Highly efficient asymmetric synthesis of vinylic amino alcohols by znpromoted benzoyloxyallylation of chiral N-tert-butanesulfinyl imines: Facile and rapid access to (-)-cytoxazone

Article abstract of DOI:10.1002/chem.200900801

An efficient and convenient α-hydroxyallylation approach for the asymmetric synthesis of a variety of βamino-α-vinyl alcohols has been successfully developed. A wide range of vinylic amino alcohol derivatives could be obtained in very good yields and with

Full text of DOI:10.1002/chem.200900801

FULL PAPER
DOI: 10.1002/chem.200900801
Highly Efficient Asymmetric Synthesis of Vinylic Amino Alcohols by Zn-
Promoted Benzoyloxyallylation of Chiral N-tert-Butanesulfinyl Imines: Facile
and Rapid Access to (À)-Cytoxazone
Min Liu,[a] Xing-Wen Sun,[a] Ming-Hua Xu,*[a, b] and Guo-Qiang Lin*[a]
Abstract: An efficient and convenient
a-hydroxyallylation approach for the
asymmetric synthesis of a variety of b-
amino-a-vinyl alcohols has been suc-
cessfully developed. A wide range of
vinylic amino alcohol derivatives could
be obtained in very good yields and
with excellent diastereomeric ratios of
up to 99:1 in favor of anti isomers by
highly diastereoselective Zn-promoted
benzoyloxyallylation of chiral N-tert-
butanesulfinyl imines with 3-bromopro-
penyl benzoate at room temperature.
In particular, excellent enantioinduc-
tion of the two new stereogenic centers
was observed, with up to 98% ee. The
method provides a new route for the
direct a-hydroxyallylation of imines in
a highly stereoselective manner. More-
over, the synthetic value of the method
has also been demonstrated by the
most concise and straightforward syn-
thesis of (À)-cytoxazone yet reported.
Keywords: amino alcohols · asym-
metric synthesis · chiral auxiliaries ·
(À)-cytoxazone · hydroxyallylation
Introduction
imines,[9] and direct asymmetric pinacol-type cross-coupling
between carbonyls and imines[10]—those with broad reaction
scope and, particularly, that allow substrates containing cer-
tain functional groups are of great interest. Although con-
siderable efforts have been made to explore the functionali-
ty limitations in many methods, the current achievements
remain far from satisfactory.
b-Amino alcohol compounds containing a-vinyl groups
are an important class of densely functionalized materials.
They serve as precursors for a-hydroxy-b-amino acids,[11] b-
hydroxy-g-amino acids,[12] and many related natural products
of biological interest. Unfortunately, despite the potential
significance of b-amino-a-vinyl alcohols as valuable building
blocks for organic synthesis and medicinal chemistry, meth-
ods for their highly stereoselective preparation are very lim-
ited.[13] In the literature, simple and direct additions of vinyl-
metal reagents such as vinylmagnesium halides to enantio-
merically pure N-protected a-amino aldehydes are often
used in the synthesis of b-amino-a-vinyl alcohol derivatives,
but mostly low to moderate diastereoselectivities are afford-
ed.[14] Moreover, the use of enantiopure starting a-amino al-
dehydes could sometimes be a disadvantage because of their
relatively poorer availability.
b-Amino alcohols are important structural motifs present in
many natural products and pharmaceutical compounds.[1]
They have also been used as powerful chiral ligands or aux-
iliaries in asymmetric synthesis.[2] Over the past two decades,
the asymmetric synthesis of b-amino alcohol derivatives has
attracted much attention.[3] Among the successful strategies
developed for obtaining optically active b-amino alcohols—
such as asymmetric aminohydroxylation,[4] ring-opening of
chiral epoxides[5] or aziridines,[6] nucleophilic addition to
protected a-hydroxyimines or a-aminocarbonyls,[7] a-alkox-
yenolate addition to imine derivatives,[8] catalytic asymmet-
ric Mannich-type reactions of a-hydroxyketones and
[a] M. Liu, Dr. X.-W. Sun, Prof. Dr. M.-H. Xu, Prof. G.-Q. Lin
Key Laboratory of Synthetic Chemistry of Natural Substances
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences, 345 Lingling Road
Shanghai 200032 (China)
Fax : (+86)21-5080-7388
E-mail: xumh@mail.sioc.ac.cn
lingq@mail.sioc.ac.cn
[b] Prof. Dr. M.-H. Xu
Shanghai Institute of Materia Medica
Chinese Academy of Sciences, Zuchongzhi Road
Shanghai 201203 (China)
The addition of an a-hydroxyallyl carbanion to a carbonyl
imino compound (Scheme 1) represents another, very
straightforward, type of route to b-amino-a-vinyl alcohol de-
rivatives, but less progress with this approach has been ach-
ieved because of the poorer electrophilicities of imines rela-
E-mail: xumh@mail.sioc.ac.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200900801.
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Results and Discussion
It is known that 3-bromopropenyl benzoate (3-benzoyloxy-
allyl bromide)[21] is an ideal a-hydroxyallyl reagent for acy-
loxyallylation because of its easy preparation, high stability,
and remarkable reactivity. We initially examined the reac-
tion between the (R)-N-tert-butanesulfinyl imine 1a and
(E)-3-benzoyloxyallyl bromide [(E)-2] in THF in the pres-
ence of zinc metal at room temperature (Table 1). To our
Scheme 1. Direct a-hydroxyallylation approach.
tive to the corresponding carbonyl compounds and also be-
cause of severe difficulties in regio- and diastereoselectivity
control.[15,16] In particular, direct asymmetric a-hydroxyally-
lation of imino derivatives is far more rarely encountered in
the literature.[17] Excellent stereoselectivities have been ob-
tained only in some cases of reagent-controlled asymmetric
a-alkoxyallylation of azomethine derivatives with enantioen-
riched g-oxygenated allylic stannanes and boranes.[17a–c] Sev-
eral examples of the use of chiral imines as substrates have
been described, but these reactions have often given only
low to moderate levels of stereocontrol.[15c,17d–e] Although
the ring-opening of chiral vinylaziridines with oxygen nucle-
ophiles provides an alternative route to b-amino-a-vinyl al-
cohols,[18] multiple synthetic operations are required. As
such, new strategies for accessing b-amino-a-vinyl alcohol
compounds with high optical purity are greatly desirable.
Here we report an efficient and convenient approach for the
asymmetric synthesis of a variety of b-amino-a-vinyl alco-
hols by highly diastereoselective Zn-promoted a-hydroxyal-
lylation of N-tert-butanesulfinyl imines at room temperature.
N-tert-Butanesulfinyl imines have recently shown versatile
applicability in the asymmetric synthesis of various chiral
amines.[19,20] In an earlier work, we successfully developed
an efficient method for the highly diastereoselective synthe-
sis of chiral homoallylic amines by Zn-mediated allylation
of enantioenriched N-tert-butanesulfinyl imines at room
temperature.[20d] More recently, we reported our further dis-
covery of a simple and mild system in aqueous media for In-
mediated asymmetric allylation of N-sulfinyl imines to give
chiral homoallylic amines and 3-allylisoindolinone deriva-
tives with excellent diastereoselectivity.[20e] Encouraged by
these successes in allylation chemistry, we wondered wheth-
er this N-sulfinyl imine strategy could be extended to asym-
metric a-hydroxyallylation for the synthesis of optically
active b-amino-a-vinyl alcohols (Scheme 2).
Table 1. Initial examination of benzoyloxyallylation.
