Regioselective and reductive cleavage of allyl ethers by NaBH 4-HOAc

Article abstract of DOI:10.1016/j.tet.2013.03.020

β-Enaminals were successfully synthesized in good to excellent yields by the reaction of C2-formylglycals with primary amines. Subsequent reaction with NaBH₄ in HOAc led to unexpected reductive cleavage of allyl ether, i.e., the hydrodealkoxylation took place to produce the corresponding 3-deoxy-β-enaminals. In contrast, the reaction of β-enaminals with Zn/HOAc performed H4-elimination to afford a diene product. The result was attributed to the formation of a common eneiminium ion intermediate, and the different reduction reactivity.

Full text of DOI:10.1016/j.tet.2013.03.020

Tetrahedron 69 (2013) 3991e3999
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Regioselective and reductive cleavage of allyl ethers by
NaBH4eHOAc
Zi-Ping Lin a, Fung Fuh Wong a, Yen-Bo Chen a, Chun-Hung Lin b, Min-Tsang Hsieh c,
,
Jin-Cherng Lien a, Yin-Hsuan Chou a, Hui-Chang Lin a
*
a Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan
b Institute of Biological Chemistry, Academia Sinica, No. 128, Academia Road, Section 2, Nan-Kang, Taipei 11529, Taiwan
c Chinese Medicinal Research and Development Center, China Medical University Hospital, No. 2, Yude Rd., Taichung 40447, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
b
-Enaminals were successfully synthesized in good to excellent yields by the reaction of C2-formylglycals
with primary amines. Subsequent reaction with NaBH4 in HOAc led to unexpected reductive cleavage of
allyl ether, i.e., the hydrodealkoxylation took place to produce the corresponding 3-deoxy- -enaminals.
In contrast, the reaction of -enaminals with Zn/HOAc performed H4-elimination to afford a diene
Received 29 November 2012
Received in revised form 20 February 2013
Accepted 5 March 2013
b
b
Available online 15 March 2013
product. The result was attributed to the formation of a common eneiminium ion intermediate, and the
different reduction reactivity.
Keywords:
Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
b
-Enaminal
Reductive cleavage
Sodium borohydride
Regioselectivity
Formylglycal
1. Introduction
molecules,3e9 including pyrrole,2 pyridine,3 pyrazole,4 isoxazole,5
isothiazole,6 benzo[g]quinoline,7 benzo[f]quinoline,7 and quinoline.8
b-Enaminals are enamines that are conjugated with aldehyde.
Several methods were developed previously to prepare b-
They have been shown to be useful in synthetic chemistry.
For example, (E)-(3R,4R,5R)-1-benzylanimo-2-formyl-5-hydroxy-
3,4,6-tri-O-benzyl-hex-1-ene (compound 9) can be protected and
reduced to give compound 1 that served as a key precursor in the
enaminal, such as the condensation reaction of malondialdehyde
with amine,7 the hydrolysis of 2-methyl-1-phenylamino-3-
phenylimino-1-propene,8 the pyrolysis of Meldrum’s acid de-
rivatives,9 Michael addition of -ethoxyacrolein and p-toluidine,10
b
synthesis of noeuromycin 2, a potent inhibitor of
dases discovered by Bols and co-workers1 (see Fig. 1). As a matter of
fact, -enaminals are versatile synthetic building blocks and have
been extensively investigated for preparation of various important
a
- and
b
-glucosi-
the condensation reaction of malondialdehyde and amino acid
derivatives,11 the iodotrichlorosilane-induced reactions of aromatic
aldehydes with acrylonitrile,12 and the amination of propargyl al-
dehyde.13 To the best of our knowledge, there is no report to derive
b
Bn
OH
H
OH
OH OR
OH OBn N
H
HO
N
BnO
HO
NH
OH
R
OH
OH
OBn CHO
9
1
noeuromycin (2)
Fig. 1. Enamine 9 serves as a key intermediate in the synthesis of noeuromycin (2).
from C-2-formylglycal. Herein we reported one-step conversion
from C2-formylglycals to -enaminals. Interestingly further treat-
ment of -enaminals with NaBH4 in HOAc or Zn/HOAc did not re-
duce the double bond or aldehyde. Instead, regioselective reduction
b
b
* Corresponding author. Tel.: þ886 4 22053366x5612; fax: þ886 4 22078083;
e-mail addresses: lhc550005@yahoo.com.tw, huichang@mail.cmu.edu.tw (H.-C. Lin).
0040-4020/$ e see front matter Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.03.020

3992
Z.-P. Lin et al. / Tetrahedron 69 (2013) 3991e3999
was observed to remove the allyl ether to generate a common
eneiminium ion intermediate, followed by either reduction or H4-
spectrum,
enaminal 9, respectively.
d 158.9 and 110.0 were assigned to C1 and C2 of b-
elimination to produce the corresponding 3-deoxy-
dienes, respectively.
b
-enaminals or
Originally our plan was to reduce the double bond or/and
the aldehyde. Palmieri and co-workers16 successfully reduced
b
-enamino ketones to
our surprise, the same reaction turned out to be a different outcome
in our hand. Rather than obtain the expected -amino alcohol 18,
N-octyl-3-deoxy- -enaminal 19 was found to be the resulting
g-amino alcohol by using NaBH4 in HOAc. To
2. Results and discussion
g
b
C-2-Formylglycals 3e6 that had been prepared by Vils-
meiereHaack reactions14 of
D-glucals or D-galactals were subjected
product, as shown in Scheme 1. Apparently the borohydride func-
tioned to result in the reductive cleavage of allyl ether. To search for
the optimal conditions, several organic solvents were studied, in-
cluding CH2Cl2, THF, MeOH, acetonitrile (MeCN), and HOAc (entries
1e5 of Table 2). Except for HOAc, no reaction was found in these
organic solvents. The result supported the idea that acidic condition
is critical to the reductive cleavage. Our focus was then shifted to
to Michael addition15 with 1.1 equiv of primary amines (including
benzylamine, n-butylamine, and n-octylamine) in MeOH for
10 min. The products, b-enaminals 7e17, were obtained in 87e95%
with high selectivity (ratio of E/Z-isomers: 85:15w93:7, Table 1).
The major products were determined as the (E)-isomers according
to the resonance of the enamine hydrogen (NH). The chemical shift
the use of borohydride. (E)-(3R,4R,5R)-b-Enaminal 7 in HOAc was
of the (Z)-isomer (
isomer ( 7.15) because only the former isomer is able to form the
intramolecular hydrogen bonding between the NH and the car-
d 10.5) was more downfield than that of (E)-
treated with 1.0 equiv of NaBH4, NaCNBH3 or Na(OAc)3BH at room
temperature for 10 min (see entries 5e7 of Table 2). The use of
NaBH4 gave the highest isolated yield of product 19 (90%).
d
bonyl oxygen. The structures of (E)-b-enaminals were additionally
characterized by 1H and 13C NMR, DEPT, COSY and other spectro-
Reductive cleavage of allylic oxygen-containing functional
groups was widely used in organic synthesis,17e32 including allyl
ether,17e25 allyl ester,26e29 allyl alcohol,30,31 or allyl carbonate.32
A number of catalytic reagents were investigated, such as PdeC/
HCO2NH4,17 Pd(dppe)Cl2/LiBHEt3,18 CeCl3$7H2OeNaI,19 NaBH4/I2,20
Pd(PPh3)4/NaBH4,21 polymethylhydrosiloxaneeZnCl2/Pd(PPh3)4,22
SmI2/H2O/amine,23 NaBH4/RuCl3,24 NaBH4/NiCl2/MeOH,25 Pd(0)/
Ph2SiH2/ZnCl2,26 FeCl3$6H2O,27 Ti(O-i-Pr)4/TMSCl/Mg or Ti(O-i-
Pr)4/MgBr2/Mg,28 PdCl2,29 Et3SiH/TFA,30 H3[PW12O40]$nH2O/
Et3SiH,31 and Pd2(dba)3/Bu3P.32 Nevertheless, a few methods were
scopic methods. For example, compound 9 possessed a character-
istic broad resonance at
d 7.15 in correspondence with the amino
proton, and a doublet resonance at
d
6.88 (J¼13.6 Hz) that corre-
lates with the alkene proton at C1. In the corresponding 13C NMR
Table 1
The Michael addition of C-2-formylglycals 3e6 with primary amines
R4
O
R2
R3 NHR5
R1
HO
H
R1
R3
R5NH2 (1.1 equiv)
reported to reductively cleave allyl ethers from
b-enamino carbonyl
R4
compounds.30a,34
MeOH
rt, 10'
87-95 %
R2
Furthermore, seven (E)-(3R,4R,5R)-b-enaminals (8e14) were
CHO
7-17
O
3-6
H
examined under the same condition. Exclusive regioselectivity was
observed, i.e., the 3-alkoxy ether was reductively removed to give
the desired products (20e26) in 87e94% yields (see Table 3). The
Product Compounds 7e17a
product structures were rigorously determined by using 1H and 13
C
Substrate Compounds 3e6
R1
R2
R3
R4
R5
Yields (%) (E/Z)b
NMR, DEPT, COSY and other spectroscopic methods. For example,
the 1H NMR spectrum of N-benzyl-1,2,3-trideoxy-
-enaminal (21)
showed the characteristic signals, including the resonances of the
NH at 6.74e6.68 (m), H3a at 2.28 (dd), and H3b at 2.50 (dd). In
the corresponding 13C NMR spectrum,
160.2, 110.8, and 24.2 were
assigned for C1eC3 of 21, respectively.
Meanwhile, (E/Z)-(3R,4S,5R)- -enaminals 15e17 (that are
b
3
3
3
4
4
5
5
5
6
6
6
OBn
OBn
OBn
OMe
OMe
OPent
OPent
OPent
H
H
H
H
H
H
H
H
H
OBn
OBn
OBn
OMe
OMe
OBn
OBn
OBn
OMe
OMe
7
8
9
10
11
n-Oct 87
n-Bu 95
89:11
91:9
93:7
90:10
93:7
91:9
90:10
92:8
87:13
85:15
88:12
Bn
n-Oct 91
Bn 91
91
d
d
d
d
OPent OPent 12
OPent OPent 13
OPent OPent 14
n-Oct 93
n-Bu 92
b
Bn
90
4-epimers of compounds 7e9, respectively) were examined under
the same reaction condition (i.e., the treatment with NaBH4 in
HOAc at room temperature for 10 min). In addition to the desirable
3-deoxy products 27e29 in 72e85% yields (Table 4), we observed
the formation of the diene side products 30e32 in 5e22% yields,
respectively, which is realized to occur via H4-elimination.
