, entry 11); however, for others there is only slight
improvement (Table 1, entry 10). Procedures employing
other chelating ligands such as DPPE, DPPP, and
DPPBenzene or 1,10-phenanthroline derivatives resulted
A plausible catalytic cycle for amination of aryl triflates
is shown in Scheme 1. The mixture of Pd(OAc) and bis-
2
10a
(
phosphine) (P-P) reacts to form (P-P)Pd(OAc)
2
which
in little or no product formation.8 In some cases, Pd
(dba)
2
, presumably due to
2
3
gave lower yields than Pd(OAc)
(
9) (a) Amatore has shown that the oxidative addition of iodobenzene
to mixtures of Pd(dba) /2 PPh proceeds 10 times more slowly than
oxidative addition of iodobenzene to Pd(PPh . Amatore, C.; J utand,
2
3
(
7) Louie, J .; Driver, M. S.; Hamann, B. C.; Hartwig, J . F. J . Org.
Chem. 1997, 62, 1268-1273.
8) DPPF ) 1,1′-Bis(diphenylphosphino)ferrocene; DPPE ) 1,2-bis-
diphenylphosphino)ethane; DPPP ) 1,3-bis(diphenylphosphino)pro-
pane; DPPBenzene ) 1,2-bis(diphenylphosphino)benzene.
3 4
)
A.; Khalil, F.; M’Barki, M. A.; Mottier, L. Organometallics 1993, 12,
3168-3178. (b) In the catalytic amination of aryl bromides, added dba
(dibenzylideneacetone) slows the coupling reaction. Wolfe, J . P.;
Buchwald, S. L. Unpublished results.
(
(

1
266 J . Org. Chem., Vol. 62, No. 5, 1997
Wolfe and Buchwald
Sch em e 1
of compounds estimated to be g95% pure as determined by
H NMR and either capillary GC (known compounds) or
1
combustion analysis (new compounds). The procedures de-
scribed in the Experimental Section are representative, thus
the yields may differ from those given in Table 1.
5
2
,4-Dim eth ylp h en yl Tr ifla te.1 The procedure of Stille14
1
gave 3.34 g (88%) of a colorless oil. H NMR (CDCl
3
, 300 MHz)
δ 2.33 (s, 6H), 7.00-7.15 (m, 3H); 13C NMR (CDCl
, 300 MHz)
3
δ 16.2, 20.7, 118.7 (q, J ) 318 Hz), 120.9, 128.1, 130.4, 132.7,
-
1
1
1
38.2, 146.5; IR (neat, cm ) 2930, 1493, 1421, 1248, 1143,
089, 876. Anal. Calcd for C SO : C, 42.52; H, 3.57.
9
H
9
3 3
F
Found: C, 42.48; H, 3.62.
4
-Ben zoylp h en yl Tr ifla te.16 The procedure of Stille14 gave
.24 g (86%) of a colorless oil which solidified upon standing
4
1
to give a white solid, mp 41-42 °C. H NMR (CDCl
.41 (d, 2H, J ) 8.7 Hz), 7.52 (t, 2H, J ) 7.3 Hz), 7.64 (t, 1H,
J ) 7.5 Hz), 7.80 (d, 2H, J ) 7.1 Hz), 7.91 (d, 2H, J ) 8.8 Hz);
3
, 300 MHz)
7
1
3
C NMR (CDCl
3
, 300 MHz) δ 118.7 (q, J ) 319 Hz), 121.3,
1
28.5, 129.9, 132.1, 133.0, 136.7, 137.5, 151.9, 194.7; IR (KBr,
-
1
cm ) 3068, 1665, 1597, 1497, 1427, 1278, 1251, 1218, 1141,
88. Anal. Calcd for C14 SO : C, 50.91; H, 2.75. Found:
C, 50.86; H, 2.91.
8
H
9
4 3
F
is then reduced under the reaction conditions to a
1
0b
zerovalent Pd species [“(P-P)Pd”].
