TETRAHEDRON

Pergamon Tetrahedron 56 (2000) 5157±5162

A Base-Catalyzed Domino-Isomerization±Hydroamination
ReactionÐA New Synthetic Route to Amphetamines
Christian G. Hartung,a Claudia Breindl,b Annegret Tillacka and Matthias Bellera,*
a
Institut fuÈr Organische Katalyseforschung (IfOK) an der UniversitaÈt Rostock e.V., Buchbinderstraûe 5-6, D-18055 Rostock, Germany
b
Institut fuÈr Anorganische Chemie der Technischen UniversitaÈt MuÈnchen, Lichtenbergstraûe 4, D-85747 Garching, Germany
Received 28 March 2000; accepted 18 May 2000

AbstractÐAn ef®cient synthesis of pharmaceutically interesting amphetamines by a base-catalyzed domino-isomerization±hydroamination

reaction is presented. Starting from allylbenzene and various primary or secondary amines, the basic structural pattern of amphetamines is
synthesized directly in yields of up to 91% in the presence of catalytic amounts of n-butyllithium. q 2000 Elsevier Science Ltd. All rights
reserved.

Introduction Most of these reactions have disadvantages because they

require complicated substrates as starting materials in
New amination reactions are of general interest in synthetic combination with a hydrogen donor, they use stoichiometric
organic and industrial chemistry because of the importance amounts of toxic mercury salts or they produce at least one
of amines and their derivatives as natural products, pharma- equivalent of a salt as a by-product.
cological agents, ®ne chemicals and dyes. The direct addi-
tion of N-nucleophiles to alkenesÐthe hydroamination
reactionÐis the most atom economic and elegant way to Results and Discussion
synthesize amines, since in principle no by-products are
formed.1 The low prices and ubiquitous availability of the In 1998, Seijas and VaÂzquez-Tato et al. demonstrated that
substrates are further advantages of the hydroamination in the synthesis of 2-phenylethylamines can be performed by
contrast to classical amination reactions. Although transi- the addition of lithium amides to styrene derivatives.11 In
tion metal complexes,1 lanthanide catalysts2 and traditional the ®rst step the lithium amide was prepared in a stoichio-
acids3 as well as bases4 have been used as catalysts for the metric reaction of the amine with n-butyllithium. The subse-
hydroamination of ole®ns, so far no ef®cient general quent addition to the styrene derivative is performed with a
methodology has been developed. Therefore, a general 2.5-fold excess of the lithium amide. For instance, the
hydroamination reaction is still one of the major goals in conversion of b-methylstyrene and different amines leads
catalysis research.5 to amphetamine derivatives in yields of 33±58%. In earlier
work we showed that styrene derivatives are hydroaminated
Derivatives of 2-amino-1-phenylpropane (amphetamines) with amines, even in the presence of only catalytic amounts
belong to the psychopharmacologically active class of of bases, in excellent yields of up to 99%.12 Consequently,
sympathomimetic drugs and are of pharmacological interest we were interested in developing an ef®cient method for
not only because of the stimulating and inhibiting effect on preparing amphetamines in a catalytic hydroamination
the central nervous system, but also due to their anti-in¯am- reaction.
matory activity and ability to inhibit several enzymes.6 In
general, classical methods for synthesizing the C±N bond in In view of our earlier work,12 the base-catalyzed conversion
amphetamines are the reductive amination reactions of the of alkenes and amines with n-butyllithium seemed to be a
appropriate ketones,7 reactions of aryl aldehydes with promising approach to this goal. Due to the considerably
nitroalkanes and subsequent reduction,8 amidomercura- lower price of allylbenzene compared to b-methylstyrene
tion±demercuration of ole®ns9 or N-alkylation of ammonia, (ca. 5-fold)13 we were interested in the direct synthesis of
primary and secondary amines using alkylating agents.10 amphetamines via base-catalyzed domino-reaction14 of
allylbenzenes. Preliminary studies revealed that under the
reaction conditions required for base-catalyzed hydro-
Keywords: domino-isomerization±amination reaction; base-catalysis;
hydroamination; amphetamines.
amination, it should be possible to isomerize allylbenzene
* Corresponding author. Tel.: 149-381-4669313; fax: 149-381-4669324; to yield b-methylstyrene.15 Thus, as a model reaction to
e-mail: [email protected] generate amphetamine derivatives we studied the reaction