OBn OBn
OBn OBn
OBn OBn
OBn
OBn
OBn
15
16
17
n-Oct 87
n-Bu 90
H
H
Bn
91
a
The reactions were carried out with primary amines.
b
The E-isomer is the major product. The ratio of E/Z-isomers (in the range of
85:15w93:7) was determined by 1H NMR integration.
H
n-Oct
n-Oct
H
(1.0 equiv)
NaBH4
OH OBn N
OH
N
BnO
BnO
BnO
HOAc
rt, 10 min
OBn CHO
7
OBn CHO
19
H
n-Oct
OH OBn N
(x)
OBn CH2OH
18
Scheme 1.

Z.-P. Lin et al. / Tetrahedron 69 (2013) 3991e3999
3993
Table 2
Interestingly the dienes 30e32 became the sole products in
92e94% yields if the reactions occurred in the presence of HOAc
Different solvents used in the regioselective hydrodebenzyloxylationsa
Entry
Solvent
Reducing agent
Yield of 19b (%)
only and the reaction time (of
b-enaminals 7e9 or 15e17) was
prolonged from the original 10 min to 1.5 or 4 h (Scheme 2).
Compounds 30e32 were further acetylated to produce 33e35 in all
95% yields, respectively, for the purpose of easy product
characterization.
A plausible mechanism is proposed to explain the regiose-
lectivity (Scheme 3). In the initial stage, the nitrogen of the enamine
moiety is expected to be protonated under acidic condition. The
proton likely translocates to the oxygen of the C3-benzyl ether via
[1,5]-shift, in concert with C3-debenzyloxylation and the formation
of eneiminium ion (i.e., compound 38 is the intermediate). The
intermediate can be subjected to either reduction by NaBH4 to
1
2
3
4
5
6
7
MeOH
CH2Cl2
THF
MeCN
HOAc
HOAc
HOAc
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
NaCNBH3
Na(OAc)3BH
0
0
0
0
90
88
11
a
The reactions were the same as shown in Scheme 1 except that different
solvents and borohydrides were examined here.
b
Isolated yields.
Table 3
Regioselective hydrodealkoxylations of b-enaminals 8.e14
produce 3-deoxy-b-enaminals (29), or H4-elimination to afford the
OH R2 NHR4
NHR4
diene product (32). Apparently, the former reaction is favored in
the competition. It is interesting that under the same condition
only the reduction products were obtained in the reactions of b-
enaminals 7e14 (see Table 3).
OH
R3
NaBH4 (1.0 eq.)
R3
R1
R1
HOAc
rt, 10'
87-94%
CHO
CHO
Watson and co-workers were able to reduce the CeC double
bond of
-enamino ketones by using Zn/HOAc.33 The procedure was
utilized to reduce the -enaminal 8, but the desirable product (39)
did not form, neither did 3-deoxy- -enaminal (19). Instead, a diene
8-14
20-26
b
b
Substrate
Compounds 8e14
Compounds 20e26a,b
b
R1
R2
R3
R4
Product
Yields (%)
product (31) was obtained in 82% yield after 4 h reaction at room
temperature. When compound 19 was subjected to the same
treatment (Zn/HOAc at room temperature), a cyclized/eliminated
product (41) was obtained in 50% yield, plus 45% unreacted starting
material. Together with the aforementioned studies with NaBH4 in
HOAc, our results supported the idea that the two reactions (NaBH4
in HOAc and Zn/HOAc) likely occur via the same initial stage to give
a common intermediate, i.e., the protonation and subsequent proton
translocation leading to formation of an eneiminium ion (as shown
8
9
OBn
OBn
OBn
OBn
n-Bu
Bn
20
21
22
23
24
25
26
89
90
87
87
94
88
92
OBn
OBn
10
11
12
13
14
OMe
OMe
OPent
OPent
OPent
OMe
OMe
OPent
OPent
OPent
OMe
OMe
OPent
OPent
Opent
n-Oct
Bn
n-Oct
n-Bu
Bn
a
Isolated yields.
All the products were determined to be (E)-isomers.
b
Table 4
Regioselective hydrodebenzyloxylation of b-enaminals 15e17
OBn NHR
OH
NHR
OH
OH
NHR
NaBH4 (1.0 eq.)
HOAc
BnO
4
1
BnO
BnO
+
3
2
5
6
rt, 10'
CHO
OBn CHO
30-32
CHO
OBn
15-17
OBn
27-29
Substrate
Compounds 15e17
Reduction product
Yieldsa,b (%)
Elimination product
Yieldsa (%)
R
15
16
17
n-Oct
n-Bu
Bn
27 (75)
28 (72)
29 (85)
30 (19)
31 (22)
32 (5)
a
Isolated yields.
b
The reduction products were determined to be all (E)-isomers.
Ac
R
OAc
N
OH OBn NH2R
OH
NHR
Ac2O
BnO
HOAc
rt, 4 h
BnO
BnO
BnO
pyridine
OBn CHO
OBn CHO
OBn CHO
33 R = n-Oct (95%)
34 R = n-Bu (95%)
35 R = Bn (95%)
7 R = n-Oct
8 R = n-Bu
9 R = Bn
30 R = n-Oct (94%)
31 R = n-Bu (90%)
32 R = Bn (92%)
OH OBn NH2R
OH
NHR
HOAc
rt, 1.5 h
BnO
OBn CHO
OBn CHO
15 R = n-Oct
16 R = n-Bu
17 R = Bn
30 R = n-Oct (94%)
31 R = n-Bu (90%)
32 R = Bn (92%)
Scheme 2.

3994
Z.-P. Lin et al. / Tetrahedron 69 (2013) 3991e3999
Mechanism:
OH
NHBn
OH
NHBn
OBn NHBn
OH
NaBH4
HOAc
BnO
BnO
BnO
+
H4
BnO
OBn CHO
(major)
OBn CHO
CHO
(minor)
17
29
32
HOAc
NaBH4
Bn
H
N
H
Bn
H
Bn
N
OH
O
HO
BnO
BnO
H4-elimination
H4
BnO
CHO
H4
BnO
CHO
36
38
proton
[1,5]-shift
HOBn
Bn
H
O
NHBn
HO
BnO
H4
BnO
CHO
37
Scheme 3.
in Scheme 3). Nevertheless, the reducing power of Zn is lower than
that of borohydride, which explains the reason why the reduction is
much slower than H4-elimination in the reaction of Zn/HOAc. The
elimination thus became exclusive to give a diene product. More-
Likewise, other 3-deoxy-
derwent the same intramolecular cyclization/elimination to gener-
ate 3-deoxy-C-2-formylglycals 41e43 in 95e97% yields (Table 5).
In conclusion, in addition to preparing
addition of C2-formylglycal with primary amines, we discovered
the unprecedented reduction of -enaminals by using NaBH4/
HOAc, i.e., C3-allyl ether was removed. The formation of enei-
minium ion intermediate was thus proposed, which also
explained the different outcome of the Zn/HOAc reaction. The
b
-enaminals (19e23 and 27e29) all un-
b-enaminals by Michael
over, when 3-deoxy-b-enaminal 19 reacted with Zn/HOAc, the
intramolecular cyclization appeared to be predominant as compared
to any possible reaction. Even in the absence of Zn, the reaction of 19
still resulted in the same product (41) in 55% yield at room tem-
perature for 24 h, and in 96% at 80 ꢀC for 20 min (Scheme 4).
b
n-Bu
H
n-Bu
H
n-Bu
H
N
OH
OBn N
OH
OBn N
OH
Zn/HOAc
rt, 4 h
82%
BnO
BnO
BnO
BnO
BnO
(X)
OBn
CHO
OBn
CHO
OBn
CHO
8
31
39
H
N
n-Oct
OBn
O
H
OH
Zn/HOAc
rt, 24h
+
19 (45%)
CHO
OBn
H
n-Oct
O
H
N
HO
H
19
BnO
41 (50%)
(X)
OBnCHO
H
40
HOAc
41
19
80 oC
20 min
96%
Scheme 4.

Z.-P. Lin et al. / Tetrahedron 69 (2013) 3991e3999
3995
Table 5
(1H, s, CHO), 7.28e7.10 (15H, m, ArH), 6.79e6.77 (1H, m, NH), 6.74
(1H, d, J1,NH¼14.0 Hz, H1), 4.96 (1H, d, J3,4¼2.4 Hz, H3), 4.49 (1H, d,
Ja,b¼11.2 Hz, CH2Ph), 4.46 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 4.43 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.36 (1H, d, Ja,b¼11.2 Hz, CH2Ph), 4.29 (1H, d,
Ja,b¼11.2 Hz, CH2Ph), 4.25 (1H, d, Ja,b¼11.2 Hz, CH2Ph), 4.03 (1H, br s,
H5), 3.60 (1H, dd, J4,3¼2.4 Hz, J4,5¼7.2 Hz, H4), 3.57e3.55 (2H, m,
H6), 2.87e2.77 (3H, m, H10, OH), 1.21e1.04 (12H, m, H20, H30, H40,
H50, H60, H70), 0.80 (3H, t, J¼6.8 Hz, H80); 13C NMR (CDCl3, 100 MHz)
3-Deoxy-C-2-formylglycals obtained via consecutive cyclization and elimination of
3-deoxy-enaminals
R3
R2
NHR4
HO
H
O
R3
R1
HOAc
80 oC, 20'
95-97%
R1
R2
CHO
O
H
d
187.55, 159.31, 138.15, 137.87, 137.55, 128.35, 128.34, 128.30, 128.29,
19-23, 27-29
41-43
128.22, 128.21, 128.14, 128.13, 127.95, 127.94, 127.90, 127.89, 127.80,
127.67, 127.59, 108.96, 81.89, 74.60, 74.29, 73.38, 71.16, 71.15, 70.18,
49.22, 31.69, 30.58, 29.02, 29.01, 26.41, 22.56, 14.06; LRMS (FAB) m/z
(rel intens) 574 (Mþþ1, 2), 302 (28), 210 (19), 91 (100), 54 (22);
HRMS (FAB) m/z calcd for C36H48NO5 (Mþþ1) 574.3527, found
574.3525. Anal. Calcd for C36H47NO5; C: 75.36; H: 8.26. Found: C:
75.38; H: 8.30.
