Amination of allylic alcohols in water at room temperature

Article abstract of DOI:10.1021/ol900235s

The "trick" to carrying out regiocontrolled aminations of allylic alcohols in water as the only medium is use of a nanomicelle's interior as the organic reaction solvent. When HCO2Me is present, along with the proper base and source of catalytic Pd, allylic amines are cleanly formed at room temperature.

Full text of DOI:10.1021/ol900235s

Amination of Allylic Alcohols in Water
at Room Temperature
Takashi Nishikata and Bruce H. Lipshutz*
Department of Chemistry & Biochemistry
University of California
Santa Barbara, CA 93106
Supporting Information
I.
General procedures
Synthesis of allylic amine
(S2)
(S2 - S4)
(S4)
II.
III. References
Spectra Data
IV.
(S5 – S19)
S1

General Information
PTS (Polyoxyethanyl-α-tocopheryl sebacate ) was obtained from Zymes, LLC (PTS is also
obtained
from
Sigma-Aldrich,
catalog
#698717)),
[Pd(allyl)Cl]2,
and
Biphep
Dppf
(2,2’-bis(diphenylphosphino)-1,1’-biphenyl)
(1,1’-bis(diphenylphosphino)ferrocene) from STREM. These and all commercially
available chemicals were used as supplied. For TLC analyses precoated Kieselgel 60
F254 plates (Merck, 0.25 mm thick) were used; for column chromatography Silica Flash®
P60 (SiliCycle, 40-63 μm) was used. Reactions were monitored using a Hewlett-Packard
1
HP6890 gas chromatograph. H and 13C NMR spectra were obtained using a Varian
UNITY INOVA 400 MHz NMR spectrometer. High resolution mass analyses were
obtained using a VG70 double-focusing magnetic sector instrument (VG Analytical) for
EI and a PE Sciex QStar Pulsar quadrupole/TOF instrument (API) for ESI.
General procedure
Allylic alcohol 1 (0.75 mmol), amine 2 (0.5 mmol), dppf (0.025 mmol), base (1.5 mmol) and
[Pd(allyl)Cl]2 (0.0125 mmol) were sequentially added under argon to a reaction tube
equipped with a stir bar and a septum. PTS solution (1.0 mL, 2 wt %), and HCO2Me (2.0
mmol) were added by syringe and vigorously stirred for 20 h. After the reaction, the
contents of the flask were diluted with brine and extracted with EtOAc. The solution
obtained was dried over anhydrous MgSO4, filtered, and concentrated by rotary
evaporation. The residue was purified by flash chromatography eluting with
hexane/EtOAc to afford the product.
Compounds 3a,[1] 3b,[2] 3c,[3] 3d,[4] and 3g,[5] are known.
NBn2
(E)-N,N-Dibenzyl-2-undecenylamine (3e).
Following the general procedure, using 1d (256 mg, 1.5 mmol), 2a (99 mg, 0.5 mmol),
[Pd(allyl)Cl]2 (4.5 mg, 0.0125 mmol), Biphep (13 mg, 0.025 mmol), K2CO3 (207 mg, 1.5
mmol), 2 wt % PTS solution (1.0 mL) and HCO2Me (0.12 mL, 2 mmol), yielded the allylic
amine 3e (148 mg, 84%), 1H NMR (CDCl3) δ: 0.88 (t, 6.9 Hz, 3H), 0.12-0.13 (m, 12H), 2.03
(dd, J = 6.5 and 13.5 Hz, 2H), 3.01 (d, J = 6.2 Hz, 2H), 3.57 (s, 4H), 5.52 (dt, J = 6.2 and
15.3 Hz, 1H), 5.59 (dt, J = 6.5 and 15.3 Hz, 1H), 7.23 (t, J = 7.4 Hz, 2H), 7.31 (t, J = 7.4 Hz,
4H), 7.37 (d, J = 7.2 Hz, 4H). 13C NMR (CDCl3) δ: 14.34, 22.89, 29.39, 29.51, 29.59, 29.67,
32.09, 32.67, 55.72, 57.79, 126.8, 127.2, 128.3, 128.9, 134.4, 140.0; HREIMS calcd for
C25H35N(M+): 349.2769; found 349.2761.
S2