0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S 0040-402 0(00)00436-1
5158 C. G. Hartung et al. / Tetrahedron 56 (2000) 5157±5162

Table 1. n-Butyllithium-catalyzed hydroamination of allylbenzene (1) with piperidine (2) (allylbenzene±piperidine ratio 2:1; 20 mol% n-BuLi refers to
piperidine)

Entry Temperature (8C) Solvent Additive (mol%) Yield of 3 (%)a

1 Room temperature THF ± 89

2 278 to room temperature THF ± 91
3 50 THF ± 85
4 100 THF ± 60
5 Room temperature THF TMEDAb (20) 88
6c Room temperature THF ± 68
7 Room temperature Toluene ± 20
8 Room temperature Toluene TMEDAb (20) 88
9 Room temperature Pentane TMEDAb (20) 60
a
Yields refer to piperidine and were determined by GC with internal standard (hexadecane).
b
TMEDA: tetramethylethylenediamine.
c
Allylbenzene±piperidine ratio 1:1.

of allylbenzene (1) and piperidine (2) (Table 1). Indeed, in benzene and piperidine, product 3 is obtained in 68%
the presence of catalytic amounts of n-butyllithium yield (entry 6). In general, the hydroamination of allyl-
(0.2 equiv.) a fast isomerization of allylbenzene to the benzene can also be performed in nonpolar solvents
thermodynamically more stable isomer b-methylstyrene is such as toluene or pentane in the presence of tetra-
observed at room temperature. The subsequent hydroamina- methylethylenediamine (TMEDA) as the co-catalyst.
tion of b-methylstyrene proceeds regioselectively (.99%) TMEDA is needed for the solvation and deaggregation
to yield N-2-(1-phenyl)propyl-piperidine 3. As shown in of n-butyllithium and the resulting lithium amides
Table 1 the reaction gave the best yields of product 3 (entries 7, 8, 9). Remarkably, no oligomers of b-methyl-
(89±91%) using an allylbenzene±piperidine ratio of 2:1 in styrene were detected applying these nonpolar solvents.
tetrahydrofuran as the solvent at room temperature.
Oligomers of b-methylstyrene are obtained as side- The scope of the new domino-isomerization±hydroamina-
products by an anionic polymerization reaction. The tion reaction is demonstrated in the reaction of allylbenzene
amount of oligomers increases at higher reaction and 4-phenyl-1-butene with various primary and secondary
temperature. Using an equimolar amount of allyl- amines (Table 2 and Scheme 1).

Table 2. n-Butyllithium-catalyzed hydroamination of allylbenzene (1) with primary and secondary amines (allylbenzene±amine ratio 2:1; 20 mol% n-BuLi
refers to the amine)

Entry Amine Product Temperature (8C) Solvent Additive (mol%) Yield of amphetamine (%)a

1 4 Room temperature THF ± 44

2 50 THF ± 88
3 100 Toluene TMEDAb (20) 38
4 5 50 THF ± 65
5 50 Toluene TMEDAb (20) 22

6 6 50 THF TMEDAb (20) 32 (de 8%)

7 100 Toluene TMEDAb (20) 36 (de 0%)
8 7 50 THF ± 62
9 100 Toluene TMEDAb (20) 41
10 8 Room temperature THF ± 66
11 50 Toluene TMEDAb (20) 36
12c 9 120 THF KOtBu (30) 54

a
Yields refer to the amine and were determined by GC with internal standard (hexadecane).
b
TMEDA: tetramethylethylenediamine.
c
Allylbenzene±aniline ratio 1:1; mixture of 30 mol% n-BuLi and 30 mol% KOtBu.
 C. G. Hartung et al. / Tetrahedron 56 (2000) 5157±5162 5159

Scheme 1.