Entry[a]
Solvent
t [h]
Yield [%][b]
dr[c]
ee [%][d]
1[e]
2[e]
3[f]
THF
3
12
3
12
12
12
69
95
85
96
95
41
98:2
99:1
99:1
98:2
99:1
99:1
84
96
79
92
96
97
HMPA[g]
THF
4[f]
HMPA[g]
HMPA
THF
5[e,h]
6[e,i]
[a] The reaction was performed with imine 1a (0.25 mmol) and Zn/2
(0.5 mmol) in dry solvent (5 mL) at RT, unless otherwise noted. [b] Iso-
lated yield of product 3a. [c] Diastereomeric ratio for the acetate deriva-
tive of product 3a after the removal of the sulfinyl moiety. [d] Enantio-
meric excess for the acetate derivative of compound 3a after the removal
of the sulfinyl moiety. [e] Pure E isomer of 2 was used. [f] E/Z mixture
(31:69) of 2 was used. [g] H2O (10 mL) was used as additive. [h] The reac-
tion was performed with imine 1a (5 mmol) and (E)-2 (10 mmol) in
HMPA (100 mL) containing H2O (0.2 mL) at RT. [i] In was used instead
of Zn.
delight, the reaction proceeded well and afforded the ex-
pected benzoyloxyallylation product with excellent syn/anti
diastereoselectivity in 69% yield (Table 1, entry 1), although
minor formation of the hydrolysis product 4a (about 10%)
was also detected. When HMPA was used as solvent, very
gratifyingly, the reaction gave solely the benzoyloxyallyla-
tion product 3a in 95% yield (entry 2). Unlike in reported
cases of allylation of benzylideneanilines,[15b] it is noteworthy
that no internal migration of the benzoyl group was ob-
served either in THF or in HMPA systems, probably as a
result of the decreased nucleophilic capability of the sulfinyl
nitrogen.
To improve understanding of the stereochemical outcome
of the reaction, the benzoyloxyallylation product 3a ob-
tained in entry 1 of Table 1 was chosen for conversion into a
related cyclic compound for further NMR studies. As illus-
trated in Scheme 3, removal of the sulfinyl group under
acidic conditions, followed by acetyl protection, afforded the
corresponding vinylic amino alcohol 5a in good yield. The
use of LC-MS and chiral HPLC analysis of 5a clearly re-
vealed the diastereoselectivity (98:2 dr) and enantioselectivi-
ty (84% ee) of asymmetric benzoyloxyallylation in THF
(Table 1, entry 1). Subsequent debenzoylation of derivative
5a in NaOH/MeOH and cyclization of the resulting product
Scheme 2. Proposed asymmetric a-hydroxyallylation procedure.
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Asymmetric Synthesis of Vinylic Amino Alcohols
FULL PAPER
both cases (Table 1, entries 3 and 4). Notably, with the E
isomer of 2 the same levels both of diastereoselectivity
(99:1 dr) and of enantioselectivity (96% ee) could be ob-
tained in HMPA even on a gram scale (Table 1, entry 5).
In addition, replacement of zinc with indium in the same
benzoyloxyallylation reaction was also tested. Interestingly,
excellent stereoselectivities (99:1 dr, 97% ee) could be ach-
ieved in THF, but the yield was not ideal (41%) even after
12 h (entry 6). When HMPA was used as solvent, no reac-
tion was observed.
Scheme 3. Stereochemistry determination.
with CDI (1,1’-carbonyldiimidazole), followed by hydroge-
nation, provided the cis-configured oxazolidinone derivative
6a. The cis configuration of 6a was confirmed by the cou-
pling constant (J4,5 =7.6 Hz) between H-4 and H-5,[22] and by
NOE experimentation. Accordingly, the major diastereoiso-
mer 5a was assigned as anti. By the same method and
through comparison with the HPLC trace of 5a, the benzoy-
loxyallylic addition in HMPA was also found to be highly
anti-selective (99:1). To our pleasure, the reaction provided
a much improved enantioselectivity, and an excellent ee
value of 96% was obtained (Table 1, entry 2). It should be
noted that a reversal of stereofacial selectivity was again
achieved as we had previously found in the simple allylic ad-
dition (entry 2 vs entry 1), suggesting different transition
states in THF and HMPA. Fortunately, with a single crystal
of the benzoyloxyallylation product 3a obtained from (S)-
N-sulfinyl imine 1a in the HMPA system, the absolute con-
figuration of the two newly generated stereocenters was un-
ambiguously determined by X-ray crystallography to be
(1R,2S) (Figure 1). Thus, treatment of the enantiopure (R)-
To explain the observed results, we proposed two differ-
ent transition state models—TS-1 and TS-3 (Scheme 4)—for
the reactions under different conditions. As described in the
Scheme 4. Mechanistic proposals relating to reaction stereocontrol.
previous studies[20d] of simple allylation of N-sulfinyl imines
with allyl bromide, in a THF system a six-membered cyclic
chair transition state model is believed to be preferred and
the allylzinc is thought to coordinate both to the imine ni-
trogen and to sulfinyl oxygen. In the benzoyloxyallylation
reaction, however, because of the steric repulsion between
the imine phenyl group and the benzoyloxy group attached
to the allylzinc reagent (see TS-2), a six-membered boat-like
transition state (TS-1) should be favored, accordingly lead-
ing to the dominance of the (1R,2S)-anti-amino alcohol
product when the (R)-N-tert-butanesulfinyl imine is em-
ployed. In a HMPA system, according to our previous hy-
pothesis, the acyclic anti periplanar transition state TS-3, in
which the allylzinc moiety is coordinated to the Lewis base
(HMPA) rather than to the sulfinyl oxygen, is likely to be
involved. As depicted, the nucleophilic attack of the corre-
sponding benzoyloxyallylzinc reagent would be expected to
take place predominately from the less sterically hindered
Figure 1. X-ray crystal structure of 3a produced from the (S)-N-sulfinyl
imine with the HMPA system.
N-sulfinyl imine 1a with 3-benzoyloxyallyl bromide (2) in
the presence of zinc at room temperature either in THF or
in HMPA gave the major products (1R,2S)-anti-3a and
(1S,2R)-anti-3a, respectively.
We also examined the benzoyloxyallylation of the (R)-N-
tert-butanesulfinyl imine 1a with an E/Z mixture (~31:69) of
3-benzoyloxyallyl bromide (2) rather than the E isomer,
both in THF and in HMPA systems. Although the same ex-
cellent levels of diastereoselectivity were observed, the
enantioselectivities were slightly reduced, by about 5% in
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M.-H. Xu, G.-Q. Lin et al.
re-face of the imine to deliver the (1S,2R)-anti-amino alco-
hol product. Thus, simply by tuning the reaction solvent it is
possible to achieve a remarkable reversal of diastereofacial
selectivity to afford the desired stereochemical outcome.
With optimal conditions identified, we turned our atten-
tion to investigation of the reaction scope and generality. As
summarized in Table 2, a series of (R)-N-tert-butanesulfinyl
stereoselectivity was dramatically improved to 98:2, but the
enantioselectivity remained moderate (81% ee).
With this highly diastereoselective and enantioselective
Zn-promoted a-hydroxyallylation approach to hand, we
sought to demonstrate its synthetic utility by the efficient
asymmetric synthesis of (À)-cytoxazone. Cytoxazone is a se-
lective modulator of Th2 cytokine secretion isolated from
Streptomyces sp.[23] Because of its important biological activ-
ity, the development of efficient asymmetric routes to cytox-
azone and its stereoisomers have recently attracted consider-
able attention from organic chemists.[24] Despite the progress
achieved, a method for convenient and rapid access to the
optically active cytoxazone target is still in great demand.
