Regio-selective reduction of the C-C double bonds in α,β- unsaturated acyl 4-substituted oxazolidin-2-ones and oxazolidine-2-thiones

Article abstract of DOI:10.1016/j.tet.2011.11.038

Selective saturation of the conjugated C-C double bonds in the title compounds was examined in a systematic way for the first time. Many established protocols effective for similar reduction of α,β-unsaturated ketones and esters in the literature were found to be inapplicable in the present context. The most satisfactory results were finally obtained using the DIBAL-H/MeLi/CuI/HMPA/THF conditions.

Full text of DOI:10.1016/j.tet.2011.11.038

Tetrahedron 68 (2012) 846e850
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Regio-selective reduction of the CeC double bonds in a,b-unsaturated acyl
4-substituted oxazolidin-2-ones and oxazolidine-2-thiones
*
Shao-Gang Li, Jian-Wei Jin, Yikang Wu
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road,
Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 October 2011
Received in revised form 4 November 2011
Accepted 15 November 2011
Available online 22 November 2011
Selective saturation of the conjugated CeC double bonds in the title compounds was examined in
a systematic way for the first time. Many established protocols effective for similar reduction of a,b-
unsaturated ketones and esters in the literature were found to be inapplicable in the present context. The
most satisfactory results were finally obtained using the DIBAL-H/MeLi/CuI/HMPA/THF conditions.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Reduction
Alkenes
Chiral auxiliary
Hydride
Stereochemistry
1. Introduction
straightforward access to 1 is the N-acylation2 of the chiral aux-
iliary 23 with the corresponding carboxylic acid 3. However, ex-
N-acyl oxazolidinones (e.g., 1) are the key precursors in Evans
asymmetric alkylation and aldol reactions (Scheme 1).1 Since their
introduction in the early 1980s, these reactions have found
countless successful applications in enantioselective synthesis of
a diverse of optically active compounds.
ceptions also exist. For instance, for those N-acyl oxazolidinones
exemplified by 9, especially when the R00 contains multi stereo-
genic centers and functionalities, it is often more convenient to
derive such species from 8,4 which in turn may be constructed
from 6 and 7 (Scheme 2).
O
O
O
O
Alkylation
R'
O
N
O
O
O
NH
Bn
H
6
O
O
O
O
R''
R
R''
O
O
N
Bn
4
2
O
N
R''
O
N
R
O
Aldol
reaction
Bn
O
O
OH
O
8
9
Bn
Bn
O
N
?
1
OEt
OEt
O
N
R'
?
HO
3
P
Bn
O
R
R
7
5
Bn
Scheme 2. An alternative route to the N-acyl oxazolidinones.
Scheme 1. The most common route to N-acyl oxazolidinones and their applications.
In many cases so far documented in the literature the R (in 1,
As the selective reduction of the conjugated CeC double bonds
in species like 8 is an essential step in such an approach and to our
knowledge no systematic investigations5 on this type of reductions
have ever been reported, we performed the present work in con-
nection with some on-going total synthesis projects. The results are
given below.
Scheme 1) is
a simple alkyl group. Therefore, the most
* Corresponding author. E-mail addresses: yikang@sioc.ac.cn, yikangwu@
mail.sioc.ac.cn (Y. Wu).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.11.038

S.-G. Li et al. / Tetrahedron 68 (2012) 846e850
847
2. Results and discussion
Table 2
Outline for the conjugate reduction of 10bela
There have been quite a few established protocols that were
shown to be effective for selective reduction of the conjugate CeC
double bonds in a,b-unsaturated ketones and esters. Because of the
apparent structural similarity as far as the conjugate system is
concerned, we first examined those conditions listed in Table 1,
using the readily accessible 10a as the substrate (Scheme 3).
Entry
1
Substrate
Product (yield)
O
O
O
O
O
N
OTBS
O
N
OTBS
11b (87%)
Bn
Bn
10b
O
O
O
O
O
Table 1
OBn
OBn
TMS
Reduction of 10a into 11a under different conditions
O
N
O
N
2
3
Entry
Conditions
Yield of 11a
1
2
3
4
5
6
K-Selectride/THF/ꢀ78 ꢁC
0a
Bn
Bn
11c (90%)
10c
Super Hydride/THF/0 ꢁ
C
0b
Sm/I2/THF/MeOH/0 ꢁ
LiAlH4/CuI/THF/0 ꢁ
C
0b
O
O
O
C
57%c
27%d
95%e
CuI/MeLi/DIBAL-H/HMPA/THF/ꢀ78 ꢁ
C
C
O
N
O
O
N
CuI/MeLi/DIBAL-H/HMPA/THF/ꢀ78 ꢁ
TMS
Bn
a
Bn
11d (100%)
The chiral auxiliary 2 was completely cut off from the acyl chain.
