Diastereoselective Barbier-type and palladium-mediated allylation of optically active aldimine with allylindium reagents

Full text of DOI:10.1021/jo015719j

7516
J . Org. Chem. 2001, 66, 7516-7518
Sch em e 1
Dia ster eoselective Ba r bier -Typ e a n d
P a lla d iu m -Med ia ted Allyla tion of Op tica lly
Active Ald im in e w ith Allylin d iu m Rea gen ts
Reiko Yanada,* Akira Kaieda, and Yoshiji Takemoto
Graduate School of Pharmaceutical Sciences,
Kyoto University, Yoshida, Sakyo-ku,
Kyoto 606-8501, J apan
3 bearing a methoxy group were employed. Then we first
examined the allylation reaction of imine 3 with In and
allyl bromide under the typical Barbier-type conditions.
But the result was not satisfactory, giving the desired
product 4a in low yield. Previously, Paquette et al.
reported that indium-mediated allylations of carbonyl
compounds possessing a hydroxy group proceeded with
high diastereoselectivity.2,6 We next investigated the
allylation reaction of imine 2 in expectation of good
results by improving several conditions. When the reac-
tion was carried out in the presence of imine 2, 1.5 equiv
of In and 1.5 equiv of allyl halides in DMF at room
temperature (method A), (S,S)-allylation product 4a 7 was
obtained in high yields and high diastereoselectivities
(Table 1, runs 1 and 2). The allylation reaction did not
proceed when allyl chloride was used (run 3). Similar
allylation with various allylic bromides proceeded regio-
selectively by attack of the γ-carbon of the allylindium
reagents to the imine 2 (runs 4-9). Also in our experi-
ments, high diastereoselectivities to C1′ were obtained
(runs 1-9). When the γ position had two substituents,
the reaction did not proceed (run 10).
Next, a different allylation method (method B) was
examined to extend the reaction to other allylic sub-
strates. Recently, Araki et al. reported the umpolung of
π-allylpalladium(II) complexes (electrophile) with InI.8
Although we adapted this procedure to imine 2, most of
the starting material was recovered with a trace amount
of an allylated compound. After many experiments with
other palladium-mediated methods, we found that the
use of In and I2 in place of InI dramatically enhanced
the allylation reaction via umpolung. The allylation of
the optically active imine 2 gave compound 4a in 95%
yield as the sole product (run 11). It would be considered
that similarly an allylindium species (nucleophile) was
formed in situ via a π-allylpalladium(II) complex (elec-
trophile) with In and I2.9 Our method is economical,
because reagents such as cheap In and I2 can be used
instead of expensive InI. Although Tuck et al. had
previously reported a convenient synthetic method of
InI,10 it took much time and labor to prepare the reagent.
ryanada@pharm. kyoto-u.ac.jp
Received April 28, 2001
The first ionization potential of indium (In) (5.8 eV) is
as low as that of Li and Na. Therefore, it is easy for
indium to affect SET (single electron transfer) processes.
In addition, indium is comparatively stable in air, and
the toxicity observed in many metals is little known in
In.1 For these reasons, In is one of the most notable
metals at present, and its usefulness in organic synthesis
has been studied in terms of green chemistry.2 Whereas
numerous allylation reactions of carbonyl compounds
with In have been reported,3 there are few reports on the
allylation reactions of imines with In due to their poor
reactivity compared with the corresponding carbonyl
compounds. Thus far, three allylation reactions of opti-
cally active imines such as 1 have been reported, and all
of these utilized the chelation of iminoester 1 with In to
attain moderate to good diastereoselectivities (50-90%
de).4 Here, we report that the Barbier-type allylation of
the optically active imino alcohol-type aldimine 2 pro-
ceeded with high regio- and stereoselectivity by a more
effective chelation control via 2 (method A). Further-
more, we have developed a novel one-pot allylation of 2
with an In/Pd(PPh3)4 bimetallic system (method B)
(Scheme 1).