Substrate
Compounds 19e23, 27e29
Compounds 41e43a
R1
R2
R3
R4
Product
Yields (%)
19
20
21
22
23
27
28
29
OBn
OBn
OBn
OMe
OMe
H
H
H
H
H
OBn
OBn
OBn
OMe
OMe
OBn
OBn
OBn
n-Oct
n-Bu
Bn
n-Oct
Bn
n-Oct
n-Bu
Bn
41
41
41
42
42
43
43
43
96
95
97
95
96
97
96
97
H
OBn
OBn
OBn
3.2.2. (E)-(3R,4R,5R)-1-n-Butylamino-2-formyl-5-hydroxy-3,4,6-tri-
O-benzyl-hex-1-ene (8). Pale yellow solid; mp 78e79 ꢀC; IR (CHCl3)
H
H
2926, 1616, 1595, 1211, 1062 cmꢂ1; 1H NMR (CDCl3, 400 MHz)
d 8.92
a
Isolated yields.
(1H, s, CHO), 7.32e7.16 (15H, m, ArH), 6.78 (2H, br s, NH, H1), 5.02
(1H, d, J3,4¼2.0 Hz, H3), 4.55 (1H, d, Ja,b¼11.2 Hz, CH2Ph), 4.52 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.48 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 4.42 (1H, d,
Ja,b¼11.2 Hz, CH2Ph), 4.35 (1H, d, Ja,b¼11.2 Hz, CH2Ph), 4.31 (1H, d,
Ja,b¼11.2 Hz, CH2Ph), 4.08 (1H, br s, H5), 3.65 (1H, dd, J4,3¼2.0 Hz,
J4,5¼7.2 Hz, H4), 3.63e3.61 (2H, m, H6), 2.89e2.86 (2H, m, H10),
1.24e1.10 (4H, m, H20, H30), 0.76 (3H, t, J¼7.2 Hz, H40); 13C NMR
treatment of
product.
b-enaminals with Zn/HOAc generated a diene
3. Experimental section
3.1. General procedure
(CDCl3, 100 MHz)
d 187.55, 159.25, 138.29, 137.98, 137.65, 128.38,
128.37, 128.34, 128.33, 128.27, 128.26, 128.18, 128.17, 127.98, 127.97,
127.92, 127.91, 127.83, 127.69, 127.61, 109.19, 82.05, 74.78, 74.33,
73.45, 71.31, 71.26, 70.34, 48.89, 32.62, 19.60, 13.51; LRMS (FAB) m/z
(rel intens) 518 (Mþþ1, 11), 246 (67), 154 (38), 136 (13), 91 (100);
HRMS (FAB) m/z calcd for C32H40NO5 (Mþþ1) 518.2901, found
518.2918. Anal. Calcd for C32H39NO5; C: 74.25; H: 7.59. Found: C:
74.31; H: 7.64.
All purchased chemicals were of reagent grade. All reactions
were carried out under a nitrogen atmosphere and monitored by
TLC analysis (layer thickness: 250 mm). Column chromatography
was carried out with silica gel 60 (70e230 mesh for gravity column,
or 230e400 mesh for flash column). Commercially available re-
agents were directly used without further purification unless oth-
erwise noted. Dichloromethane, ethyl acetate, hexanes, and
methanol were purchased from Mallinckrodt Chemical Co. The
following compounds were purchased from Acros Chemical Co,
including benzylamine, n-butylamine, n-octylamine, tri-O-acetyl-
3.2.3. (E)-(3R,4R,5R)-1-Benzylamino-2-formyl-5-hydroxy-3,4,6-tri-O-
benzyl-hex-1-ene (9). Pale yellow oil; IR (CHCl3) 2924, 1676, 1598,
1207, 1064 cmꢂ1 1H NMR (CDCl3, 400 MHz)
; d 8.93 (1H, s, CHO),
7.31e6.99 (21H, m, ArH, NH), 6.88 (1H, d, J1,NH¼13.6 Hz, H1), 5.01
(1H, br s, H3), 4.54 (1H, d, Ja,b¼11.2 Hz, CH2Ph), 4.50 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.46 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 4.40 (1H, d,
Ja,b¼11.2 Hz, CH2Ph), 4.30 (1H, d, Ja,b¼11.2 Hz, CH2Ph), 4.24 (1H, d,
Ja,b¼11.2 Hz, CH2Ph), 4.06e4.00 (2H, m, H5, CH2Ph), 3.90 (1H, dd,
J¼4.0 Hz, Ja,b¼14.8 Hz, CH2Ph), 3.65 (1H, dd, J4,3¼1.2 Hz, J4,5¼6.8 Hz,
H4), 3.60e3.59 (2H, m, H6), 2.91 (1H, br s, OH); 13C NMR (CDCl3,
D-glucal, tri-O-acetyl-D-galactal, benzyl bromide, methyl iodide, n-
pentyl iodide, phosphoryl chloride, sodium borohydride, sodium
cyanoborohydride, sodium triacetoxyborohydride, tetrahydrofu-
ran, dichloromethane, acetonitrile, acetic acid, methanol. Proton
NMR spectra were recorded at a Bruker spectrometer (400 or
500 MHz) with CDCl3 (dH 7.24) and DMSO-d6 (dH 2.50) as the in-
ternal standard; 13C NMR spectra were recorded at 100 or 125 MHz
with CDCl3 [dC 77.0 (central line of a triplet)]. Splitting patterns are
shown by the abbreviations, such as s (singlet), d (doublet), t
(triplet), q (quartet), and m (multiplet).
50 MHz)
d 187.89, 158.91, 138.21, 137.89, 137.34, 137.00, 128.81,
128.80, 128.37, 128.36, 128.35, 128.34, 128.33, 128.32, 128.31, 128.01,
128.00, 127.91, 127.90, 127.89, 127.75, 127.74, 127.67, 127.66, 127.38,
127.37, 110.06, 82.01, 74.77, 74.33, 73.40, 71.43, 71.20, 70.18, 52.70;
LRMS (FAB) m/z (rel intens) 552 (Mþþ1, 4), 136 (10), 105 (14), 91
(100); HRMS (FAB) m/z calcd for C35H38NO5 (Mþþ1) 552.2744, found
552.2760. Anal. Calcd for C35H37NO5; C: 76.20; H: 6.76. Found: C:
76.23; H: 6.84.
3.2. Standard procedure for Michael addition of C-2-
formylglycals to prepare b-enaminal derivatives (7e17)
To a solution of C-2-formylglycals (3e6) (1.0 equiv) in MeOH
(2 mL) was added primary amine (1.0 equiv). The resulting solution
was stirred at room temperature for 10 min, concentrated under
reduced pressure, and re-dissolved in CH2Cl2 (50 mL). The solution
was washed with H2O (20 mLꢁ2), brine (20 mLꢁ2), and concen-
trated under reduced pressure. The dry residue was purified by
3.2.4. (E)-(3R,4R,5R)-2-Formyl-5-hydroxy-1-n-octylamino-3,4,6-tri-
O-methyl-hex-1-ene (10). Pale yellow oil; 1H NMR (CDCl3,
500 MHz) d 8.87 (1H, s, CHO), 6.87e6.79 (2H, m, H1, NH), 4.67 (1H,
d, J3,4¼2.0 Hz, H3), 3.89e3.86 (1H, m, H5), 3.49e3.47 (2H, m, H6),
3.33 (3H, s, OCH3), 3.31 (3H, s, OCH3), 3.22 (1H, dd, J4,3¼2.0 Hz,
J4,5¼7.0 Hz, H4), 3.19e3.14 (6H, m, OCH3, OH, H10),1.53e1.47 (2H, m,
H20),1.30e1.16 (10H, m, H30, H40, H50, H60, H70), 0.81 (3H, t, J¼6.5 Hz,
silica gel column chromatography with EtOAc/Hex (7:10) to give b-
enaminals (7e17) in 80e96% yields.
H80); 13C NMR (CDCl3, 125 MHz)
d 187.80, 159.13, 109.05, 83.88,
3.2.1. (E)-(3R,4R,5R)-2-Formyl-5-hydroxy-1-n-octylamino-3,4,6-tri-
76.17, 73.64, 69.93, 59.92, 58.99, 56.61, 49.43, 31.68, 31.21, 29.11,
29.10, 26.39, 22.55, 14.00; LRMS (EI) m/z (rel intens) 345 (Mþ, 1),
266 (13), 250 (33), 226 (100), 208 (19); HRMS (EI) m/z calcd for
O-benzyl-hex-1-ene (7). Pale yellow solid; mp 62e63 ꢀC; IR (CHCl3)
2926, 1651, 1597, 1207, 1064 cmꢂ1; 1H NMR (CDCl3, 400 MHz)
d 8.85

3996
Z.-P. Lin et al. / Tetrahedron 69 (2013) 3991e3999
C18H35NO5 (Mþ) 345.2515, found 345.2522. Anal. Calcd for
C18H35NO5; C: 62.58; H: 10.21. Found: C: 62.63; H: 10.24.