10d
b
No species with an intact oxazolidinone ring could found in the product
mixture.
O
O
c
O
O
The remainder of the product mixture were side product(s) without the oxa-
O
O
O
O
zolidinone moiety.
4
5
6
N
O
N
d
Using 1.2 mol equiv (with respect to 10a) of DIBAL-H with most of the starting
10a unreacted.
e
10e
Bn
O
11e (96%)
Bn
Using 8 mol equiv of DIBAL-H with the starting 10a fully consumed.
O
O
O
I
I
O
O
O
O
O
N
O
O
N
O
N
O
N
Bn
11f (78%)
Bn
10f
Bn
Bn
O
O
O
O
O
11a
10a
N
N
O
N
Scheme 3. The model reaction used for screening the conditions.
Bn
Bn
10g
11g (96%)
The results are listed in Table 1. Under the K-Selectride (KBH(sec-
Bu)3) conditions, which had led to satisfactory 1,4-reduction of
some cyclic enones in the literature,6 neither the desired 11a nor
any other species with an intact oxazolidinone ring in the molecule
was detected (Table 1, entry 1).
O
O
O
O
N
Ph
10h
O
Ph
7
8
9
11h (94%)
Bn
Bn
Super Hydride (LiBHEt3) is also one of the reducing agents that
may result in 1,4-reductions. Using this reagent Nagamitsu and
Omura7 recently achieved regioselective 1,4-reduction of a cyclic
amide. Unfortunately, when applied to the reduction of 10a only
reductive ring-opening of the oxazolidinone occurred (Table 1,
entry 2). Similar results were also observed with SmI2, which was
quite successful with Nagata’s8 substrate but appeared in-
compatible with the oxazolidinone rings (Table 1, entry 3).
The outcome with LiAlH4/CuI9 was much better (Table 1, entry
4). Under such conditions the desired 11a could be isolated in 57%
yield. Nevertheless, all the remaining components in the product
mixture did not have the oxazolidinone moiety, making this pro-
tocol less attractive for further studying.
Boc
N
Boc
N
O
O
S
O
O
O
N
O
O
N
11i (96%)
Bn
Bn
10i
S
S
O
O
O
O
N
N
11j (77%)
10j
S
O
The yield of 11a was only 27% when performing the reduction
under the DIBAL-H (1.2 equiv)/MeLi/CuI/HMPA10 conditions (Table
1, entry 5). However, as the remainder of the product mixture
was the unreacted starting 10a rather than undesired side products.
Further improvements were thus still possible. Indeed, when we
increased the amount of the added DIBAL-H from 1.2 to 8 mol equiv
(with respect to substrate 10a), all starting 10a was reduced,
affording the anticipated 11a in 95% isolated yield (Table 1, entry 6).
With such a satisfactory set of mild conditions in hand, we next
set out to examine the 1,4-reduction with a range of other sub-
strates. The main results are summarized in Table 2. Generally
speaking, the reduction with the DIBAL-H/MeLi/CuI/HMPA
O
N
10
O
O
N
11k (64%)
11l (94%)
10k
Ph
Ph
S
S
O
O
N
O
N
11
Bn
Bn
10l
a
All reductions were performed in THF at ꢀ78 ꢁC for 70 min in the presence of
DIBAL-H (8 mol equiv, with respect to 10)/MeLi (0.5 mol equiv)/CuI (0.5 mol equiv)/
HMPA (10 mol equiv).

848
S.-G. Li et al. / Tetrahedron 68 (2012) 846e850
proceeded very well, with the chiral auxiliary in the substrates
remained intact while the CeC double bonds in conjugation with
the N-acyl carbonyl group were cleanly saturated. Quite a few dif-
ferent functional groups and protecting groups, such as a Me3Si
protected triple bond, an isolated double bond with an iodine and
a cyclic ketal, were all well-tolerated (Table 2, entries 1e5).
