Ring opening of nonactivated 2-(1-aminoalkyl) aziridines: Unusual regio- and stereoselective C-2 and C-3 cleavage

Article abstract of DOI:10.1021/jo034440v

We have studied the ring opening of nonactivated amino aziridines 1 by water under acidic conditions. Depending on the acid used, amino aziridines are cleaved at C-3 or C-2 with high regioselectivity, and total stereoselectivity, affording chiral 2,3-diam

Full text of DOI:10.1021/jo034440v

Rin g Op en in g of Non a ctiva ted 2-(1-Am in oa lk yl) Azir id in es:
Un u su a l Regio- a n d Ster eoselective C-2 a n d C-3 Clea va ge
J os e´ M. Concell o´ n* and Estela Riego
Departamento de Qu ı´ mica Org a´ nica e Inorg a´ nica, Facultad de Qu ´ı mica, Universidad de Oviedo,
J uli a´ n Claver ı´ a 8, 33071 Oviedo, Spain
jmcg@sauron.quimica.uniovi.es
Received April 7, 2003
We have studied the ring opening of nonactivated amino aziridines 1 by water under acidic
conditions. Depending on the acid used, amino aziridines are cleaved at C-3 or C-2 with high
regioselectivity, and total stereoselectivity, affording chiral 2,3-diaminoalkan-1-ols 3 or 1,3-
diaminoalkan-2-ols 4 in high yield.
In tr od u ction
SCHEME 1. C-3 Rin g Op en in g of Am in o
Azir id in es 1
Chiral aziridines are useful synthetic intermediates for
the synthesis of biologically important compounds be-
cause of their ability to undergo nucleophilic ring opening
1
reactions. Hence, control of the regio- and stereoselec-
tivity of the ring opening is essential for this purpose.
Over the past few years a great number of ring opening
reactions of aziridines have been reported.1 However,
c,2
in these reactions, nonactivated aziridine2j has been
potentially able to furnish the synthetically important
chiral 1,2-amino alcohols.5
scarcely used in comparison with activated aziridines.
Moreover, to the best of our knowledge, there are very
few examples in the literature in which the regioselec-
tivity of the ring opening of a determined activated
Recently, we reported the synthesis of nonactivated
enantiopure amino aziridines 1 (Scheme 1) by reduction
of R-amino ketimines derived from 1-aminoalkyl chlo-
6
romethyl ketones. The ring opening of these aziridines
aziridine with the same nucleophile is different depend-
ing on the reaction conditions.3
with heteronucleophiles was able to provide differently
functionalized diamino compounds. Herein, we report the
ring opening of amino aziridines by water with total
regio- and stereoselectivity at C-2 and C-3, obtaining
chiral 2,3-diaminoalkan-1-ols 3 and 1,3-diaminoalkan-
In addition, water has been used as the nucleophile in
stereocontrolled ring opening reactions of nonactivated
4
aziridines to a limited extent, despite this process being
2
-ols 4.
*
To whom correspondence should be addressed. Fax: 34-98-510-
4-46.
1) (a) Tanner, D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599. (b)
3
(
Resu lts a n d Discu ssion
Pearson, W. H.; Lian, B. W.; Bergmeier, S. C. In Comprehensive
Heterocyclic Chemistry II; Padwa, A., Ed.; Pergamon: Oxford, UK,
Ring opening reactions of amino aziridines 1 with
water were carried out in acidic conditions to activate
the aziridine ring. First, we tested the use of protic acids
in this process. Thus, treatment of 1 with 1 equiv of
p-toluenesulfonic acid (TsOH) in a 7/1 CH CN/H O
3 2
mixture afforded 2,3-diaminoalkan-1-ols 3 with high
yield, as shown in Table 1.
The reaction proceeded very smoothly at room tem-
perature (24 h are required), while when a refluxing
temperature was used the reaction was completed in only
1
1
996; Vol. 1A, pp 1-60. (c) McCoull, W.; Davis, F. A. Synthesis 2000,
347.
(2) (a) Wu, J .; Hou, X.-L.; Dai, L.-X. J . Org. Chem. 2000, 65, 1344.
(
b) Kim, B. M.; Bae, S. J .; So, S. M.; Yoo, H. T.; Chang, S. K.; Lee, J .