Ja,b¼11.0 Hz, CH2Ph), 4.60 (1H, d, Ja,b¼11.0 Hz, CH2Ph), 4.44 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.40 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 4.35 (1H, d,
Ja,b¼11.0 Hz, CH2Ph), 4.28 (1H, d, Ja,b¼11.0 Hz, CH2Ph), 3.84 (1H, dd,
J4,3¼4.5 Hz, J4,5¼4.5 Hz, H4), 3.70 (1H, br s, H5), 3.49e3.45 (2H, m,
H6), 2.89e2.85 (2H, m, H10), 1.23e1.02 (12H, m, H20, H30, H40, H50,
H60, H70), 0.81 (3H, t, J¼7.0 Hz, H80); 13C NMR (CDCl3, 125 MHz)
3.2.5. (E)-(3R,4R,5R)-1-Benzylamino-2-formyl-5-hydroxy-3,4,6-tri-O-
methyl-hex-1-ene (11). Pale yellow solid; mp 105e106 ꢀC; IR (CHCl3)
2931, 1651, 1593, 1211, 1089 cmꢂ1; 1H NMR (CDCl3, 400 MHz)
d 8.91
(1H, s, CHO), 7.32e7.20 (6H, m, ArH, NH), 6.93 (1H, d, J1,NH¼13.6 Hz,
H1), 4.68 (1H, br s, H3), 4.36 (2H, d, J¼6.4 Hz, CH2Ph), 3.89e3.86 (1H,
m, H5), 3.49e3.44 (2H, m, H6), 3.32 (3H, s, OCH3), 3.23e3.18 (7H, m,
d 187.97, 159.52, 138.18, 138.17, 138.09, 128.55, 128.54, 128.38, 128.37,
128.36, 128.32, 128.31, 128.30, 127.85, 127.84, 127.83, 127.73, 127.72,
127.62, 127.58, 108.03, 81.63, 74.83, 74.51, 73.36, 71.08, 71.03, 70.71,
49.50, 31.72, 30.61, 29.07, 29.05, 26.36, 22.58, 14.04; LRMS (EI) m/z
(rel intens) 573 (Mþ, 1), 326 (10), 224 (30), 108 (42), 91 (100); HRMS
(EI) m/z calcd for C36H47NO5 (Mþ) 573.3454, found 573.3448. Anal.
Calcd for C36H47NO5; C: 75.36; H: 8.26. Found: C: 75.38; H: 8.27.
H4, OCH3); 13C NMR (CDCl3, 100 MHz)
d 188.15, 158.92, 137.51,
128.82, 128.81, 127.93, 127.17, 127.16, 109.88, 83.63, 76.14, 73.53,
69.71, 59.79, 58.95, 56.69, 52.99; LRMS (FAB) m/z (rel intens) 324
(Mþþ1, 25), 292 (38), 218 (36), 204 (82), 91 (100); HRMS (FAB) m/z
calcd for C17H26NO5 (Mþþ1) 324.1805, found 324.1798. Anal. Calcd
for C17H25NO5; C: 63.14; H: 7.79. Found: C: 63.18; H: 7.85.
3.2.10. (E)-(3R,4S,5R)-1-n-Butylamino-2-formyl-5-hydroxy-3,4,6-tri-
O-benzyl-hex-1-ene (16). Pale yellow oil; IR (CHCl3) 2927, 1613,1597,
3.2.6. (E)-(3R,4R,5R)-2-Formyl-5-hydroxy-1-n-octylamino-3,4,6-tri-
1213, 1061 cmꢂ1 1H NMR (CDCl3, 500 MHz)
; d 8.84 (1H, s, CHO),
O-pentyl-hex-1-ene (12). Pale yellow oil; IR (CHCl3) 2927,1656,1606,
7.34e7.16 (15H, m, ArH), 7.05e7.01 (1H, m, NH), 6.73 (1H, d,
J1,NH¼14.0 Hz, H1), 4.89 (1H, d, J3,4¼3.5 Hz, H3), 4.64 (1H, d,
Ja,b¼11.0 Hz, CH2Ph), 4.60 (1H, d, Ja,b¼11.0 Hz, CH2Ph), 4.44 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.40 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 4.35 (1H, d,
Ja,b¼11.5 Hz, CH2Ph), 4.29 (1H, d, Ja,b¼11.5 Hz, CH2Ph), 3.84 (1H, dd,
J4,3¼4.5 Hz, J4,5¼4.5 Hz, H4), 3.71e3.68 (1H, m, H5), 3.49e3.45 (2H,
m, H6), 2.90e2.86 (2H, m, H10), 1.13e1.03 (4H, m, H20, H30), 0.72 (3H,
1222, 1089 cmꢂ1 1H NMR (CDCl3, 500 MHz)
; d 8.83 (1H, s, CHO),
6.94e6.91 (1H, m, NH), 6.77 (1H, d, J1,NH¼13.5 Hz, H1), 4.76 (1H, br s,
H3), 3.89 (1H, br s, H5), 3.50 (2H, br s, H6), 3.44e3.04 (9H, m, OCH2,
H4, H10), 2.91 (1H, d, J¼7.0 Hz, OH), 1.51e1.37 (8H, m, CH2, H20),
1.24e1.21 (22H, m, CH2, H30, H40, H50, H60, H70), 0.81e0.80 (12H, m,
CH3); 13C NMR (CDCl3,125 MHz)
d 187.61,159.24,110.05, 82.19, 75.07,
72.66, 71.80, 71.53, 70.22, 69.54, 49.33, 31.73, 31.10, 30.02, 29.49,
29.32, 29.18, 29.14, 28.39, 28.30, 28.21, 26.57, 22.57, 22.54, 22.51,
22.48, 13.98, 13.97, 13.96, 13.95; LRMS (EI) m/z (rel intens) 513 (Mþ,
1), 306 (82), 282 (80), 224 (51), 196 (62), 71 (100); HRMS (EI) m/z
calcd for C30H59NO5 (Mþ) 513.4393, found 513.4399. Anal. Calcd for
C30H59NO5; C: 70.13; H: 11.57. Found: C: 70.14; H: 11.59.
t, J¼7.0 Hz, H40); 13C NMR (CDCl3, 125 MHz)
d 187.97, 159.55, 138.18,
138.16, 138.08, 128.56, 128.55, 128.38, 128.37, 128.36, 128.31, 128.30,
128.29, 127.88, 127.83, 127.82, 127.76, 127.75, 127.62, 127.58, 108.07,
81.62, 74.84, 74.15, 73.35, 71.10, 71.03, 70.72, 49.16, 32.59, 19.49,
13.50; LRMS (FAB) m/z (rel intens) 518 (Mþþ1, 11), 246 (67), 154 (38),
136 (13), 91 (100); HRMS (FAB) m/z calcd for C32H40NO5 (Mþþ1)
518.2901, found 518.2918. Anal. Calcd for C32H39NO5; C: 74.25; H:
7.59. Found: C: 74.31; H: 7.64.
3.2.7. (E)-(3R,4R,5R)-1-n-Butylamino-2-formyl-5-hydroxy-3,4,6-tri-
O-pentyl-hex-1-ene (13). Pale yellow oil; IR (CHCl3) 2931, 1651,
1606, 1211, 1091 cmꢂ1
;
1H NMR (CDCl3, 500 MHz)
d
8.83 (1H, s,
3.2.11. (E)-(3R,4S,5R)-1-Benzylamino-2-formyl-5-hydroxy-3,4,6-tri-
CHO), 6.96e6.91 (1H, m, NH), 6.77 (1H, d, J1,NH¼14.0 Hz, H1), 4.76
(1H, d, J3,4¼2.0 Hz, H3), 3.90e3.87 (1H, m, H5), 3.51e3.50 (2H, m,
H6), 3.44e3.06 (9H, m, OCH2, H4, H10), 2.93 (1H, br s, OH),1.56e1.15
(22H, m, CH2, H20, H30), 0.89e0.80 (12H, m, CH3, H40); 13C NMR
O-benzyl-hex-1-ene (17). Pale yellow oil; IR (CHCl3) 2918, 1654,
1600, 1207, 1066 cmꢂ1 1H NMR (CDCl3, 500 MHz)
; d 8.87 (1H, s,
CHO), 7.39e7.35 (1H, m, NH), 7.29e6.94 (20H, m, ArH), 6.83 (1H, d,
J1,NH¼13.5 Hz, H1), 4.89 (1H, br s, H3), 4.62 (1H, d, Ja,b¼11.0 Hz,
CH2Ph), 4.59 (1H, d, Ja,b¼11.0 Hz, CH2Ph), 4.43 (1H, d, Ja,b¼12.0 Hz,
CH2Ph), 4.39 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 4.34 (1H, d, Ja,b¼11.5 Hz,
CH2Ph), 4.27 (1H, d, Ja,b¼11.5 Hz, CH2Ph), 4.05e4.03 (2H, m, CH2Ph),
3.86 (1H, dd, J4,3¼4.5 Hz, J4,5¼4.5 Hz, H4), 3.73e3.70 (1H, m, H5),
(CDCl3, 125 MHz) d 187.61, 159.26, 110.06, 82.18, 75.06, 72.67, 71.80,
71.53, 70.21, 69.54, 49.00, 33.12, 30.01, 29.47, 29.31, 28.38, 28.29,
28.19, 22.52, 22.49, 22.48, 19.70, 13.97, 13.96, 13.94, 13.59; LRMS (EI)
m/z (rel intens) 457 (Mþ, 1), 266 (24), 250 (57), 239 (30), 226 (100),
168 (47); HRMS (EI) m/z calcd for C26H51NO5 (Mþ) 457.3767, found
457.3762. Anal. Calcd for C26H51NO5; C: 68.23; H: 11.23. Found: C:
68.27; H: 11.25.
3.48 (2H, d, J¼5.0 Hz, H6); 13C NMR (CDCl3, 125 MHz)
d 188.34,
159.39, 138.16, 137.96, 137.92, 137.27, 128.81, 128.80, 128.51, 128.50,
128.39, 128.38, 128.37, 128.33, 128.32, 128.31, 128.30, 127.88, 127.87,
127.86, 127.80, 127.79, 127.61, 127.60, 127.07, 127.06, 109.16, 81.63,
74.94, 73.38, 73.37, 71.08, 70.93, 70.89, 52.73; LRMS (EI) m/z (rel
intens) 551 (Mþ, 1), 304 (15), 202 (7),107 (7), 91 (100); HRMS (EI) m/
z calcd for C35H37NO5 (Mþ) 551.2672, found 551.2661. Anal. Calcd for
C35H37NO5; C: 76.20; H: 6.76. Found: C: 76.24; H: 6.79.