According to the retrosynthetic analysis of the (À)-cytox-
azone molecule (Scheme 5), an expedient synthesis should
be readily achievable through the use of the corresponding
Table 2. Diastereoselective benzoyloxyallylation of (R)-N-tert-butanesul-
finyl imines in the HMPA system.
Entry[a]
1
R
3
Yield[b] [%] anti/syn[c] ee [%][d]
1
2
3
4
5
6
7
8
1a C6H5
3a 95
3b 99
3c 99
3d 99
3e 98
3 f 99
3g 99
3h 98
99:1
98:2
97:3
95:5
98:2
95:5
97:3
99:1
99:1
98:2
99:1
99:1
99:1
99:1
98:2
79:21
79:21
78:22
98:2
96
93
93
93
95
98
96
90
98
98
92
93
86
93
95
87
80
85
81
1b 4-FC6H4
1c 2-ClC6H4
1d 3-ClC6H4
1e 4-ClC6H4
1 f 3-BrC6H4
1g 4-BrC6H4
1h 2-CH3C6H4
9
1i
1j
4-CH3C6H4
4-CH3SC6H4
3i
3j
96
98
10
11
12
13
14
15
16
17
18
19
1k 3-MeOC6H4
1l 4-MeOC6H4
1m 2,4-(MeO)2C6H3 3m 75
1n 2,4-Cl2C6H3
1o b-naphthyl
1p C6H5CH2CH2
1q CH3CH2CH2
3k 99
3l 99
3n 99
3o 96
3p 98
3q 90
3r 89
3s 94
1r
ACHTUNGTRENNUNG(CH3)2CHCH2
1s C6H11
[a] The reaction was performed with imine
1 (0.25 mmol), Zn/2
(0.5 mmol), and H2O (10 mL) in dry HMPA (5 mL) at RT. [b] Isolated
yield. [c] Diastereomeric ratio for the acetate derivative of product 3
after the removal of the sulfinyl moiety. [d] Enantiomeric excess for the
acetate derivative of product 3 after the removal of the sulfinyl moiety.
Scheme 5. Synthesis of (À)-cytoxazone through asymmetric benzoyloxy-
allylation.
anti-b-amino-a-vinyl alcohol 7 as the key intermediate.
Indeed, as indicated in entry 12 of Table 2, asymmetric ben-
zoyloxyallylation of the (R)-N-sulfinyl imine 1l with (E)-3-
benzoyloxyallyl bromide 2 provided the (1S,2R)-anti-amino
alcohol 3l in excellent yield (99%), diastereoselectivity
(99:1 dr), and enantioselectivity (93% ee). Accordingly, the
benzoyloxyallylation of the corresponding (S)-N-sulfinyl
imine was carried out also under HMPA conditions to give
the desired (1R,2S)-anti-amino alcohol product with 98:2 dr
and 92% ee. Removal of the benzoyl group with NaOH in
methanol (1%) and of the sulfinyl group under acidic condi-
tions (HCl/MeOH), followed by treatment with CDI (1,1’-
carbonyldiimidazole), gave the enantiomerically enriched
oxazolidone 8 in 89% yield, and this was smoothly convert-
ed into (À)-cytoxazone by oxidation of the double bond
with O3 and subsequent reduction of the ozonide with
sodium borohydride by the literature procedure.[24g] On
comparison of the optical rotation, the absolute stereochem-
istry of the prepared compound was found to be fully consis-
imines bearing a range of R substituents were examined in
reactions with (E)-3-benzoyloxyallyl bromide (2) in HMPA
in the presence of zinc (2 equiv). In most cases, the benzoy-
loxyallylation proceeded in good yields and with excellent
diastereoselectivities to afford various highly optically active
b-amino-a-vinyl alcohol products. For aromatic substrates, it
was found that the position and property of the substituent
on the benzene ring did not significantly affect either the re-
activity or the selectivity of the reaction (entries 1–15). Very
high enantioselectivities (98% ee) were achieved in the
cases of imines 1 f, 1i, and 1j (entries 6, 9, and 10).
The use of aliphatic substrates were also examined (en-
tries 16–19). Decreases both in diastereoselectivity (78:22–
79:21 dr) and in enantioselectivity (80–87% ee) were ob-
served with use of the less sterically hindered N-sulfinyl
imines of 3-phenylpropanal (1p), butanal (1q), and 3-meth-
ylbutanal (1r) (entries 16–18). When the more bulky cyclo-
hexyl imine (1s) was employed (entry 19), the reaction dia-
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Asymmetric Synthesis of Vinylic Amino Alcohols
FULL PAPER
tent with that of the known (À)-cytoxazone {[a]2D1 À70.0 (c=
0.1, MeOH); lit.[23] [a]D25 À71 (c=0.1, MeOH); lit.[24l] [a]2D4
À70.9 (c=0.1, MeOH)}. The total synthesis of (À)-cytoxa-
zone had thus been easily achieved in three linear steps
(82% overall yield) from the (S)-N-tert-butanesulfinyl imine
of p-anisaldehyde. Similarly, (+)-cytoxazone could be ob-
tained in the same way. To the best of our knowledge, this
approach represents one of the most convenient and effi-
cient syntheses of cytoxazone reported to date.
The residue was purified by silica gel column chromatography to afford
the corresponding benzoyloxyallylation product 3.
General procedure for Zn-promoted benzoyloxyallylation of chiral N-
tert-butanesulfinyl imines in HMPA: H2O (10 mL) was added at room
temperature under argon to
a suspension of activated zinc powder
(32 mg, 0.5 mmol), 3-benzoyloxyallyl bromide (121 mg, 0.5 mmol), and
the (R)-N-tert-butanesulfinyl imine (0.25 mmol) in dry HMPA (5 mL,
Caution: TOXIC). The reaction mixture was stirred at RT for 12 h,
quenched with aqueous HCl (1m, 5 mL), and extracted with ethyl ace-
tate. The combined organic layers were dried over anhydrous Na2SO4, fil-
tered, and concentrated. The residue was purified by silica gel column
chromatography to afford the corresponding benzoyloxyallylation prod-
uct 3.
AHCTUNGTERG(NNUN 1S,2R)-1-((R)-1,1-Dimethylethylsulfinamido)-1-phenylbut-3-en-2-yl ben-
Conclusions
zoate (3a): [a]2D8 39.4 (c=1.02, CHCl3); 1H NMR (500 MHz, CDCl3): d=
1.19 (s, 9H), 3.77 (d, J=5.2 Hz, 1H), 4.79 (dd, J1 =J2 =5.0 Hz, 1H), 5.30
(d, J=10.6 Hz, 1H), 5.37 (d, J=17.2 Hz, 1H), 5.74–5.81 (m, 1H), 5.92–
5.74 (m, 1H), 7.27–7.57 (m, 8H), 8.01–8.02 ppm (m, 2H); 13C NMR
(125 MHz, CDCl3): d=22.6, 56.5, 61.3, 76.4, 119.3, 127.9, 128.2, 128.4,
128.5, 129.5, 129.9, 132.2, 133.1, 138.2, 165.4 ppm; FT-IR (film): n˜ =3325,
2985, 1711, 1455, 1269, 1062, 718, 701 cmÀ1; ESI-MS: m/z (%): 372.2
[M+H]+, 394.2 [M+Na]+; HRMS (MALDI): m/z: calcd for
C21H25NO3SNa: 394.1462 [M+Na]+; found: 394.1447.