We have already reported the reductive allylation
reaction of the optically active imines 3 with samarium-
(0) and allyl halides.5 In this reaction, high diastereose-
lectivities were obtained when the optically active imines
(1) (a) Roychowdhury, M. Am. Ind. Hyg. Assoc. J . 1993, 54, 607-
614. (b) Chapin, R. E.; Harris, M. W.; Hunter, E. S., III; Davis, B. J .;
Collins, B. J .; Lockhart, A. C. Fundam. Appl. Toxicol. 1995, 27, 140-
148. (c) Nakajima, M.; Sasaki, M.; Kobayashi, Y.; Ohno, Y.; Usami,
M. Teratog. Carcinog. Mutagen. 1999, 19, 205-209.
(2) Paquette, L. A. In Green Chemistry: Frontiers in Benign Chemi-
cal Synthesis and Processing; Anastas, P., Williamson, T., Eds.; Oxford
University Press: New York, 1998.
(3) (a) Cintas, P. Synlett 1995, 1087-1096. (b) Isaac, M.; Chan, T.-
H. Tetrahedron Lett. 1995, 36, 8957-8960. (c) Diana, S.-C. H.; Sim,
K.-Y.; Loh, T.-P. Synlett 1996, 263-264. (d) Loh, T.-P.; Li, X.-R.
Tetrahedron Lett. 1997, 38, 869-872. (e) Loh, T.-P.; Zhou, J .-R.; Li,
X.-R. Tetrahedron Lett. 1999, 40, 9333-9336. (f) Choudhury, P. K.;
Foubelo, F.; Yus, M. Tetrahedron 1999, 55, 10779-10788. (g) Li, C.-
J .; Chan, T.-H. Tetrahedron 1999, 55, 11149-11176. (h) Paquette, L.;
Rothhaar, R. R. J . Org. Chem. 1999, 64, 217-224. (i) Nair, V.; J ayan,
C. N. Tetrahedron Lett. 2000, 41, 1091-1094. (j) Chappell, M.;
Halcomb, R. L. Org. Lett. 2000, 2, 2003-2005.
(4) (a) Beuchet, P.; Marrec, N.; Mosset, P. Tetrahedron Lett. 1992,
33, 5959-5960. (b) Basile, T.; Bocoum, A.; Savoia, D.; Umani-Ronchi,
A. J . Org. Chem. 1994, 59, 7766-7773. (c) Loh, T.-P.; Sook-Chiang,
D.; Xu, K.-C.; Sim. K-Y. Tetrahedron Lett. 1997, 38, 865-868.
(5) (a) Negoro, N.; Yanada, R.; Okaniwa, M.; Yanada, K.; Fujita, T.
Synlett 1998, 835-836. (b) Yanada, R.; Negoro, N.; Okaniwa, M.; Ibuka,
T. Tetrahedron 1999, 55, 13947-13956. (c) Yanada, R.; Negoro, N.;
Okaniwa, M.; Miwa, Y.; Taga, T.; Yanada, K.; Fujita, T. Synlett 1999,
537-540. (d) Yanada, R.; Ibuka, T. J . Synth. Org. Chem. J pn. 2000,
58, 597-605. (e) Yanada, R.; Okaniwa, M.; Kaieda, A.; Ibuka, T.;
Takemoto, Y. J . Org. Chem. 2001, 66, 1283-1286.
(6) (a) Kim, E.; Gordon, D. M.; Schmid, W.; Whitesides, G. M. J .
Org. Chem. 1993, 58, 5500-5507. (b) Isaac, M. B.; Chan, T.-H.
Tetrahedron Lett. 1995, 36, 8957-8960. (c) Paquette, L. A.; Mitzel, T.