H.; Kang, J . Org. Lett. 2001, 3, 2349. (c) Vicario, J . L.; Bad ´ı a, D.;
Carrillo, L. J . Org. Chem. 2001, 66, 5801. (d) Sabitha, G.; Babu, R. S.;
Rajkumar, M.; Reddy, C. S.; Yadav, J . S. Tetrahedron Lett. 2001, 42,
3
955. (e) Paul, B. J .; Hobbs, E.; Buccino, P.; Hudlicky, T. Tetrahedron
Lett. 2001, 42, 6433. (f) Mao, H.; J oly, G. J .; Peeters, K.; Hoornaert,
G. J .; Compernolle, F. Tetrahedron 2001, 57, 6955. (g) Xiong, C.; Wang,
W.; Cai, C.; Hruby, V. J . J . Org. Chem. 2002, 67, 1399. (h) Aggarwal,
V. K.; Alonso, E.; Ferrara, M.; Spey, S. E. J . Org. Chem. 2002, 67,
2
335. (i) Yadav, J . S.; Reddy, B. V. S.; Sadashiv, K.; Harikishan, K.
Tetrahedron Lett. 2002, 43, 2099. (j) Anand, R. V.; Pandey, G.; Singh,
V. K. Tetrahedron Lett. 2002, 43, 3975.
0
.5-1 h. These more drastic conditions did not affect the
(
3) Only the ring opening of activated 2,3-aziridino alcohols by
different hydride and methyl-transfer reagents led to regio- and
stereoselective C-2 and C-3 cleavage, depending on the chelate effect
of the reagent: (a) Tanner, D.; He, H. M.; Somfai, P. Tetrahedron 1992,
(5) The 1,2-amino alcohol moiety is a common structural component
in naturally occurring and synthethic molecules, as well as being used
as a chiral auxiliary: (a) Bergmeier, S. C. Tetrahedron 2000, 56, 2561.
(b) Ager, D. J .; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96, 835.
(6) Concell o´ n, J . M.; Bernad, P. L.; Riego, E.; Garc ´ı a-Granda, S.;
Forc e´ n-Acebal, A. J . Org. Chem. 2001, 66, 2764. A later alternative
synthesis of N,N-dibenzylamino aziridines: Reetz, M. T.; Lee, W. K.
Org. Lett. 2001, 3, 3119.
4
8, 6069. (b) Tanner, D.; He, H. M. Tetrahedron 1992, 48, 6079. (c)
Tanner, D.; Gautun, O. R. Tetrahedron 1995, 51, 8279.
4) (a) Davis, F. A.; Zhou, P. Tetrahedron Lett. 1994, 35, 7525. (b)
(
Katagiri, T.; Takahashi, M.; Fujimura, Y.; Ihara, H.; Uneyama, K. J .
Org. Chem. 1999, 64, 7323.
1
0.1021/jo034440v CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/17/2003
J . Org. Chem. 2003, 68, 6407-6410
6407

Concell o´ n and Riego
TABLE 2. C-2 Rin g Op en in g of Am in o Azir id in es 1
TABLE 1. C-3 Rin g Op en in g of Am in o Azir id in es 1
entry
producta
R1
R2
conditions
yield (%)b
entry
product
R1
R2
yield (%)a
b
1
2
3
4
5
6
7
8
3a
3a
3b
3b
3c
3c
3d
3e
Me
Me
Me
Me
i-Bu
i-Bu
i-Bu
Bn
Bn
Bn
Pr
80 °C, 1 h
20 °C, 24 h
80 °C, 1 h
20 °C, 24 h
80 °C, 0.5 h
80 °C, 0.5 h
80 °C, 0.5 h
80 °C, 0.5 h
72c
1
2
3
4
5
6
4a
4b
4c
4d
4e
4f
Me
Me
i-Bu
i-Bu
Bn
Bn
Pr
Bn
allyl
Bn
Bn
40
38
81
78
75
76
d
b
90
76
92
c
d
Pr
Bn
Bn
allyl
Bn
78
e
TBSO-CH2
75
74
a
Isolated yield after column chromatography based on the
starting amino aziridine 1. b This product was isolated together
with the corresponding regioisomer 3 in a 7/1 ratio, and the
starting amino aziridine 1. Regioselectivity was determined by
300-MHz 1H and C NMR analysis of the crude products 4.
a
Unless otherwise noted, TsOH was used as protic acid.
b
Isolated yield after column chromatography based on the starting
amino aziridine 1. This product was isolated together with the
corresponding regioisomer 4 (see text). Regioselectivity was de-
termined by 300-MHz H and C NMR analysis of the crude
products 3. Isolated yield of the crude product based on the
c
13
1
13
SCHEME 3. Rin g Op en in g of Am in o Ep oxid es 5
a n d 6
d
e
starting amino aziridine 1. Concentrated H2SO4 was used as
protic acid.