Oxidative addition
Gen er a l P r oced u r es for t h e Ca t a lyt ic Am in a t ion of
Ar yl Tr ifla tes. Methods A and B: A Schlenk tube was
charged with palladium acetate (0.01 mmol, 2 mol % Pd),
BINAP (0.011 mmol, 2.2 mol %) (method A) or Tol-BINAP
(0.011 mmol, 2.2 mol %) (method B), and sodium tert-butoxide
(0.7 mmol). To this mixture was added a solution of aryl
triflate (0.5 mmol) and amine (0.6 mmol) in toluene (2 mL,
of aryl triflate to this species forms the palladium aryl
cation 1 which likely exists as a tight ion pair in toluene.11
Amine coordination follows to give 2 which is deproto-
nated by NaOtBu to afford palladium amido complex 3.
Reductive elimination from 3 yields the arylamine and
regenerates the Pd(0) catalyst.
In conclusion, we have demonstrated the first pal-
ladium-catalyzed amination of aryl triflates. This pro-
tocol further expands the scope of catalytic amination
methodology and allows for the conversion of phenols to
anilines.
0
.25 M in aryl halide) via syringe. The mixture was heated
to 80 °C with stirring until the triflate had been consumed as
judged by GC analysis. The mixture was cooled to room
temperature, taken up in ether, filtered, and concentrated. The
crude material was purified by flash chromatography on silica
gel.
Method C: A Schlenk tube was charged with tris(diben-
zylideneacetone)dipalladium(0) (0.0125 mmol, 5 mol % Pd),
BINAP (0.0275 mmol, 5.5 mol %), sodium tert-butoxide (0.7
mmol), and toluene (20 mL). To this mixture was added a
solution of aryl triflate (0.5 mmol) and amine (0.6 mmol) in
toluene (5 mL, 0.02 M in aryl halide after addition) via syringe.
The mixture was heated to 80 °C with stirring until the triflate
had been consumed as judged by GC analysis (2-8 h). The
mixture was cooled to room temperature, taken up in ether,
filtered, and concentrated. The crude material was purified
by flash chromatography on silica gel.
Exp er im en ta l Section
Gen er a l. All reactions were carried out under an argon
atmosphere in oven-dried glassware. Elemental analyses were
performed by E & R Microanalytical Laboratory Inc., Corona,
N.Y. Toluene was continuously refluxed and freshly distilled
under nitrogen from molten sodium. Triflic anhydride, 1-naph-
thyl triflate, and 1,1′-bis(diphenylphosphino)ferrocene were
purchased from Aldrich Chemical Co. and were used without
further purification. Morpholine, pyrrolidine, piperidine, hex-
ylamine, aniline, 1-methylpiperazine, N-benzylmethylamine,
and 1,4-dioxa-8-azaspiro[4.5]decane were purchased from Al-
drich Chemical Co. and were passed through alumina before
use. Sodium tert-butoxide was purchased from Aldrich Chemi-
cal Co. and stored in a Vacuum Atmospheres glovebox under
nitrogen. Pyridine was distilled from calcium hydride and
stored over molecular sieves. Palladium acetate was pur-
chased from Alfa Chemical Co. and used without further
purification. BINAP and Tol-BINAP were purchased from
Strem Chemical Co. and used without further purification.
Aryl triflates were prepared according to the procedure of
Method D: A Schlenk tube was charged with palladium
acetate (0.01 mmol, 2 mol % Pd), BINAP (0.011 mmol, 2.2 mol
%), sodium tert-butoxide (0.7 mmol), toluene (1.5 mL), and
amine (0.6 mmol). The mixture was heated to 80 °C with
stirring, and a solution of the triflate (0.5 mmol) in toluene
(0.5 mL) was added dropwise to the reaction mixture over 30
min via syringe. After the addition was complete, the mixture
was heated at 80 °C with stirring until the triflate had been
consumed as judged by GC analysis. The mixture was cooled
to room temperature, taken up in ether, filtered, and concen-
trated. The crude material was purified by flash chromatog-
1
4
12
13
Stille. 4-tert-Butylphenyl triflate, 4-cyanophenyl triflate,
raphy on silica gel.