As shown in Table 2 most of the applied amines give benzenes. The reaction is easily performed and does not
improved yields of hydroamination products at higher require expensive reagents. Further investigations on stereo-
reaction temperatures compared to piperidine. As an selective variants of this method are currently under
example morpholine reacts with allylbenzene at 508C to investigation.
give the corresponding amphetamine in 88% yield, while
the reaction at room temperature leads to only a 44% yield
(Table 2, entries 1, 2). With toluene as the solvent, in Experimental
general higher temperatures are required, however, the
yields are lower compared to tetrahydrofuran (22±41% Chemicals were obtained from Aldrich and Fluka and used
yield, entries 3, 5, 9, 11); but advantageously no oligomers without further puri®cation. All operations were carried out
of the alkene are formed. Apart from cyclic and acyclic under an argon atmosphere. Solvents and amines were dried
secondary amines primary amines such as benzylamine or according to standard procedures. NMR spectra (1H, 13C)
n-butylamine produce the corresponding products in tetra- were recorded with a 400 MHz Bruker ARX 400 instrument
hydrofuran as the solvent in yields of 65 and 62%, respec- (1H: 400.1 MHz, 13C: 100.6 MHz). 1H and 13C NMR chemi-
tively. (Table 2, entries 4, 8). The catalytic hydroamination cal shift were referenced to tetramethylsilane (0 ppm) and
reaction with the chiral amine S-(2)-a-methylbenzylamine CDCl3 (77.0 ppm), respectively. Coupling constants are
only resulted in the formation of diastereomeric mixtures reported in Hertz. Elemental analyses were performed by
(diastereomeric excess ,10%) in yields of 32 and 36% the Microanalytical Laboratory at IfOK Rostock. GC±MS
(Table 2, entries 6, 7). Interestingly, anilines may be used spectra were measured with a Hewlett±Packard gas chro-
successfully in this new domino-amination reaction. Due to matograph GC 5890 equipped with a mass-selective detec-
the lower nucleophilicity of lithium anilides compared to tor MS 5989 A. Quantitative analyses were performed with
aliphatic amides the addition of KOtBu as the second base a Hewlett±Packard GC 6890 instrument using a HP-5 capil-
is needed to generate the more ionic and therefore more lary column in conjunction with a ¯ame ionization detector
reactive potassium anilides in situ in low concentrations.12a (GC/FID). Column chromatography was carried out using
Hence, in the presence of a mixture of 0.3 equiv. n-butyl- silica gel 60 (0.063±0.2 mm Fluka). The hydroamination
lithium and 0.3 equiv. KOtBu, aniline reacts with allyl- reactions were performed in Aldrich Ace-pressure tubes
benzene to give the amphetamine derivative in 54% yield (30 ml). (Caution: The required safety measures should be
(Table 2, entry 12). taken when performing reactions under pressure.)

We would like to emphasize that tertiary (double alkylated) General procedure

amines were produced in yields ,1% in the reactions of
allylbenzene with primary amines. This makes the method The amine (2.5 mmol) and 100 ml hexadecane (internal
especially attractive for the selective synthesis of `second- standard) were dissolved in 5 ml dry tetrahydrofuran in an
ary amphetamines' because typical nucleophilic substitu- Ace-pressure tube under an argon atmosphere. 20 mol%
tion procedures with primary amines gave mixtures of n-butyllithium (1.6 M n-BuLi solution in hexane) was
secondary, tertiary and even quaternary amines. Further- added slowly at room temperature. The solution was stirred
more, the reaction of benzylamine is noteworthy, since the for 10 min and then allylbenzene (5 mmol) was added. The
benzyl group is easily removed by hydrogenation with H2/ intensive coloured solutions were reacted for 20 h at the
Pd/C to give 1-phenyl-2-aminopropane in 65% overall yield de®ned temperature. After cooling to room temperature,
by GC analysis. the solution was quenched with 2 ml water, whereby a
discolouration of the solution was observed. The products
The presented domino-isomerization±hydroamination reac- were isolated by acidi®cation of the mixture with 5 ml of
tion has also been expanded to aryl ole®ns whereby the 1 M HCl followed by addition of 5 ml dichloromethane.
double bond is separated from the aryl group by two CH2- The resulting aqueous phase was collected and the organic
units. In the reaction of 4-phenyl-1-butene 10 with piper- phase was extracted three times with 5 ml of 1 M HCl. The
idine 2, the 2-amino-1-phenylbutane derivative 11 is combined aqueous phases were neutralized with solid
produced in 59% yield in tetrahydrofuran as the solvent at Na2CO3 and were extracted ®ve times with 5 ml dichloro-
508C (Scheme 1). In toluene 11 can be obtained in 50% methane. The organic phases were washed with water and
yield without any formation of oligomers. dried over MgSO4. After removal of the solvent in vacuo the
products were isolated by column chromatography.
In conclusion, we have found that amphetamine derivatives
can be produced atom-ef®ciently by a new base-catalyzed N-2-(1-Phenyl)propyl-piperidine (3). According to the
domino-isomerization±hydroamination reaction of allyl- general procedure piperidine (2.5 mmol; 247 ml) and allyl-
5160 C. G. Hartung et al. / Tetrahedron 56 (2000) 5157±5162