In summary, we have developed an efficient approach for
the asymmetric synthesis of b-amino alcohol compounds
containing a-vinyl groups through highly diastereoselective
Zn-promoted Barbier-type a-hydroxyallylations of N-tert-
butanesulfinyl imines with 3-benzoyloxyallyl bromide at
room temperature. The method provides a new route for
the direct a-hydroxyallylation of imines in a highly stereose-
lective manner. With the effective stereocontrol provided by
the tert-butanesulfinyl group, benzoyloxyallyl addition to
imine derivatives offers an attractive route to a variety of
anti-b-amino-a-vinyl alcohols with excellent yields, diaste-
reoselectivities, and enantioselectivities. Moreover, the syn-
thetic value of the protocol has been demonstrated by the
most concise and straightforward synthesis to date of (À)-
cytoxazone. We believe that this promising methodology
and the obtained valuable vinylic amino alcohols will find
widespread use in asymmetric synthesis. Further explora-
tions are now in progress in our laboratories.
Crystallographic data for (1R,2S)-3a (C21H25NO3S): T=293(2) K; wave-
length: 0.71073 ꢁ; crystal system: triclinic, space group: P1; unit cell di-
mensions: a=5.7901 (12), b=9.569(2), c=10.630(2) ꢁ, a=106.961, b=
100.943, g=107.0128; V=513.72(18) ꢁ3; Z=1; 1calcd =1.201 MgmÀ3
;
FACHTNUTRGENG(UN 000)=198; final R indices [I>2s (I)]: R1 =0.0603, wR2 =0.1520; R indi-
ces (all data), R1 =0.0688, wR2 =0.1572; 2905 reflections measured, 2468
unique (Rint =0.1172).
AHCTUNGTERG(NNUN 1S,2R)-1-((R)-1,1-Dimethylethylsulfinamido)-1-(4-fluorophenyl)but-3-
en-2-yl benzoate (3b): [a]D26 31.8 (c=1.03, CHCl3); 1H NMR (500 MHz,
CDCl3): d=1.19 (s, 9H), 3.74 (d, J=5.9 Hz, 1H), 4.77 (dd, J1 =J2 =
5.1 Hz, 1H), 5.30–5.39 (m, 2H), 5.73–5.80 (m, 1H), 5.89–5.91 (m, 1H),
7.04–7.08 (m, 2H), 7.41–7.46 (m, 4H), 7.56–7.59 (m, 1H), 7.99–8.01 ppm
(m, 2H); 13C NMR (125 MHz, CDCl3): d=22.5, 56.5, 60.8, 76.3, 115.4,
115.5, 119.6, 128.5, 129.5, 129.6, 129.7, 129.8, 132.1, 133.2, 134.01, 134.03,
161.5, 163.5, 165.4 ppm; FT-IR (film): n˜ =3434, 3313, 2968, 2928, 1708,
1512, 1049, 712 cmÀ1; ESI-MS: m/z (%): 390.2 [M+H]+, 412.2 [M+Na]+;
HRMS (MALDI): m/z: calcd for C21H24NO3SFNa: 412.1373 [M+Na]+;
found: 412.1353.
Experimental Section
AHCTUNGTERG(NNUN 1S,2R)-1-(2-Chlorophenyl)-1-((R)-1,1-dimethylethylsulfinamido)but-3-
en-2-yl benzoate (3c): [a]D26 26.2 (c=0.97, CHCl3); 1H NMR (400 MHz,
CDCl3): d=1.20 (s, 9H), 4.01 (d, J=7.4 Hz, 1H), 5.23 (dd, J=7.2, 5.7 Hz,
1H), 5.32 (d, J=10.5 Hz, 1H), 5.38 (d, J=17.1 Hz, 1H), 5.81–5.90 (m,
1H), 5.93–5.96 (m, 1H), 7.20–7.29 (m, 2H), 7.36–7.44 (m, 3H), 7.50–7.55
(m, 2H), 7.99–8.01 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=22.5,
56.7, 58.2, 75.4, 119.5, 126.9, 128.4, 129.3, 129.4, 129.6, 129.8, 129.9, 132.2,
133.1, 133.4, 136.1, 165.0 ppm; FT-IR (KBr): n˜ =3318, 3085, 3044, 2964,
1716, 1269, 1066, 761, 718 cmÀ1; ESI-MS: m/z (%): 406.2 [M+H]+, 428.2
[M+Na]+; HRMS (MALDI): m/z: calcd for C21H24NO3SClNa: 428.1077
[M+Na]+; found: 428.1058.
General: Chiral N-tert-butanesulfinyl imines were prepared from the
chiral N-tert-butanesulfinyl amine and the corresponding aldehydes by
the known method.[25] THF was distilled from sodium/benzophenone, and
HMPA (Caution: toxic compound) was distilled from CaH2. Zinc dust
was activated by stirring for 5 min with HCl (1m), followed by washing
successively with water, acetone, and ether and drying with a heat gun.
Reactions were monitored by thin layer chromatography (TLC) on glass
plates coated with silica gel with fluorescent indicator (Huanghai
HSGF254). Flash chromatography was performed on silica gel (Huanghai
300–400) with hexane/EtOAc as eluent. Mass spectra were recorded on a
HP-5989 instrument and HRMS were measured on a Finnigan MA+
AHCTUNGTERG(NNUN 1S,2R)-1-(3-Chlorophenyl)-1-((R)-1,1-dimethylethylsulfinamido)but-3-
en-2-yl benzoate (3d): [a]D26 33.4 (c=1.05, CHCl3); 1H NMR (400 MHz,
CDCl3): d=1.19 (s, 9H), 3.76 (d, J=5.9 Hz, 1H), 4.76 (dd, J=5.8, 4.2 Hz,
1H), 5.31–5.40 (m, 2H), 5.71–5.79 (m, 1H), 5.76–5.91 (m, 1H), 7.26–7.31
(m, 3H), 7.43–7.47 (m, 3H), 7.56–7.58 (m, 1H), 8.00–8.02 ppm (m, 2H);
13C NMR (100 MHz, CDCl3): d=22.6, 56.7, 60.9, 76.1, 119.7, 126.3, 128.2,
128.5, 129.6, 129.8, 131.9, 133.3, 134.5, 140.2, 165.3 ppm; FT-IR (KBr):
n˜ =3428, 2960, 2922, 1709, 1262, 1115, 1051, 715, 699 cmÀ1; ESI-MS: m/z
(%): 406.2 [M+H]+, 428.2 [M+Na]+; HRMS (MALDI): m/z: calcd for
C21H24NO3SClNa: 428.1072 [M+Na]+; found: 428.1058.
mass spectrometer. Infrared spectra were measured on
a Perkin–
Elmer 983 spectrometer. NMR spectra were recorded on a Varian or a
Bruker spectrometer (300 MHz, 400 MHz, or 500 MHz), and chemical
shifts are reported in d (ppm) referenced to an internal TMS standard
for H NMR and CDCl3 (77.0 ppm) for 13C NMR. Optical rotations were
1
measured on a JASCO P-1030 polarimeter with a sodium lamp.