1
4
4
-methoxyphenyl triflate, and 2-(2-propenyl)phenyl triflate
N-(p-Cya n op h en yl)m or p h olin e.16 General procedure A
have been previously reported and adequately characterized
in the literature. Preparative flash chromatography was
performed on ICN Biomedicals Silitech 32-63d silica gel.
Yields in Table 1 refer to isolated yields (average of two runs)
1
gave 31 mg (33%) of a yellow solid, mp 65-66 °C. H NMR
(
4
CDCl
3
, 300 MHz) δ 3.23 (t, 4H, J ) 4.9 Hz), 3.82 (t, 4H, J )
13
.8 Hz), 6.81 (d, 2H, J ) 9.6 Hz), 7.47 (d, 2H, J ) 9.5 Hz);
C
NMR (CDCl
1
3
, 300 MHz) δ 47.2, 66.4, 100.8, 114.0, 119.8, 133.5,
-1
53.5; IR (KBr, cm ) 2981, 2218, 1606, 1518, 1246, 1182, 1116.
(
10) (a) Ozawa, F.; Kubo, A.; Hayashi, T. Chem. Lett. 1992, 2177-
180. (b) P NMR analysis of the crude reaction mixture of the
amination on an aryl bromide showed no trace of the monophosphine
oxide of BINAP, suggesting that the ligand is not responsible for the
reduction of the Pd(II) precatalyst to Pd(0) in these reactions. This is
in contrast to what has been seen for asymmetric Heck arylations.
Wolfe J . P.; Buchwald, S. L. Unpublished results.
Anal. Calcd for C11
H, 6.50.
H
12NO: C, 70.19; H, 6.43. Found: C, 69.97;
3
1
2
N-(p-ter t-Bu tylp h en yl)p ip er id in e. General procedure A
1
gave 70 mg (64%) of a white solid, mp 37-38 °C. H NMR
(CDCl , 300 MHz) δ 1.29 (s, 9H), 1.50-1.60 (m, 2H), 1.67-
3
1.75 (m, 4H), 3.11 (t, 4H, J ) 5.5 Hz), 6.89 (d, 2H, J ) 9.7
(
(
11) J utand, A.; Mosleh, A. Organometallics 1995, 14, 1810-1817.
12) Larhed, M.; Andersson, C.-M.; Hallberg, A. Tetrahedron 1994,
13
Hz), 7.26 (d, 2H, J ) 9.8 Hz); C NMR (CDCl , 300 MHz) δ
3
5
1
5
0, 285-304.
13) Cabri, W.; Candiani, I.; Bedeschi, A.; Penco, S. J . Org. Chem.
992, 57, 1481-1486.
14) Echavarren, A. M.; Stille, J . K. J . Am. Chem. Soc. 1987, 109,
478-5486.
(
(15) McMurry, J . E.; Mohanraj, S. Tetrahedron Lett. 1983, 24, 2723-
2726.
(16) Kotsuki, H.; Kobayashi, S.; Suenaga, H.; Nishizawa, H. Syn-
thesis 1990, 1145-1147.
(

Palladium-Catalyzed Amination of Aryl Triflates
4.3, 26.0, 31.4, 33.9, 50.9, 116.2, 125.7, 141.9, 150.0; IR (KBr,
J . Org. Chem., Vol. 62, No. 5, 1997 1267
2
N-(p-Ben zoylp h en yl)p yr r olid in e. General procedure A
-
1
1
cm ) 2930, 1609, 1518, 1237, 820. Anal. Calcd for C15
C, 82.89; H, 10.67. Found: C, 82.78; H, 10.91.