M. J . Am. Chem. Soc. 1996, 118, 1931-1937. (d) Paquette, L. A.; Mitzel,
T. M. J . Org. Chem. 1996, 61, 8799-8804.
(7) (a) Bocoum, A.; Savoia, D.; Umani- Ronchi, A. J . Chem. Soc.,
Chem. Commun. 1993, 1542. (b) Basile, T.; Bocoum, A.; Savoia, D.;
Umani-Ronchi, A. J . Org. Chem. 1994, 59, 7766. (c) Alvaro, G.; Pacioni,
P.; Savoia, D. Chem. Eur. J . 1997, 3, 726.
(8) (a) Araki et al. reported recently that umpolung of the π-al-
lylpalladium(II) with indium(I) salts proceeded smoothly to provide
allylindium(III) reagents. The 1H NMR spectrum of allylindium(III)
compound in DMF-d7 revealed the allylic protons at δ 2.08 ppm (2H).
Araki, S.; Kamei, T.; Hirashita, T.; Yamamura, H.; Kawai, M. Org.
Lett. 2000, 2, 847-849. (b) Ohno, H.; Hamaguchi, H.; Tanaka, T. Org.
Lett. 2000, 2, 2161-2163.
(9) In (1.5 equiv), I2 (0.75 equiv), Pd(PPh3)4 (5 mol %) or In (2 equiv),
I2 (2 equiv), Pd(PPh3)4 (5 mol %) and imine 2 were used for the
preparation of InI.
10.1021/jo015719j CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/29/2001

Notes
J . Org. Chem., Vol. 66, No. 22, 2001 7517
Ta ble 1. In d iu m -Med ia ted Dia ster eoselective Allyla tion to Im in e 2
run
method
R1
R2
R3
X
reaction time (h)
product 4
yield (%)
de (C1′, %)
dr (C2′)
1
2
3
4
5
6
7
8
9
10
11c
12c
13d
14d
15d
A
A
A
A
A
A
A
A
A
A
B
B
B
B
B
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Et
Me
H
H
H
H
H
Br
I
1
1
24
1
4a
4a
4a
4b
4c
4d
4e
4f
95
96
trace
91
48
79
47
60
21
0
95
92
81
52
24
>99
>99
Cl
Br
Br
Br
Br
Br
Br
Br
OAc
OCO2Et
OPh
Cl
Me
CO2Me
>99
94:6
>99
>99
b
H
3
H
H
H
H
H
H
H
H
H
H
Me
Et
Ph
H
Me
H
H
H
H
H
24
24
24
24
24
3
5:1a
5:1a
b
4e
>99
4:1a
4a
4a
4a
4a
4a
>99
>99
>99
95:5
89:11
3
15
15
24
OH
a
b
Diastereomeric ratios (dr) of C2′ position were determined by 1H NMR spectra. Only this reaction, a mixture of four diastereoisomers
1
was obtained. The ratio of the products by H NMR is 82:6:4:8. The major isomer is thought to be the (S,S,R)- or (S,S,S)-isomer based on
the allylation mechanism. c The reactions were carried out by using optically active imine (1 mmol), allyl halide (1.5 mmol), Pd(PPh3)4 (5
d
mol %), indium (1.5 mmol), and iodine (0.75 mmol) in DMF. The reactions were carried out by using optically active imine (1 mmol),
allyl halide (1.5 mmol), Pd(PPh3)4 (5 mol %), indium (2 mmol), and iodine (2 mmol) in DMF.
economical palladium-mediated allylation of imine 2 has
been established. By removing the chiral auxiliary unit
of these â-amino alcohol derivatives, it is possible to
obtain the optically active homoallylamine in high yield.5a,5b
In addition, the induction to optically active â-amino acid
derivatives5d,12 and γ- lactams,13 etc., is also possible.
F igu r e 1. Plausible mechanism of indium-mediated diaste-
reoselective allylation.
Exp er im en ta l Section
By using method B, allyl acetate, allyl carbamate, allyl
All reactions were carried out under a positive pressure of
argon or nitrogen. 1H NMR spectra were recorded on a J EOL
J NM-EX-270 or J EOL J NM-LA-500 spectrometer using tetra-
methylsilane (TMS) as an internal standard. 13C NMR spectra
were recorded on a J EOL J NM-EX-270 (67.8 MHz) spectrometer.
