Stereoselective allylation reactions of acyclic and chiral α-amino-β-hydroxy aldehydes

Article abstract of DOI:10.1016/j.tetasy.2017.07.002

Stereoselective allylation reactions of acyclic and chiral α-amino-β-hydroxy aldehydes affording chiral β-amino-α,γ-diols are described. Several Lewis acids (BF₃·OEt₂, SnCl₄, TiCl₄, ZnCl₂, and MgBr₂·OEt₂) were employed to mediate the allylation reactions. The reactions of anti-α-NHCbz-β-OTBS substrates mediated by SnCl₄ afforded syn-selective products. The same reaction conditions also gave satisfactory results for the reactions of syn-α-NHCbz-β-OTBS substrates. The mechanism involves α-chelation between the amido group and aldehyde oxygen.

Full text of DOI:10.1016/j.tetasy.2017.07.002

Tetrahedron: Asymmetry 28 (2017) 1053–1060
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereoselective allylation reactions of acyclic and chiral
a-amino-b-hydroxy aldehydes
In-Soo Myeong, Yong-Taek Lee, Sang-Hyun Lee, Changyoung Jung, Jin-Seok Kim, Seok-Hwi Park,
⇑
Jihun Kang, Seung-Jong Lee, In-Hae Ye, Won-Hun Ham
School of Pharmacy, Sungkyunkwan University, Seobu-ro 2066, Suwon-si, Gyeonggi-do 16419, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Stereoselective allylation reactions of acyclic and chiral a-amino-b-hydroxy aldehydes affording chiral b-
Received 8 May 2017
Revised 19 June 2017
Accepted 12 July 2017
Available online 7 August 2017
amino-
employed to mediate the allylation reactions. The reactions of anti-
by SnCl4 afforded syn-selective products. The same reaction conditions also gave satisfactory results for
the reactions of syn- -NHCbz-b-OTBS substrates. The mechanism involves -chelation between the
amido group and aldehyde oxygen.
a
,
c
-diols are described. Several Lewis acids (BF3ꢀOEt2, SnCl4, TiCl4, ZnCl2, and MgBr2ꢀOEt2) were
a
-NHCbz-b-OTBS substrates mediated
a
a
Ó 2017 Elsevier Ltd. All rights reserved.
1. Introduction
stereoselective nucleophilic addition to N,N-dibenzylamino
aldehydes derived from amino acids.1 d After Reetz, many studies
Vicinal amino alcohols, known as
a-amino alcohols, and
on nucleophilic additions of a-amino-b-hydroxy aldehydes
aminopolyols, with simple or complex structures, are important
(Fig. 3B) and Garner’s aldehyde (Fig. 3C) have been reported to
achieve more complicated amino alcohols. For example,
Kiyooka,9 Dondoni,10 Coleman,11 Marshall,12 Joullié,13 Jurczak,14
Molinski,15 Somfai,16 and Koskinen17 widely explored this field.
Nevertheless, most of these reactants have achiral b-hydroxy
groups or primary b-alcohols, and the reactions of bis-stereogenic
structural motifs of natural products and medicinal agents.1
b-Amino-a,c-diols, one class of amino polyols, is ubiquitous in
bioactive natural products. For example, amikacin, kanamycin A,
NK 1012-2, amphotericin B, neuraminic acid, and castanospermine
have b-amino-
The typical synthetic methods for simple
(i) addition reactions to
-amino aldehydes;2 (ii) addition reactions
to
-hydroxy aldimines;3 (iii) reductions of -amino ketones;4 and
(iv) reductions of
-hydroxy ketimines (Fig. 2).5 Herein we have
focused on addition reactions to -amino aldehydes. Although
many researchers studied the synthesis of -amino alcohols, the
synthesis of aminopolyols has rarely been studied. Herein, we
demonstrated a synthetic method for b-amino- -diols by using
Lewis acid mediated stereoselective allylation of doubly stere-
a,c-diol substructures (Fig. 1).
a-amino alcohols are
a-amino-b-hydroxy aldehydes have rarely been reported. Marshall
a
et al. reported a rare example using modified Garner’s aldehyde
derived from threonine (Fig. 3D);12 however, moderate 12:88
(1:7.3) and 83:17 (4.9:1) syn/anti ratios were obtained. Jurczak
a
a
a
a
et al. studied stereoselective allylation of
hydes with single stereogenic center (Fig. 3B),14 and the results
were explained by -chelation via SnCl4 and b-chelation via TiCl4.
a-amino-b-hydroxy alde-
a
a
a,c
Reactions of cyclic and complex molecules such as piperidines18
(Fig. 3E) and pyrrolidines19 (Fig. 3F) have been well reported.
Moreover, we previously reported an example of acyclic and chiral
b-hydroxy aldehydes (Fig. 3G) to synthesize (ꢁ)-swainsonine.20
Sakurai allylation reactions were conducted using TiCl4: the use
of 1.5 equiv of TiCl4 afforded the desired anti-product. This stereos-
electivity arises from b-chelation via TiCl4.
ogenic a-amino-b-hydroxy aldehydes.
After the pioneering study by Cram in 1952,6 diastereoselective
and enantioselective aldehyde additions have been extensively
explored. The stereocontrol of these reactions was explained using
the Felkin–Anh and chelation models,1c,7 and they were classified
as thermal and Lewis acid-promoted reactions.8
As shown in earlier studies, stereoselective allylation has been
Stereoselective addition to
a-amino aldehydes (Fig. 3A) was
studied in bis-stereogenic a-amino-b-hydroxy aldehyde, however
studied by Reetz et al. who reported Lewis acid mediated
the results and mechanism were not well established. This study
attempts to explore the stereoselective allylation of amino acid
derived bis-stereogenic
which has not been previously reported.
a-amino-b-hydroxy aldehydes (Fig. 3H),
⇑
Corresponding author.
E-mail address: whham@skku.edu (W.-H. Ham).
http://dx.doi.org/10.1016/j.tetasy.2017.07.002
0957-4166/Ó 2017 Elsevier Ltd. All rights reserved.

1054
I.-S. Myeong et al. / Tetrahedron: Asymmetry 28 (2017) 1053–1060
OH
H2N
HO
OH
OH
O
H
OH
OH
OH
OH
H
O
H
O
OH
OH
H
HO
HO
O
O
NH2
OH
H
O
HO
HO
O
O
NH2
OH
HO
O
O
O
NH2
H2N
NH2
H2N
N
H
H2N
NH2
OH
H2N
OH
H2N
OH
Amikacin
Kanamycin A
NK 1012-2
OH
O
O
H
O
OH
OH
HO
OH
OH
H
O
OH
HO2C
O
OH
H
OH
HO
O
OH
NH2
OH
Neuraminic acid
N
NH2
O
HO
H
OH
HO
Amphotericin B
Castanospermine
Figure 1. Bioactive amino alcohols and amino polyols.
i) addition reactions to
ii) addition reactions to
α
-hydroxy aldimines
OTBS
OTBS
OBn
OTBS
α
-amino aldehydes
HO
HO
HO
HO
R
NHCbz
R=Me
O
OH
H
NBnCbz
NHBoc
NHCbz
3
R1
*
-
-
R1
R2
H-
H
*
1
2a
4
R2
OH
*
2b R=Et
NH2
NH
R1
2c
2d
R=Bn
*
R2
R=iPr
NH2
O
OH
R1
OTBS
OTBS
R
OBn
H-
R1
*
*
R2
R2
HO
HO
HO
NH2
NH
NHBoc
5
NHCbz
6a R=Me
NHCbz
7
iii) reductions to
-amino ketones
iv) reductions to
-hydroxy ketimines
6b
R=Et
α
α
6c R=allyl
6d R=Ph
Figure 2. Schematic diagram affording simple vic-amino alcohols.
Figure 4. Scope of anti- and syn-a-amino-b-hydroxy alcohols.