H
23N:
gave 62 mg (49%) of a yellow solid, mp 138 °C. H NMR
(CDCl
6.54 (d, 2H, J ) 9.6 Hz), 7.40-7.55 (m, 3H), 7.71 (d, 2H, J )
8.1 Hz), 7.80 (d, 2H, J ) 9.5 Hz); 13C NMR (CDCl
, 300 MHz)
δ 25.4, 47.5, 110.5, 124.1, 127.9, 129.3, 130.9, 132.9, 139.4,
3
, 300 MHz) δ 2.01-2.09 (m, 4H), 3.35-3.42 (m, 4H),
N-(p-ter t-Bu tylp h en yl)-N′-m eth ylp ip er a zin e. General
procedure A gave 86 mg (74%) of a tan solid, mp 82-83 °C.
3
1
H NMR (CDCl , 300 MHz) δ 1.29 (s, 9H), 2.35 (s, 3H), 2.57 (t,
3
-
1
4
H, J ) 5.0 Hz), 3.19 (t, 4H, J ) 4.8 Hz), 6.88 (d, 2H, J ) 8.9
150.8, 195.0; IR (KBr, cm ) 2852, 1654, 1601, 1574, 1540,
1
3
Hz), 7.29 (d, 2H, J ) 8.8 Hz); C NMR (CDCl
3
cm ) 2961, 1521, 1458, 1295, 1244, 1150, 820. Anal. Calcd
for C15 : C, 77.53; H, 10.41. Found: C, 77.69; H, 10.29.
3
, 300 MHz) δ
1400, 1320, 1285, 1150. Anal. Calcd for C17
H
17NO: C, 81.24;
1.4, 33.9, 46.1, 49.2, 55.2, 115.7, 125.8, 142.3, 148.9; IR (KBr,
H, 6.82. Found: C, 81.39; H, 6.92.
N-(p-Ben zoylp h en yl)m or p h olin e.
-
1
16,19
General procedure
H
24
N
2
A gave 67 mg (50%) of a yellow solid, mp 137-138 °C (lit. mp
140 °C).16 H NMR (CDCl
Hz), 3.83 (t, 4H, J ) 4.9 Hz), 6.85 (d, 2H, J ) 9.6 Hz), 7.38-
1
, 300 MHz) δ 3.29 (t, 4H, J ) 4.7
N-(p-ter t-Bu tylp h en yl)p yr r olid in e. General procedure
3
1
A gave 68 mg (67%) of a white solid, mp 38-39 °C. H NMR
1
3
(
3
CDCl
3
, 300 MHz) δ 1.29 (s, 9H), 1.95-2.01 (m, 4H), 3.22-
7.55 (m, 3H), 7.68-7.71 (m, 2H), 7.76 (d, 2H, J ) 8.7 Hz);
C
.30 (m, 4H), 6.53 (d, 2H, J ) 8.7 Hz), 7.27 (d, 2H, J ) 8.7
NMR (CDCl , 300 MHz) δ 47.5, 66.5, 113.1, 127.7, 128.0, 129.5,
3
1
3
-1
Hz); C NMR (CDCl
1
3
, 300 MHz) δ 25.4, 31.6, 33.7, 47.6, 111.3,
131.5, 132.4, 138.6, 154.0, 195.2; IR (KBr, cm ) 2966, 1639,
1597, 1236, 924.
-1
25.9, 137.9, 145.9; IR (KBr, cm ) 2962, 1522, 1364, 811. Anal.
N-Ben zyl-N-m eth yl-1-n a p h th yla m in e.20 General proce-
Calcd for C14H21N: C, 82.70; H, 10.41. Found: C, 82.95; H,
1
1
0.60.