benzene (5 mmol; 662 ml) were reacted in the presence of 662 ml) were reacted in the presence of 20 mol% n-BuLi
20 mol% n-BuLi solution (0.5 mmol; 313 ml) at room solution (0.5 mmol; 313 ml) and 20 mol% tetramethylethyl-
temperature. The residue was puri®ed by column chromato- enediamine (0.5 mmol, 75 ml) at 508C. The residue was
graphy (n-hexane/ethyl acetateˆ3:1) to afford 3 as a colour- puri®ed by column chromatography (n-hexane/ethyl
less oil.ÐYield: 89% (GC); 84% (isolated).Ð 1H NMR acetateˆ2:1) to afford the diastereomeric mixture of 6 as
(CDCl3, 258C, d ˆppm): 7.24 (m, 2H, phenyl); 7.15 (m, a colourless oil.ÐYield: 32% (GC); 30% (isolated).Ð 1H
3H, phenyl); 3.00 (dd, 2J(H,H)ˆ12.9 Hz, 3J(H,H)ˆ3.8 Hz, NMR (CDCl3, 258C, d ˆppm): 7.36±6.94 (m, 2£10H,
1H, Ph±CH2); 2.76 (ddq, 3J(H,H)ˆ10.1 Hz, 3J(H,H)ˆ phenyl); 3.93, 3.88 (2£q, 3J(H,H)ˆ6.6 Hz, 2£1H,
6.5 Hz, 3J(H,H)ˆ3.8 Hz, 1H, Ph±CH2 ±CH); 2.54 (m, 4H, Ph±CHMe±N); 2.88, 2.66 (2£dd, 2J(H,H)ˆ12.9 Hz,
N±CH2); 2.36 (dd, 2J(H,H)ˆ12.9 Hz, 3J(H,H)ˆ10.1 Hz, 3
J(H,H)ˆ 5.0 Hz, 2£1H, Ph±CH2); 2.77, 2.65 (2£m,
1H, Ph±CH2); 1.59 (m, 4H, N±CH2 ±CH2); 1.43 (m, 2H, 2£1H, Ph±CH2 ±CH); 2.59, 2.50 (2£dd, 2J(H,H)ˆ12.9 Hz,
N±CH2 ±CH2 ±CH2); 0.91 (d, 3J(H,H)ˆ6.5 Hz, 3H, CH3). 3
J(H,H)ˆ7.5 Hz, 2£1H, Ph±CH2); 1.46 (2£s, 2£1H, NH);
13
C NMR (CDCl3, 258C, d ˆppm): 141.0, 129.2, 128.1, 1.31, 1.27 (2£d, 3J(H,H)ˆ6.7 Hz, 2£3H, Ph±CH(CH3)±N);
125.7, 62.1, 49.6, 39.1, 26.4, 24.9, 14.2. GC±MS: 1.05, 0.92 (2£d, 3J(H,H)ˆ6.3 Hz, 2£3H, Ph±CH2 ±CH±
m/zˆ203 [M1], 112 [M12C6H5 ±CH2], 91, 69. MS (CI, CH3). 13C NMR (CDCl3, 258C, d ˆppm): 146.1, 145.4,
isobutane): 204 [M11H], 112 [M12C6H5 ±CH2], 86. 139.5, 139.3, 129.4, 129.2, 128.4, 128.3, 128.3, 128.2,
Anal. Calcd for C14H21N: C 82.70, H 10.41, N 6.89. 126.8, 126.6, 126.5, 126.3, 126.1, 125.9, 55.3, 54.8, 51.9,
Found: C 82.68, H 10.42, N 6.85. 50.8, 44.2, 42.5, 25.0, 24.5, 21.1, 19.9. GC±MS: m/zˆ239
[M1], 148 [M12C6H5 ±CH2], 105 [C6H5 ±CH±CH3], 91,
N-2-(1-Phenyl)propyl-morpholine (4). According to the 79. Anal. Calcd for C17H21N: C 85.30, H 8.84, N 5.85.
general procedure morpholine (2.5 mmol; 218 ml) and allyl- Found: C 85.20, H 8.88, N 5.86.