Previous works
but we did not detect any diastereomers by TLC or NMR
O
O
O
O
Me
spectroscopy in any of the experiments. The reactions of 2,3-anti-
R3
H
H
OR3
*
N
*
*
H
H
O
O
a-NHBoc-b-OTBS substrate 1 did not give satisfactory results
NR1R2
NR1R2
N
D
R1
Boc
(entries 1 and 2). The Sakurai allylation of 2,3-anti- -NHCbz-b-
a
A
B
C
OTBS substrate 2b mediated by BF3ꢀOEt2 failed (entry 3). When
allylSnBu3 was used as the nucleophile, the reaction afforded a
moderately 4,5-syn-selective product in a good yield (entry 4).
Sakurai allylation mediated by SnCl4 produced a highly 4,5-syn-
selective product in a good yield (entry 5). The reaction with
allylSnBu3 afforded the same stereoselectivity, but with a slightly
lower yield than the reaction with allylSiMe3 (entry 6). Changes
in Lewis acid did not provide satisfactory results, especially when
the reaction was mediated by MgBr2ꢀOEt2, where the major pro-
duct was the 4,5-anti-product (entries 7–9). Grignard reaction
without Lewis acid also did not afford the stereocontrolled product
This work
OR3
O
OR2
OR2
O
O
O
O
O
OBz
*
N
*
H
*
H
R3
*
R4
H
*
H
*
N
R3
R1
R1
NR1R2
H
NHCbz
G
E
F
Figure 3. Substrates of a-amino-b-hydroxy aldehydes.
2. Results and discussion
Bis-stereogenic -amino-b-hydroxy alcohols shown in Figure 4
(entry 10). Similar reactions of 2,3-anti-a-NHCbz-b-OBn 3 were
a
conducted. AllylSnBu3 attack mediated by BF3ꢀOEt2 and allylSiMe3
attack mediated by SnCl4 and TiCl4 afforded 4,5-syn-oriented ratios
(entries 11–13). Grignard reaction without Lewis acid did not
afford the stereocontrolled product (entry 14). Moreover, reactions
were prepared by reported methods with slight modifications.21
The full details are described in Supporting Information. The pri-
mary alcohols are easily converted to the corresponding aldehydes
without epimerization using Dess–Martin periodinane.22 Test reac-
tions were conducted with 1, 2b, 3, and 4 in the anti-cases and 5,
6b, and 7 in the syn-cases (R4 of Fig. 3H is Et). Further experiments
to examine substrate scope (2a, 2c, 2d, 6a, 6c, and 6d) are also
described (vide infra).
of 2,3-anti-a-NBnCbz-b-OBn substrate 4 were also investigated;
the reaction using allylSnBu3 nucleophile and BF3ꢀOEt2 resulted
in a poor stereoselectivity (entry 15). The reactions mediated by
SnCl4 and TiCl4 resulted in low yields (entries 16 and 17).
The R4 group shown in Figure 3H for the substrates shown in
Table 1 is an ethyl group; further experiments were conducted
by changing the R4 group. Scheme 1 shows that the R group was
2.1. Allyl additions to anti-
a
-amino-b-hydroxy aldehydes
i
changed to Me, Pr, and Bn in the anti-cases. The reaction condi-
The results of the allylation reactions of 2,3-anti-
a
-amino-b-
tions were selected from entry 5, Table 1 with the highest syn-
selective ratio and yield. All the reactions shown in Scheme 1
afforded syn-selective products in good yields. An interesting trend
was observed: the smaller the R group, the higher the ratio.
hydroxy aldehydes after the Dess–Martin oxidation of the corre-
sponding primary alcohols are shown in Table 1. If epimerization
reactions occurred, diastereomeric products would be detected,

I.-S. Myeong et al. / Tetrahedron: Asymmetry 28 (2017) 1053–1060
1055
Table 1
Allylation reactions of 2,3-anti-a-amino-b-hydroxy aldehydes
1. Dess-Martin
Periodinane
CH2Cl2, rt
OH OR3
4
OR3
3
NR1R2
OH OR3
4
2
5
3
5
3
HO
2.
SiMe3
NR1R2
NR1R2
Lewis acid,
4,5-anti
4,5-syn
CH2Cl2, -78 oC
R1R2=HBoc, R3=TBS
R1R2=HBoc, R3=TBS
R1R2=HCbz, R3=TBS
R1R2=HBoc, R3=TBS
R1R2=HCbz, R3=TBS
1
8
9
10
8'
9'
10'
R R =HCbz, R3=TBS
R1R2=HCbz, R3=Bn
R1R2=BnCbz, R3=TBS
1
2
2b
3
R R =HCbz, R3=Bn
R R =HCbz, R3=Bn
1
2
1
2
4
11 R1R2=BnCbz, R3=TBS
11' R1R2=BnCbz, R3=TBS
Entry
R1 R2
R3
Lewis acid
t (h)
syn:antia (Yield)b
1
2
HBoc
HBoc
HCbz
HCbz
HCbz
HCbz
HCbz
HCbz
HCbz
HCbz
HCbz
HCbz
HCbz
HCbz
BnCbz
BnCbz
BnCbz
TBS
SnCl4
TiCl4
BF3ꢀOEt2
BF3ꢀOEt2
SnCl4
SnCl4
TiCl4
ZnCl2
MgBr2ꢀOEt2
—
1
1
3
3
1
1
1
12
5
1
3
1
3
1
12
3
3
8:80 = 5:1 (66%)
N/Rc,d
TBS
TBS
TBS
TBS
TBS
TBS
TBS
TBS
TBS
Bn
Bn
Bn
Bn
TBS
TBS
TBS
3
N/Rd
4e
9:90 = 6:1 (78%)
9:90 = 10:1 (83%)
9:90 = 10:1 (72%)
9:90 = 2:1 (72%)
N/Rd
9:90 = 1:6 (54%)
9:90 = 2:1 (60%)
10:100 = 3:1 (75%)
10:100 = 10:1 (72%)
10:100 = 4:1 (56%)
10:100 = 2:1 (57%)
11:110 = 2:1 (46%)
Trace
5
6e
7
8f
9f
10f,g
11e
12
13
14f,g
15e
16
17
BF3ꢀOEt2
SnCl4
TiCl4
—
BF3ꢀOEt2
SnCl4
TiCl4
Trace
a
Ratios were determined by 1H NMR.
b
c
d
e
f
Yields refer to two-step yields of mixed isomers.
The starting material was not detected and degraded compounds were observed.
No Reaction.
AllylSnBu3 was employed instead of AllylSiMe3.
Reaction proceeded at 0 °C.
AllylMgBr was employed instead of AllylSiMe3.
g
obtained (entry 6); however, when TiCl4 was used, a poor stereos-
elective product was obtained (entry 7).
Scheme 2 shows that the R group may be changed to Me, allyl,
and Ph in the syn-cases. The reaction conditions were selected
from entry 3, Table 2 with the highest syn-selective ratio and yield.
1. Dess-Martin Periodinane
CH2Cl2, rt
OH OTBS
OTBS
R
HO
R
2.
SiMe3
NHCbz
NHCbz
SnCl4, CH2Cl2, –78 °C
1 h
All the reactions shown in Scheme
2 afforded syn-selective
OH OTBS
NHCbz
OH OTBS
OH OTBS
OH OTBS
products in good yields. The interesting trend in the anti-case
was also observed in syn-case: the smaller the R group, the higher
the ratio.
Bn
NHCbz
13 (from 2c)
NHCbz
9 (from 2b)
NHCbz
14 (from 2d)
12
2a
(from
)
The mechanisms shown in Figure 5 were rationalized by
a-
syn/anti=15:1a, 77%b syn/anti=10:1a, 83%b syn/anti=10:1a, 76%b syn/anti=7:1a, 84%b
chelation (five- and/or seven-membered cyclic TS) between the
amido group and aldehyde oxygen. The anti-selectivity results
shown in entry 9, Table 1 and entry 5, Table 2 can be attributed
to the fact that MgBr2ꢀOEt2 acted as a monodentate ligand
(Felkin–Anh model). Notably, a comparison of results shown in
entries 4 and 7, Table 2 indicates the existence of b-chelation
between the oxygen of benzyl group and aldehyde oxygen via TiCl4
in syn-cases. The unexpected syn-selectivity in entry 13, Table 1
seems to be due to the presence of a vicinal ethyl group; the re-face
of aldehyde carbonyl fixed by b-chelation is congested rather than
the opposite face.