dure A gave 76 mg (61%) of a colorless oil. H NMR (CDCl
3
,
N-p-An isid ylp yr r olid in e.17 General procedure A gave 56
300 MHz) δ 2.78 (s, 3H), 4.28 (s, 2H), 7.10 (d, 1H, J ) 7.3 Hz),
1
mg (63%) of a white solid, mp 40-41 °C. H NMR (CDCl
3
3
NMR (CDCl
1
1
3
,
7.25-7.50 (m, 8H), 7.55 (d, 1H, J ) 8.4 Hz), 7.80-7.88 (m,
1H), 8.32-8.40 (m, 1H); 13C NMR (CDCl
, 300 MHz) δ 41.7,
00 MHz) δ 1.90-2.02 (m, 4H), 3.20-3.28 (m, 4H), 3.76 (s,
H), 6.53 (d, 2H, J ) 9.0 Hz), 6.84 (d, 2H, J ) 9.1 Hz); 13
, 300 MHz) δ 25.3, 48.2, 55.9, 112.5, 115.0, 143.2,
50.7; IR (KBr, cm ); IR (KBr, cm ) 2962, 1516, 1371, 1283,
238, 1044, 814.
3
C
61.5, 115.6, 123.2, 123.8, 125.3, 125.7, 127.0, 128.26, 128.35,
-
1
3
134.9, 138.8, 150.2; IR (neat, cm ) 3048, 1575, 1396, 724.
-
1
-1
21
N-P h en yl-1-n a p h th yla m in e. General procedure A gave
2
1
68 mg (62%) of a yellow solid, mp 56-57 °C (lit. mp 62 °C).
1
N-(2,4-Dim eth ylp h en yl)ben zyla m in e. General proce-
H NMR (CDCl
3
, 300 MHz) δ 5.90 (s, br, 1H), 6.80-7.00 (m,
1
dure A gave 79 mg (75%) of a colorless oil. H NMR (CDCl
3
,
3H), 7.02-7.20 (m, 2H), 7.22-7.60 (m, 5H), 7.80-8.05 (m, 2H);
1
3
3
2
00 MHz) δ 2.15 (s, 3H), 2.23 (s, 3H), 3.73 (s, br, 1H), 4.35 (s,
3
C NMR (CDCl , 300 MHz) δ 115.9, 117.3, 120.4, 121.8, 122.9,
H), 6.52 (d, 1H, J ) 7.2 Hz), 6.89-6.91 (m, 2H), 7.26-7.41
125.6, 126.0, 126.1, 127.7, 128.5, 129.3, 134.7, 138.7, 144.7;
1
3
-1
(m, 5H); C NMR (CDCl
3
, 300 MHz) δ 17.5, 20.3, 48.5, 110.2,
IR (KBr, cm ) 3408, 3051, 1576, 1307, 742.
1
22.0, 126.3, 127.1, 127.3, 127.5, 128.6, 130.9, 139.7, 143.8;
N-[2-(2-P r op en yl)p h en yl]h exyla m in e. General proce-
dure A gave 60 mg (55%) of a colorless oil which was a 3/1
mixture (determined by GC, NMR) of the title compound and
its olefin regioisomer trans-N-[2-(1-propenyl)phenyl]hexyl-
-
1
IR (neat, cm ) 3438, 2916, 1515. Anal. Calcd for C15
C, 85.26; H, 8.11. Found: C, 85.34; H, 8.25.
H17N:
N-(p-ter t-Bu tylp h en yl)h exyla m in e. General procedure
1
A gave 62 mg (53%) of a colorless oil. H NMR (CDCl
3
, 300
amine (olefin stereochemistry assigned based on the coupling
1
MHz) δ 0.90 (t, 3H, J ) 6.8 Hz), 1.27 (s, 9H), 1.28-1.45 (m,
constant of olefinic protons). H NMR (CDCl
3
, 300 MHz) δ
6
1
H), 1.55-1.66 (m, 2H), 3.08 (t, 2H, J ) 6.6 Hz), 3.51 (s, br,
H), 6.56 (d, 2H, J ) 8.9 Hz), 7.20 (d, 2H, J ) 8.9 Hz); 13
, 300 MHz) δ 14.0, 22.6, 26.9, 29.6, 31.5, 31.6,
0.88-0.92 (m, 4H), 1.25-1.47 (m, 4H), 1.55-1.70 (m, 11H),
1.90 (dd, 1H, J ) 1.3, 6.1 Hz), 3.05-3.15 (m, 3H), 3.28 (d, 2H,
J ) 6.5 Hz), 3.68 (s, br, 1H), 5.05-5.15 (m, 2H), 5.85-6.10
(m, 2 H), 6.38 (d, 1H, J ) 15.6 Hz), 6.55-6.70 (m, 3H), 7.00-
C
NMR (CDCl
3
1
3
-
1
3.8, 44.2, 112.4, 125.9, 139.8, 146.2; IR (neat, cm ) 3412,
616, 1520. Anal. Calcd for C15 23N: C, 82.34; H, 11.66.