General procedure for Zn-promoted benzoyloxyallylation of chiral N-
tert-butanesulfinyl imines in THF: Freshly distilled dry THF (5 mL) was
added at room temperature under argon to a Schlenk flask containing ac-
tivated zinc powder (32 mg, 0.5 mmol), 3-benzoyloxyallyl bromide
(121 mg, 0.5 mmol), and the (R)-N-tert-butanesulfinyl imine (52 mg,
0.25 mmol). The mixture was then stirred at RT for 3 h, quenched with
brine (5 mL), and extracted with ethyl acetate. The combined organic
layers were dried over anhydrous Na2SO4, filtered, and concentrated.
AHCTUNGTERG(NNUN 1S,2R)-1-(4-Chlorophenyl)-1-((R)-1,1-dimethylethylsulfinamido)but-3-
en-2-yl benzoate (3e): [a]D26 47.1 (c=1.03, CHCl3); 1H NMR (400 MHz,
CDCl3): d=1.19 (s, 9H), 3.76 (d, J=6.1 Hz, 1H), 4.76 (dd, J=6.0, 4.4 Hz,
1H), 5.30–5.40 (m, 2H), 5.72–5.78 (m, 1H), 5.89–5.91 (m, 1H), 7.33–7.40
(m, 4H), 7.43–7.46 (m, 2H), 7.55–7.60 (m, 1H), 7.99–8.01 ppm (m, 2H);
13C NMR (100 MHz, CDCl3): d=22.5, 56.6, 60.8, 76.2, 119.6, 128.5, 128.7,
Chem. Eur. J. 2009, 15, 10217 – 10224
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10221

M.-H. Xu, G.-Q. Lin et al.
129.3, 129.5, 129.8, 132.0, 133.2, 134.1, 136.7, 165.3 ppm; FT-IR (film): n˜ =
3434, 2958, 1715, 1317, 1270, 1114, 1053, 931, 712 cmÀ1; ESI-MS: m/z
(%): 406.2 [M+H]+, 428.2 [M+Na]+; HRMS (MALDI): m/z: calcd for
C21H25ClO3NS: 406.1219 [M+H]+; found: 406.1238.
HRMS (MALDI): m/z: calcd for C22H27NO4SNa: 424.1570 [M+Na]+;
found: 424.1553.
AHCTUNGTERG(NNUN 1S,2R)-1-((R)-1,1-Dimethylethylsulfinamido)-1-(4-methoxyphenyl)but-3-
en-2-yl benzoate (3l): [a]D27 41.9 (c=1.03, CHCl3); 1H NMR (400 MHz,
CDCl3): d=1.19 (s, 9H), 3.68 (d, J=5.5 Hz, 1H), 3.80 (s, 3H), 4.73 (dd,
J1 =J2 =4.9 Hz, 1H), 5.28–5.39 (m, 2H), 5.74–5.80 (m, 1H), 5.89–5.92 (m,
1H), 6.88–6.92 (m, 2H), 7.34–7.38 (m, 2H), 7.42–7.46 (m, 2H), 7.68–7.59
(m, 1H), 8.01–8.03 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=22.6,
55.2, 56.4, 60.9, 76.4, 113.9, 119.3, 128.4, 129.1, 129.6, 130.0, 130.3, 132.5,
133.1, 159.4, 165.4 ppm.; FT-IR (film): n˜ =3431, 3310, 2958, 2929, 1710,
1261, 1051, 713 cmÀ1; ESI-MS: m/z (%): 402.3 [M+H]+, 424.2 [M+Na]+;
HRMS (MALDI): m/z: calcd for C22H27NO4SNa: 424.1573 [M+Na]+;
found: 424.1553.
ACHTUNGTRENNUNG(1S,2R)-1-(3-Bromophenyl)-1-((R)-1,1-dimethylethylsulfinamido)but-3-
en-2-yl benzoate (3 f): [a]D25 34.2 (c=0.97, CHCl3); 1H NMR (400 MHz,
CDCl3): d=1.19 (s, 9H), 3.82 (d, J=5.6 Hz, 1H), 4.74 (dd, J1 =J2 =
5.0 Hz, 1H), 5.30–5.39 (m, 2H), 5.71–5.79 (m, 1H), 5.89–5.92 (m, 1H),
7.24 (td, J=5.7, 1.6 Hz, 1H), 7.36 (d, J=7.8 Hz, 1H), 7.43–7.47 (m, 3H),
7.55–7.59 (m, 1H), 7.64 (s, 1H), 8.00–8.06 ppm (m, 2H); 13C NMR
(100 MHz, CDCl3): d=22.5, 56.5, 60.8, 76.0, 119.6, 122.5, 126.7, 128.4,
129.5, 129.7, 129.9, 131.1, 131.3, 131.9, 133.2, 140.4, 165.2 ppm; FT-IR
(KBr): n˜ =3337, 2926, 1712, 1519, 1320, 1267, 1061, 714, 684 cmÀ1; ESI-
MS: m/z (%): 450.1 [M+H]+, 472.1
calcd for C21H24NO3SBrNa: 472.0572 [M+Na]+; found: 472.0553.
ACHTUNGTRENNUNG(1S,2R)-1-(4-Bromophenyl)-1-((R)-1,1-dimethylethylsulfinamido)but-3-
[M+Na]+; HRMS (MALDI): m/z:
ACHTUNGTRENNUNG
AHCTUNGTERG(NNUN 1S,2R)-1-(2,4-Dimethoxyphenyl)-1-((R)-1,1-dimethylethylsulfinamido)-
but-3-en-2-yl benzoate (3m): [a]2D5 À15.1 (c=1.01, CHCl3); 1H NMR
(500 MHz, CDCl3): d=1.19 (s, 9H), 3.73 (s, 3H), 3.81 (s, 3H), 4.23 (d,
J=8.7 Hz, 1H), 4.82 (dd, J=8.3, 5.9 Hz, 1H), 5.23–5.34 (m, 2H), 5.80–
5.94 (m, 2H), 6.40–6.45 (m, 2H), 7.23 (d, J=8.1 Hz, 1H), 7.35–7.53 (m,
3H), 7.91–7.94 ppm (m, 2H); 13C NMR (125 MHz, CDCl3): d=22.5, 55.3,
55.4, 56.4, 59.0, 75.9, 98.9, 104.5, 118.3, 119.4, 128.3, 129.5, 129.7, 129.8,
132.9, 133.5, 157.8, 160.6, 165.2 ppm; FT-IR (film): n˜ =3336, 2958, 1712,
1519, 1267, 1118, 1061, 714 cmÀ1; ESI-MS: m/z (%): 432.3 [M+H]+, 454.3
[M+Na]+; HRMS (MALDI): m/z: calcd for C23H29NO5SNa: 454.1675
[M+Na]+; found: 454.1659.
en-2-yl benzoate (3g): [a]D28 48.9 (c=1.05, CHCl3); 1H NMR (400 MHz,
CDCl3): d=1.18 (s, 9H), 3.73 (d, J=5.1 Hz, 1H), 4.74 (dd, J1 =J2 =
5.2 Hz, 1H), 5.30–5.40 (m, 2H), 5.71–5.79 (m, 1H), 5.88–5.91 (m, 1H),
7.31–7.33 (m, 2H), 7.43–7.52 (m, 4H), 7.56–7.58 (m, 1H), 7.99–8.01 ppm
(m, 2H); 13C NMR (100 MHz, CDCl3): d=22.6, 56.6, 60.9, 76.2, 119.7,
122.3, 128.5, 129.6, 129.7, 129.8, 131.7, 132.0, 133.3, 137.3, 165.4 ppm; FT-
IR (film): n˜ =3339, 2956, 2923, 1713, 1267, 1064, 988, 714 cmÀ1; ESI-MS:
m/z (%): 450.2 [M+H]+, 472.2 [M+Na]+; HRMS (MALDI): m/z: calcd
for C21H25NO3SBr: 450.0752 [M+H]+; found: 450.0733.