Scheme 1. syn-Selective allylation reactions of several anti-a-NHCbz-b-OTBS
aldehydes. aRatios were determined by 1H NMR and the stereochemistry of the
products was determined by comparing the J values of the vicinal protons with
those of the corresponding rigid oxazolidinone rings.23 Compounds 9 and 90 were
easily converted to the corresponding oxazolidinones, consistent (cis > trans) with
those reported,9 and other compounds showed similar TLC Rf values and 1 H and 13
C
NMR patterns as compound 9. bYields refer to the two-step yields of mixed isomers.
2.2. Allylation reactions to syn-a-Amino-b-hydroxy aldehydes
After conducting the reactions of 2,3-anti-
aldehydes, those of the 2,3-syn- -amino-b-hydroxy aldehydes
were investigated, and the results are summarized in Table 2.
The reactions of 2,3-syn- -NHBoc-b-OTBS substrate 5 did not give
satisfactory results (entries 1 and 2). The Sakurai allylation reac-
tions of 2,3-syn- -NHCbz-b-OTBS substrate 6b mediated by SnCl4
a-amino-b-hydroxy
a
3. Conclusion
a
The stereoselective allylation reactions of acyclic and chiral
amino-b-hydroxy aldehydes are reported. The reactions of anti-
and syn- -NHCbz-b-OTBS substrates mediated by SnCl4 afforded
syn-selective products in good yield. The reaction mechanism
involves -chelation between the amido group and aldehyde
a-
a
and TiCl4 afforded 4,5-syn-selective products (entries 3 and 4),
and the Sakurai allylation mediated by MgBr2ꢀOEt2 produced a
slightly 4,5-anti-oriented product (entry 5). The reactions of 2,3-
a
a
syn-
a-NHCbz-b-OBn substrate 7 were also conducted. When SnCl4
oxygen. Further studies and total syntheses are underway, and
was used as the additive, a highly 4,5-syn-selective product was
the results will be reported in due course.

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I.-S. Myeong et al. / Tetrahedron: Asymmetry 28 (2017) 1053–1060
Table 2
Allylation reactions of 2,3-syn-a-amino-b-hydroxy aldehydes
1. Dess-Martin
Periodinane
CH2Cl2, rt
OH OR3
4
OR3
3
NR1R2
OH OR3
4
2
5
3
5
3
HO
2.
SiMe3
Lewis acid,
CH2Cl2, -78 oC
NR1R2
NR1R2
4,5-anti
4,5-syn
R1R2=HBoc, R3=TBS
R R =HCbz, R =TBS
R R =HBoc, R =TBS
R R =HBoc, R =TBS
1
2
3
1
2
3
5
15
16
17
15'
16'
17'
1
2
3
1
2
3
1
2
3
6b
7
R R =HCbz, R =TBS
R R =HCbz, R =TBS
1
2
3
1
2
3
R1R2=HCbz, R3=Bn
R R =HCbz, R =Bn
R R =HCbz, R =Bn
Entry
R1R2
R3
Lewis acid
t (h)
syn:antia (Yield)b
1
2
3
4
5c
6
7
HBoc
HBoc
HCbz
HCbz
HCbz
HCbz
HCbz
TBS
TBS
TBS
TBS
TBS
Bn
SnCl4
TiCl4
SnCl4
TiCl4
2
4
1
3
12
1
15:150 = 1:1 (61%)
15:150 = 3:1 (54%)
16:160 = 10:1 (83%)
16:160 = 6:1 (65%)
16:160 = 1:2 (57%)
17:170 = 10:1 (62%)
17:170 = 1:2 (56%)
MgBr2ꢀOEt2
SnCl4
Bn
TiCl4
3
a
Ratios were determined by 1H NMR.
Yields refer to two-step yields of mixed isomers.
Reaction proceeded at 0 °C.
b
c
1. Dess-Martin Periodinane
OTBS
TMS or CDCl3 as the internal standard, and coupling constants
are reported in Hertz. The IR spectra were measured with an FT-
IR spectrometer. The mass spectroscopic data were obtained with
a high-resolution mass spectrometer using a magnetic sector—
electric sector double focusing analyzer. Flash chromatography
was performed using mixtures of ethyl acetate and hexane as the
eluents. Unless otherwise noted, all non-aqueous reactions were
performed under an argon atmosphere with commercial grade
reagents and solvents. Tetrahydrofuran (THF) was distilled from
sodium and benzophenone (indicator). Dichloromethane (CH2Cl2)
was distilled from calcium hydride.
OH OTBS
CH2Cl2, rt
R
HO
R
2.
SiMe3
NHCbz
NHCbz
SnCl4, CH2Cl2, –78 °C
1 h
OH OTBS
NHCbz
OH OTBS
OH OTBS
NHCbz
OH OTBS
Ph
NHCbz
NHCbz
18
6a
16 (from 6b)
19
6c
20 (from 6d)
(from
)
(from
)
syn/anti=12:1a, 74%b syn/anti=10:1a, 83%b syn/anti=6:1a, 52%b
syn/anti=8:1a, 53%b
Scheme 2. syn-Selective allylation reactions of several syn-a-NHCbz-b-OTBS alde-
hydes. aRatios were determined by 1H NMR and the stereochemistry of products
was determined by comparing the J values of the vicinal protons with those of the
corresponding rigid oxazolidinone rings.23 Compounds 16, and 160 were easily
converted to the corresponding oxazolidinones, consistent (cis > trans) with those
reported,9 and other compounds showed similar TLC Rf values and 1H and 13C NMR
patterns as compound 16. bYields refer to the two-step yields of mixed isomers.
4.2. General procedure for the Sakurai type allylation reaction
To a solution of the primary alcohol 2b (54 mg, 0.09 mmol) in
anhydrous dichloromethane (0.3 ml) Dess-Martin periodinane
(59 mg, 0.14 mmol) was added at room temperature. The reaction
mixture was stirred at ambient temperature for 2 h. The mixture
was diluted with Et2O then saturated NaHCO3 (53 mg, 0.63 mmol)
and Na2S2O3 (172 mg, 0.354 mmol) were added and the heteroge-
neous mixture was stirred at room temperature until the organic
layer was clear. The organic phase was washed with brine. Dried
with mgSO4 and concentrated in vacuo. The resulting substance
was immediately used without further purification. A solution of
SnCl4 (0.14 ml, 0.14 mmol; 1.0 M in THF) slowly was added to a
solution of above in anhydrous CH2Cl2 (0.9 ml) at ꢁ78 °C. This solu-
tion was stirred for 5 min. at the same temperature and
allyltrimethylsilane (0.03 ml, 0.18 mmol) was dropwised to this
reaction mixture at ꢁ78 °C. The mixture was stirred at ꢁ78 °C until
TLC showed complete reaction. The reaction was quenched with
aqueous saturated NaHCO3, diluted with EtOAc and the organic
phase was washed with saturated brine. Dried with mgSO4 then
concentrated in vacuo. Purification by silica gel chromatography
(hexane/EtOAc = 10:1) gave products 9 (single isomer) as a color-
less oil in 83% yield.
M
M
M
O
OTBS
OBn
O
O
H
NHCbz
O
NH
R
*
CbzHN
OTBS
OTBS
H
H
H
*
H
*
H
R
R
Allyl-
Felkin–Anh
Allyl-
Allyl-
α-chelation
α-chelation
(5-membered cyclic TS) (7-membered cyclic TS)
OH OTBS
OH OTBS
*
R
*
R
NHCbz
syn
NHCbz
anti
Figure 5. Mechanisms of allylation reactions of a-NHCbz-b-OTBS aldehydes.