Optical rotations were measured with a J ASCO DIP-360 digital
polarimeter. Nominal (LRMS) and exact mass (HRMS) spectra
phenyl ether, allyl chloride, and allyl alcohol could be
used as the allylation reagent. The allylation products
were obtained in good to moderate yield and in high
diastereoselectivity, respectively (runs 11-14).
1
To clarify the difference in the above results, the H
NMR spectrum of the allylindium compounds was taken
by methods A and B in CDCl3. The experiments revealed
the allylic proton signals at δ 1.7 (major) and 2.1 (minor)
ppm after 30 min and 1 h of the reaction. These chem-
ical shifts are in good accordance with the reported data
of the allylindium(I) and allylindium(III) species, re-
spectively.8a,11 Because only the allylindium(III) species
were obtained from Araki’s method, it can be assumed
that it is difficult to effect allylation of inactive imine 2.
It is thought that the allylindium intermediate coor-
dinates with both the hydroxy and nitrogen functions of
imine 2 as Figure 1. Owing to this conformation, the
bulky isopropyl group of the chiral auxiliary selectively
shields the re face of the imine 2, and hence, the allylic
addition proceeds from the si face. This supported the
high diastereoselectivity of these reactions.
were recorded on
a J EOL J MS-HX/HX-110A instrument.
Metallic indium was purchased from Kojundo Chemical Labora-
tory Co., Ltd ($0.80-1.00 per gram). For flash chromatography,
silica gel FL60D (Fuji Silysia Chemical Ltd.) was employed.
Gen er a l P r oced u r e for th e Ba r bier -Typ e Allyla tion
Rea ction of Im in e 2 (Meth od A). The mixture of imine 2 (1
mmol), In (1.5 mmol) and allyl bromide (1.5 mmol) in DMF (5
mL) was stirred for 1 h at room temperature under nitrogen.
The reaction mixture was evaporated. AcOEt and 1 N aqueous
HCl were added to the resulting suspension and stirred for 30
min. Aqueous NaOH (30%) was added to the resulting solution
until neutral. The solution was stirred for 10 min. The mixture
was extracted with AcOEt. The extract was washed with brine,
dried over anhydrous potassium carbonate, and concentrated
under reduced pressure. The mixture was purified by flash silica
gel column chromatography with hexane/AcOEt ) 8:1 to give
the title compound 4a (95% yield).
Gen er a l P r oced u r e for th e P a lla d iu m -Med ia ted Allyla -
tion Rea ction of Im in e 2 (Meth od B). The mixture of imine
2 (1 mmol), Pd (PPh3)4 (5 mol %), In (1.5 mmol), I2 (0.75 mmol),
and allyl acetate (1.5 mmol) in DMF (5 mL) was stirred for 1 h
at room temperature under nitrogen. The reaction mixture was
evaporated. AcOEt and 1 N aqueous HCl were added to the
resulting suspension and stirred for 30 min. Then 30% aqueous
NaOH was added to the resulting solution until neutral. The
In summary, we have developed the first regio- and
stereoselective allylation of imine 2 bearing a hydroxy
group on the chiral auxilialy under the Barbier-type
conditions and revealed that the chelation between the
nitrogen and hydroxy groups of the imine 2 with In is
crucial for the high stereoselectivity. In addition, a new
(10) Freeland, B. H.; Tuck, D. G. Inorg. Chem. 1976, 15, 475-476.
(11) (a) Araki, S.; Ito, H.; Butsugan, Y. J . Org. Chem. 1988, 53,
1833-1835. (b) Araki, S.; Ito, H.; Katsumura, N.; Butsugan, Y. J .
Organomet. Chem. 1989, 369, 291-296. (c) Chan, T. H.; Yang, Y. J .
Am. Chem. Soc. 1999, 121, 3228-3229.
(12) Ichihara O.; Davies, S. G. J . Synth. Org. Chem. J pn. 1997, 55,
42-50.