AHCTUNGTREG(NNUN 1S,2R)-1-(2,4-Dichlorophenyl)-1-((R)-1,1-dimethylethylsulfinamido)but-
1
3-en-2-yl benzoate (3n): [a]D26 34.5 (c=0.99, CHCl3); H NMR (300 MHz,
CDCl3): d=1.20 (s, 9H), 4.05 (d, J=7.8 Hz, 1H), 5.19–5.23 (m, 1H),
5.32–5.41 (m, 2H), 5.78–5.94 (m, 2H), 7.26–7.30 (m, 1H), 7.39–7.48 (m,
4H), 7.55–7.60 (m, 1H), 7.99–8.02 ppm (m, 2H); 13C NMR (100 MHz,
CDCl3): d=22.5, 56.8, 57.7, 75.2, 119.7, 127.3, 128.4, 129.5, 129.6, 130.4,
131.9, 133.3, 134.1, 134.5, 134.8, 165.0 ppm; FT-IR (film): n˜ =2923, 1722,
1561, 1475, 1268, 1110, 1026, 711 cmÀ1; ESI-MS: m/z (%): 440.2 [M+H]+,
462.2 [M+Na]+; HRMS (MALDI): m/z: calcd for C21H23NO3SNaCl2:
462.0685 [M+Na]+; found: 462.0668.
ACHTUNGTRENNUNG(1S,2R)-1-((R)-1,1-Dimethylethylsulfinamido)-1-o-tolylbut-3-en-2-yl ben-
zoate (3h): [a]2D7 26.0 (c=1.03, CHCl3); 1H NMR (500 MHz, CDCl3): d=
1.18 (s, 9H), 2.50 (s, 3H), 3.73 (d, J=5.2 Hz, 1H), 5.06 (dd, J1 =J2 =
4.6 Hz, 1H), 5.33 (d, J=9.4 Hz, 1H), 5.42 (d, J=15.4 Hz, 1H), 5.82–5.86
(m, 2H), 7.17–7.24 (m, 3H), 7.42–7.45 (m, 3H), 7.54–7.57 (m, 1H),
8.02 ppm (d, J=7.7 Hz, 2H); 13C NMR (125 MHz, CDCl3): d=19.7, 22.6,
56.3, 56.4, 76.0, 119.7, 126.2, 127.1, 127.9, 128.4, 129.6, 130.0, 130.7, 132.1,
133.1, 136.0, 136.8, 165.3 ppm; FT-IR (KBr): n˜ =3323, 2983, 2965, 2928,
1718, 1268, 1112, 1064, 719, 706 cmÀ1; ESI-MS: m/z (%): 386.2 [M+H]+,
408.3 [M+Na]+; HRMS (MALDI): m/z: calcd for C22H27NO3SNa:
408.1623 [M+Na]+; found: 408.1604.
AHCTUNGTERG(NNUN 1S,2R)-1-((R)-1,1-Dimethylethylsulfinamido)-1-(naphthalen-2-yl)but-3-
en-2-yl benzoate (3o): [a]D27 59.2 (c=1.00, CHCl3); 1H NMR (400 MHz,
CDCl3): d=1.21 (s, 9H), 3.89 (d, J=5.7 Hz, 1H), 4.97 (dd, J1 =J2 =
4.9 Hz, 1H), 5.30 (d, J=10.6 Hz, 1H), 5.39 (d, J=17.2 Hz, 1H), 5.76–5.84
(m, 1H), 6.02–6.04 (m, 1H), 7.42–7.51 (m, 4H), 7.55–7.60 (m, 2H), 7.83–
7.90 (m, 4H), 8.03–8.05 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=
22.6, 56.6, 61.3, 76.4, 119.5, 125.6, 126.3, 126.4, 127.3, 127.7, 128.1, 128.4,
128.5, 129.6, 129.9, 132.1, 133.10, 133.12, 133.2, 135.6, 165.5 ppm; FT-IR
(film): n˜ =3464, 3345, 3046, 2952, 1713, 1266, 1115, 1060, 715 cmÀ1; ESI-
MS: m/z (%): 422.2 [M+H]+, 444.3 [M+Na]+; HRMS (MALDI): m/z:
calcd for C25H27NO3SNa: 444.1621 [M+Na]+; found: 444.1604.
ACHTUNGTRENNUNG(1S,2R)-1-((R)-1,1-Dimethylethylsulfinamido)-1-p-tolylbut-3-en-2-yl ben-
zoate (3i): [a]2D9 49.6 (c=1.06, CHCl3); 1H NMR (400 MHz, CDCl3): d=
1.19 (s, 9H), 2.33 (s, 3H), 3.71 (d, J=5.6 Hz, 1H), 4.75 (dd, J1 =J2 =
4.9 Hz, 1H), 5.27–5.39 (m, 2H), 5.74–5.82 (m, 1H), 5.90–5.92 (m, 1H),
7.15–7.18 (m, 2H), 7.32 (d, J=7.7 Hz, 2H), 7.43 (t, J=7.6 Hz, 2H), 7.54–
7.58 (m,1H), 8.01–8.03 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=
21.0, 22.5, 56.4, 61.1, 76.4, 119.2, 127.8, 128.4, 129.2, 129.5, 130.0, 132.3,
133.0, 135.2, 137.9, 165.4 ppm; FT-IR (film): n˜ =3338, 3061, 2953, 2923,
2852, 1712, 1267, 1118, 1062, 987, 715, 700 cmÀ1; ESI-MS: m/z (%): 386.3
[M+H]+, 408.3 [M+Na]+; HRMS (MALDI): m/z: calcd for
C22H27NO3SNa: 408.1621 [M+Na]+; found: 408.1604.
4-((R)-1,1-Dimethylethylsulfinamido)-6-phenylhex-1-en-3-yl
benzoate
(3p): [a]2D6 À20.9 (c=1.03, CHCl3); 1H NMR (400 MHz, CDCl3): d=1.21
(s, 9H), 1.82–1.96 (m, 1H), 2.03–2.14 (m, 1H), 2.76–3.00 (m, 2H), 3.24
(d, J=7.2 Hz, 1H), 3.56–3.66 (m, 1H), 5.29–5.42 (m, 2H), 5.54–5.57 (m,
1H), 5.82–5.94 (m, 1H), 7.16–7.22 (m, 1H), 7.25–7.30 (m, 4H), 7.41–7.47
(m, 2H), 7.54–7.60 (m, 1H), 8.01–8.05 ppm (m, 2H); 13C NMR
(100 MHz, CDCl3): d=22.6, 31.7, 33.8, 56.2, 58.9, 77.3, 119.1, 126.0, 128.3,
128.4, 128.5, 129.5, 129.9, 132.4, 133.1, 141.0, 165.3 ppm; FT-IR (film): n˜ =
3494, 3130, 3027, 2955, 2860, 1712, 1266, 1027, 713 cmÀ1; ESI-MS: m/z
(%): 400.3 [M+H]+, 422.3 [M+Na]+; HRMS (MALDI): m/z: calcd for
C23H29NO3SNa: 422.1778 [M+Na]+; found: 422.1760.