NBn2
(E)-N,N-Dibenzyl-2-butenylamine (3f).
Following the general procedure, using 1e (108 mg, 1.5 mmol), 2a (99 mg, 0.5 mmol),
[Pd(allyl)Cl]2 (4.5 mg, 0.0125 mmol), Biphep (13 mg, 0.025 mmol), K2CO3 (207 mg, 1.5
mmol), 2 wt % PTS solution (1.0 mL) and HCO2Me (0.12 mL, 2 mmol), yielded the allylic
amine 3f (101 mg, 81%), 1H NMR (CDCl3) δ: 1.70 (dd, J = 1.0 and 6.1 Hz, 3H), 3.00 (d, J =
5.9 Hz, 2H), 3.57 (s, 4H), 5.56 (dtq, J = 1.3, 6.1 and 18.3 Hz, 1H), 5.61 (qt, J = 6.0 and 18.3
Hz, 1H), 7.23 (t, J = 7.3 Hz, 2H), 7.31 (t, J = 7.3 Hz, 4H), 7.37 (d, J = 7.4 Hz, 4H). 13C NMR
(CDCl3) δ: 18.08, 55.63, 57.7, 126.8, 128.2, 128.5, 128.9, 140.0; HREIMS calcd for
C18H21N(M+): 251.1674; found 251.1602.
Ph
N
H
(E)-N-(3-phenyl-2-propenyl)-2-methylaniline (3h).
Following the general procedure, using 1a (100 mg, 0.75 mmol), 2c (53 mg, 0.5 mmol),
[Pd(allyl)Cl]2 (4.5 mg, 0.0125 mmol), Dppf (14 mg, 0.025 mmol), K2CO3 (207 mg, 1.5
mmol), 2 wt % PTS solution (1.0 mL) and HCO2Me (0.12 mL, 2 mmol), yielded the allylic
amine 3h (89 mg, 80%), 1H NMR (CDCl3) δ: 2.22 (s, 3H), 3.73 (brs, 1H), 4.02 (dd, J = 1.5
and 6.3 Hz, 2H), 6.42 (dt, J = 5.8 and 15.9 Hz, 1H), 6.68 (d, J = 15.9 Hz, 1H), 6.73 (t, J =
7.8 Hz, 2H), 7.12 (d, J= 7.8 Hz, 1H), 7.18 (t, J = 7.8 Hz, 1H), 7.28 (t, J = 7.3 Hz, 1H), 7.36
(t, J = 7.8 Hz, 2H), 7.43 (d, J = 7.3 Hz, 2H). 13C NMR (CDCl3) δ: 17.51, 46.14, 109.9, 117.1,
122.0, 126.2, 127.0, 127.1, 127.5, 128.5, 130.0, 131.5, 136.7, 145.8; HREIMS calcd for
C16H17N(M+): 223.1361; found 223.1359.
CO2Me
Ph
N
Bn
Ph
(E)-N-Benzyl-N-(3-phenyl-2-propenyl)phenylalanine methyl ester (3i).
Following the general procedure, using 1h (67 mg, 0.5 mmol), 2d (160 mg, 0.6 mmol),
[Pd(allyl)Cl]2 (4.5 mg, 0.0125 mmol), Biphep (13 mg, 0.025 mmol), K2CO3 (207 mg, 1.5
mmol), 2 wt % PTS solution (1.0 mL) and HCO2Me (0.12 mL, 2 mmol), yielded the allylic
amine 3i (154 mg, 80%), 1H NMR (CDCl3) δ: 2.97 (dd, J = 8.3 and 13.8 Hz, 1H), 3.11 (dd, J
= 7.0, and 13.8 Hz, 1H), 3.25 (dd, J = 7.8, and 10.6 Hz, 1H), 3.50 (dd, J = 5.0, and 14.6 Hz,
S3

1H), 3.60 (d, J = 14.3 Hz, 1H), 3.70 (s, 3H), 3.76 (t, J = 8.2 Hz, 1H), 4.02 (d, J = 14.3 Hz,
1H), 6.02 (ddd, J = 5.0, 7.7 and 15.9 Hz, 1H), 6.46 (d, J = 15.9 Hz, 1H), 7.11-7.29 (m, 15H).
13C NMR (CDCl3) δ: 35.8, 51.1, 52.7, 54.3, 63.2, 126.1, 126.7, 127.2, 127.7, 128.08, 128.09,
128.3, 128.4, 129.3, 132.1, 136.9, 138.3, 139.3, 172.9 ; HRESIMS calcd for
C26H28NO2(MH+): 386.2120; found 386.2106.
Me
Ph
N
Naftifine (3j).
Following the general procedure, using 1h (67 mg, 0.5 mmol), 2e (128 mg, 0.75 mmol),
[Pd(allyl)Cl]2 (4.5 mg, 0.0125 mmol), Biphep (13 mg, 0.025 mmol), K2CO3 (207 mg, 1.5
mmol), 2 wt % PTS solution (1.0 mL) and HCO2Me (0.12 mL, 2 mmol), yielded the allylic
amine 3j (118 mg, 83%), 1H NMR (CDCl3) δ: 2.29 (s, 3H), 3.29 (d, J = 6.4 Hz, 2H), 3.96 (s,
2H), 6.38 (dt, J = 6.4, 16.0 Hz, 1H), 6.60 (d, J = 16.0 Hz, 1H), 7.23-7.57 (m, 9H), 7.81 (d, J
= 8.0 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 8.31 (d, J = 7.2 Hz, 1H). 13C NMR (CDCl3) δ: 42.4,
60.0, 60.32, 124.5, 125.0, 125.5, 125.8, 126.2, 127.30, 127.37, 127.5, 127.8, 128.3, 128.4,
132.4, 132.5, 133.8, 134.8, 137.0; HREIMS calcd for C21H21N(M+): 287.1670; found 287.1684.
References
(1) Miyabe, H.; Matsumura, A.; Moriyama, K.; Takemoto, Y. Org. Lett. 2004, 6, 4631.
(2) Kimura, M.; Futamata, M.; Shibata, K.; Tamaru, Y. Chem. Commun. 2003, 234.
(3) Benito, A. P.; Alonso, J. M. Chem. Eur. J. 2003, 9, 5793.
(4) Katritzky, A. R.; Nair, S. K.; Qiu, G. Synthesis 2002, 199.
(5) Watson, I. D. G.; Yudin,A. K. J. Am. Chem. Soc. 2005, 127, 17516.
S4

3a
S5

3b
S6

3c
S7

3d
S8

1
3e
5
S39

3e
S10

3f
S11

3f
S12

3g
S13

3h
S14

3h
S15

3i
S16

3i
S17

3j
S18

3j
S19