4. Experimental
4.1. General
4.3. tert-Butyl (2R,3S)-3-(tert-butyldimethylsilyloxy)-1-hydrox-
ypentan-2-ylcarbamate 1
Crude oil; [
2930, 2884, 2857, 1693, 1501, 1472, 1365, 1251, 1170, 1052, 834,
774 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.09 (d, J = 9.4 Hz, 6H),
0.88–0.91 (m, 9H), 0.93 (t, J = 7.5 Hz, 3H), 1.45 (s, 9H), 1.60 (dq,
a] cmax 3450, 3151,
25 = +27.3 (c 1.0, CHCl3); IR (neat)
D
Optical rotations were measured with a polarimeter in the sol-
vent specified. 1H and 13C NMR spectroscopic data were recorded
with an FT-NMR spectrometer at 125, 175, 500, or 700 MHz.
Chemical shift values are reported in parts per million relative to
;

I.-S. Myeong et al. / Tetrahedron: Asymmetry 28 (2017) 1053–1060
1057
J = 14.5, 7.5 Hz, 2H), 3.08 (d, J = 9.8 Hz, 1H), 3.52–3.67 (m, 2H), 3.91
(t, J = 5.6 Hz, 1H), 4.05 (d, J = 10.9 Hz, 1H), 5.33 (d, J = 7.3 Hz, 1H);
13C NMR (101 MHz, CDCl3) d ꢁ4.7, 10.0, 17.9, 25.8, 27.5, 28.4,
52.8, 62.2, 79.4, 155.8; HRMS (EI+) [(M)+] m/z calcd for C16H35NO4-
Si 333.2335; found 333.2334.
MHz, CDCl3) d 1.01 (t, J = 7.4 Hz, 3H), 1.59 (dq, J = 14.2, 7.2 Hz, 1H),
1.76 (dq, J = 14.2, 7.1 Hz, 1H), 2.90 (br. s, 1H), 3.65 (td, J = 6.4,
3.9 Hz, 2H), 3.78 (dd, J = 7.9, 3.6 Hz, 1H), 3.99 (dd, J = 11.5, 2.5 Hz,
1H), 4.47 (d, J = 11.4 Hz, 1H), 4.65 (d, J = 11.4 Hz, 1H), 5.11 (s,
2H), 5.58 (d, J = 8.2 Hz, 1H), 7.28–7.43 (m, 10H); 13C NMR (101
MHz, CDCl3) d 9.9, 23.9, 53.3, 61.9, 66.8, 72.8, 82.8, 127.9, 128.0,
128.1, 128.2, 128.6, 136.5, 137.9, 156.4; HRMS (EI+) [(M)+] m/z
calcd for C20H25NO4 343.1784; found 343.1781.
4.4. Benzyl (2R,3S)-3-(tert-butyldimethylsilyloxy)-1-hydroxy-
butan-2-ylcarbamate 2a
Crude oil; [
a
]
D
25 = +36.3 (c 1.0, CHCl3); IR (neat)
cmax 3338, 2929,
4.9. Benzyl benzyl(2R,3S)-3-(tert-butyldimethylsilyloxy)-1-hydr-
2856, 2342, 1702, 1512, 1463, 1253, 1055, 834, 776, 697 cmꢁ1; 1H
NMR (400 MHz, CDCl3) d 0.03–0.10 (m, 6H), 0.85–0.92 (m, 9H),
1.25 (d, J = 6.4 Hz, 3H), 3.04 (d, J = 8.9 Hz, 1H), 3.49 (dd, J = 8.1,
3.0 Hz, 1H), 3.58–3.69 (m, 1H), 4.12 (d, J = 11.7 Hz, 1H), 4.19 (dd,
J = 6.4, 2.6 Hz, 1H), 5.12 (d, J = 2.6 Hz, 2H), 5.61 (d, J = 7.8 Hz, 1H),
7.29–7.41 (m, 5H); 13C NMR (101 MHz, CDCl3) d ꢁ5.2, ꢁ4.7, 17.8,
20.7, 25.7, 55.8, 61.8, 66.8, 71.6, 128.1, 128.5, 136.5, 156.2; HRMS
(EI+) [(M)+] m/z calcd for C18H31NO4Si 353.2022; found 353.2020.
oxypentan-2-yl)carbamate 4
Crude oil; [a] cmax 3457, 2930,
25 = +18.3 (c 1.0, CHCl3); IR (neat)
D
2856, 1697, 1497, 1455, 1362, 1252, 1118, 1077, 1005, 836, 774,
699 cmꢁ1
;
1H NMR (400 MHz, CDCl3) d ꢁ0.10–0.18 (m, 6H),
0.81–0.97 (m, 12H), 1.38–1.62 (m, 2H), 2.75 (br. s, 1H), 3.68–3.92
(m, 3H), 4.20–4.38 (m, 1H), 4.40–4.59 (m, 1H), 4.60–4.83 (m,
1H), 5.10–5.26 (m, 2H), 7.15–7.47 (m, 10H); 13C NMR (101 MHz,
CDCl3) d ꢁ4.8, ꢁ4.3, 8.1, 18.0, 25.9, 26.7, 51.2, 62.4, 67.5, 72.2,
127.3, 127.4, 127.9, 128.1, 128.5, 128.7, 136.3, 138.5, 157.0; HRMS
(EI+) [(M)+] m/z calcd for C26H39NO4Si 457.2648; found 457.2646.
4.5. Benzyl (2R,3S)-3-(tert-butyldimethylsilyloxy)-1-hydroxy-
pentan-2-ylcarbamate 2b
Crude oil; [
a]
D
25 = +8.0 (c 1.0, CHCl3); IR (neat) cmax 3446, 2954,
4.10. tert-Butyl (2R,3R)-3-(tert-butyldimethylsilyloxy)-1-hydrox-
2930, 2884, 2857, 2359, 2341, 2291, 1704, 1511, 1463, 1254, 1054,
835, 775, 696 cmꢁ1; 1H NMR (400 MHz, CDCl3) d 0.07 (d, J = 2.5 Hz,
6H), 0.89 (s, 9H), 0.95 (t, J = 7.5 Hz, 3H), 1.62 (dq, J = 14.5, 7.5 Hz,
2H), 3.04 (s, 1H), 3.58–3.71 (m, 2H), 3.88–3.97 (m, 1H), 4.08 (d,
J = 11.0 Hz, 1H), 5.13 (s, 2H), 5.57 (d, J = 7.7 Hz, 1H), 7.29–7.40
(m, 5H); 13C NMR (101 MHz, CDCl3) d ꢁ4.8, ꢁ4.6, 9.9, 17.9, 25.8,
27.5, 53.2, 62.0, 66.7, 128.1, 128.5, 136.5, 156.2; HRMS (EI+)
[(M)+] m/z calcd for C19H33NO4Si 367.2179; found 367.2176.
ypentan-2-ylcarbamate 5
Crude oil; [a] cmax 3444, 2930,
25 = +83.5 (c 0.2, CHCl3); IR (neat)
D
2857, 1695, 1496, 1365, 1253, 1171, 1080, 835, 775 cmꢁ1; 1H NMR
(400 MHz, CDCl3) d 0.04–0.11 (m, 6H), 0.83–0.92 (m, 12H), 1.40–
1.49 (m, 9H), 1.49–1.65 (m, 2H), 2.50–2.65 (m, 1H), 3.59 (m, 1H),
3.64 (d, J = 6.0 Hz, 1H), 3.70 (dd, J = 13.5, 6.3 Hz, 1H), 3.77 (t,
J = 6.7 Hz, 1H), 4.90 (d, J = 8.1 Hz, 1H); 13C NMR (101 MHz, CDCl3)
d ꢁ4.8, ꢁ4.2, 9.8, 18.0, 25.8, 27.3, 28.4, 54.1, 64.5, 72.9, 79.6,
156.9; HRMS (EI+) [(M)+] m/z calcd for C16H35NO4Si 333.2335;
found 333.2336.