(13) (a) Dembe´le´, Y. A.; Belaud, C.; Villie´ras, J . Tetrahedron:
Asymmetry 1992, 3, 511-514. (b) Nyzam, V.; Belaud, C.; Zammattio,
F.; Villieras, J . Tetrahedron: Asymmetry 1996, 7, 1835-1843.

7518 J . Org. Chem., Vol. 66, No. 22, 2001
Notes
solution was stirred for 10 min. The mixture was extracted with
AcOEt. The extract was washed with brine, dried over anhy-
drous potassium carbonate, and concentrated under reduced
pressure. The mixture was purified by flash silica gel column
chromatography (hexane/AcOEt ) 9:1) to give the title compound
4a 7 (95% yield).
4.3, 11.0 Hz, 1H, CHOH), 5.12 (dd, J ) 1.8, 17.1 Hz, 1H, CHd),
5.20 (dd, J ) 1.8, 10.4 Hz, 1H, CHd), 5.62 (ddd, J ) 10.1, 10.1,
17.1 Hz, 1H, CH2dCH), 7.23-7.33 (m, Ph, 5H); 13C NMR (CDCl3)
δ 12.0, 19.4, 19.8, 24.6, 29.5, 53.6, 59.7, 61.3, 63.8, 117.5, 127.2,
128.1, 128.4, 140.7, 143.5. Anal. Calcd for C17H27NO: C, 78.11;
H, 10.41; N, 5.36. Found: C, 78.13; H, 10.69; N, 5.18.
3-Met h yl-(2S)-[3-m et h yl-(1S)-p h en ylb u t -3-en yla m in o]-
(2S)-[2-E t h yl-(1S)-p h en ylbu t -3-en yla m in o]3-m et h ylbu -
ta n -1-ol, 4e (m in or ): colorless oil; Rf ) 0.3, hexane/AcOEt )
3:1; 1H NMR (CDCl3) δ 0.83, 0.88 (d, J ) 7.0 Hz, 6H, CH(CH3)2),
0.84 (dd, J ) 7.3, 7.3 Hz, 3H, CH3), 1.02-1.26 (m, 2H, CH3CH2),
1.69-1.73 (m, 1H,Me2CH), 2.16-2.19 (m, 1H, CHiPr), 2.23-2.30
(1H, m, allyl CH2), 3.41 (dd, J ) 3.7, 11.0 Hz, 1H, CH2OH), 3.58
(dd, J ) 4.3, 11.0 Hz, 1H, CH2OH), 3.68 (d, J ) 8.5 Hz, 1H,
PhCH), 5.04-5.10 (m, 2H, CH2d), 5.41 (ddd, J ) 10.1, 10.1, 16.8
Hz, 1H, CH2dCH), 7.05-7.47 (m, Ph, 5H). Anal. Calcd for
C17H27NO: C, 78.11; H, 10.41; N, 5.36. Found: C, 77.85; H, 10.70;
N, 5.30.