The DIBAL-H derived reducing species are bound to being ste-
rically bulky. Therefore, whether the steric crowding at the re-
ducing sites would affect the efficiency of the desired conjugate
reduction deserves particular attention. It is interesting to note that
several substrates with a substituent at the allylic position, such as
10f and 10g, still gave rather high yields of the 1,4-reduction
products (Table 2, entries 5 and 6).
Additional conjugation is apparently present in substrates 10h
and 10i (Table 2, entries 7 and 8). In a sense, these compounds are
also similar to those allylic substituted substrates and consequently
may suffer substantially increased steric crowding at the CeC
double bond compared with those linear substrates (Table 2, en-
tries 1e4). Interestingly, the yields for the corresponding 1,4-
reduction products turned out to be very good. It is also notewor-
thy that the Boc (tert-butoxycabonyl) protecting group on the
pyrrole (10i) survived the reduction.
Apart from the above mentioned N-acyl oxazolidinones, we also
briefly examined the corresponding oxazolidinethiones, which are
often more labile to reductive cleavage (a main advantage for in-
troducing such sulfur-containing chiral auxiliaries) than the similar
oxazolidinone auxiliaries. Indeed, when the chiral auxiliary in the
substrate is an oxazolidinethione, reductive cleavage of the auxil-
iary became more significant. However, as the last three entries in
Table 2 show, it is still possible to acquire the desired 1,4-reduction
products in reasonably good yields.
380 Infrared Spectrometer. ESI-MS data were acquired on a Shi-
madzu LCMS-2010EV mass spectrometer. MALDI-HRMS data were
obtained with a Bruker APEXIII 7.0 Tesla FT-MS or an Agilent 6538
UHD Accurate-Mass Q-TOF spectrometer. Optical rotations were
measured on a Jasco P-1030 Polarimeter. Melting points (un-
corrected) were measured on a hotstage melting point apparatus
equipped with a microscope.
4.2. Synthesis
4.2.1. General procedure for the preparation of the reduction sub-
strates 10 (WittigeHorner reaction). i-Pr2NEt (3.0 mmol) was added
to a solution of 711 (or a similar Horner reagent as required,
1.0 mmol), LiCl (4.0 mmol), and the aldehyde (1.3 mmol) in MeCN
(5 mL) stirred in an ice-water bath. The mixture was stirred at the
same temperature for 4 h before being partitioned between water
(10 mL) and Et2O (70 mL). The phases were separated. The aqueous
layer was back extracted with Et2O (10 mLꢂ2). The combined or-
ganic layers were washed with brine and dried over anhydrous
Na2SO4. Removal of the solvent by rotary evaporation and column
chromatography (EtOAc/PE) on silica gel gave the condensation
product 10.
Data for 10a (a white solid, 58% yield): mp 69e69 ꢁC (very
sharp). ½a 2D5
ꢃ
ꢀ55.0 (c 1.00, CHCl3). 1H NMR: (400 MHz, CDCl3)
d
7.37e7.15 (m, 7H), 4.77e4.67 (m, 1H), 4.25e4.12 (m, 2H), 3.33 (dd,
J¼13.3, 3.0 Hz, 1H), 2.79 (dd, J¼13.3, 7.3 Hz, 1H), 2.30 (dt, J¼6.0,
7.3 Hz, 2H), 1.57e1.45 (m, 2H), 1.40e1.21 (m, 10H), 0.88 (t, J¼7.0 Hz,
3H); 13C NMR (100 MHz, CDCl3)
d 165.1, 153.4, 152.0, 135.4, 129.4,
128.9, 127.3, 120.3, 66.0, 55.3, 37.9, 32.7, 31.8, 29.3, 29.17, 29.15, 28.1,
22.6, 14.0; FT-IR (KBr) 2956, 2924, 2854, 1783, 1681, 1355, 1205,
1054, 1002, 988, 732, 713 cmꢀ1. ESI-MS m/z 366.1 ([MþNa]þ); ESI-
HRMS calcd for C21H29NO3Na ([MþNa]þ) 366.2040, found
366.2045.