4.6. Benzyl (2R,3S)-3-(tert-butyldimethylsilyloxy)-1-hydroxy-4-
phenylbutan-2-ylcarbamate 2c
Crude oil; [
2951, 2928, 2888, 2855, 2361, 1702, 1497, 1455, 1339, 1253, 1053,
979, 937, 903, 834, 809, 775, 739, 697 cmꢁ1 1H NMR (400 MHz,
a
]
25 = +16.5 (c 1.0, CHCl3); IR (neat)
c
max 3446, 3031,
4.11. Benzyl (2R,3R)-3-(tert-butyldimethylsilyloxy)-1-hydrox-
ybutan-2-ylcarbamate 6a
D
;
CDCl3) d ꢁ0.24 (s, 3H), 0.02 (s, 3H), 0.86 (s, 9H), 2.88 (dd, J = 15.9,
7.2 Hz, 3H), 3.01 (d, J = 9.7 Hz, 1H), 3.55 (dd, J = 7.2, 2.6 Hz, 1H),
3.65 (ddd, J = 11.6, 9.8, 2.8 Hz, 2H), 4.18 (d, J = 11.7 Hz, 1H), 4.34
(td, J = 6.2, 2.6 Hz, 1H), 5.09 (d, J = 7.5 Hz, 1H), 7.16–7.40 (m,
10H); 13C NMR (101 MHz, CDCl3) d ꢁ5.2, ꢁ4.8, 17.9, 25.8, 41.2,
53.8, 62.1, 66.8, 76.5, 126.7, 128.1, 128.5, 128.6, 129.4 136.4,
137.3, 156.1; HRMS (EI+) [(M)+] m/z calcd for C24H35NO4Si
419.2335; found 429.2337.
Crude oil; [
3066, 3032, 2953, 2929, 2856, 2356, 1721, 1497, 1455, 1254,
1216, 1082, 1028, 837, 777, 748, 698 cmꢁ1 1H NMR (400 MHz,
a]
25 = +22.7 (c 1.0, CHCl3); IR (neat) cmax 3447,
D
;
CDCl3) d 0.08 (s, 6H), 0.89 (s, 9H), 1.19 (d, J = 6.2 Hz, 3H), 2.37
(br. s, 1H), 3.54–3.77 (m, 3H), 4.13 (q, J = 5.9 Hz, 1H), 5.13 (s,
2H), 5.20 (d, J = 7.3 Hz, 1H), 7.30–7.43 (m, 5H); 13C NMR (101
MHz, CDCl3) d ꢁ5.0, ꢁ4.2, 18.0, 20.9, 25.8, 57.8, 64.1, 67.0, 67.6,
128.2, 128.6, 136.3, 157.2; HRMS (EI+) [(M)+] m/z calcd for
C18H31NO4Si 353.2022; found 353.2021.
4.7. Benzyl (2R,3S)-3-(tert-butyldimethylsilyloxy)-1-hydroxy-4-
methylpentan-2-ylcarbamate 2d
4.12. Benzyl (2R,3R)-3-(tert-butyldimethylsilyloxy)-1-hydroxy-
pentan-2-ylcarbamate 6b
Crude oil; [
2929, 2856, 2361, 1700, 1514, 1471, 1253, 1051, 836, 775,
696 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.08 (d, J = 5.5 Hz, 6H),
0.88–0.94 (m, 9H), 0.98 (t, J = 6.7 Hz, 6H), 1.84 (dq, J = 13.7,
6.8 Hz, 1H), 2.91 (dd, J = 9.3, 1.6 Hz, 1H), 3.68 (m, 2H), 3.78 (ddd,
J = 8.1, 6.2, 3.2 Hz, 1H), 4.06 (d, J = 11.6 Hz, 1H), 5.13 (s, 2H), 5.51
(d, J = 7.8 Hz, 1H), 7.29–7.41 (m, 5H); 13C NMR (101 MHz, CDCl3)
d ꢁ4.3, ꢁ4.1, 18.2, 19.1, 26.0, 32.0, 53.0, 62.7, 66.7, 80.8, 128.1,
128.5, 136.5, 156.1; HRMS (EI+) [(M)+] m/z calcd for C20H35NO4Si
381.2335; found 381.2334.
a] cmax 3446, 2956,
25 = +27.5 (c 1.0, CHCl3); IR (neat)
D
Crude oil; [
2857, 1704, 1503, 1464, 1254, 1216, 1080, 1004, 835, 776,
697 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.03–0.12 (m, 6H), 0.85–
a] cmax 3440, 2929,
25 = +19.4 (c 0.5, CHCl3); IR (neat)
D
;
;
0.93 (m, 12H), 1.43–1.65 (m, 2H), 2.29 (t, J = 5.3 Hz, 1H), 3.62 (dt,
J = 10.5, 6.0 Hz, 1H), 3.70 (ddd, J = 10.6, 5.9, 4.4 Hz, 1H), 3.77–3.86
(m, 2H), 5.07–5.20 (m, 3H), 7.30–7.43 (m, 5H); 13C NMR (101
MHz, CDCl3) d ꢁ4.9, ꢁ4.1, 9.9, 18.0. 25.9, 27.3, 54.4, 64.2, 67.0,
72.8, 128.1, 128.2, 128.6, 136.3, 157.2; HRMS (EI+) [(M)+] m/z calcd
for C19H33NO4Si 367.2179; found 367.2176.
4.8. Benzyl (2R,3S)-3-(benzyloxy)-1-hydroxypentan-2-ylcarba-
4.13. Benzyl (2R,3R)-3-(tert-butyldimethylsilyloxy)-1-hydroxy-
mate 3
hex-5-en-2-ylcarbamate 6c
Crude oil; [
a]
25 = +46.2 (c 1.0, CHCl3); IR (neat)
c
max 3410, 2963,
1H NMR (400
Crude oil; [
2927, 2856, 2360, 1706, 1504, 1470, 1331, 1254, 1216, 1090, 1024,
a] cmax 3440, 2953,
25 = +21.6 (c 1.0, CHCl3); IR (neat)
D
D
2361, 1697, 1519, 1454, 1240, 1063, 740, 697 cmꢁ1
;

1058
I.-S. Myeong et al. / Tetrahedron: Asymmetry 28 (2017) 1053–1060
915, 837, 776. 697 cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 0.03–0.16
4.18. Benzyl (3S,4R,5S)-3-(tert-butyldimethylsilyloxy)-5-hydrox-
yoct-7-en-4-ylcarbamate 9
(m, 6H), 0.79–0.97 (m, 9H), 2.19–2.41 (m, 2H), 3.53–3.63 (m,
1H), 3.64–3.75 (m, 1H), 3.80 (q, J = 7.1 Hz, 1H), 3.95 (dd,
J = 7.1 Hz, 5.6 Hz, 1H), 5.03–5.23 (m, 5H), 5.76 (ddt, J = 17.2, 10.0,
7.8 Hz, 1H), 7.29–7.45 (m, 5H); 13C NMR (101 MHz, CDCl3) d
ꢁ4.9, ꢁ4.1, 18.0, 25.8, 39.2, 54.8, 63.8, 67.0, 70.8, 118.3, 128.3,
Crude oil; [a] cmax 3347, 2952,
25 = +14.0 (c 0.5, CHCl3); IR (neat)
D
2857, 2833, 1723, 1501, 1470, 1254, 1031, 837, 777 cmꢁ1; 1H NMR
(400 MHz, CDCl3) d 0.00–0.09 (m, 6H), 0.83–0.90 (m, 9H), 0.93 (t,
J = 7.5 Hz, 3H), 1.64 (dq, J = 11.5, 7.3 Hz, 2H), 2.17 (dt, J = 13.8,
6.9 Hz, 1H), 2.31 (dt, J = 14.0, 7.1 Hz, 1H), 3.56–3.64 (m, 2H), 3.95
(tt, J = 6.0, 2.2 Hz, 1H), 4.19 (t, J = 6.9 Hz, 1H), 5.02–5.19 (m, 4H),
5.50 (d, J = 8.8 Hz, 1H), 5.81 (dddd, J = 18.6, 10.6, 7.2, 6.1 Hz, 1H),
7.29–7.42 (m, 5H); 13C NMR (101 MHz, CDCl3) d ꢁ4.8, ꢁ4.6, 9.9,
17.8, 25.7, 25.8, 27.5, 38.1, 53.4, 66.7, 68.9, 118.0, 128.0, 128.5,
128.6, 133.5, 136.4, 157.0; HRMS (EI+) [(M)+] m/z calcd for C20H32
-
NO4Si 379.2179; found 379.2177.