bu ta n -1-ol, 4b: colorless oil; Rf ) 0.3, hexane/AcOEt ) 3:1; [R]18
D
1
-46.3 (c 1.0, CHCl3); H NMR (CDCl3) δ 0.80, 0.85 (d, J ) 6.7
Hz, 6H, CH(CH3)2), 1.67 (dqq, J ) 6.7, 6.7, 6.7 Hz, 1H, CHMe2),
1.71 (s, 3H, CH3), 2.22 (ddd, J ) 4.2, 4.2, 6.7 Hz, 1H, CHiPr),
2.31 (dd, J ) 6.1, 13.4 Hz, 1H, CHCN), 2.43 (dd, J ) 7.9, 13.4
Hz, 1H, CHCN), 3.40, 3.61 (dd, J ) 4.2, 10.7 Hz, 2H, CH2OH),
3.82 (dd, J ) 6.1, 7.9 Hz, 1H, PhCH), 4.70, 4.77 (d, J ) 1.5 Hz,
2H, CH2d), 7.22-7.33 (m, 5H, Ph); 13C NMR (CDCl3) δ 19.0,
19.4, 22.4, 29.4, 47.2, 58.4, 59.9, 61.1, 113.2, 127.0, 127.1, 128.3,
142.8, 144.3. Anal. Calcd for C16H25NO: C, 77.68; H, 10.19; N,
5.66. Found: C, 77.80; H, 10.31; N, 5.48.
(2S)-[(1S)-2-Dip h en ylbu t-3-en yla m in o]-3-m eth ylbu ta n -
2-[[(1S)-H yd r oxym et h yl-2-m et h ylp r op yla m in o]-(3S)-2-
p h en yleth yl]a cr ylic Acid Meth yl Ester , 4c: colorless oil; Rf
) 0.1, hexane/AcOEt ) 3:1; H NMR (CDCl3) δ 0.81, 0.85 (d, J
1-ol, 4f (m a jor ): colorless oil; Rf ) 0.3, hexane/AcOEt ) 3:1;
1
[R]18 +10.8 (c 1.0, CHCl3); H NMR (CDCl3) δ 0.70, 0.73 (d, J
D
1
) 6.7 Hz, 6H, 2 × CH3), 1.52 (dqq, J ) 6.7, 6.7, 6.7 Hz, 1H,
Me2CH), 2.10 (ddd, J ) 3.7, 4.0, 6.7 Hz, 1H, CHiPr), 3.28, 3.46
(dd, J ) 3.7, 10.1 Hz, 2H, CH2OH), 3.53 (dd, J ) 8.5, 8.2 Hz,
1H, allyl CH), 3.90 (d, J ) 8.9 Hz, 1H, PhCH), 4.82 (dd, J ) 1.2,
17.1 Hz, 1H, CH2dCH), 4.91 (dd, J ) 1.2, 10.1 Hz, 1H, CH2d
CH), 0.5.86 (ddd, J ) 8.2, 10.1, 17.1 Hz, 1H, Ph, CHd), 7.22-
7.33 (m, Ph, 10H); 13C NMR (CDCl3) δ 19.0, 19.5, 29.1, 57.5,
59.4, 61.1, 64.8, 116.6, 126.7, 127.2, 128.0, 128.1, 128.2, 128.6,
138.6, 142.0, 142.1; LRMS (CI) m/z, 310 (MH+), 192; HRMS calcd
for C21H28NO (MH+) 309.4452, found 310.2163. Anal. Calcd for
) 6.7 Hz, 6H, CH(CH3)2), 1.67 (dqq, J ) 6.7, 6.7, 6.7 Hz, 1H,
CHMe2), 2.24 (ddd, J ) 4.0, 4.0, 6.7 Hz, 1H, CHiPr), 2.57 (dd, J
) 6.7, 13.7 Hz, 1H,allyl CH), 2.77 (dd, J ) 7.9, 13.7 Hz, 1H,
allyl CH), 3.36, 3.58 (dd, J ) 4.0, 11.0 Hz, 2H, CH2OH), 3.74 (s,
3H, CO2CH3), 3.85 (dd, J ) 6.7, 7.6 Hz, 1H, PhCH), 5.43 (d, J )
1.2 Hz, 1H, CHd), 6.09 (d, J ) 1.2 Hz, 1H, CHd), 7.24-7.33
(m, Ph, 5H); 13C NMR (CDCl3) δ 18.9, 19.5, 29.4, 41.0, 51.9, 59.8,
59.9, 61.0, 126.7, 127.0, 127.2, 128.4, 138.0, 143.5, 168.0; LRMS
(FAB) m/z, 292 (M+). Anal. Calcd for C17H25NO3: C, 70.70; H,
8.65; N, 4.81. Found: C, 70.35; H, 8.72; N, 4.67.
C
21H27NO: C, 81.51; H, 8.79; N, 4.53. Found: C, 81.35; H, 8.89;
N, 4.38.