3. Conclusions
Data for 10b (a colorless oil, 58% yield): ½a D24
ꢀ42.65 (c 1.00,
ꢃ
Regio-selective reduction of the CeC double bonds in conjuga-
tion with the N-acyl carbonyl groups in a series of oxazolidinones
and oxazolidinethiones was examined systematically for the first
time. Several sets of conditions that were shown to be effective for
CHCl3). 1H NMR (400 MHz, CDCl3)
d 7.37e7.17 (m, 7H), 4.77e4.69
(m, 1H), 4.24e4.13 (m, 2H), 3.77 (t, J¼6.2 Hz, 1H), 3.33 (dd, J¼13.5,
2.8 Hz, 1H), 2.80 (dd, J¼13.5, 8.5 Hz, 1H), 2.52 (dt, J¼6.2, 12.9 Hz,
1H), 0.90 (s, 9H), 0.07 (s, 6H); 13C NMR (100 MHz, CDCl3)
d 164.8,
conjugate reduction of
a
,
b
-unsaturated ketones, esters or amides
153.4, 148.4, 135.3, 129.4, 128.9, 127.3, 121.8, 66.1, 61.6, 55.2, 37.8,
36.2, 25.9, 18.3, ꢀ5.4; FT-IR (film) 2954, 2928, 2857, 1782, 1683,
1637, 1100, 837, 777, 701 cmꢀ1. ESI-MS m/z 412.3 ([MþNa]þ); ESI-
HRMS calcd for C21H31NO4SiNa ([MþNa]þ) 412.1915, found
412.1914.
were checked in the present context. Because of the presence of the
chiral auxiliary, the 1,4-reduction of the N-acyl oxazolidinones and
oxazolidenethiones was apparently more complicated than the
corresponding reduction of
a,b-unsaturated ketones, esters or
amides. Cleavage (cutting-off) and/or ring-opening of the chiral
auxiliaries were observed with several sets of conditions. However,
the DIBAL-H/MeLi/CuI/HMPA combination gave good to excellent
yields of the desired products. Because this reduction protocol has
the functional group compatibility apparently different from that
for hydrogenation4a or catecholborane reduction,4b it may greatly
complement the existing methodologies and provide more facile
access to the N-acyl oxazolidinones and oxazolidinethiones con-
taining multi stereogenic centers and functionalities.
Data for 10c (a yellowish oil, 76% yield): ½a D24
þ46.7 (c 1.00,
ꢃ
CHCl3); 1H NMR (300 MHz, CDCl3)
d 7.38e7.19 (m, 12H), 4.77e4.67
(m, 1H), 4.51 (s, 2H), 4.24e4.13 (m, 2H), 3.52 (t, J¼6.1 Hz, 2H), 3.33
(dd, J¼13.3, 3.3 Hz, 1H), 2.79 (dd, J¼13.3, 9.6 Hz, 1H), 2.42 (dt, J¼7.4,
7.7 Hz, 2H), 1.83 (tt, J¼7.7, 6.1 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d
165.0, 153.4, 151.0, 138.4, 135.4, 129.4, 128.9, 128.4, 127.6, 127.5,
127.3, 120.6, 72.9, 69.3, 66.1, 55.3, 37.8, 29.4, 28.2; FT-IR (film) 3065,
3022, 2924, 2848, 1770, 1681, 1489, 1451, 1092, 913, 745, 696 cmꢀ1
.
ESI-MS m/z 402.2 ([MþNa]þ); ESI-HRMS calcd for C23H25NO4Na
([MþNa]þ) 402.1676, found 402.1675.
4. Experimental
4.1. General
Data for 10d (a white solid, 78% yield): mp 64e65 ꢁC ½a D24
ꢀ27.1
ꢃ
(c 0.28, CHCl3). 1H NMR (400 MHz, CDCl3)
d 7.37e7.15 (m, 7H),
4.78e4.67 (m, 1H), 4.25e4.14 (m, 2H), 3.34 (dd, J¼13.3, 3.0 Hz, 1H),
2.80 (dd, J¼13.3, 10.4 Hz, 1H), 2.33 (dt, J¼6.9, 6.4 Hz, 2H), 2.25 (t,
J¼6.8 Hz, 2H), 1.67e1.55 (m, 4H). 0.15 (s, 9H); 13C NMR (100 MHz,
THF was distilled over Na/Ph2CO under N2 prior to use. HMPA
was stirred with CaH2 for several days (using a flat balloon to collect
the gas evolved) before being distilled under vacuum prior to use.