3.2.8. (E)-(3R,4R,5R)-1-Benzylamino-2-formyl-5-hydroxy-3,4,6-tri-O-
pentyl-hex-1-ene (14). Pale yellow oil; IR (CHCl3) 2927, 1647, 1602,
1205, 1089 cmꢂ1 1H NMR (CDCl3, 400 MHz)
; d 8.96 (1H, s, CHO),
7.40e7.27 (6H, m, ArH, NH), 6.97 (1H, d, J1,NH¼13.2 Hz, H1), 4.84 (1H,
br s, H3), 4.44 (1H, dd, J¼4.4, 14.8 Hz, CH2Ph), 4.36 (1H, dd, J¼7.2 Hz,
Ja,b¼14.8 Hz, CH2Ph), 3.95 (1H, br s, H5), 3.58e3.57 (2H, m, H6),
3.49e3.27 (7H, m, H4, OCH2), 2.97 (1H, br s, OH), 1.61e1.15 (18H, m,
3.3. Standard procedure for regioselective reductive cleavage
of allyl ethers to prepare 1,2,3-trideoxy-2-formyl-hex-1-ene
derivatives (19e29)
CH2), 0.92e0.83 (9H, m, CH3); 13C NMR (CDCl3, 100 MHz)
d 187.98,
158.83, 137.31, 128.88, 128.87, 128.06, 127.42, 127.41, 111.01, 82.14,
75.12, 72.68, 71.76, 71.53, 70.15, 69.69, 53.03, 29.94, 29.31, 29.30,
28.29, 28.22, 28.21, 22.51, 22.47, 22.43, 14.01, 13.96, 13.90; LRMS (EI)
m/z (rel intens) 491 (Mþ, 1), 236 (18), 212 (15), 91 (100); HRMS (EI)
m/z calcd for C29H49NO5 (Mþ) 491.3611, found 491.3618. Anal. Calcd
for C29H49NO5; C: 70.84; H: 10.04. Found: C: 70.88; H: 10.07.
To a solution of
b-enaminal (7e17) (1.0 equiv) in acetic acid
(2 mL) was added sodium borohydride (1.0 equiv). The resulting
solution was stirred at room temperature for 10 min, concentrated
under reduced pressure, and re-dissolved in CH2Cl2 (50 mL). The
mixture was washed with H2O (20 mLꢁ2), brine (20 mLꢁ2), and
concentrated under reduced pressure. The dry residue was purified
by silica gel column chromatography with EtOAc/Hex (3:4) to give
1,2,3-trideoxy-2-formyl-hex-1-enes (19e29) in 72e94% yields.
3.2.9. (E)-(3R,4S,5R)-2-Formyl-5-hydroxy-1-n-octylamino-3,4,6-tri-
O-benzyl-hex-1-ene (15). Pale yellow oil; IR (CHCl3) 2924, 1654,
1602, 1207, 1062 cmꢂ1 1H NMR (CDCl3, 500 MHz)
; d 8.84 (1H, s,
CHO), 7.29e7.18 (15H, m, ArH), 7.05e7.01 (1H, m, NH), 6.73 (1H, d,
J1,NH¼14.0 Hz, H1), 4.89 (1H, d, J3,4¼3.5 Hz, H3), 4.64 (1H, d,
3.3.1. (E)-(4R,5R)-1,2,3-Trideoxy-2-formyl-5-hydroxy-1-n-octyla-
25
nimo-4,6-di-O-benzyl-hex-1-ene (19). Pale yellow oil; [
a
]
D
þ7.3 (c

Z.-P. Lin et al. / Tetrahedron 69 (2013) 3991e3999
3997
0.74, CHCl3); IR (CHCl3) 2924, 1649, 1591, 1269, 1072 cmꢂ1; 1H NMR
(CDCl3, 400 MHz) 8.81 (1H, s, CHO), 7.32e7.17 (10H, m, ArH), 6.79
0.82 (3H, t, J¼6.7 Hz, H80); 13C NMR (CDCl3, 125 MHz)
d
189.35,
d
160.39, 110.33, 82.34, 73.37, 70.75, 59.06, 58.27, 48.87, 31.68, 30.86,
29.09, 29.08, 26.39, 23.48, 22.54, 14.00; LRMS (EI) m/z (rel intens)
315 (Mþ, 1), 266 (10), 147 (24), 146 (100); HRMS (EI) m/z calcd for
C17H33NO4 (Mþ) 315.2403, found 315.2410. Anal. Calcd for
C17H33NO4; C: 64.73; H: 10.54. Found: C: 64.77; H: 10.58.
(1H, d, J1,NH¼13.6 Hz, H1), 6.30e6.24 (1H, m, NH), 4.57 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.50 (1H, d, Ja,b¼11.2 Hz, CH2Ph), 4.47 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.46 (1H, d, Ja,b¼11.2 Hz, CH2Ph), 4.17 (1H, br s,
OH), 3.75e3.71 (1H, m, H4), 3.66 (1H, dd, J6a,5¼2.8 Hz, J6a,6b¼9.6 Hz,
H6a), 3.58 (1H, dd, J6b,5¼4.8 Hz, J6b,6a¼9.6 Hz, H6b), 3.49e3.46 (1H,
m, H5), 2.88e2.82 (2H, m, H10), 2.76 (1H, dd, J3a,4¼4.0 Hz,
J3a,3b¼15.2 Hz, H3a), 2.36 (1H, dd, J3b,4¼3.2 Hz, J3b,3a¼15.2 Hz, H3b),
1.23e1.02 (12H, m, H20, H30, H40, H50, H60, H70), 0.82 (3H, t, J¼6.8 Hz,
3.3.5. (E)-(4R,5R)-1-Benzylanimo-1,2,3-trideoxy-2-formyl-5-hydroxy-
25
4,6-di-O-methyl-hex-1-ene (23). Pale yellow oil; [
a
]
ꢂ1.0 (c 0.19,
D
CHCl3); IR (CHCl3) 2922, 1693, 1606, 1217, 1091 cmꢂ1
;
1H NMR
H80); 13C NMR (CDCl3, 100 MHz)
d
189.57, 160.60, 138.03, 137.98,
(CDCl3, 400 MHz) 8.90 (1H, s, CHO), 7.34e7.19 (5H, m, ArH), 6.97
d
128.54, 128.53, 128.32, 128.31, 128.22, 128.21, 127.99, 127.98, 127.97,
127.62, 109.72, 80.25, 73.50, 73.17, 70.95, 70.73, 48.82, 31.69, 30.58,
29.07, 29.02, 26.30, 24.33, 22.58, 14.07; LRMS (FAB) m/z (rel intens)
468 (Mþþ1, 28), 196 (25), 109 (29), 91 (94), 55 (100); HRMS (FAB)
m/z calcd for C29H42NO4 (Mþþ1) 468.3108, found 468.3115. Anal.
Calcd for C29H41NO4; C: 74.48; H: 8.84. Found: C: 74.52; H: 8.87.
(1H, d, J1,NH¼13.6 Hz, H1), 6.69e6.66 (1H, m, NH), 4.38 (1H, d,
J¼5.6 Hz, CH2Ph), 4.37 (1H, d, J¼5.6 Hz, CH2Ph), 3.68 (1H, br s, OH),
3.51e3.46 (2H, m, H6a, H5), 3.41e3.36 (1H, m, H6b), 3.34e3.30 (4H,
m, H4, OCH3), 3.28 (3H, s, OMe), 2.61 (1H, dd, J3a,4¼4.8 Hz,
J3a,3b¼15.2 Hz, H3a), 2.45 (1H, dd, J3b,4¼3.6 Hz, J3b,3a¼15.2 Hz, H3b);
13C NMR (CDCl3, 100 MHz)
d 189.83, 160.07, 137.46, 128.94, 128.93,
128.00, 127.10, 127.09, 111.25, 82.27, 73.31, 70.60, 59.09, 58.25, 52.51,
23.46; LRMS (EI) m/z (rel intens) 293 (Mþ, 1), 244 (10), 174 (10), 91
(100); HRMS (EI) m/z calcd for C16H23NO4 (Mþ) 293.1627, found
293.1620. Anal. Calcd for C16H23NO4; C: 65.51; H: 7.90. Found: C:
65.55; H: 7.96.
3.3.2. (E)-(4R,5R)-1-n-Butylanimo-1,2,3-trideoxy-2-formyl-5-
25
hydroxy-4,6-di-O-benzyl-hex-1-ene (20). Pale yellow oil; [
a
]
þ5.1
(c 1.26, CHCl3); IR (CHCl3) 2927,1651,1593,1215,1072 cmꢂ1; 1DH NMR
(CDCl3, 400 MHz)
d 8.81 (1H, s, CHO), 7.27e7.17 (10H, m, ArH), 6.78
(1H, d, J1,NH¼13.6 Hz, H1), 6.27e6.24 (1H, m, NH), 4.56 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.51 (1H, d, Ja,b¼11.2 Hz, CH2Ph), 4.47 (2H, d,
Ja,b¼12.0 Hz, CH2Ph), 3.72e3.68 (1H, m, H4), 3.66 (1H, dd,
J6a,5¼2.8 Hz, J6a,6b¼10.0 Hz, H6a), 3.57 (1H, dd, J6b,5¼4.8 Hz,
J6b,6a¼10.0 Hz, H6b), 3.51e3.47 (1H, m, H5), 2.88e2.84 (2H, m, H10),
2.73 (1H, dd, J3a,4¼4.0 Hz, J3a,3b¼14.8 Hz, H3a), 2.38 (1H, dd,
J3b,4¼3.2 Hz, J3b,3a¼14.8 Hz, H3b), 1.11e1.06 (4H, m, H20, H30), 0.75
3.3.6. (E)-(4R,5R)-1,2,3-Trideoxy-2-formyl-5-hydroxy-1-n-octyla-
nimo-4,6-di-O-pentyl-hex-1-ene (24). Pale yellow oil; [
a
]
25 ꢂ32.6 (c
D
1.05, CHCl3); IR (CHCl3) 2926, 1654, 1597, 1292, 1095 cmꢂ1; 1H NMR
(CDCl3, 500 MHz)
d
8.85 (1H, s, CHO), 6.86 (1H, d, J1,NH¼13.5 Hz, H1),
6.54e6.52 (1H, m, NH), 3.72 (1H, br s, OH), 3.59e3.51 (2H, m, OCH2),
3.42e3.32 (6H, m, H4, H5, H6, OCH2), 3.18e3.14 (2H, m, H10), 2.65
(1H, dd, J3a,4¼3.0 Hz, J3a,3b¼15.0 Hz, H3a), 2.36 (1H, dd, J3b,4¼2.5 Hz,
J3b,3a¼15.0 Hz, H3b), 1.52e1.45 (6H, m, CH2), 1.23e1.21 (18H, m,
(3H, t, J¼6.8 Hz, H40); 13C NMR (CDCl3, 100 MHz)
d 189.49, 160.44,
138.11, 138.08, 128.50, 128.49, 128.31, 128.30, 128.20, 128.19, 127.97,
127.93, 127.92, 127.60, 109.94, 80.36, 73.52, 73.11, 71.09, 70.89, 48.47,
32.61, 24.30, 19.47, 13.51; LRMS (FAB) m/z (rel intens) 412 (Mþþ1,
36), 181 (9), 140 (36), 91 (100); HRMS (FAB) m/z calcd for C25H34NO4
(Mþþ1) 412.2482, found 412.2500. Anal. Calcd for C25H33NO4; C:
72.96; H: 8.08. Found: C: 72.99; H: 8.91.