SCHEME 2. C-2 Rin g Op en in g of Am in o
Azir id in es 1
yield of the reaction or the purity of products. Only
compounds 3a and 3b (Table 1, entries 1 and 3) were
1
isolated together with a small amount (8%, 300-MHz H
of amino aziridines 1 was totally regio- and stereoselec-
tive, as shown by the 1H and C NMR spectra of 4.
However, unlike the previous reaction, the aziridine
suffers an unusual ring opening at C-2, with retention
of the configuration at this center.
NMR spectroscopy) of the product corresponding to a ring
opening at C-2 with retention of the configuration, as
explained later. When the reaction took place at room
temperature, the regioselectivity improved in a ratio of
13
1
9/1.
1
i
The assignment of this unexpected regio- and stereo-
chemistry was made after carrying out the ring opening
In the case of aziridines with R ) Bu, Bn (Table 1,
entries 5-7), no regioisomers or byproducts were ob-
served by NMR analysis (300 MHz) of the crude reaction
of 2,3-diaminoalkan-1-ols 3 at reflux temperature.
Nevertheless, when the reaction was carried out with
sulfuric acid under the previous conditions, the starting
amino aziridines were recovered together with unidenti-
fied byproducts.
The acid-promoted ring opening reaction of amino
aziridines 1 in the presence of water could take place
through highly reactive aziridinium salts 2 (Scheme 1),
which suffer an attack by water at the less hindered
position.
9
reaction of epoxides 5 and 6 with benzylamine (Scheme
3
). Under these conditions, the epoxide ring is opened at
the less substituted oxirane carbon, and consequently,
the stereochemistry of the C-2 in the epoxide and in the
product has not changed.10 By comparison of data for the
products from epoxides and the corresponding compounds
4
(from 1), we can affirm that the diamino alcohols
derived from 5 and 4 are the same. Likewise, the ring
opening of amino aziridines 1 with TsOH must have
taken place on C-3.
The stereochemistry in the ring opening reaction of
amino aziridines 1 in the presence of BF
3
2
‚OEt could be
In addition, the effect of Lewis acids on the ring
opening reaction of amino aziridines 1 was examined. To
explained with a double inversion at C-2 in the aziridine
ring. For this matter, an anchimeric assistance of the
dibenzylamino group in amino aziridines is proposed, and
the reaction could take place through aziridinium salt 9
do this, BF
in Lewis acid-catalyzed ring openings of aziridine
Thus, a solution of amino aziridines 1 in dry acetoni-
trile was treated with 1 equiv of BF ‚OEt , and heated
3
‚OEt
2
was chosen, since it is commonly used
1
c,2g,7
(
Scheme 4).11
3
2
In this way, after the coordination of the aziridine
nitrogen to the Lewis acid, an intramolecular ring
opening reaction at C-2, with the consequent inversion
for 1 h. The hydrolysis of the reaction mixture led to 1,3-
diaminoalkan-2-ols 4 in high yields (Scheme 2, Table 2).
Once more, excepting compounds 4 with R1 ) Me
(Table 2, entries 1 and 2), which were isolated together
(
9) Barluenga, J .; Baraga n˜ a, B.; Concell o´ n, J . M. J . Org. Chem. 1995,
60, 6696.
(10) Unpublished results, except for the ring opening of 6 (R
Bn): Concell o´ n, J . M.; Cuervo, H.; Fern a´ ndez-Fano, R. Tetrahedron
with the regioisomers 3a ,b in a 7/1 ratio in the best
8
1
)
examples (conversion ) 72%), the ring opening reaction
2
001, 57, 8983.
(
7) (a) Bodenan, J .; Chanet-Ray, J .; Vessiere, R. Synthesis 1992, 288.
b) Dauban, P.; Dodd, R. H. J . Org. Chem. 1997, 62, 4277. (c) Cantrill,
A. A.; Osborn, H. M. I.; Sweeney, J . Tetrahedron 1998, 54, 2181.
8) Longer reaction times or the use of 1.5 equiv of BF ‚OEt led to
a 3/1 mixture of regioisomers.