(2S)-[(1S)-2-Dip h en ylbu t-3-en yla m in o]3-m eth yl-bu ta n -
3-Met h yl-(2S)-[2-m et h yl-(1S)-p h en ylb u t -3-en yla m in o]-
bu ta n -1-ol, 4d (m a jor ): colorless oil; Rf ) 0.3, hexane/AcOEt
) 3:1; [R]16 -84.4 (c 1.0, CHCl3); 1H NMR (CDCl3) δ 0.77 (d, J
1-ol, 4f (m in or -1): colorless oil; Rf ) 0.3, hexane/AcOEt ) 3:1;
1H NMR (CDCl3) δ 0.43, 0.64 (d, J ) 7.0 Hz, 6H, 2 × CH3), 1.76
(m, 1H, Me2CH), 2.23 (ddd, J ) 4.3, 4.3, 8.5 Hz, 1H, CHiPr),
2.94-3.50 (m, 3H, CH2OH, allyl CH), 3.96 (d, J ) 10.1 Hz, 1H,
PhCH), 4.65 (d, J ) 16.8 Hz, 1H, CH2dCH), 4.80 (d, J ) 10.4
Hz, 1H, CH2dCH), 5.73 (ddd, J ) 7.6,10.6, 16.8 Hz, 1H, CH)),
6.94-7.47 (m, Ph, 10H); LRMS (CI) m/z 310 (MH+), 192; HRMS
calcd for C21H28NO (MH+) 309.4452, found 310.2180.
(2S)-[(1S)-2-Dip h en ylbu t-3-en yla m in o]-3-m eth ylbu ta n -
1-ol, 4f (m in or -2): colorless oil; Rf ) 0.3, hexane/AcOEt ) 3:1;
1H NMR (CDCl3) δ 0.78, 0.83 (d, J ) 6.7 Hz, 6H, 2 × CH3), 1.66
(m, 1H, Me2CH), 2.15 (m, 1H, CHiPr), 2.94-3.50 (m, 2H, CH2-
OH, allyl CH), 3.60 (dd, J ) 3.7, 10.7 Hz, 1H, CH2OH), 3.89 (d,
J ) 8.5 Hz, 1H, PhCH), 5.17 (d, J ) 17.7 Hz, 1H, CH2dCH),
5.19 (d, J ) 10.4 Hz, 1H, CH2dCH), 0.6.15-6.25 (m, 1H, CHd),
6.94-7.47 (m,10H, Ph); LRMS (CI) m/z 310 (MH+), 192; HRMS
calcd for C21H28NO (MH+) 309.4452, found 310.2166.
(2S)-[(1S)-2-Dip h en ylbu t-3-en yla m in o]-3-m eth ylbu ta n -
1-ol, 4f (m in or -3). colorless oil; Rf ) 0.3, hexane/AcOEt ) 3:1;
1H NMR (CDCl3) δ 0.85, 0.89 (d, J ) 7.0 Hz, 6H, 2 × CH3), 1.96
(m, 1H, Me2CH), 2.34 (ddd, J ) 4.3, 4.3, 8.5 Hz, 1H, CHiPr),
2.94-3.50 (m, 3H, CH2OH, allyl CH), 3.93 (d, J ) 9.5 Hz, 1H,
PhCH), 5.26 (d, J ) 10.1 Hz, 1H, CH2dCH), 5.32 (d, J ) 17.1
Hz, 1H, CH2dCH), 0.6.19 (ddd, J ) 10.1, 10.1, 17.1 Hz, 1H, Ph,
CHd), 6.94-7.47 (m, Ph, 10H); LRMS (CI) m/z 310 (MH+), 192;
HRMS Calcd for C21H28NO (MH+) 309.4452, found 310.2180.