Addition of air/moisture sensitive reagents was done using syringe
techniques. PE (for chromatography) stands for petroleum ether
(bp 60e90 ꢁC). Column chromatography was performed on silica
gel (300e400 mesh) under slightly positive pressure. NMR spectra
were recorded on a Bruker Avance 400 NMR spectrometer oper-
ating at 400 MHz for proton. IR spectra were measured on a Nicolet
CDCl3)
d 167.0, 153.4, 151.3, 135.4, 129.4, 129.0, 127.3, 120.6, 106.9,
84.1, 66.1, 55.3, 37.9, 32.2, 28.0, 27.2, 19.6, 0.1; FT-IR (KBr) 2939,
2173, 1781, 1638, 1635, 1355, 842, 760, 700 cmꢀ1. ESI-MS m/z 406.2
([MþNa]þ); MALDI-HRMS calcd for C22H29NO3SiNa ([MþNa]þ)
406.1809, found 406.1811.
Data for 10e (a white solid, 98% yield): mp 71e72 ꢁC ½a D24
þ52.4
ꢃ
(c 1.00, CHCl3). 1H NMR (400 MHz, CDCl3)
d 7.38e7.15 (m, 7H),
4.76e4.69 (m, 1H), 4.24e4.15 (m, 2H), 4.02e3.94 (m, 4H), 3.35 (dd,

S.-G. Li et al. / Tetrahedron 68 (2012) 846e850
849
J¼13.5, 3.2 Hz, 1H), 2.79 (dd, J¼13.5, 9.8 Hz, 1H), 2.66 (d, J¼7.1 Hz,
2H), 1.37 (s, 3H); 13C NMR (100 MHz, CDCl3)
164.6, 153.3, 145.6,
ESI-HRMS calcd for C13H13NO2SNa ([MþNa]þ) 270.0559, found
d
270.0570.
135.3, 129.4, 128.9, 127.3, 123.2, 108.9, 66.1, 64.8, 55.3, 42.4, 37.8,
24.3; FT-IR (KBr) 2983, 2921, 1780, 1704, 1682, 1638, 1488, 1361,
1288, 1211, 1143, 1051, 761, 702 cmꢀ1. ESI-MS m/z 354.1 ([MþNa]þ);
ESI-HRMS calcd for C18H21NO5Na ([MþNa]þ) 354.1312, found
354.1324.
Data for 10l (a white solid, 60% yield): mp 93e94 ꢁC ½a D23
þ72.2
ꢃ
(c 1.30, CHCl3). 1H NMR (400 MHz, CDCl3)
d
7.71 (d, J¼5.4 Hz, 1H),
7.38e7.16 (m, 5H), 7.09 (dd, J¼15.5, 6.4 Hz, 1H), 4.98e4.84 (m, 1H),
4.38e4.23 (m, 2H), 3.43 (d, J¼11.8 Hz, 1H), 2.79 (dd, J¼13.0, 10.5 Hz,
1H), 3.32e2.18 (m, 1H), 1.93e1.61 (m, 5H), 1.43e1.10 (m, 5H); 13C
Data for 10f (a yellowish oil, 46% yield): ½a D28
ꢃ
ꢀ22.2 (c 1.00,
NMR (100 MHz, CDCl3) d 185.5, 166.5, 155.9, 135.2, 129.3, 128.8,
CHCl3). 1H NMR (300 MHz, CDCl3)
d
7.38e7.07 (m, 7H), 6.10 (s, 1H),
127.2, 119.5, 70.4, 60.0, 40.7, 37.4, 31.4, 31.3, 25.8, 25.5; FT-IR (KBr)
3062, 3027, 2926, 2852, 1681, 1632, 1474, 1343, 1228, 1193, 1008,
966, 966 cmꢀ1. ESI-MS m/z 330.2 ([MþH]þ); MALDI-HRMS calcd for
C19H24NO2S ([MþH]þ) 330.1522, found 330.1527.
5.79 (s, 1H), 4.78e4.68 (m, 1H), 4.25e4.14 (m, 2H), 3.33 (dd, J¼13.2,
3.8 Hz, 1H), 2.87e2.75 (m, 2H), 2.54 (dd, J¼14.3, 7.0 Hz, 1H), 2.39
(dd, J¼14.3, 7.0 Hz, 1H), 1.12 (d, J¼6.7 Hz 3H); 13C NMR (100 MHz,
CDCl3)
d 164.9, 154.1, 153.3, 135.3, 129.4, 128.9, 127.6, 127.3, 119.5,
109.1, 66.1, 55.2, 50.8, 37.8, 35.9, 18.1; FT-IR (film) 2963, 2923, 1775,
1680, 1632, 1354, 1210, 895, 701 cmꢀ1. ESI-MS m/z 426.0 ([MþH]þ);
ESI-HRMS calcd for C18H21NO3I ([MþH]þ) 426.0566, found
426.0573.