ACHTUNGTRENNUNG(1S,2R)-1-((R)-1,1-Dimethylethylsulfinamido)-1-[4-(methylthio)phenyl]-
but-3-en-2-yl benzoate (3j): [a]2D7 60.2 (c=1.05, CHCl3); 1H NMR
(300 MHz, CDCl3): d=1.15 (s, 9H), 2.43 (s, 3H), 3.74 (d, J=5.7 Hz, 1H),
4.70 (dd, J1 =J2 =4.7 Hz, 1H), 5.25–5.37 (m, 2H), 5.68–5.79 (m, 1H),
5.73–5.89 (m, 1H), 7.21 (d, J=7.8 Hz, 2H), 7.34 (d, J=8.1 Hz, 2H), 7.41
(t, J=3.8 Hz, 2H), 7.54 (t, J=7.2 Hz, 1H), 7.99 ppm (d, J=7.5 Hz, 2H);
13C NMR (75 MHz, CDCl3): d=15.4, 22.4, 56.3, 60.7, 76.1, 119.3, 126.1,
128.2, 128.3, 129.4, 129.7, 132.0, 133.0, 134.7, 138.5, 165.2 ppm; FT-IR
(film): n˜ =3340, 2976, 2958, 2921, 1713, 1268, 1114, 1060, 717, 703 cmÀ1
;
ESI-MS: m/z (%): 418.3 [M+H]+, 440.3 [M+Na]+; HRMS (MALDI):
m/z: calcd for C22H27O3NS2Na: 440.1343 [M+Na]+; found: 440.1325.
4-((R)-1,1-Dimethylethylsulfinamido)hept-1-en-3-yl
benzoate
(3q):
1H NMR (400 MHz, CDCl3): d=0.95 (t, J=7.0 Hz, 3H), 1.18 (s, 9H),
1.40–1.69 (m, 4H), 3.08 (d, J=6.4 Hz, 1H), 3.57–3.63 (m, 1H), 5.33 (d,
J=10.8 Hz, 1H), 5.38 (d, J=17.2 Hz, 1H), 5.51–5.52 (m, 1H), 5.85–5.94
(m, 1H), 7.40–7.44 (m, 2H), 7.53–7.57 (m, 1H), 8.02 ppm (d, J=7.6 Hz,
2H); 13C NMR (100 MHz, CDCl3): d=13.7, 19.0, 22.6, 34.4, 56.1, 58.9,
77.2, 119.1, 128.3, 129.5, 132.2, 133.0, 133.4, 165.4 ppm; FT-IR (KBr): n˜ =
3233, 3070, 2959, 2872, 1721, 1270, 1111, 1069, 713 cmÀ1; ESI-MS: m/z
(%): 338.2 [M+H]+, 360.2 [M+Na]+ ; HRMS (MALDI): m/z: calcd for
C18H27NO3SNa: 360.1604 [M+Na]+; found: 360.1612.
ACHTUNGTRENNUNG(1S,2R)-1-((R)-1,1-Dimethylethylsulfinamido)-1-(3-methoxyphenyl)but-3-
en-2-yl benzoate (3k): [a]D26 33.9 (c=0.96, CHCl3); 1H NMR (500 MHz,
CDCl3): d=1.19 (s, 9H), 3.75–3.80 (m, 4H), 4.77 (dd, J1 =J2 =4.9 Hz,
1H), 5.31 (d, J=10.6 Hz, 1H), 5.39 (d, J=17.2 Hz, 1H), 5.76–5.83 (m,
1H), 5.91–5.93 (m, 1H), 6.84–6.86 (m, 1H), 6.94–7.03 (m, 2H), 7.27–7.30
(m, 1H), 7.44 (t, J=7.7 Hz, 2H), 7.56 (t, J=7.4 Hz, 1H), 8.02–8.04 ppm
(m, 2H); 13C NMR (125 MHz, CDCl3): d=22.5, 55.2, 56.5, 61.2, 76.4,
113.6, 113.7, 119.3, 120.1, 128.4, 129.5, 129.9, 132.2, 133.1, 139.8, 159.6,
165.3 ppm; FT-IR (film): n˜ =3337, 2960, 2835, 1713, 1600, 1272, 1068,
4-((R)-1,1-Dimethylethylsulfinamido)-6-methylhept-1-en-3-yl
benzoate
717, 711 cmÀ1
;
ESI-MS: m/z (%): 402.2 [M+H]+, 424.2 [M+Na]+;
(3r): 1H NMR (400 MHz, CDCl3): d=0.93–0.99 (m, 6H), 1.18 (s, 9H),
10222
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ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Chem. Eur. J. 2009, 15, 10217 – 10224

Asymmetric Synthesis of Vinylic Amino Alcohols
FULL PAPER
1.46–1.52 (m, 2H), 1.83–1.93 (m, 1H), 3.05 (d, J=7.2 Hz, 1H), 3.64–3.70
(m, 1H), 5.34 (d, J=10.4 Hz, 1H), 5.38 (d, J=17.2 Hz, 1H), 5.50–5.51
(m, 1H), 5.85–5.94 (m, 1H), 7.41–7.46 (m, 2H), 7.53–7.57 (m, 1H),
8.03 ppm (d, J=7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=21.7, 22.6,
23.1, 24.0, 41.4, 56.1, 57.1, 77.4, 119.2, 128.3, 129.5, 132.2, 133.0, 133.4,
165.4 ppm; FT-IR (KBr): n˜ =3231, 3068, 2957, 2869, 1720, 1270, 1111,
for 40 min, the solvent was removed in vacuo, and H2O (10 mL) was
added. The solution was extracted with ethyl acetate, dried over anhy-
drous Na2SO4, and concentrated in vacuo. The residue was dissolved in
methanol (5 mL) and mixed with a solution of dry HCl in 1,4-dioxane
(4n, 5 mL). The mixture was stirred at RT for 0.5 h, neutralized with am-
monia, and extracted with EtOAc. After concentration of the combined
organic phases under reduced pressure, 1,1-carbonyldiimidazole (CDI,
6 mmol, 810 mg) and N,N-4-dimethylaminopyridine (DMAP, 1 mmol,
122 mg) were added to a solution of the resulting crude product in fresh
THF (10 mL). The mixture was stirred at room temperature for 18 h and
was then quenched with saturated aqueous NH4Cl (10 mL). The aqueous
phase was extracted with EtOAc, washed with brine, dried over anhy-
drous Na2SO4, filtered, and concentrated in vacuo. Purification by flash
1069, 713 cmÀ1 ESI-MS: m/z (%): 352.2 [M+H]+, 374.2 [M+Na]+;
;
HRMS (MALDI): m/z: calcd for C19H29NO3SNa+: 374.1760 [M+Na]+;
found: 374.1779.