benzene (5 mmol; 662 ml) were reacted in the presence of
20 mol% n-BuLi solution (0.5 mmol; 313 ml) at 508C. The N-n-Butyl-N-2-(1-phenyl)propyl-amine (7). According to
residue was puri®ed by column chromatography (n-hexane/ the general procedure n-butylamine (2.5 mmol; 247 ml) and
ethyl acetateˆ1:1) to afford 4 as a colourless oil.ÐYield: allylbenzene (5 mmol; 662 ml) were reacted in the presence
88% (GC); 80% (isolated).Ð 1H NMR (CDCl3, 258C, of 20 mol% n-BuLi solution (0.5 mmol; 313 ml) at 508C.
d ˆppm): 7.26 (m, 2H, phenyl); 7.16 (m, 3H, phenyl); The residue was puri®ed by column chromatography (n-
3.72 (m, 4H, O±CH2); 2.99 (dd, 2J(H,H)ˆ13.1 Hz, hexane/ethyl acetateˆ1:2) to afford 7 as a colourless
3
J(H,H)ˆ4.4 Hz, 1H, Ph±CH2); 2.75 (ddq, 3J(H,H)ˆ oil.ÐYield: 62% (GC); 54% (isolated).Ð 1H NMR
9.7 Hz, 3J(H,H)ˆ6.5 Hz, 3J(H,H)ˆ4.4 Hz, 1H, Ph±CH2 ± (CDCl3, 258C, d ˆppm): 7.27 (m, 2H, phenyl); 7.17 (m,
CH); 2.60 (m, 4H, N±CH2); 2.39 (dd, 2J(H,H)ˆ13.1 Hz, 3H, phenyl); 2.87 (sext, 3J(H,H)ˆ3J(H,H)ˆ6.5 Hz, 1H,
3
J(H,H)ˆ9.7 Hz, 1H, Ph±CH2); 0.94 (d, 3J(H,H)ˆ6.5 Hz, Ph±CH2 ±CH); 2.73 (dd, 2J(H,H)ˆ13.3 Hz, 3J(H,H)ˆ
3H, CH3). 13C NMR (CDCl3, 258C, d ˆppm): 140.3, 129.2, 6.5 Hz, 1H, Ph±CH2); 2.65 (ddd, 2J(H,H)ˆ11.1 Hz,
3
128.2, 125.8, 67.3, 61.6, 49.0, 39.1, 14.2. GC±MS: J(H,H)ˆ8.1 Hz, 3J(H,H)ˆ6.5 Hz, 1H, N±CH2); 2.58 (dd,
m/zˆ114 [M12C6H5 ±CH2], 91, 70. MS (CI, isobutane): 2
J(H,H)ˆ13.3 Hz, 3J(H,H)ˆ6.5 Hz, 1H, Ph±CH2); 2.51
206 [M11H], 114 [M12C6H5 ±CH2]. Anal. Calcd for (ddd, 2J(H,H)ˆ11.1 Hz, 3J(H,H)ˆ7.6 Hz, 3J(H,H)ˆ
C13H19NO: C 76.06, H 9.33, N 6.82. Found: C 76.06, H 6.7 Hz, 1H, N±CH2); 1.40 (m, 2H, N±CH2 ±CH2); 1.37 (s,
9.19, N 6.88. 1H, NH); 1.25 (sext, 3J(H,H)ˆ3J(H,H)ˆ7.4 Hz, 2H, CH2 ±
CH2 ±CH3); 1.04 (d, 3J(H,H)ˆ6.5 Hz, 3H, CH±CH3); 0.85
N-2-(1-Phenyl)propyl-N-benzylamine (5). According to (t, 3J(H,H)ˆ7.4 Hz, 3H, CH2 ±CH3). 13C NMR (CDCl3,
the general procedure benzylamine (2.5 mmol; 273 ml) 258C, d ˆppm): 139.5, 129.2, 128.3, 126.1, 54.7, 47.0,
and allylbenzene (5 mmol; 662 ml) were reacted in the 43.6, 32.3, 20.4, 20.2, 13.9. GC±MS: m/zˆ191 [M1], 176