CH2), 0.83e0.82 (9H, m, CH3); 13C NMR (CDCl3, 125 MHz)
d 189.40,
160.32, 110.45, 80.41, 71.60, 71.41, 71.03, 70.96, 48.89, 31.72, 31.02,
30.05, 29.33, 29.14, 29.12, 28.35, 28.32, 26.50, 24.07, 22.57, 22.52,
22.50, 14.01, 13.98, 13.97; LRMS (EI) m/z (rel intens) 427 (Mþ, 3), 315
(20), 208 (14), 196 (100), 71 (52); HRMS (EI) m/z calcd for C25H49NO4
(Mþ) 427.3662, found 427.3649. Anal. Calcd for C25H49NO4; C: 70.21;
H: 11.55. Found: C: 70.25; H: 11.59.
3.3.3. (E)-(4R,5R)-1-Benzylanimo-1,2,3-trideoxy-2-formyl-5-hydroxy-
25
4,6-di-O-benzyl-hex-1-ene (21). Pale yellow oil; [
a
]
þ12.3 (c 0.62,
D
CHCl3); IR (CHCl3) 2922, 1645, 1598, 1217, 1072 cmꢂ1
;
1H NMR
3.3.7. (E)-(4R,5R)-1-Butylanimo-1,2,3-trideoxy-2-formyl-5-hydroxy-
25
(CDCl3, 400 MHz) 8.95 (1H, s, CHO), 7.38e7.06 (15H, m, ArH), 6.97
d
4,6-di-O-pentyl-hex-1-ene (25). Pale yellow oil; [
a
]
ꢂ32.2 (c 0.59,
D
(1H, d, J1,NH¼13.6 Hz, H1), 6.74e6.68 (1H, m, NH), 4.64 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.58 (1H, d, Ja,b¼11.2 Hz, CH2Ph), 4.55 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.53 (1H, d, Ja,b¼11.2 Hz, CH2Ph), 4.14 (2H, d,
J¼6.0 Hz, CH2Ph), 3.83e3.79 (1H, m, H4), 3.74 (1H, dd, J6a,5¼2.8 Hz,
J6a,6b¼9.6 Hz, H6a), 3.65 (1H, dd, J6b,5¼5.2 Hz, J6b,6a¼9.6 Hz, H6b),
3.61e3.57 (1H, m, H5), 2.82 (1H, dd, J3a,4¼4.0 Hz, J3a,3b¼14.8 Hz,
H3a), 2.50 (1H, dd, J3b,4¼3.6 Hz, J3b,3a¼14.8 Hz, H3b); 13C NMR
CHCl3); IR (CHCl3) 2929, 1654, 1597, 1215, 1093 cmꢂ1
;
1H NMR
(CDCl3, 500 MHz)
d
8.85 (1H, s, CHO), 6.86 (1H, d, J1,NH¼13.5 Hz, H1),
6.54e6.51 (1H, m, NH), 3.73 (1H, br s, OH), 3.59e3.51 (2H, m, OCH2),
3.44e3.33 (6H, m, H4, H5, H6, OCH2), 3.20e3.16 (2H, m, H10), 2.65
(1H, dd, J3a,4¼3.0 Hz, J3a,3b¼14.5 Hz, H3a), 2.36 (1H, dd, J3b,4¼2.5 Hz,
J3b,3a¼14.5 Hz, H3b), 1.55e1.19 (6H, m, CH2), 1.35e1.18 (10H, m, CH2),
0.89e0.81 (9H, m, CH3); 13C NMR (CDCl3, 125 MHz)
d 189.39, 160.33,
(CDCl3, 100 MHz)
d
190.01, 160.25, 137.99, 137.88, 137.40, 128.79,
110.47, 80.41, 71.59, 71.42, 71.04, 70.95, 48.55, 33.05, 30.02, 29.32,
28.34, 28.31, 24.04, 22.50, 22.49, 19.64, 13.97, 13.96, 13.60; LRMS (EI)
m/z (rel intens) 371 (Mþ, 3), 140 (100), 109 (11), 71 (24); HRMS (EI)
m/z calcd for C21H41NO4 (Mþ) 371.3036, found 371.3031. Anal. Calcd
for C21H41NO4; C: 67.88; H: 11.12. Found: C: 67.92; H: 11.14.
128.78, 128.56, 128.55, 128.35, 128.34, 128.24, 128.23, 127.99, 127.98,
127.97, 127.83, 127.67, 127.04, 127.03, 110.80, 80.10, 73.50, 73.08,
70.92, 70.75, 52.09, 24.23; LRMS (FAB) m/z (rel intens) 446 (Mþþ1,
79), 181 (24), 174 (71), 154 (95), 91 (100); HRMS (FAB) m/z calcd for
C28H32NO4 (Mþþ1) 446.2326, found 446.2325. Anal. Calcd for
C28H31NO4; C: 75.48; H: 7.01. Found: C: 75.51; H: 7.05.
3.3.8. (E)-(4R,5R)-1-Benzylanimo-1,2,3-trideoxy-2-formyl-5-hydroxy-
25
4,6-di-O-pentyl-hex-1-ene (26). Pale yellow oil; [
a
]
þ54.5 (c 0.06,
D
3.3.4. (E)-(4R,5R)-1,2,3-Trideoxy-2-formyl-5-hydroxy-1-n-octyla-
CHCl3); IR (CHCl3) 2924, 1654, 1595, 1217, 1089 cmꢂ1
;
1H NMR
nimo-4,6-di-O-methyl-hex-1-ene (22). Pale yellow oil; [
a
]
25 þ37.8 (c
(CDCl3, 500 MHz) 8.90 (1H, s, CHO), 7.33e7.19 (5H, m, ArH), 6.96
d
D
0.11, CHCl3); 1H NMR (CDCl3, 500 MHz)
d
8.84 (1H, s, CHO), 6.87 (1H,
(1H, d, J1,NH¼13.0 Hz, H1), 6.89e6.87 (1H, m, NH), 4.36 (2H, d,
J¼5.0 Hz, CH2Ph), 3.56e3.31 (9H, m, H4, H5, H6, OH, OCH2), 2.66 (1H,
d, J3a,3b¼15.0 Hz, H3a), 2.42 (1H, d, J3b,3a¼15.0 Hz, H3b), 1.54e1.09
(12H, m, CH2), 0.82e0.75 (6H, m, CH3); 13C NMR (CDCl3, 125 MHz)
d, J1,NH¼13.5 Hz, H1), 6.40e6.37 (1H, m, NH), 3.79 (1H, br s, OH), 3.49
(1H, dd, J6a,5¼2.5 Hz, J6a,6b¼9.5 Hz, H6a), 3.46e3.43 (1H, m, H5), 3.39
(1H, dd, J6b,5¼5.5 Hz, J6b,6a¼9.5 Hz, H6b), 3.36 (3H, s, OCH3),
3.34e3.29 (4H, m, H4, OCH3), 3.20e3.16 (2H, m, H10), 2.62 (1H, dd,
J3a,4¼4.5 Hz, J3a,3b¼15.0 Hz, H3a), 2.40 (1H, dd, J3b,4¼3.0 Hz,
J3b,3a¼15.0 Hz, H3b), 2.27 (1H, dd, J3b,4¼8.0 Hz, J3b,3a¼14.0 Hz, H3b),
1.52e1.47 (2H, m, H20), 1.24e1.21 (10H, m, H30, H40, H50, H60, H70),
d
189.83,159.97,137.50,128.93,128.92,128.02,127.24,127.23,109.98,
80.48, 71.63, 71.43, 71.01, 70.96, 52.47, 29.85, 29.34, 28.33, 28.29,
24.07, 22.51, 22.44, 14.01, 13.96; LRMS (EI) m/z (rel intens) 405 (Mþ,
3), 300 (20), 213 (14), 174 (92), 91 (100); HRMS (EI) m/z calcd for

3998
Z.-P. Lin et al. / Tetrahedron 69 (2013) 3991e3999
C24H39NO4 (Mþ) 405.2879, found 405.2870. Anal. Calcd for
C24H39NO4; C: 71.07; H: 9.69. Found: C: 71.12; H: 9.75.
reaction mixture was concentrated under reduced pressure and re-
dissolved in CH2Cl2 (50 mL). The resulting solution was washed
with H2O (20 mLꢁ2), brine (20 mLꢁ2), and concentrated under
reduced pressure. The dry residue was purified by silica gel column
chromatography with EtOAc/Hex (2:3) to give the diene products
(33e35) in 85e90% yields.