D
) 6.7 Hz, 3H, CHCH3), 0.81 (d, J ) 6.7 Hz, 6H, CHCH3, CH3),
1.63 (dqq, J ) 6.7, 6.7, 6.7 Hz, 1H, CHMe2), 2.12 (brs, 2H, NH,
OH), 2.12 (ddd, J ) 3.7, 4.0, 7.0 Hz, 1H, CHiPr), 2.37 (ddq, J )
7.6, 7.6, 7.6 Hz, 1H, MeCH), 3.38 (d, J ) 8.2 Hz, 1H, PhCH),
3.40 (dd, J ) 3.7, 11.0 Hz, 1H, CH2OH), 3.58 (dd, J ) 4.3, 11.0
Hz, 1H, CH2OH), 5.10 (dd, J ) 1.2, 10.1 Hz, 1H, CH2)), 5.11
(dd, J ) 0.9, 17.1 Hz, 1H, CH2d), 5.81 (ddd, J ) 8.2, 10.4, 17.1
Hz, 1H, CH2dCH), 7.21-7.33 (m, Ph, 5H); 13C NMR (CDCl3) δ
17.9, 19.1, 19.5, 29.2, 45.2, 59.5, 61.1, 64.8, 115.3, 127.1, 127.7,
128.2, 142.2, 142.9. Anal. Calcd for C16H25NO: C, 77.68; H,
10.19; N, 5.66. Found: C, 77.42; H, 10.23; N, 5.63.
3-Met h yl-(2S)-[2-m et h yl-(1S)-p h en ylb u t -3-en yla m in o]-
bu ta n -1-ol, 4d (m in or ): colorless oil; Rf ) 0.3, hexane/AcOEt
) 3:1; 1H NMR (CDCl3) δ 0.83, 0.88 (d, J ) 7.0 Hz, 6H, CH-
(CH3)2), 1.00 (d, J ) 7.0 Hz, 3H, CH3), 1.71 (dqq, J ) 7.0, 7.0,
7.0 Hz, 1H, CHMe2), 2.18-2.19 (m, 1H, CHiPr), 2.41 (brs, 2H,
NH, OH), 2.51-2.55 (m, 1H, MeCH), 3.41 (dd, J ) 3.4, 11.0 Hz,
1H, CH2OH), 3.57-3.61 (m, 2H, CH2OH, PhCH), 5.00 (d, J )
9.3 Hz, 1H, CH2d), 5.00 (d, J ) 16.0 Hz, 1H, CH2d), 5.61 (ddd,
J ) 7.9, 9.3, 17.0 Hz, 1H, CH2dCH), 7.16-7.32 (m, Ph, 5H); 13
C
NMR (CDCl3) δ 16.9, 19.1, 19.6, 29.3, 43.8, 59.1, 60.6, 63.9, 115.4,
126.9, 127.9, 128.0, 140.6, 141.4. Anal. Calcd for C16H25NO: C,
77.68; H, 10.19; N, 5.66. Found: C, 77.73; H, 10.42; N, 5.42.
(2S)-[2-E t h yl-(1S)-p h en ylb u t -3-en yla m in o]3-m et h ylb u -
ta n -1-ol, 4e (m a jor ): colorless oil; Rf ) 0.3, hexane/AcOEt )
1
3:1; [R]17 -79.7 (c 0.94, CHCl3); H NMR (CDCl3) δ: 0.75 (t, J
D
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for new compounds 4 are provided. This material is
available free of charge via the Internet at http://pubs.acs.org.
) 7.3 Hz, 3H, CH3), 0.76, 0.79 (d, J ) 6.7 Hz, 6H, CH(CH3)2),
1.01-1.11 (m, 1H, CH3CH), 1.17-1.25 (m, 1H, CH3CH), 1.62
(dqq, J ) 6.7, 6.7, 6.7 Hz, 1H,Me2CH), 2.10-2.16 (m, 2H,
CHiPr, allyl CH), 2.58 (brs, 2H, NH, OH), 3.41 (dd, J ) 3.7, 11.0
Hz, 1H, CHOH), 3.46 (d, J ) 8.5 Hz, 1H, PhCH), 3.58 (dd, J )
J O015719J