(11) Previously, other N,N-dibenzylated aziridinium salts were
(
proposed as intermediates in reactions of 2,3-epoxyamines: (a) Liu,
Q.; Marchington, A. P.; Boden, N.; Rayner, C. M. J . Chem. Soc., Perkin
Trans. 1 1997, 511. (b) Liu, Q.; Marchington, A. P.; Rayner, C. M.
Tetrahedron 1997, 53, 15729.
(
3
2
6
408 J . Org. Chem., Vol. 68, No. 16, 2003

Nonactivated 2-(1-Aminoalkyl) Aziridines
(
(
2 CH), 126.9 (CH), 65.6 (CH), 64.1 (CH), 54.3 (2 CH
CH ), 46.3 (CH ), 20.0 (CH ); IR (neat) 3396, 3321, 1102;
O 374.2358, found 374.2331.
2
), 54.2
2
2
3
HRMS calcd for C25
30 2
H N
(
-)-(2R,3S)-3-Diben zyla m in o-2-(p r op yla m in o)bu ta n -1-
25
ol (3b): R
f
0.12 (CH
2
Cl
); H NMR (300 MHz, CDCl
H), 3.81 (AB syst., J ) 13.2 Hz, 2 × 2 H), 3.77-3.71 (m, 1 H),
.92 (dd, J ) 12.5, 6.8 Hz, 1 H), 2.72 (dd, J ) 12.5, 5.1 Hz, 1
H), 2.61-2.53 (m, 3 H), 1.60-1.48 (m, 2 H), 1.18 (d, J ) 6.3
2
/MeOH/NH
3
90/1/1); [R]
D
-30.0 (c
1
0
.96, CHCl
3
3
) δ 7.35-7.22 (m, 10
F IGURE 1. Attack to the aziridinium salt 9 at C-2.
2
SCHEME 4. P r op osed Mech a n ism for
Tr a n sfor m a tion of 1 in to 4
13
Hz, 3 H), 0.98 (t, J ) 7.4 Hz, 3 H); C NMR (75 MHz, CDCl
δ 139.3 (2 C), 128.9 (4 CH), 128.2 (4 CH), 127.0 (2 CH), 66.0
3
)
(
(
CH), 63.8 (CH), 54.4 (2 CH
CH ), 20.1 (CH ), 11.7 (CH ); IR (neat) 3396, 3314, 1106.
-)-(2R,3S)-2-Ben zyla m in o-3-d iben zyla m in o-5-m eth yl-
2 2 2
), 52.0 (CH ), 47.0 (CH ), 23.0
2
3
3
(
2
0
h exa n -1-ol (3c): R
29.6 (c 1.21, CHCl
.24 (m, 15 H), 3.84 (AB syst., J ) 13.4 Hz, 2 H), 3.82 (AB
syst., J ) 13.1 Hz, 2 × 2 H), 3.63-3.58 (m, 1 H), 2.98 (dd, J )
2.5, 6.6 Hz, 1 H), 2.74 (dd, J ) 12.5, 4.6 Hz, 1 H), 2.65-2.58
m, 1 H), 1.97-1.83 (m, 1 H), 1.26-1.22 (m, 2 H), 0.94 (d, J )
.6 Hz, 3 H), 0.92 (d, J ) 6.6 Hz, 3 H); 13C NMR (75 MHz,
CDCl ) δ 140.1 (C), 139.1 (2 C), 129.0 (4 CH), 128.4 (2 CH),
28.3 (4 CH), 128.0 (2 CH), 127.1 (2 CH), 127.0 (CH), 67.2
CH), 63.1 (CH), 54.4 (2 CH ), 54.2 (CH ), 46.3 (CH ), 43.7
), 21.4 (CH ); IR (neat) 3414, 3333,
O: C, 80.73; H, 8.71; N, 6.72.
f
0.30 (hexane/ethyl acetate 1/1); [R]
D
1
-
7
3 3
); H NMR (300 MHz, CDCl ) δ 7.43-
1
(
6
3
1
(
2
2
2
of its configuration, would occur by means of the nucleo-
philic attack of the dibenzylamino group, affording aziri-
dinium salt 9. Then, water from the hydrolysis process
would attack the intermediate compound 9 at C-2, which
would suffer the second inversion of configuration, yield-
ing 1,3-diaminoalkan-2-ols 4.