4.14. Benzyl (1R,2R)-1-(tert-butyldimethylsilyloxy)-3-hydroxy-
1-phenylpropan-2-ylcarbamate 6d
Crude oil; [
a
]
25 = ꢁ7.8 (c 1.0, CHCl3); IR (neat)
cmax 3438, 3033,
128.6, 134.1, 136.6, 156.1; HRMS (EI+) [(M)+] m/z calcd for C22H37
-
NO4Si 407.2492; found 407.2492.
D
2953, 2928, 2885, 2856, 2358, 1703, 1504, 1454, 1253, 1216, 1094,
1065, 1018, 835, 776, 746, 698 cmꢁ1 1H NMR (400 MHz, CDCl3) d
;
ꢁ0.15 (s, 3H), 0.05 (s, 3H), 0.90 (s, 9H), 2.32 (br. s, 1H), 3.61–3.73
(m, 2H), 3.82 (dd, J = 8.3, 3.2 Hz, 1H), 4.90–5.07 (m, 3H), 5.20 (d,
J = 7.8 Hz, 1H), 7.22–7.40 (m, 10H); 13 C NMR (101 MHz, CDCl3) d
ꢁ5.2, ꢁ4.7, 18.1, 25.8, 59.0, 62.9, 66.8, 73.4, 126.2, 127.7, 128.1,
128.2, 128.5, 136.4, 141.4, 156.6; HRMS (EI+) [(M)+] m/z calcd for
4.19. Benzyl (3S,4R,5R)-3-(tert-butyldimethylsilyloxy)-5-hydro-
xyoct-7-en-4-ylcarbamate 90
Crude oil; [
2928, 2856, 2361, 1704, 1512, 1463, 1409, 1333, 1252, 1063,
1027, 910, 834, 773, 739, 696 cmꢁ1 1H NMR (400 MHz, CDCl3)
a]
25 = +21.5 (c 0.2, CHCl3); IR (neat) cmax 3423,
D
C23H33NO4Si 415.2179; found 415.2176.
;
d 0.09 (d, J = 2.6 Hz, 6H), 0.84–0.92 (m, 9H), 0.96 (t, J = 7.3 Hz,
3H), 1.53 (dt, J = 13.9, 7.2 Hz, 2H), 2.22 (dt, J = 13.4, 7.7 Hz,
1H), 2.45 (dd, J = 13.4, 6.2 Hz, 1H), 2.67–2.81 (m, 1H), 3.72–
3.91 (m, 3H), 4.95 (d, J = 8.2 Hz, 1H), 5.07–5.19 (m, 4H), 5.89
(ddt, J = 16.9, 9.7, 7.2 Hz, 1H), 7.30–7.40 (m, 5H); 13C NMR
4.15. Benzyl (2R,3R)-3-(benzyloxy)-1-hydroxypentan-2-ylcarba-
mate 7
Crude oil; [
3033, 2962, 2878, 2345, 1701, 1510, 1455, 1217, 1065, 1027,
740, 697 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.96 (t, J = 7.5 Hz,
a]
25 = +32.6 (c 1.0, CHCl3); IR (neat) cmax 3419,
D
(101 MHz, CDCl3)
d
ꢁ4.6, ꢁ4.4, 9.7, 18.0, 25.8, 26.8, 38.5,
;
57.4, 66.9, 71.5, 75.5, 117.9, 128.1, 128.2, 128.5, 135.0, 156.7;
HRMS (EI+) [(M)+] m/z calcd for C22H37NO4Si 407.2492; found
407.2492.
3H), 1.57 (dt, J = 14.3, 7.4 Hz, 1H), 1.70–1.91 (m, 1H), 2.42 (br. s,
1H), 3.59 (t, J = 6.4 1H), 3.63–3.70 (m, 1H), 3.71–3.80 (m, 1H),
3.83–3.92 (m, 1H), 4.45 (d, J = 11.3 Hz, 1H), 4.65 (d, J = 11.3 Hz,
1H), 5.11 (s, 2H), 5.29 (d, J = 8.9 Hz, 1H), 7.28–7.41 (m, 10H);
13C NMR (101 MHz, CDCl3) d 10.0, 23.3, 53.8, 64.2, 67.0, 72.0,
79.9, 127.8, 128.0, 128.1, 128.2, 128.3, 128.6, 136.3, 137.9,
157.0; HRMS (EI+) [(M)+] m/z calcd for C20H25NO4Si 343.1784;
found 343.1786.
4.20. Benzyl (3S,4R,5S)-3-(benzyloxy)-5-hydroxyoct-7-en-4-ylcar-
bamate 10
Crude oil; [
2937, 2358, 1697, 1505, 1455, 1328, 1215, 1065, 1027, 914, 736,
696 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.98 (t, J = 7.4 Hz, 3H),
a]
25+30.5 (c 1.0, CHCl3); IR (neat) cmax 3417, 3033,
D
;
4.16. tert-Butyl (3S,4R,5S)-3-(tert-butyldimethylsilyloxy)-5-hydro-
xyoct-7-en-4-ylcarbamate 8
1.58 (dq, J = 14.3, 7.2 Hz, 1H), 1.77 (dq, J = 14.1, 7.0 Hz, 1H), 2.11–
2.21 (m, 1H), 2.22–2.33 (m, 1H), 3.23 (br. s, 1H) 3.61–3.70 (m,
2H), 4.12 (t, J = 6.9 Hz, 1H), 4.43 (d, J = 11.3 Hz, 1H), 4.62–4.69
(m, 1H), 5.03–5.17 (m, 4H), 5.53 (d, J = 8.7 Hz, 1H), 5.71–5.86 (m,
1H), 7.22–7.41 (m, 10H); 13C NMR (101 MHz, CDCl3) d 9.9, 24.1,
38.2, 54.1, 66.7, 68.7, 73.2, 84.0, 118.0, 127.9, 128.1, 128.2, 128.3,
128.5, 128.6, 134.2, 136.6, 137.8, 156.3; HRMS (EI+) [(M)+] m/z
calcd for C23H29NO4 383.2097; found 383.2092.
Crude oil; [
2857, 2359, 1717, 1691, 1496, 1390, 1365, 1251, 1172, 1043, 836,
776 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.09 (d, J = 7.8 Hz, 6H),
a] cmax 3442, 2930,
25 = +31.9 (c 1.0, CHCl3); IR (neat)
D
;
0.86–0.95 (m, 12H), 1.41–1.52 (m, 9H), 1.56–1.69 (m, 2H), 2.17
(dt, J = 14.0, 7.1 Hz, 1H) 2.31 (dt, J = 14.0, 7.1 Hz, 1H), 3.52 (dd,
J = 8.8, 1.6 Hz, 1H), 3.64 (s, 1H), 3.94 (ddd, J = 8.1, 6.1, 2.4 Hz, 1H),
4.17 (t, J = 6.9 Hz, 1H), 5.06–5.17 (m, 2H), 5.82 (ddt, J = 17.2, 10.1,
7.1 Hz, 1H); 13C NMR (101 MHz, CDCl3) d ꢁ4.0, ꢁ3.8, 10.7, 18.7,
26.6, 29.2, 29.5, 39.0, 53.7, 69.9, 78.9, 80.1, 118.6, 135.2, 156.5;
HRMS (EI+) [(M)+] m/z calcd for C19H39NO4Si 373.2648; found
373.2648.