3.3.9. (E)-(4R,5R)-1,2,3-Trideoxy-2-formyl-5-hydroxy-1-n-octyla-
nimo-4,6-di-O-benzyl-hex-1-ene (27). Pale yellow oil; [
a
]
25 þ41.0 (c
0.20, CHCl3); IR (CHCl3) 2924, 1656, 1589, 1207, 1066 cmꢂD1; 1H NMR
(CDCl3, 500 MHz)
d 8.82 (1H, s, CHO), 7.28e7.19 (10H, m, ArH), 6.75
(1H, d, J1,NH¼14.0 Hz, H1), 6.18e6.15 (1H, m, NH), 4.62 (1H, d,
Ja,b¼11.5 Hz, CH2Ph), 4.52 (1H, d, Ja,b¼11.5 Hz, CH2Ph), 4.46 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.41 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 3.54e3.41
(4H, m, H4, H5, H6), 3.09e2.98 (2H, m, H10), 2.72 (1H, dd,
J3a,4¼5.0 Hz, J3a,3b¼14.0 Hz, H3a), 2.28 (1H, dd, J3b,4¼8.5 Hz,
J3b,3a¼14.0 Hz, H3b), 1.36e1.34 (2H, m, H20), 1.22e1.18 (10H, m, H30,
H40, H50, H60, H70), 0.81 (3H, t, J¼7.0 Hz, H80); 13C NMR (CDCl3,
3.4.1. (E)-(5R)-1-(N-Acetyl-octylanimo)-1,2,3-trideoxy-2-formyl-5-O-
acetyl-4,6-di-O-benzyl-hex-1,3-diene (33). Pale yellow oil; [
a
]
25 ꢂ2.3
D
(c 1.21, CHCl3); IR (CHCl3) 2924, 1682, 1605, 1227, 1080 cmꢂ1
;
1H
NMR (CDCl3, 500 MHz)
d 9.24 (1H, s, CHO), 7.43e7.10 (11H, m, ArH,
H1), 5.59 (1H, s, H3), 5.51 (1H, t, J¼5.5 Hz, H5), 4.70 (1H, d,
Ja,b¼11.0 Hz, CH2Ph), 4.62 (1H, d, Ja,b¼11.5 Hz, CH2Ph), 4.48 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.45 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 3.66 (2H, d,
J5,6¼6.0 Hz, H6), 3.63e3.60 (2H, m, H10), 2.10 (3H, s, Ac), 2.04 (3H, s,
Ac), 1.30e1.10 (12H, m, H20, H30, H40, H50, H60, H70), 0.79 (3H, t,
125 MHz)
d 188.63, 159.44, 138.23, 137.93, 128.40, 128.39, 128.37,
128.36, 128.28, 128.27, 127.86, 127.85, 127.80, 127.74, 109.49, 77.71,
73.47, 72.56, 71.50, 71.19, 48.94, 31.73, 30.91, 29.12, 29.11, 26.44,
23.34, 22.59, 14.05; LRMS (EI) m/z (rel intens) 467 (Mþ, 1), 392 (11),
208 (10),196 (43), 91 (100); HRMS (EI) m/z calcd for C29H41NO4 (Mþ)
467.3036, found 467.3030. Anal. Calcd for C29H41NO4; C: 74.48; H:
8.84. Found: C: 74.52; H: 8.88.
J¼7.0 Hz, H80); 13C NMR (CDCl3, 125 MHz)
d 192.01, 170.88, 169.86,
154.97, 145.65, 137.67, 136.76, 128.40, 128.39, 128.38, 128.37, 128.02,
127.76, 127.68, 127.67, 127.64, 127.63, 119.01, 102.14, 73.22, 72.13,
72.12, 69.97, 31.73, 31.72, 29.30, 29.11, 28.93, 26.30, 22.56, 22.23,
21.06, 14.03; LRMS (EI) m/z (rel intens) 549 (Mþ, 1), 356 (6), 107 (10),
91 (100); HRMS (EI) m/z calcd for C33H43NO6 (Mþ) 549.3090, found
549.3095. Anal. Calcd for C33H43NO6; C: 72.10; H: 7.90. Found: C:
72.14; H: 7.95.
3.3.10. (E)-(4S,5R)-1-Butylanimo-1,2,3-trideoxy-2-formyl-5-hydroxy-
4,6–di-O-benzyl-hex-1-ene (28). Pale yellow oil; [
a
]
25 þ62.6 (c 0.23,
D
CHCl3); IR (CHCl3) 2924, 1651, 1591, 1213, 1066 cmꢂ1
;
1H NMR
(CDCl3, 500 MHz)
d
8.83 (1H, s, CHO), 7.28e7.19 (10H, m, ArH), 6.74
3.4.2. (E)-(5R)-1-(N-Acetyl-butylanimo)-1,2,3-trideoxy-2-formyl-5-
25
(1H, d, J1,NH¼13.5 Hz, H1), 6.16e6.12 (1H, m, NH), 4.62 (1H, d,
Ja,b¼11.5 Hz, CH2Ph), 4.52 (1H, d, Ja,b¼11.5 Hz, CH2Ph), 4.46 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.41 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 3.54e3.41
(4H, m, H4, H5, H6), 3.09e2.97 (2H, m, H10), 2.72 (1H, dd,
J3a,4¼5.0 Hz, J3a,3b¼14.0 Hz, H3a), 2.65 (1H, br s, OH), 2.27 (1H, dd,
J3b,4¼8.0 Hz, J3b,3a¼14.0 Hz, H3b), 1.37e1.31 (2H, m, H20), 1.25e1.17
(2H, m, H30), 0.82 (3H, t, J¼7.0 Hz, H40); 13C NMR (CDCl3, 125 MHz)
O-acetyl-4,6-di-O-benzyl-hex-1,3-diene (34). Pale yellow oil; [a]
ꢂ1.3 (c 0.52, CHCl3); IR (CHCl3) 2932, 1682, 1605, 1227, 1080 cmꢂD1
;
1H NMR (CDCl3, 500 MHz)
d 9.24 (1H, s, CHO), 7.44e7.10 (11H, m,
ArH, H1), 5.59 (1H, s, H3), 5.52 (1H, t, J¼5.0 Hz, H5), 4.70 (1H, d,
Ja,b¼11.0 Hz, CH2Ph), 4.63 (1H, d, Ja,b¼11.5 Hz, CH2Ph), 4.49 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.45 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 3.66 (2H, d,
J5,6¼6.0 Hz, H6), 3.64e3.60 (2H, m, H10), 2.10 (3H, s, Ac), 2.04 (3H, s,
Ac), 1.29e1.10 (4H, m, H20, H30), 0.78 (3H, t, J¼7.5 Hz, H40); 13C NMR
d
188.65, 159.39, 138.26, 137.97, 128.40, 128.39, 128.37, 128.36,
128.28, 128.27, 127.85, 127.84, 127.80, 127.73, 109.56, 77.76, 73.46,
72.58, 71.55, 71.24, 48.61, 32.93, 23.37, 19.60, 13.59; LRMS (EI) m/z
(rel intens) 411 (Mþ, 1), 164 (13), 140 (74), 91 (100); HRMS (EI) m/z
calcd for C25H33NO4 (Mþ) 411.2410, found 411.2405. Anal. Calcd for
C25H33NO4; C: 72.96; H: 8.08. Found: C: 72.99; H: 8.10.
(CDCl3, 125 MHz) d 192.00, 170.88, 169.89, 154.96, 145.63, 137.67,
136.76, 128.41, 128.40, 128.39, 128.38, 128.03, 127.77, 127.71, 127.70,
127.65,127.64, 118.98,102.15, 73.23, 72.14, 72.13, 69.96, 31.03, 22.22,
21.06, 19.56, 19.55, 13.80; LRMS (EI) m/z (rel intens) 493 (Mþ,1), 300
(27), 270 (12), 91 (100); HRMS (EI) m/z calcd for C29H35NO6 (Mþ)
493.2464, found 493.2460. Anal. Calcd for C29H35NO6; C: 70.60; H:
7.20. Found: C: 70.65; H: 7.26.
3.3.11. (E)-(4S,5R)-1-Benzylanimo-1,2,3-trideoxy-2-formyl-5-O-ace-
25
tyl-4,6-di-O-benzyl-hex-1-ene (29). Pale yellow oil; [
a]
þ75.1 (c
D
0.71, CHCl3); IR (CHCl3) 2920, 1651, 1597, 1215, 1068 cmꢂ1; 1H NMR
(CDCl3, 500 MHz) 8.87 (1H, s, CHO), 7.28e7.09 (15H, m, ArH), 6.84
3.4.3. (E)-(5R)-1-(N-Acetyl-benzylanimo)-1,2,3-trideoxy-2-formyl-5-
25
d
O-acetyl-4,6-di-O-benzyl-hex-1,3-diene (35). Pale yellow oil; [a]
(1H, d, J1,NH¼13.5 Hz, H1), 6.49e6.46 (1H, m, NH), 4.61 (1H, d,
Ja,b¼11.5 Hz, CH2Ph), 4.51 (1H, d, Ja,b¼11.5 Hz, CH2Ph), 4.44 (1H, d,
Ja,b¼11.5 Hz, CH2Ph), 4.40 (1H, d, Ja,b¼11.5 Hz, CH2Ph), 4.21 (1H, d,
J¼6.0 Hz, CH2Ph), 4.20 (1H, d, J¼6.0 Hz, CH2Ph), 3.57e3.46 (3H, m,
H4, H5, H6a), 3.42 (1H, dd, J6b,5¼4.5 Hz, J6b,6a¼9.0 Hz, H6b), 2.73 (1H,
dd, J3a,4¼5.5 Hz, J3a,3b¼14.0 Hz, H3a), 2.32 (1H, dd, J3b,4¼8.0 Hz,
þ17.0 (c 0.88, CHCl3); IR (CHCl3) 2931, 1682, 1605, 1211, 1080 cmꢂD1
;
1H NMR (CDCl3, 500 MHz)
d 9.26 (1H, s, CHO), 7.72e6.94 (11H, m,
ArH, H1), 5.41 (1H, t, J¼5.5 Hz, H5), 5.38 (1H, s, H3), 4.89 (1H, d,
Ja,b¼17.0 Hz, CH2Ph), 4.83 (1H, d, Ja,b¼17.5 Hz, CH2Ph), 4.69 (1H, d,
Ja,b¼11.0 Hz, CH2Ph), 4.61 (1H, d, Ja,b¼11.5 Hz, CH2Ph), 4.45 (1H, d,
Ja,b¼12.5 Hz, CH2Ph), 4.42 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 3.61 (2H, d,
J5,6¼5.0 Hz, H6), 2.07 (3H, s, Ac), 1.88 (3H, s, Ac); 13C NMR (CDCl3,
J3b,3a¼14.0 Hz, H3b); 13C NMR (CDCl3, 125 MHz)
d 189.02, 159.07,
138.15, 137.92, 137.64, 128.87, 128.86, 128.38, 128.37, 128.34, 128.33,
128.25, 128.24, 127.86, 127.85, 127.84, 127.77, 127.72, 127.09, 127.08,
110.51, 77.61, 73.43, 72.53, 71.50, 71.11, 52.34, 23.38; LRMS (EI) m/z
(rel intens) 445 (Mþ, 1), 198 (12), 174 (22), 91 (100); HRMS (EI) m/z
calcd for C28H31NO4 (Mþ) 445.2253, found 445.2246. Anal. Calcd for
C28H31NO4; C: 75.48; H: 7.01. Found: C: 75.52; H: 7.06.