(CH
2
), 24.8 (CH), 24.0 (CH
3
3
1
102. Anal. Calcd for C28
H
36 2
N
Found: C, 80.56; H, 8.73; N, 6.70.
(
-)-(2R,3S)-2-Allyla m in o-3-d ib en zyla m in o-5-m et h yl-
20
h exa n -1-ol (3d ): R
f
0.12 (hexane/ethyl acetate 1/1); [R]
D
1
-
7
15.8 (c 1.08, CHCl
.22 (m, 10 H), 5.96 (ddt, J ) 17.1, 10.2, 5.7 Hz, 1 H), 5.26
dd, J ) 17.1, 1.7 Hz, 1 H), 5.18 (dd, J ) 10.2, 1.4 Hz, 1 H),
3 3
); H NMR (300 MHz, CDCl ) δ 7.37-
1
However, the aziridinium salts 9 with R ) Me, and
(
the corresponding intermediate 8, could be in an equi-
librium, although displaced in favor of 9, wherefore
compounds 3a ,b were also obtained after hydrolysis.
The total regioselectivity observed in the ring opening
of intermediate aziridinium salt 9 with water could be
explained by means of formation of a hydrogen bond
3.83 (AB syst., J ) 13.2 Hz, 2 × 2 H), 3.65-3.59 (m, 1 H),
3.28-3.25 (m, 2 H), 2.96 (dd, J ) 12.7, 7.0 Hz, 1 H), 2.71 (dd,
J ) 12.7, 4.4 Hz, 1 H), 2.63-2.56 (m, 1 H), 1.96-1.82 (m, 1
1
3
H), 1.25 (t, J ) 6.6 Hz, 2 H), 0.93 (d, J ) 6.6 Hz, 6 H);
NMR (75 MHz, CDCl ) δ 139.1 (2 C), 136.7 (CH), 128.9 (4 CH),
28.3 (4 CH), 127.0 (2 CH), 115.8 (CH ), 67.3 (CH), 63.0 (CH),
4.4 (2 CH ), 52.6 (CH ), 46.4 (CH ), 43.7 (CH ), 24.7 (CH),
4.0 (CH ), 21.4 (CH ); IR (neat) 3414, 3331, 1644, 1103; HRMS
C
3
1
5
2
2
2
2
2
2
between water and a fluorine atom of the BF
3
moiety in
3
3
9
, as shown in Figure 1. Thus, C-2 would be the carbon
24 34 2
calcd for C H N O 366.2671, found 366.2673.
most accessible to the oxygen atom of water, and the
reaction would take place through this carbon.
(-)-(2R,3S)-2-Ben zyla m in o-3-d iben zyla m in o-4-p h en yl-
20
bu ta n -1-ol (3e): R
(
2
f
0.24 (hexane/ethyl acetate 1/1); [R]
); H NMR (300 MHz, CDCl ) δ 7.43-7.22 (m,
0 H), 3.90-3.83 (m, 1 H), 3.84 (AB syst., J ) 13.2 Hz, 2 × 2
H), 3.82 (AB syst., J ) 13.1 Hz, 2 H), 3.07-2.96 (m, 2 H), 2.86
dd, J ) 12.5, 4.8 Hz, 1 H), 2.79-2.73 (m, 1 H), 2.60 (dd, J )
D
-0.5
1
c 0.64, CHCl
3
3
In conclusion, we have achieved the ring opening of
amino aziridines 1 with different regioselectivity, and in
totally stereoselective form, obtaining chiral 2,3-diami-
noalkan-1-ols or 1,3-diaminoalkan-2-ols in high yield. At
present, we are studying ring opening reactions of amino
aziridines 1 with other nucleophiles.
(
1
(
13
4.0, 8.5 Hz, 1 H); C NMR (75 MHz, CDCl
3 C), 129.2 (2 CH), 129.0 (4 CH), 128.3 (6 CH), 128.1 (2 CH),
128.0 (2 CH), 127.0 (3 CH), 126.0 (CH), 70.7 (CH), 61.8 (CH),
3
) δ 139.9 (C), 139.0
5
3
4
4.4 (2 CH
333, 1128; HRMS calcd for C31
50.3138.