presence of 20 mol% n-BuLi solution (0.5 mmol; 313 ml) [M12CH3], 100 [M12C6H5 ±CH2], 91, 77. Anal. Calcd for
at 508C. The residue was puri®ed by column chromato- C13H21N: C 81.61, H 11.06, N 7.32. Found: C 81.44, H
graphy (n-hexane/ethyl acetateˆ4:1) to afford 5 as a colour- 10.99, N 7.20.
less oil.ÐYield: 65% (GC); 60% (isolated).Ð 1H NMR
(CDCl3, 258C, d ˆppm): 7.29±7.12 (m, 10H, phenyl); 3.83 N-n-Butyl-N-methyl-N-2-(1-phenyl)propyl-amine (8).
(d, 2J(H,H)ˆ13.3 Hz, 1H, Ph±CH2 ±N); 3.72 (d, According to the general procedure n-butylmethylamine
2
J(H,H)ˆ13.3 Hz, 1H, Ph±CH2 ±N); 2.92 (sext, 1H, (2.5 mmol; 296 ml) and allylbenzene (5 mmol; 662 ml)
3
J(H,H)ˆ3J(H,H)ˆ6.3 Hz, 1H, Ph±CH2 ±CH); 2.76 (dd, were reacted in the presence of 20 mol% n-BuLi solution
2
J(H,H)ˆ13.3 Hz, 3J(H,H)ˆ6.3 Hz, 1H, Ph±CH2 ±CH); (0.5 mmol; 313 ml) at room temperature. The residue was
2.62 (dd, 2J(H,H)ˆ13.3 Hz, 3J(H,H)ˆ6.3 Hz, 1H, Ph± puri®ed by column chromatography (n-hexane/ethyl
CH2 ±CH); 1.54 (s, 1H, NH); 1.08 (d, 3J(H,H)ˆ6.3 Hz, acetateˆ3:1) to afford 8 as a colourless oil.ÐYield: 66%
3H, CH3). 13C NMR (CDCl3, 258C, d ˆppm): 140.4, (GC); 61% (isolated).Ð 1H NMR (CDCl3, 258C, d ˆppm):
139.4, 129.3, 128.3, 128.3, 127.9, 126.8, 126.1, 53.7, 51.2, 7.26 (m, 2H, phenyl); 7.17 (m, 3H, phenyl); 2.94 (dd,
43.5, 20.1. GC±MS: m/zˆ134 [M12C6H5 ±CH2], 91, 65. 2
J(H,H)ˆ12.5 Hz, 3J(H,H)ˆ4.0 Hz, 1H, Ph±CH2); 2.89
MS (CI, isobutane): 226 [M11H], 134 [M12C6H5 ±CH2]. (m, 1H, Ph±CH2 ±CH); 2.44 (m, 2H, N±CH2); 2.38 (dd,
2
Anal. Calcd for C16H19N: C 85.28, H 8.50, N 6.22. Found: C J(H,H)ˆ12.5 Hz, 3J(H,H)ˆ9.5 Hz, 1H, Ph±CH2); 2.28 (s,
85.19, H 8.51, N 6.19. 3H, N±CH3); 1.46 (m, 2H, N±CH2 ±CH2); 1.31 (m, 2H,
CH2 ±CH2 ±CH3); 0.91 (t, 3J(H,H)ˆ7.3 Hz, 3H, CH2 ±
N-(S)-1-Phenylethyl-N-2-(1-phenyl)propyl-amine (6). CH3); 0.90 (d, 3J(H,H)ˆ6.9 Hz, 3H, CH±CH3). 13C NMR
According to the general procedure S-(2)-a-methylbenzyl- (CDCl3, 258C, d ˆppm): 140.8, 129.2, 128.2, 125.7, 60.3,
amine (2.5 mmol; 318 ml) and allylbenzene (5 mmol; 53.2, 39.0, 37.1, 30.4, 20.7, 14.1, 13.9. GC±MS: m/zˆ205
 C. G. Hartung et al. / Tetrahedron 56 (2000) 5157±5162 5161