125 MHz) d 191.90, 171.27, 169.94, 154.91, 145.23, 137.66, 136.93,
136.80, 128.81, 128.80, 128.39, 128.38, 128.37, 128.03, 128.02, 127.77,
127.76, 127.75, 127.74, 127.73, 127.41, 127.40, 125.96, 119.20, 101.55,
73.25, 72.09, 72.08, 69.92, 31.02, 22.18, 20.91; LRMS (EI) m/z (rel
intens) 527 (Mþ, 1), 394 (6), 289 (25), 91 (100); HRMS (EI) m/z calcd
for C32H33NO6 (Mþ) 527.2308, found 527.2300. Anal. Calcd for
C32H33NO6; C: 72.90; H: 6.30. Found: C: 72.94; H: 6.36.
3.4. Standard procedure to prepare the diene derivatives
(33e35)
3.5. Standard procedure for cyclization of 3-deoxy-b-enami-
nals to produce 3-deoxy-C-2-formylglycals (41e43)
The solution of b-enaminals (7e9 or 15e17) (1.0 equiv) in acetic
acid (2 mL) was stirred at room temperature for 1.5e4 h, concen-
trated under reduced pressure, and then re-dissolved in pyridine
(2 mL). The resulting mixture was mixed with acetic anhydride
(2.5 equiv), followed by stirring at room temperature for 1 h. The
The solution of 3-deoxy-b-enaminals (19e23 or 27e29)
(1.0 equiv) in HOAc (3 mL) was stirred at 80 ꢀC for 20 min, con-
centrated under reduced pressure, and then re-dissolved in CH2Cl2
(50 mL). The resulting mixture was washed with H2O (20 mLꢁ2),

Z.-P. Lin et al. / Tetrahedron 69 (2013) 3991e3999
3999
Moore, L.; Truesdale, A.; Leitner, P.; Besterman, J. M. J. Med. Chem. 1993, 36,
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brine (20 mLꢁ2), and concentrated under reduced pressure. The
dry residue was purified by silica gel column chromatography with
EtOAc/Hex (1:4) to give 3-deoxy-C-2-formylglycals (41e43) in
95e97% yields.
3.5.1. 1,5-Anhydro-4,6-di-O-benzyl-2,3-dideoxy-2-C-formyl-D-er-
5. (a) De, D.; Mague, J. T.; Byers, L. D.; Krogstad, D. J. Tetrahedron Lett. 1995, 36,
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5152e5160; (i) Mitchinson, A.; Blackaby, W. P.; Bourrain, S.; Carling, R. W.;
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H.; Huszar, D.; Lawson, D.; Lewis, P. M.; Nadella, M. V. P.; Oza, V.; Pontz, T.;
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5421e5422.
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15. Lin, Z. P.; Lin, H. C.; Wu, H. H.; Chou, H. W.; Lin, S. K.; Sung, K. C.; Wong, F. F.
Tetrahedron Lett. 2009, 50, 5120e5122.
ythro-hex-1-enitol (41). Pale yellow oil; [
a]
25 þ65.7 (c 0.28, CHCl3);
D
IR (CHCl3) 2940, 1676, 1625, 1197, 1095 cmꢂ1 1H NMR (CDCl3,
;
500 MHz) d 9.24 (1H, s, CHO), 7.29e7.19 (11H, m, ArH, H1), 4.61 (1H,
d, Ja,b¼12.0 Hz, CH2Ph), 4.52 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 4.49 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.44 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 4.14e4.11
(1H, m, H5), 3.77e3.73 (1H, m, H4), 3.72e3.68 (2H, m, H6), 2.64
(1H, dd, J3a,4¼5.0 Hz, J3a,3b¼16.5 Hz, H3a), 2.20 (1H, dd, J3b,4¼7.5 Hz,
J3b,3a¼16.5 Hz, H3b); 13C NMR (CDCl3, 125 MHz)
d 189.88, 163.45,
137.60, 137.54, 128.49, 128.48, 128.47, 128.46, 127.92, 127.88, 127.80,
127.79, 127.75, 127.74, 116.96, 79.45, 73.64, 70.99, 68.47, 68.35,
22.46; LRMS (EI) m/z (rel intens) 338 (Mþ, 1), 221 (10), 141 (8), 91
(100); HRMS (EI) m/z calcd for C21H22O4 (Mþ) 338.1518, found
338.1514. Anal. Calcd for C21H22O4; C: 74.54; H: 6.55. Found: C:
74.59; H: 6.61.
3.5.2. 1,5-Anhydro-4,6-di-O-methyl-2,3-dideoxy-2-C-formyl-D-er-
ythro-hex-1-enitol (42). Pale yellow oil; [
a
]
D
25 þ70.8 (c 0.24, CHCl3);
IR (CHCl3) 2935, 1672, 1624, 1200, 1105 cmꢂ1 1H NMR (CDCl3,
;
500 MHz)
d 9.25 (1H, s, CHO), 7.23 (1H, s, H1), 4.09e4.06 (1H, m,
H5), 3.57 (2H, d, J6,5¼4.0 Hz, H6), 3.52e3.48 (1H, m, H4), 3.35 (6H, s,
OCH3), 2.60 (1H, dd, J3a,4¼5.0 Hz, J3a,3b¼16.5 Hz, H3a), 2.14 (1H, dd,
J3b,4¼7.0 Hz, J3b,3a¼16.5 Hz, H3b); 13C NMR (CDCl3, 125 MHz)
d
189.93, 163.29, 116.85, 79.07, 71.01, 70.65, 59.46, 56.68, 21.70;
LRMS (EI) m/z (rel intens) 186 (Mþ, 1), 91 (100); HRMS (EI) m/z calcd
for C9H14O4 (Mþ) 186.0892, found 186.0896. Anal. Calcd for
C9H14O4; C: 58.05; H: 7.58. Found: C: 58.12; H: 7.65.
3.5.3. 1,5-Anhydro-4,6-di-O-benzyl-2,3-dideoxy-2-C-formyl-
D
-threo-
25
hex-1-enitol (43). Pale yellow oil; [
(CHCl3) 2945, 1674, 1635, 1195, 1090 cmꢂ1
500 MHz) 9.25 (1H, s, CHO), 7.27e7.17 (11H, m, ArH, H1), 4.56 (1H,
a]
D
þ74.2 (c 0.62, CHCl3); IR
;
1H NMR (CDCl3,
d
16. Cimarelli, C.; Giuli, S.; Palmieri, G. Tetrahedron: Asymmetry 2006, 17,
d, Ja,b¼12.0 Hz, CH2Ph), 4.49 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 4.42 (1H, d,
Ja,b¼12.0 Hz, CH2Ph), 4.33 (1H, d, Ja,b¼12.0 Hz, CH2Ph), 4.17e4.14 (1H,
m, H5), 3.88 (1H, br s, H4), 3.72 (1H, dd, J6a,5¼7.0 Hz, J6a,6b¼10.0 Hz,
H6a), 3.65 (1H, dd, J6b,5¼5.5 Hz, J6b,6a¼10.0 Hz, H6b), 2.61 (1H, dd,
J3a,4¼2.5 Hz, J3a,3b¼17.5 Hz, H3a), 2.17 (1H, dd, J3b,4¼3.5 Hz,
1308e1317.
17. Ganguly, N. C.; Dutta, S.; Datta, M. Tetrahedron Lett. 2006, 47, 5807e5810.
18. Kim, H. J.; Su, L.; Jung, H.; Koo, S. Org. Lett. 2011, 13, 2682e2685.
19. Thomas, R. M.; Reddy, G. S.; Lyengar, D. S. Tetrahedron Lett. 1999, 40,
7293e7294.
20. Thomas, R. M.; Mohan, H.; Iyengar, D. S. Tetrahedron Lett. 1997, 38,
4721e4724.
21. (a) Forsyth, D. A.; Estes, M. R.; Lucas, P. J. Org. Chem. 1982, 47, 4380e4382; (b)
Beugelmans, R.; Bourdet, S.; Bigot, A.; Zhu, J. Tetrahedron Lett. 1994, 35,
4349e4350.
J3b,3a¼17.5 Hz, H3b); 13C NMR (CDCl3, 125 MHz)
d 190.41, 163.95,
137.58, 137.48, 128.47, 128.46, 128.45, 128.44, 127.92, 127.89, 127.88,
127.87, 127.80, 127.79, 116.75, 78.65, 73.61, 70.96, 68.60, 67.63, 21.18;
LRMS (EI) m/z (rel intens) 338 (Mþ, 1), 221 (8), 125 (11), 91 (100);
HRMS (EI) m/z calcd for C21H22O4 (Mþ) 338.1518, found 338.1510.
Anal. Calcd for C21H22O4; C: 74.54; H: 6.55. Found: C: 74.56; H: 6.57.
22. Chandrasekhar, S.; Reddy, C. R.; Rao, R. J. Tetrahedron 2001, 57, 3435e3438.
ꢀ
23. Dahlen, A.; Sundgren, A.; Lahmann, M.; Oscarson, S.; Hilmersson, G. Org. Lett.
2003, 5, 4085e4088.
24. Babler, J. H.; White, N. A.; Kowalski, E.; Jast, J. R. Tetrahedron Lett. 2011, 52,
745e748.
25. Yin, B. L.; Cai, C. B.; Lai, J. Q.; Zhang, Z. R.; Huang, L. Adv. Synth. Catal. 2011, 353,
3319e3324.
Acknowledgements
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27. Wang, J.; Huang, W.; Zhang, Z.; Xiang, X.; Liu, R.; Zhou, X. J. Org. Chem. 2000, 74,
3299e3304.
28. Ohkubo, M.; Mochizuki, S.; Sano, T.; Kawaguchi, Y.; Okamoto, S. Org. Lett. 2007,
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The authors thank the National Science Council of Taiwan
(NSC100-2113-M-039-001-MY2) and China Medical University,
Taiwan (CMU99-S-32) for their financial support.
29. Yuan, C.; Hollingsworth, R. I. Tetrahedron Lett. 2011, 52, 5421e5423.
30. (a) Comins, D. L.; Hiebel, A. C.; Huang, S. Org. Lett. 2001, 3, 769e771; (b)
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