4.21. Benzyl (3S,4R,5R)-3-(benzyloxy)-5-hydroxyoct-7-en-4-ylcar-
bamate 100
Crude oil; [
a]
D
25 = +29.4 (c 0.5, CHCl3); IR (neat)
c
max 3420, 3032,
2938, 1698, 1516, 1455, 1248, 1065, 1027, 915, 737, 697 cmꢁ1
;
1H
NMR (400 MHz, CDCl3) d 1.02 (t, J = 7.3 Hz, 3H), 1.63 (dq, J = 13.6,
7.0 Hz, 1H), 1.72 (dq, J = 13.6, 7.0 Hz, 1H), 2.23 (m, 1H), 2.44 (m,
1H), 2.76 (br. s, 1H), 3.63 (q, J = 5.3 Hz, 1H), 3.79 (m, 1H), 3.92–
4.02 (m, 1H), 4.48–4.55 (m, 1H), 4.56–4.63 (m, 1H), 4.95 (d,
J = 9.4 Hz, 1H), 5.05–5.19 (m, 4H), 5.87 (ddt, J = 17.0, 10.0, 7.3 Hz,
1H), 7.28–7.43 (m, 10H); 13C NMR (101 MHz, CDCl3) d 9.7, 23.0,
38.6, 55.5, 67.0, 71.7, 81.3, 118.1, 127.9, 128.0, 128.1, 128.2,
128.3, 128.5, 128.6, 134.9, 136.3, 138.0, 156.6; HRMS (EI+) [(M)+]
m/z calcd for C23H29NO4 383.2097; found 383.2094.
4.17. tert-Butyl (3S,4R,5R)-3-(tert-butyldimethylsilyloxy)-5-
hydroxyoct-7-en-4-ylcarbamate 80
Crude oil; [
2857, 2360, 1696, 1503, 1391, 1366, 1252, 1172, 1064, 835,
774 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.10 (d, J = 7.1 Hz, 6H),
a] cmax 3458, 2930,
25 = +74.0 (c 0.2, CHCl3); IR (neat)
D
;
0.89–0.93 (m, 9H), 0.96 (t, J = 7.5 Hz, 3H), 1.41–1.50 (m, 9H),
1.51–1.72 (m, 2H), 2.21 (dt, J = 14.1, 6.1 Hz, 1H), 2.44 (dd,
J = 14.1, 6.7 Hz, 1H), 2.74–2.90 (m, 1H), 3.67–3.78 (m, 2H), 3.83
(td, J = 5.9, 3.6 Hz, 1H), 4.73 (d, J = 7.6 Hz, 1H), 5.09–5.22 (m, 2H),
5.91 (ddt, J = 17.1, 10.1, 7.0 Hz, 1H); 13C NMR (101 MHz, CDCl3) d
ꢁ4.7, ꢁ4.4, 9.8, 18.0, 25.8, 28.3, 29.7, 38.6, 57.4, 71.7, 75.6, 77.2,
117.5, 135.1, 156.6; HRMS (EI+) [(M)+] m/z calcd for C19H39NO4Si
373.2648; found 373.2646.
4.22. Benzyl (2S,3R,4S)-2-(tert-butyldimethylsilyloxy)-4-hydrox-
yhept-6-en-3-ylcarbamate 12
Crude oil; [
a]
25 = +67.4 (c 0.5, CHCl3); IR (neat)
c
max 3436, 2929,
D
2857, 1700, 1502, 1408, 1252, 1086, 836, 776, 697 cmꢁ1
;
1H NMR

I.-S. Myeong et al. / Tetrahedron: Asymmetry 28 (2017) 1053–1060
1059
(400 MHz, CDCl3) d 0.02–0.09 (m, 6H), 0.83–0.91 (m, 9H), 1.26 (d,
J = 6.5 Hz, 3H), 2.16 (dt, J = 13.8, 6.7 Hz, 1H), 2.32 (dt, J = 13.8,
7.0 Hz, 1H), 3.41 (dd, J = 8.7, 2.2 Hz, 1H), 3.60 (s, 1H), 4.15–4.29
(m, 2H), 5.04–5.20 (m, 4H), 5.53 (d, J = 8.8 Hz, 1H), 5.81 (ddt,
J = 17.0, 10.3, 7.1 Hz, 1H), 7.29–7.41 (m, 5H); 13C NMR (101 MHz,
CDCl3) d ꢁ4.8, ꢁ3.7, 17.9, 20.8, 25.8, 29.7, 38.6, 57.8, 66.9, 72.9,
118.1, 128.0, 128.1, 128.6, 134.2, 136.5, 156.2; HRMS (EI+) [(M)+]
m/z calcd for C21H35NO4Si 393.2335; found 393.2332.
134.3, 136.6, 137.4, 157.1; HRMS (EI+) [(M)+] m/z calcd for
23H29NO4 383.2097; found 383.2096.
C
4.27. Benzyl (2R,3R,4S)-2-(tert-butyldimethylsilyloxy)-4-hydrox-
yhept-6-en-3-ylcarbamate 18
Crude oil; [
2953, 2928, 2856, 2359, 1698, 1505, 1462, 1376, 1310, 1253, 1216,
1063, 1027, 915, 834, 774, 735, 696 cmꢁ1 1H NMR (400 MHz,
a] cmax 3438, 3071,
25 = +29.1 (c 1.0, CHCl3); IR (neat)
D
;
4.23. Benzyl (2S,3R,4S)-2-(tert-butyldimethylsilyloxy)-4-hydroxy-
1-phenylhept-6-en-3-ylcarbamate 13
CDCl3) d 0.05–0.15 (m, 6H), 0.81–0.93 (m, 9H), 1.20 (d, J = 6.2 Hz,
3H), 2.25 (t, J = 6.8 Hz, 2H), 3.03–3.28 (m, 1H), 3.57 (dt, J = 9.8,
2.5 Hz, 1H), 3.90 (td, J = 6.5, 2.0 Hz, 1H), 4.14 (dd, J = 6.2, 2.7 Hz,
1H), 5.06–5.22 (m, 4H), 5.35 (d, J = 9.7 Hz, 1H), 5.85 (ddt, J = 16.9,
10.3, 6.8 Hz, 1H), 7.30–7.43 (m, 5H); 13C NMR (101 MHz, CDCl3)
d ꢁ4.8, ꢁ3.7, 17.9, 20.8, 25.8, 29.7, 38.6, 57.8, 66.9, 72.9, 118.1,
128.1, 128.2, 128.6, 134.2, 136.5, 157.2; HRMS (EI+) [(M)+] m/z
calcd for C21H35NO4Si 393.2335; found 393.2332.
Crude oil; [a] cmax 3447, 3066,
25 = +21.2 (c 1.0, CHCl3); IR (neat)
D
3032, 2953, 2929, 2856, 2356, 1721, 1497, 1455, 1254, 1216, 1082,
1028, 837, 777, 748, 698 cmꢁ1; 1H NMR (400 MHz, CDCl3) d ꢁ0.21
(s, 3H), 0.02 (s, 3H), 0.86 (s, 9H), 2.09 (dt, J = 13.9, 6.9 Hz, 1H), 2.28
(dt, J = 14.0, 7.1 Hz, 1H), 2.83–3.01 (m, 2H), 3.48 (d, J = 8.4 Hz, 1H),
3.63 (s, 1H), 4.30–4.42 (m, 2H), 5.00–5.13 (m, 4H), 5.49 (d,
J = 8.7 Hz, 1H), 5.73 (ddt, J = 17.1, 10.0, 7.2 Hz, 1H), 7.10–7.44 (m,
10H); 13C NMR (101 MHz, CDCl3) d ꢁ5.2, ꢁ4.8, 17.9, 25.9, 38.1,
41.3, 54.1, 66.7, 69.1, 77.5, 117.9, 126.8, 128.0, 128.1, 128.5,
128.7, 129.3, 134.0, 136.5, 137.1, 156.0; HRMS (EI+) [(M)+] m/z
calcd for C27H39NO4Si 469.2648; found 469.2649.