2
), 54.1 (CH
2
), 46.3 (CH
2
), 40.8 (CH
2
); IR (neat) 3404,
34 2
H N
O 450.2671, found
Exp er im en ta l Section
Gen er a l P r oced u r e for th e Syn th esis of 2,3-Dia m i-
n oa lk a n -1-ols 3. A solution of the corresponding amino
aziridine 1 (0.2 mmol) and TsOH (0.04 g, 0.2 mmol) in
Gen er a l P r oced u r e for th e Syn th esis of 1,3-Dia m i-
n oa lk a n -2-ols 4. To a stirred solution of the corresponding
amino aziridine 1 (0.2 mmol) in dry acetonitrile (1 mL) under
acetonitrile/H
2
O (1/0.13 mL) was stirred at reflux temperature
nitrogen atmosphere was added BF
3
‚OEt
2
(0.025 mL, 0.2
for 0.5 h. Then, the reaction was hydrolyzed with an aqueous
saturated solution of sodium bicarbonate (5 mL) and extracted
with diethyl ether (3 × 5 mL). The combined organic layers
mmol) at room temperature. After being stirred at reflux
temperature for 1 h, an aqueous saturated solution of sodium
bicarbonate (5 mL) was added and the mixture was stirred at
room temperature for 5 min. Then, the aqueous phase was
extracted with diethyl ether (3 × 5 mL), and the combined
2 4
were dried (Na SO ), filtered, and concentrated in vacuo. Flash
column chromatography (silica gel, dichloromethane:MeOH:
NH 90:1:1) provided pure compound 3. Yields are given in
Table 1.
2 4
organic layers were dried (Na SO ), filtered, and concentrated
3
in vacuo. Flash column chromatography over silica gel (dichlo-
romethane:MeOH:NH 90:1:1) provided pure compounds 4.
(
-)-(2R,3S)-2-Ben zyla m in o-3-(d iben zyla m in o)bu ta n -1-
3
2
0
Yields are given in Table 2.
ol (3a ): R
H NMR (300 MHz, CDCl
f
0.16 (ethyl acetate); [R]
D
3
-43.0 (c 1.08, CHCl );
1
3
) δ 7.46-7.24 (m, 15 H), 3.84 (AB
(+)-(2S,3S)-1-Ben zyla m in o-3-(d iben zyla m in o)bu ta n -2-
2
5
syst., J ) 13.2 Hz, 2 H), 3.83 (AB syst., J ) 13.2 Hz, 2 × 2 H),
.79-3.70 (m, 1 H), 2.98 (dd, J ) 12.5, 6.8 Hz, 1 H), 2.78 (dd,
J ) 12.5, 4.8 Hz, 1 H), 2.66-2.59 (m, 1 H), 1.20 (d, J ) 6.3
ol (4a ): R 90/5/1); [R]
f
) 0.40 (dichloromethane/MeOH/ NH
3
D
1
3
+18.7 (c 0.58, CHCl ); H NMR (300 MHz, CDCl ) δ 7.41-
3
3
7.24 (m, 15 H), 3.78 (AB syst., J ) 13.1 Hz, 2 H), 3.71-3.66
(m, 1 H), 3.62 (AB syst., J ) 13.4, 2 × 2 H), 2.84-2.76 (m, 2
H), 2.46 (dd, J ) 11.8, 7.3 Hz, 1 H), 1.04 (d, J ) 6.6 Hz, 3 H);
1
3
Hz, 3 H); C NMR (75 MHz, CDCl
1
3
) δ 140.1 (C), 139.1 (2 C),
28.9 (4 CH), 128.3 (4 CH), 128.2 (2 CH), 127.9 (2 CH), 127.0
J . Org. Chem, Vol. 68, No. 16, 2003 6409

Concell o´ n and Riego
13C NMR (75 MHz, CDCl
CH), 128.3 (4 CH), 128.1 (2 CH), 127.9 (2 CH), 127.1 (2 CH),
26.6 (CH), 70.4 (CH), 56.0 (CH), 53.9 (CH ), 53.2 (2 CH ), 52.0
); IR (neat) 3387, 3336, 1145. Anal. Calcd for
O: C, 80.17; H, 8.07; N, 7.48. Found: C, 80.30; H,
) δ 140.2 (C), 138.8 (2 C), 128.9 (4
Anal. Calcd for C24
C, 78.80; H, 9.38; N, 7.59.
H
N
O: C, 78.64; H, 9.35; N, 7.64. Found:
3
34
2
1
2
2
(+)-(2S,3S)-1-ben zyla m in o-3-d iben zyla m in o-4-p h en yl-
(CH
2
), 8.1 (CH
3
bu ta n -2-ol (4e): Rf 0.21 (hexane/ethyl acetate 1/1); [R]25
D
C
25
H
30
N
2
+13.2 (c 0.78, CHCl ); H NMR (300 MHz, CDCl ) δ 7.31-
1
3
3
8
.12; N, 7.49.