4.2.2. General procedure for reduction of the CeC double bond in
conjugation with the acyl carbonyl group in N-acyl oxazolidinones
and oxazolidinethione. MeLi (1.6 M, in Et2O, 0.8 mL, 0.5 mmol) was
added to a mixture of CuI (95 mg, 0.5 mmol) in dry THF (12 mL)
stirred under N2 (balloon) in an ice-water bath. Stirring was con-
tinued at the same temperature for 15 min. The ice-water bath was
replaced by a ꢀ78 ꢁC one. With stirring, dry HMPA (1.7 mL,
10 mmol) was added, followed by DIBAL-H (1 M, in cyclohexane,
8.0 mL, 8 mmol). The mixture was stirred at the same temperature
for 70 min. Substrate 10 (1.0 mmol) was added. Stirring was con-
tinued at ꢀ78 ꢁC for another 70 min. MeOH (5 mL) was added. The
bath was allowed to warm to ambient temperature naturally. Aq
satd potassium sodium tartrate (20 mL) was added, followed by
Et2O (30 mL). The mixture stirred at ambient temperature over
night. The phases were separated. The aqueous layer was back
extracted with Et2O (20 mLꢂ2). The combined organic layers were
washed with brine and dried over anhydrous Na2SO4. Removal of
the solvent by rotary evaporation and column chromatography
(EtOAc/PE) on silica gel gave the reduction product 11.
Data for 10g (a white solid, 84% yield): mp 114e114 ꢁC (very
sharp). ½a 2D4
ꢃ
þ58.4 (c 1.03, CHCl3). 1H NMR (400 MHz, CDCl3)
d
7.37e7.11 (m, 7H), 4.77e4.67 (m, 1H), 4.23e4.13 (m, 2H), 3.34 (dd,
J¼13.3, 3.3 Hz, 1H), 2.78 (dd, J¼13.3, 9.7 Hz, 1H), 2.30e2.20 (m, 1H),
1.87e1.72 (m, 4H), 1.72e1.63 (m, 1H), 1.39e1.13 (m, 5H); 13C NMR
(100 MHz, CDCl3)
d 165.4, 156.6, 154.4, 135.4, 129.4, 128.9, 127.2,
118.1, 66.0, 55.3, 40.9, 37.9, 31.7, 31.6, 25.8, 25.6; FT-IR (KBr) 2922,
2851, 1782, 1679, 1633, 1386, 1353, 1201, 1052, 764, 734, 703 cmꢀ1
.
ESI-MS m/z 336.1 ([MþNa]þ); ESI-HRMS calcd for C19H23NO3Na
([MþNa]þ) 336.1570, found 336.1577.
Data for 10h (a white solid, 49% yield): mp 126e126 ꢁC (very
sharp). ½a 2D6
ꢃ
þ60.3 (c 1.38, CHCl3). 1H NMR (400 MHz, CDCl3)
d
7.98e7.87 (m, 2H), 6.68e6.60, (m, 2H), 7.45e7.38 (m, 3H),
7.38e7.31 (m, 2H), 7.31e7.21 (m, 3H), 4.85e4.75 (m, 1H),
4.29e4.17 (m, 2H), 3.37 (dd, J¼13.4, 3.0 Hz, 1H), 2.85 (dd, J¼13.4,
9.5 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
165.2, 153.5, 146.4,
Data for 11a (a white solid, 95% yield): mp 44e45 ꢁC ½a D24
ꢀ41.8
ꢃ
135.3, 134.5, 130.7, 129.4, 128.93, 128.87, 128.6, 127.3, 116.9, 66.1,
55.4, 37.9; FT-IR (KBr) 3058, 3059, 3028, 2914, 1776, 1677, 1619,
1389, 1211, 764, 730, 701 cmꢀ1. ESI-MS m/z 330.1 ([MþNa]þ); ESI-
HRMS calcd for C19H17NO3Na ([MþNa]þ) 330.1101, found
330.1108.