4.28. Benzyl (4R,5R,6S)-4-(tert-butyldimethylsilyloxy)-6-hydro-
xynona-1,8-dien-5-ylcarbamate 19
Crude oil; [
3076, 2952, 2928, 2856, 2332, 1699, 1641, 1504, 1471, 1328,
1254, 1216, 1083, 1028, 1002, 912, 834, 775, 697 cmꢁ1 1H NMR
a]
25 = +147.5 (c 0.2, CHCl3); IR (neat) cmax 3429,
D
;
4.24. Benzyl (3S,4R,5S)-3-(tert-butyldimethylsilyloxy)-5-hydroxy-
2-methyloct-7-en-4-ylcarbamate 14
(400 MHz, CDCl3) d 0.03–0.17 (m, 6H), 0.80–0.97 (m, 9H), 2.16–
2.29 (m, 3H), 2.36 (dt, J = 14.3, 7.0 Hz, 1H), 2.67–2.89 (m, 1H),
3.69 (dt, J = 9.7, 2.8 Hz, 1H), 3.85 (ddd, J = 7.8, 5.3, 2.6 Hz, 1H),
3.93 (dt, J = 7.8, 3.7 Hz, 1H), 5.03–5.21 (m, 6H), 5.30 (d, J = 9.5 Hz,
1H), 5.74–5.91 (m, 2H), 7.29–7.45 (m, 5H); 13C NMR (101 MHz,
CDCl3) d ꢁ4.7, ꢁ3.8, 18.0, 25.8, 38.9, 39.0, 55.6, 67.0, 72.0, 74.7,
118.2, 118.3, 128.2, 128.6, 133.6, 134.1, 136.5, 157.0; HRMS (EI+)
[(M)+] m/z calcd for C23H37NO4Si 419.2492; found 419.2494.
Crude oil; [a] cmax 3447, 2955,
25 = +32.4 (c 1.0, CHCl3); IR (neat)
D
2930, 2857, 2362, 1723, 1504, 1471, 1389, 1252, 1216, 1052, 919,
836, 774, 696 cmꢁ1; 1H NMR (400 MHz, CDCl3) d 0.08 (d, J = 3.1 Hz,
6H), 0.89–0.93 (m, 9H), 0.95 (d, J = 6.9 Hz, 3H), 1.00 (d, J = 6.7 Hz,
3H), 1.85 (dspt, J = 14.3, 7.0 Hz, 1H), 2.16 (dt, J = 13.9, 7.0 Hz, 1H),
2.29 (dt, J = 13.9, 7.0 Hz, 1H), 3.43 (s, 1H), 3.65–3.77 (m, 2H), 4.19
(t, J = 7.0 Hz, 1H), 5.03–5.16 (m, 4H), 5.44 (d, J = 8.7 Hz, 1H), 5.80
(ddt, J = 17.4, 9.9, 7.1 Hz, 1H), 7.29–7.43 (m, 5H); 13C NMR (101
MHz, CDCl3) d ꢁ4.3, ꢁ3.8, 18.2, 19.0, 20.0, 26.1, 31.9, 38.2, 53.1,
66.7, 65.6, 82.1, 118.0, 128.0, 128.1, 128.5, 134.0, 136.6, 156.0;
HRMS (EI+) [(M)+] m/z calcd for C23H39NO4Si 421.2648; found
421.2651.
4.29. Benzyl (1R,2R,3S)-1-(tert-butyldimethylsilyloxy)-3-hydroxy-
1-phenylhex-5-en-2-ylcarbamate 20
Crude oil; [a] cmax 3437, 3033,
25 = +11.5 (c 1.0, CHCl3); IR (neat)
D
2927, 2855, 2362, 1699, 1511, 1455, 1253, 1091, 1064, 916, 836,
777, 699 cmꢁ1
;
1H NMR (400 MHz, CDCl3) d ꢁ0.21 to ꢁ0.11 (m,
3H), 0.04–0.10 (m, 3H), 0.84–0.95 (m, 9H), 2.24 (t, J = 6.7 Hz, 2H),
3.65 (dd, J = 13.8, 7.1 Hz, 1H), 3.75 (ddd, J = 9.4, 5.2, 1.7 Hz, 1H),
3.81 (t, J = 6.1 Hz, 1H), 4.89 (d, J = 5.1 Hz, 1H), 4.96–5.27 (m, 4H),
5.30 (d, J = 9.4 Hz, 1H), 5.77 (ddt, J = 17.0, 9.9, 7.6 Hz, 1H), 7.21–
7.41 (m, 10H) 13C NMR (101 MHz, CDCl3) d ꢁ5.1, ꢁ4.5, 18.0, 25.8,
39.0, 59.7, 66.8, 70.0, 76.0, 118.3, 126.5, 127.8, 127.9, 128.0,
128.1, 128.3, 128.5, 134.2, 141.4, 156.7; HRMS (EI+) [(M)+] m/z
calcd for C26H37NO4Si 455.2492; found 455.2489.
4.25. Benzyl (3R,4R,5S)-3-(tert-butyldimethylsilyloxy)-5-hydro-
xyoct-7-en-4-ylcarbamate 16
Crude oil; [
a]
25 = +10.2 (c 1.0, CHCl3); IR (neat)
c
max 3441, 2931,
D
2857, 1704, 1506, 1254, 1071, 836, 775 cmꢁ1
;
1H NMR (400 MHz,
CDCl3) d 0.03–0.18 (m, 6H), 0.82–0.97 (m, 12H), 1.42–1.55 (m, 1H),
1.55–1.65 (m, 1H), 2.17–2.35 (m, 2H), 2.89 (br. s, 1H), 3.73 (dt,
J = 9.7, 2.4 Hz, 1H), 3.78–3.92 (m, 2H), 5.02–5.29 (m, 4H), 5.29 (d,
J = 9.7 Hz, 1H), 5.87 (ddt, J = 17.2, 10.2, 7.1 Hz, 1H), 7.29–7.44 (m,
5H); 13C NMR (101 MHz, CDCl3) d ꢁ4.6, ꢁ3.8, 9.8, 18.0, 25.8,
27.2, 38.8, 54.8, 66.9, 72.5, 118.1, 128.1, 128.6, 134.2, 136.5,
157.2; HRMS (EI+) [(M)+] m/z calcd for C22H37NO4Si 407.2492;
found 407.2494.
Acknowledgements
Yonsung Fine Chemicals Corporation is acknowledged with
gratitude.
A. Supplementary data
4.26. Benzyl (3R,4R,5S)-3-(benzyloxy)-5-hydroxyoct-7-en-4-ylcar-
bamate 17
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetasy.2017.07.
002.
Crude oil; [
3033, 2935, 2359, 1703, 1506, 1455, 1216, 1066, 1026, 915, 738,
697 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.97 (t, J = 7.5 Hz, 3H),
a] cmax 3437, 3065,
25 = +12.0 (c 1.0, CHCl3); IR (neat)
D
;
References
1.60 (dq, J = 14.0, 7.2 Hz, 1H), 1.79 (m, 1H), 2.22 (t, J = 6.7 Hz,
2H), 3.55–3.64 (m, 1H), 3.79–3.91 (m, 2H), 4.43 (d, J = 11.1 Hz,
1H), 4.49 (d, J = 11.0 Hz, 1H), 5.01–5.22 (m, 5H), 5.39 (d,
J = 9.8 Hz, 1H), 5.84 (ddt, J = 17.0, 10.0, 6.7 Hz, 1H), 7.27–7.42 (m,
10H); 13C NMR (101 MHz, CDCl3) d 9.9, 22.6, 29.7, 38.6, 53.7,
66.9, 71.2, 73.6, 83.9, 117.9, 128.0, 128.1, 128.2, 128.5, 128.7,
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23. The J values of trans compounds (21 and 23) were smaller than those of cis
compounds (22 and 24), consistent with the reported values (Scheme 3), see
Ref. 9.
OH OTBS
OH OTBS
OTBS
OTBS
H
H
H
H
NaH, THF
NaH, THF
NaH, THF
NaH, THF
O
O
O
O
NHCbz
NHCbz
NH
NH
J = 4.3 Hz
J = 7.2 Hz
9
9'
21
22
OH OTBS
OH OTBS
OTBS
OTBS
H
H
H
H
O
O
O
O
NHCbz
NHCbz
NH
NH
J = 3.9 Hz
J = 6.8 Hz
16
16'
23
24
Scheme 3. Coupling constant data.