[M1], 190 [M12CH3], 162 [M12CH2CH2CH3], 114 metallics 1998, 17, 1452. (b) Li, Y.; Marks, T. J. J. Am. Chem.
[M12C6H5 ±CH2], 91, 72, 58. Anal. Calcd for Soc. 1996, 118, 9295. (c) Li, Y.; Marks, T. J. J. Am. Chem. Soc.
C14H23N: C 81.89, H 11.29, N 6.82. Found: C 81.31, 1996, 118, 707. (d) Li, Y.; Marks, T. J. Organometallics 1996, 15,
H 11.19, N 6.76. 3770. (e) Haar, C. M.; Stern, C. L.; Marks, T. J. Organometallics
1996, 15, 1765. (f) Giardell, M. A.; Conticello, V. P.; Brard, L.;
N-2-(1-Phenyl)propyl-aniline (9). According to the GagneÂ, M. R.; Marks, T. J. J. Am. Chem. Soc. 1994, 116, 10241.
general procedure aniline (2.5 mmol; 228 ml) and allyl- (g) Giardello, M. A.; Conticello, V. P.; Brard, L.; Sabat, M.;
benzene (2.5 mmol; 331 ml) were reacted in the presence Rheingold, A. L.; Stern, C. L.; Marks, T. J. J. Am. Chem. Soc.
of 30 mol% n-BuLi solution (0.75 mmol; 469 ml) and 1994, 116, 10212. (h) Li, Y.; Fu, P. F.; Marks, T. J. Organo-
30 mol% KOtBu (0.75 mmol, 84 mg) at 1208C. The residue metallics 1994, 13, 439. (i) GagneÂ, M. R.; Stern, C. L.; Marks,
was puri®ed by column chromatography (n-hexane/ethyl T. J. J. Am. Chem. Soc. 1992, 114, 275. (j) GagneÂ, M. R.; Nolan,
acetateˆ15:1) to afford 9 as a colourless oil.ÐYield: 54% S. P.; Marks, T. J. Organometallics 1990, 9, 1716. (k) GagneÂ,
(GC); 50% (isolated).Ð 1H NMR (CDCl3, 258C, d ˆppm): M. R.; Marks, T. J. J. Am. Chem. Soc. 1989, 111, 4108. (l) Li,
7.28 (m, 2H, phenyl); 7.18 (m, 3H, phenyl); 7.16 (m, 2H, Y.; Marks, T. J. J. Am. Chem. Soc. 1998, 120, 1757. (m) Molander,
phenyl); 6.68 (m, 1H, phenyl); 6.62 (m, 2H, phenyl); 3.75 G. A.; Dowdy, E. D. J. Org. Chem. 1999, 64, 6515. (n) Arredondo,
(m, 1H, Ph±CH2 ±CH); 3.61 (s, 1H, NH); 2.93 (dd, V. M.; McDonald, F. E.; Marks, T. J. Organometallics 1999, 18,
2
J(H,H)ˆ13.4 Hz, 3J(H,H)ˆ4.8 Hz, 1H, Ph±CH2); 2.68 1949. (o) Arredondo, V. M.; Tian, S.; McDonald, F. E.; Marks, T. J.
(dd, 2J(H,H)ˆ13.4 Hz, 3J(H,H)ˆ7.3 Hz, 1H, Ph±CH2); J. Am. Chem. Soc. 1999, 121, 3633.
1.13 (d, 3J(H,H)ˆ6.3 Hz, 3H, CH3). 13C NMR (CDCl3, 3. (a) Brunet, J.-J.; Neibecker, D.; Niedercorn, F. J. Mol. Catal.
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13
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