J . Org. Chem. 1999, 64, 8743-8744
8743
equiv) with (9-BBN)2 in THF.9 The crude organoborane
complex is then coupled at room temperature with 1
equiv of an aryl iodide, aryl bromide, alkenyl iodide, or
enol triflate in the presence of a catalytic amount of
PdCl2(dppf)‚CH2Cl2 [dppf ) 1,1′-bis(diphenylphosphino)-
ferrocene] and excess 3 M aqueous NaOH. Aryl and vinyl
iodides and enol triflates coupled efficiently within 1 h
with the intermediate organoborane derived from 1.1
equiv of 1 using 9 mol % of PdCl2(dppf)‚CH2Cl2 (Table
1). In the aryl iodide series, no significant reactivity
differences were observed between the substrates having
electron-withdrawing (2b,c) or electron-donating (2d )
substituents. Suzuki coupling was slower for aryl bro-
mide 2e,f, yet could still be accomplished at room
temperature within 24 h if 15 mol % of PdCl2(dppf) was
utilized. For aryl bromides, yields were higher if 1.5 equiv
of the organoboron was employed.
In summary, the method described here is the most
convenient reported to date for introducing â-aminoethyl
groups into arenes and alkenes. The reaction conditions
of this one-pot â-aminoethylation procedure are suf-
ficiently mild that it should be applicable to a variety of
substrates. Since vinylcarbamates containing most car-
bamate nitrogen protecting groups are available from
Curtius rearrangement of acryloyl chloride,10 the method
illustrated here in the Cbz series should be easily adapted
to prepare â-aminoethyl products containing other ni-
trogen protecting groups.
A Su zu k i Cou p lin g Meth od for Dir ectly
In tr od u cin g a P r otected â-Am in oeth yl
Gr ou p in to Ar en es a n d Alk en es.
Con ven ien t Syn th esis of P h en eth yl a n d
Hom oa llylic Am in es
Asayuki Kamatani and Larry E. Overman*
Department of Chemistry, 516 Rowland Hall,
University of California, Irvine, California 92697-2025
Received J uly 2, 1999
Aminoethyl groups are important structural features
of a wide variety of organic molecules. Exemplary are
phenethylamines, which exhibit a diversity of pharma-
cological activities and also serve as key building blocks
in the synthesis of numerous nitrogen heterocycles and
alkaloid natural products.1 Multistep procedures are
almost always employed to introduce an aminoethyl
group into an arene or alkene. For example, a widely used
sequence for preparing phenethylamines involves Friedel-
Crafts acylation of activated arenes with N-protected
amino acid chlorides followed by reduction of the ketone
carbonyl group.2,3 Metal-assisted coupling reactions, on
the other hand, could introduce a â-aminoethyl group in
as little as one step. Earlier investigations of this
approach include the direct coupling of â-(N-benzoyl-N-
lithio)ethyllithium with aryl and alkenyl halides,4 ring-
opening of N-sulfonylaziridines with aryl and alkenyl
Grignard reagents,5 and Heck arylation of N-vinylox-
azolone followed by hydrogenation.6 Herein, we disclose
a convenient one-step Suzuki coupling method7 for
introducing alkoxycarbonyl-protected â-aminoethyl groups
into arenes and alkenes.
Exp er im en ta l Section
Gen er a l Deta ils. Benzyl vinyl carbamate was pre-
pared from acryloyl chloride using a slight modification
of a literature procedure;8 details are provided in Sup-
porting Information. Triflate 2g11 and vinyl iodides 2h -
j12 were prepared by standard procedures. General
experimental details have been described.13
Gen er al Cou plin g P r ocedu r e. P r epar ation of Ben -
zyl P h en eth ylca r ba m a te (3a ). Following a modifica-
tion of the procedure by Suzuki,9 a solution of (9-BBN)2
(0.55 mmol) and THF (4 mL) was added dropwise to a
stirring solution of benzyl vinylcarbamate 18 (1.1 mmol)
and THF (1 mL) at -10 °C. The resulting suspension was
stirred at room temperature for 4 h, during which time
the mixture became homogeneous. Aqueous 3 M NaOH
(1 mL) was added, and the resulting suspension was stir-
red for 10 min. This mixture was transferred by cannula
into a light brown solution of 2a (204 mg, 1.00 mmol),
PdCl2(dppf)‚CH2Cl2 (0.09 mmol), and THF (3 mL). The
resulting dark suspension was stirred at room temper-
ature for 1 h and diluted with hexanes (10 mL). A 2:1
(v/v) mixture of pH 7 aqueous buffer (KH2PO4-NaOH)
The one-pot reaction sequence (eq 1) starts with
hydroboration of benzyl vinylcarbamate 18 (1.1-1.5
(1) For reviews, see: (a) Bentley, K. W. Nat. Prod. Rep. 1999, 16,
367-388. (b) Lednicer, D.; Mitscher, L. A. The Organic Chemistry of
Drug Synthesis; Wiley: New York, 1997; Vol. 7; and earlier volumes
in this series.
(2) See, inter alia, Nordlander, J . E.; Payne, M. J .; Njoroge, F. G.;
Balk, M. A.; Laikos, G. D.; Vishwanath, V. M. J . Org. Chem. 1984, 49,
4107-4111.
(3) Many multistep sequences have been employed for introducing
â-aminoethyl units.1b
(9) Miyaura, N.; Ishiyama, T.; Sasaki, H.; Ishikawa, M.; Satoh, M.;
Suzuki, A. J . Am. Chem. Soc. 1989, 111, 314-321.
(10) Examples include: (a) tert-butoxycarbonyl: Hart, R. Makromol.
Chem. 1959, 32, 51-56. (b) â-(trimethylsilyl)ethoxycarbonyl: Carpino,
L. A.; Tsao, J .-H. J . Chem. Soc., Chem. Commun. 1978, 358-359.
(c) methoxycarbonyl: Hart, R. Bull. Soc. Chim. Belg. 1957, 66, 229-
242.
(4) Barluenga, J .; Montserrat, J . M.; Flo´rez, J . J . Org. Chem. 1993,
58, 5976-5980.
(5) Lin, P.-Y.; Bentz, G.; Stamm, H. J . Prakt. Chem. 1993, 335, 23-
34.
(6) Busacca, C. A.; J ohnson, R. E.; Swestock, J . J . Org. Chem. 1993,
58, 3299-3303.
(7) Review: Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-
2483.
(11) Saulnier, M. G.; Kadow, J . F.; Tun, M. M.; Langley, D. R.; Vyas,
D. M. J . Am. Chem. Soc. 1989, 111, 8320.
(8) (a) Wolfrom, M. L.; McFadden, G. H.; Chaney, A. J . Org. Chem.
1961, 26, 2597-2599. (b) Wieber, G. M.; Hegedus, L. S.; Åkermark,
B.; Michaelson, E. T. J . Org. Chem. 1989, 54, 4649-4653.
(12) (a) Kamatani, A. Ph.D. Dissertation, University of California,
Irvine, 1999. (b) Kamatani, A.; Overman, L. E. Manuscript in prepara-
tion.
10.1021/jo991064z CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/15/1999
Kamatani, Asayuki