ACHTUNGTRENNUNG(1S,2R)-1-Cyclohexyl-1-((R)-1,1-dimethylethylsulfinamido)but-3-en-2-yl
benzoate (3s): [a]2D8 À5.9 (c=1.07, CHCl3); 1H NMR (500 MHz, CDCl3):
d=1.10–1.38 (m, 15H), 1.52–1.55 (m, 1H), 1.66 (m, 1H), 1.82–1.85 (m,
3H), 2.00 (d, J=12.6 Hz, 1H), 3.20 (d, J=7.6 Hz, 1H), 3.44–3.49 (m,
1H), 5.35–5.51 (m, 2H), 5.65–5.67 (m, 1H), 5.91–6.01 (m, 1H), 7.41–7.48
(m, 2H), 7.54–7.58 (m, 1H), 8.05 ppm (d, J=7.6 Hz, 2H); 13C NMR
(125 MHz, CDCl3): d=22.8, 25.9, 26.0, 26.1, 29.1, 30.3, 39.8, 56.4, 63.8,
75.9, 119.3, 128.3, 129.6, 130.1, 132.6, 133.0, 165.5 ppm; FT-IR (film): n˜ =
3249, 3072, 2927, 2854, 1716, 1451, 1273, 1113, 1069, 713 cmÀ1; ESI-MS:
m/z (%): 378.3 [M+H]+, 400.3 [M+Na]+; HRMS (MALDI): m/z: calcd
for C21H31NO3SNa: 400.1936 [M+Na]+; found: 400.1917.
column chromatography gave oxazolidone
8 as a pale yellow solid
(0.974 g, 89%). [a]2D4 À12.0 (c=1.01, CHCl3); 1HNMR (300 MHz,
CDCl3): d=3.81 (s, 3H), 4.94 (d, J=7.5 Hz, 1H), 5.11–5.15 (m, 1H),
5.22–5.36 (m, 3H), 5.51 (brs, 1H), 6.89 (d, J=8.4 Hz, 2H), 7.13 ppm (d,
J=8.7 Hz, 2H); EI-MS: m/z (%): 219 (14.59) [M]+, 162 (92.70), 135
(100.00).
(À)-Cytoxazone: Ozone was bubbled through a solution of 8 (0.876 g,
4.0 mmol) in anhydrous CH2Cl2 (10 mL) and MeOH (20 mL) at À788C
until the blue color persisted, the excess was then purged out with N2
until decolorization, and NaBH4 (1.52 g, 40 mmol) was added at À788C.
The reaction mixture was slowly warmed to 08C, stirred at 08C for 1 h,
and concentrated in vacuo. The residue was dissolved in H2O (30 mL)
and EtOAc (200 mL), and the organic layer was separated and washed
with H2O and brine, dried over anhydrous Na2SO4, and concentrated in
vacuo. The residue was purified by column chromatography to give (À)-
cytoxazone (0.83 g, 93%) as a white solid. [a]2D1 À70.0 (c=0.1, MeOH);
1H NMR (300 MHz, [D6]DMSO): d=2.94–2.98 (m, 2H), 3.75 (s, 3H),
4.67–4.72 (m, 1H), 4.85–4.87 (m, 1H), 4.91 (d, J=8.4 Hz, 1H), 6.94 (d,
J=8.1 Hz, 2H), 7.15 (d, J=8.4 Hz, 2H), 8.08 ppm (s, 2H); 13C NMR
(100 MHz, [D6]DMSO): d=55.0, 56.1, 61.0, 80.0, 113.6, 128.0, 129.2,
158.8, 159.0 ppm; EI-MS: m/z (%): 223 (17.90) [M]+, 163 (32.59), 135
(100.00).
1-Acetamido-1-phenylbut-3-en-2-yl benzoate (anti-5a):
A solution of
HCl in 1,4-dioxane (4n, 0.2 mL) was added to a solution of the benzoy-
loxyallylation product 3a (74 mg, 0.2 mmol) obtained from the THF
system (Table 1, entry 1) in dry methanol (2 mL). The mixture was stirred
at RT for 0.5 hour and the solvent was removed in vacuo. Triethylamine
(0.4 mL) and acetic anhydride (40 mL, 0.4 mmol) were added to the solu-
tion of the resulting crude product dissolved in fresh CH2Cl2 (2 mL). The
mixture was stirred at RT for 3 h, followed by the addition of ethyl ace-
tate (30 mL). The solution was washed with brine, dried, filtered, and
concentrated in vacuo. Purification by flash column chromatography
gave the major product anti-5a as a white solid (61 mg, 99%). 1H NMR
(400 MHz, CDCl3): d=2.02 (s, 3H), 5.28–5.45 (m, 3H), 5.73–5.87 (m,
2H), 6.19 (d, J=8.0 Hz, 1H), 7.26–7.46 (m, 7H), 7.57 (t, J=7.6 Hz, 1H),
7.99 ppm (d, J=7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=23.4, 55.7,
76.5, 119.1, 127.4, 127.9, 128.5, 128.6, 129.7, 129.8, 132.4, 133.3, 137.5,
165.6, 169.3 ppm; FT-IR (film): n˜ =3271, 3071, 1713, 1648, 1272, 1106,
713, 698 cmÀ1; ESI-MS: m/z (%): 332.0 [M+Na]+, 347.8 [M+K]+, 364.0
[M+MeOH+Na]+; HRMS (MALDI): m/z: calcd for C19H19NO3Na+:
332.12572 [M+Na]+; found: 332.1257.
Acknowledgements
ACHTUNGTRENNUNG(4R,5S)-3-Acetyl-5-ethyl-4-phenyloxazolidin-2-one (cis-6a): Compound
We thank the National Natural Science Foundation of China (20672123,
20672126, 20721003, 20772017), the Chinese Academy of Sciences, the
Shanghai Rising-Star Program (08QH14027), and the Major State Basic
Research Development Program (2006CB806106) for their generous fi-
nancial support.
anti-5a (46 mg, 0.15 mol), obtained as above, was added to sodium hy-
droxide in methanol (1%). After the system had been stirred at RT for
40 min, the solvent was removed in vacuo and H2O (5 mL) was added to
the residue. The solution was extracted with ethyl acetate, dried over an-
hydrous Na2SO4, and concentrated under reduced pressure. The residue
was dissolved in anhydrous THF (5 mL) and mixed with 1,1’-carbonyldii-
midazole (CDI, 49 mg, 0.30 mmol) and NaH (36 mg, 1.5 mmol). The re-
sulting suspension was stirred under argon at RT for 18 h and filtered.
The filter cake was rinsed with ethyl acetate. The combined organic
phases were washed with HCl (1n) and sat. aqueous NaHCO3, dried, fil-
tered, and concentrated. Purification by silica gel column chromatogra-
phy gave the unsaturated oxazolidinone product in 71% yield (25 mg).
Pd/C (5 mg, 10 wt.% Pd) was carefully added to a solution of this unsatu-
rated oxazolidinone product (23 mg, 0.1 mmol) in MeOH (5 mL). The re-
action mixture was stirred under H2 for 12 h and filtered through celite.
The combined organic phases were concentrated. Purification by flash
column chromatography gave the saturated oxazolidinone derivative 6a
(21 mg, 92%). [a]2D2 À63.4 (c=0.46, CHCl3); 1H NMR (400 MHz,
CDCl3): d=0.92 (t, J=7.4 Hz, 3H), 1.21–1.27 (m, 2H), 2.53 (s, 3H), 4.65
(dt, J=5.7, 7.6 Hz, 1H), 5.38 (d, J=7.6 Hz, 1H), 7.17–7.19 (m, 2H),
7.33–7.39 ppm (m, 3H); 13C NMR (100 MHz, CDCl3): d=9.0, 22.78,
22.82, 60.1, 79.7, 126.0, 127.7, 127.8, 134.2, 153.0, 168.5 ppm; FT-IR (film):
n˜ =3034, 2973, 1782, 1709, 1372, 1317, 1201, 1047, 706 cmÀ1; ESI-MS: m/z
(%): 234.0 [M+H]+, 256.0 [M+Na]+; HRMS (MALDI): m/z: calcd for
C13H15NO3Na: 256.09441 [M+Na]+; found: 256.09470.
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Received: March 27, 2009
Revised: June 26, 2009
Published online: August 26, 2009
10224
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 10217 – 10224