+)-(2S,3S)-3-Diben zyla m in o-1-(p r op yla m in o)bu ta n -2-
ol (4b): R 0.25 (dichloromethane/MeOH/ NH
90/5/1); [R]25
30.1 (c 0.45, CHCl ); H NMR (300 MHz, CDCl ) δ 7.39-
7.29 (m, 20 H), 3.72 (AB syst., J ) 13.4 Hz, 2 × 2 H), 3.70-
3.65 (m, 1 H), 3.62 (AB syst., J ) 13.1 Hz, 2 H), 3.12 (dd, J )
13.7, 5.1 Hz, 1 H), 3.01-2.93 (m, 1 H), 2.79 (dd, J ) 13.7, 7.7
Hz, 1 H), 2.54 (dd, J ) 12.0, 2.1 Hz, 1 H), 2.43 (dd, J ) 12.0,
(
f
3
D
1
+
7
3
3
.22 (m, 10 H), 3.68 (td, J ) 7.5, 2.1 Hz, 1 H), 3.58 (AB syst.,
7.4 Hz, 1 H); 13C NMR (75 MHz, CDCl ) δ 140.1 (C), 139.4 (2
3
J ) 13.2 Hz, 2 × 2 H), 2.72-2.57 (m, 2 H), 2.56-2.48 (m, 2
C), 139.1 (C), 129.2 (2 CH), 129.0 (4 CH), 128.4 (2 CH), 128.3
(2 CH), 128.2 (4 CH), 128.1 (2 CH), 127.1 (2 CH), 127.0 (CH),
126.0 (CH), 69.6 (CH), 61.7 (CH), 54.4 (2 CH ), 53.5 (CH ), 52.3
H), 2.39 (dd, J ) 11.7, 8.3 Hz, 1 H), 1.56-1.39 (m, 2 H), 1.04
1
3
(
d, J ) 6.8 Hz, 3 H), 0.88 (t, J ) 7.4 Hz, 3 H); C NMR (75
2
2
MHz, CDCl
3
) δ 138.8 (2 C), 128.9 (4 CH), 128.4 (4 CH), 127.1
2 CH), 70.3 (CH), 56.2 (CH), 53.2 (2 CH ), 53.0 (CH ), 51.9
CH ), 23.0 (CH ), 11.6 (CH ), 8.2 (CH ); IR (neat) 3380, 3330,
144; HRMS calcd for C21 O 326.2358, found 326.2369.
+)-(2S,3S)-1-Ben zyla m in o-3-d iben zyla m in o-4-m eth yl-
h exa n -2-ol (4c): R +2.6
0.22 (hexane/ethyl acetate 1/1); [R]25
); H NMR (300 MHz, CDCl ) δ 7.34-7.23 (m,
5 H), 3.78 (AB syst., J ) 13.1 Hz, 2 H), 3.71 (td, J ) 7.4, 2.7
Hz, 1 H), 3.62 (AB syst., J ) 13.4 Hz, 2 × 2 H), 2.74 (dd, J )
1.7, 2.7 Hz, 1 H), 2.73-2.66 (m, 1 H), 2.56 (dd, J ) 11.7, 7.4
Hz, 1 H), 1.73-1.54 (m, 2 H), 1.35-1.26 (m, 1 H), 0.95 (d, J )
.3 Hz, 3 H), 0.94 (d, J ) 6.3 Hz, 3 H); 13C NMR (75 MHz,
CDCl ) δ 139.7 (C), 139.4 (2 C), 128.9 (4 CH), 128.3 (4 CH),
28.2 (2 CH), 128.1 (2 CH), 127.0 (2 CH), 126.8 (CH), 70.5
CH), 58.3 (CH), 54.0 (2 CH ), 53.7 (CH ), 52.4 (CH ), 35.1
CH ), 26.0 (CH), 23.3 (CH ), 22.7 (CH ); IR (neat) 3388, 3330,
144; HRMS calcd for C28 O 416.2828, found 416.2792.