7.20 (m, 3H); 13C NMR (CDCl
, 300 MHz) δ 14.0, 18.9, 22.6,
H
3
Found: C, 82.30, H, 11.66.
N-(2,4-Dim eth ylp h en yl)p ip er id in e. General procedure
A gave 71 mg (75%) of a colorless oil. H NMR (CDCl
26.9, 29.4, 29.5, 31.6, 36.6, 43.8, 44.1, 110.3, 116.1, 116.8, 116.9,
123.3, 126.7, 127.4, 127.7, 128.1, 128.2, 129.7, 136.3, 145.2,
146.7; IR (neat, cm ) 3421, 1604, 1512, 745. Anal. Calcd for
1
8
1
-1
3
, 300
MHz) δ 1.49-1.60 (m, 2H), 1.62-1.75 (m, 4H), 2.26 (s, 6H),
15
C H23N: C, 82.89; H, 10.67. Found: C, 83.15; H, 10.53.
2
3
1
.80 (t, 4H, J ) 5.1 Hz), 6.88-7.00 (m, 3H); 13C NMR (CDCl
3
,
Ack n ow led gm en t. We thank the National Science
00 MHz) δ 17.6, 20.7, 24.4, 26.7, 53.5, 118.9, 126.8, 131.6,
-
1
Foundation and Pfizer for their support of this research.
We thank Dr. Ross Widenhoefer and Dr. Michael
Palucki for helpful discussions. We thank Professor J .
F. Hartwig for multiple communications, a mutual
exchange of manuscripts, and providing the procedure
for the slow addition of triflate substrate.
31.9, 132.6, 150.5; IR (neat, cm ) 2933, 1503, 1226.
N-(2,4-Dim eth ylp h en yl)-1,4-d ioxa -8-a za sp ir o[4.5]d ec-
a n e. General procedure A gave 93 mg (75%) of a colorless
1
oil. H NMR (CDCl
3
, 300 MHz) δ 1.87 (t, 4H, J ) 6.1 Hz),
2
4
3
1
1
.266 (s, 3H), 2.274 (s, 3H), 2.95 (t, 4H, J ) 6.0 Hz), 4.00 (s,
H), 6.95 (d, 2H, J ) 1.7 Hz), 7.00 (s, 1H); 13C NMR (CDCl
,
3
00 MHz) δ 17.5, 20.6, 35.6, 50.3, 64.2, 107.2, 119.1, 126.9,
31.6, 132.4, 132.5, 149.4; IR (neat, cm- ) 2954, 1499, 1103,
1
J O961915S
2
038. Anal. Calcd for C15H21NO : C, 72.84; H, 8.56. Found:
(
19) Stahl, I. Chem. Ber. 1987, 120, 135-139.
C, 72.61; H, 8.48.
(20) Magnus, P.; Lacour, J .; Weber, W. J . Am. Chem. Soc. 1993, 115,
9
347-9348.
(
17) Shim, S. C.; Huh, K. T.; Park, W. H. Tetrahedron 1986, 42,
59-263.
18) Walkup, R. E.; Searles, S., J r. Tetrahedron 1985, 41, 101-106.
(21) Dictionary of Organic Compounds, 6th ed; Cadogan, J . I. G.,
2
Ley, S. V., Pattenden, G., Raphael, R. A., Rees, C. W., Eds.; Chapman
& Hill: London, 1996; p 5279.
(