+)-(2S,3S)-1-Allyla m in o-3-d ib en zyla m in o-4-m et h yl-
h exa n -2-ol (4d ): R 0.32 (dichloromethane/ MeOH/NH 90/5/
); H NMR (300 MHz, CDCl ) δ
2 2
(CH ), 31.5 (CH ); IR (neat) 3300, 1133. Anal. Calcd for
C H N O: C, 82.63; H, 7.61; N, 6.22. Found: C, 82.49; H,
31 34 2
(
(
2
2
2
2
3
3
7.67; N, 6.24.
+)-(2S,3S)-1-Ben zyla m in o-3-d iben zyla m in o-4-(ter t-bu -
t yld im et h ylsila n yloxy)b u t a n -2-ol (4f): R 0.43 (dichlo-
+25.8 (c 0.63, CHCl );
) δ 7.34-7.26 (m, 15 H), 3.87-3.80
1
30 2
H N
(
(
f
f
D
25
romethane/MeOH/NH
3
90/5/1); [R]
D
3
1
(c 0.71, CHCl
3
3
1
H NMR (300 MHz, CDCl
3
1
(
m, 3 H), 3.83 (AB syst., J ) 13.2 Hz, 2 × 2 H), 3.74 (AB syst.,
J ) 13.1 Hz, 2 H), 2.88-2.82 (m, 1 H), 2.76 (dd, J ) 12.0, 2.6
1
Hz, 1 H), 2.48 (dd, J ) 12.0, 7.1 Hz, 1 H), 0.95 (s, 9 H), 0.11 (s,
13
3
1
3
H), 0.08 (s, 3 H); C NMR (75 MHz, CDCl ) δ 140.4 (C),
39.3 (2 C), 129.1 (4 CH), 128.3 (4 CH), 128.2 (2 CH), 128.0 (2
6
3
CH), 127.0 (2 CH), 126.6 (CH), 67.0 (CH), 61.2 (CH), 59.5
1
(
CH
2
), 54.6 (2 CH
2
), 53.8 (CH
), -5.8 (CH ); IR (neat) 3422, 3330, 1091; HRMS
Si 504.3172, found 504.31858.
2 2 3
), 52.1 (CH ), 25.8 (3 CH ), 18.0
(
(
2
2
2
(C), -5.6 (CH
3
3
2
3
3
calcd for C31
H
44 2 2
N O
1
36 2
H N
(
Ack n ow led gm en t. We thank the III Plan Regional
de Investigaci o´ n del Principado de Asturias (PB-EXP01-
11) and Ministerio de Ciencia y Tecnolog ´ı a (BQU2001-
3807) for financial support. E.R. thanks the Ministerio
de Ciencia y Tecnolog ´ı a for a predoctoral fellowship.
f
3
2
5
1
1
7
5
); [R]
D
+13.7 (c 0.74, CHCl
3
3
.34-7.22 (m, 10 H), 5.89 (ddt, J ) 17.4, 10.2, 6.0 Hz, 1 H),
.15 (dd, J ) 17.4, 1.7 Hz, 1 H), 5.07 (dd, J ) 10.2, 1.7 Hz, 1
H), 3.68 (AB syst., J ) 13.4 Hz, 2 × 2 H), 3.67 (td, J ) 8.2, 2.6
Hz, 1H), 3.23-3.20 (m, 2 H), 2.68 (dd, J ) 11.7, 2.6 Hz, 1 H),
2
1
.63-2.57 (m, 1 H), 2.46 (dd, J ) 11.7, 8.2 Hz, 1 H), 1.72-
.54 (m, 2 H), 1.33-1.24 (m, 1 H), 0.94 (d, J ) 6.3 Hz, 6 H);
C NMR (75 MHz, CDCl
Su p p or tin g In for m a tion Ava ila ble: Spectroscopy data
for compounds 7 and copies of C NMR spectra for compounds
13
1
3
3
) δ 139.3 (2 C), 136.6 (CH), 128.9 (4
), 70.6 (CH), 58.6
), 35.2 (CH ), 26.1
); IR (neat) 3388, 3321, 1643, 1145.
3
, 4, and 7a . This material is available free of charge via the
CH), 128.3 (4 CH), 127.0 (2 CH), 115.6 (CH
2
Internet at http://pubs.acs.org.
(CH), 53.9 (2 CH
2
), 52.6 (CH
2
), 52.3 (CH
2
2
(CH), 23.3 (CH ), 22.8 (CH
3
3
J O034440V
6
410 J . Org. Chem., Vol. 68, No. 16, 2003