(c 1.00, CHCl3). 1H NMR (400 MHz, CDCl3)
d 7.36e7.18 (m, 5H),
4.71e4.63 (m, 1H), 4.22e4.13 (m, 2H), 3.29 (dd, J¼13.3, 3.5 Hz, 1H),
3.02e2.84 (m, 2H), 2.76 (dd, J¼13.3, 9.5 Hz, 1H), 1.74e1.62 (m, 2H),
1.43e1.19 (m, 14H), 0.88 (t, J¼6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3)
d 173.4, 153.3, 135.3, 129.4, 128.9, 127.3, 66.1, 55.1, 37.9, 35.5,
Data for 10i (a gray-brown oil, 60% yield): mp 114e114 ꢁC (very
31.8, 29.5, 29.45, 29.36, 29.27, 29.1, 24.3, 22.6,14.1; FT-IR (KBr) 3029,
2926, 2854, 1789, 1704, 1398, 1454, 1385, 1352, 1210, 1099, 1076,
1051, 762, 746, 702 cmꢀ1. ESI-MS m/z 368.2 ([MþNa]þ); ESI-HRMS
calcd for C21H31NO3Na ([MþNa]þ) 368.2196, found 368.2193.
sharp). ½a 2D3
ꢃ
þ42.1 (c 1.00, CHCl3). 1H NMR (400 MHz, CDCl3)
d 8.59
(d, J¼15.9 Hz, 1H), 7.68 (d, J¼15.9 Hz, 1H), 7.44e7.40 (m, 1H),
7.39e7.18 (m, 5H), 6.92e6.87 (m, 1H), 6.28e6.21 (m, 1H), 4.84e4.73
(m, 1H), 4.28e4.13 (m, 2H), 3.41e3.31 (m, 1H), 2.83 (dd, J¼13.3,
Data for 11b (a colorless oil, 87% yield): ½a D24
ꢀ41.33 (c 0.50,
ꢃ
9.8 Hz, 1H), 1.64 (s, 9H); 13C NMR (100 MHz, CDCl3)
d
165.1, 153.5,
CHCl3). 1H NMR (300 MHz, CDCl3)
d 7.37e7.18 (m, 5H), 4.73e4.63
148.8, 136.4, 135.4, 131.5, 129.4, 128.8, 127.2, 125.4, 116.1, 114.8, 111.6,
84.8, 66.0, 55.3, 37.8, 27.9; FT-IR (film) 2978, 2931, 2860, 1778, 1744,
1673, 1601, 1454, 1360, 1277, 1211, 1071, 846, 740, 680 cmꢀ1. ESI-MS
m/z 419.2 ([MþNa]þ); ESI-HRMS calcd for C22H24N2O5Na
([MþNa]þ) 419.1577, found 419.1592.
(m, 1H), 4.23e4.13 (m, 2H), 3.66 (t, J¼6.2 Hz, 2H), 3.30 (dd, J¼13.4,
3.3 Hz, 1H), 3.07e2.86 (m, 2H), 2.76 (dd, J¼13.4, 9.6 Hz, 1H),
1.84e1.70 (m, 2H), 1.67e1.55 (m, 2H), 0.90 (s, 9H), 0.06 (s, 6H). 13C
NMR (100 MHz, CDCl3) d 173.2, 153.4, 135.3, 129.4, 128.9, 127.3, 66.1,
62.7, 55.1, 37.9, 35.3, 32.1, 25.9, 20.6, 18.3, ꢀ5.3; FT-IR (film) 2954,
2929, 2857, 1789, 1704, 1698, 1386, 1253, 1210, 1100, 836, 744,
702 cmꢀ1. ESI-MS m/z 414.3 ([MþNa]þ); ESI-HRMS calcd for
C21H33NO4SiNa ([MþNa]þ) 414.2071, found 414.2069.
Data for 10j (a colorless oil, 71% yield): ½a D26
þ139.1 (c 1.20,
ꢃ
CHCl3). 1H NMR (400 MHz, CDCl3)
d
7.62 (d, J¼15.2 Hz, 1H),
7.02e6.90 (m, 1H), 4.61 (ddd, J¼7.8, 3.9, 3.7 Hz, 1H), 4.38e4.27 (m,
2H), 2.38e2.22 (m, 1H),1.87 (d, J¼6.9 Hz, 3H), 0.83 (d, J¼7.0 Hz, 3H),
Data for 11c (a colorless oil, 90% yield): ½a D24
þ40.2 (c 0.50,
ꢃ
0.78 (d, J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
186.0, 165.8,
CHCl3). 1H NMR (300 MHz, CDCl3)
d 7.39e7.16 (m, 10H), 4.72e4.61
145.7, 123.2, 67.6, 63.1, 28.6, 18.2, 17.9, 14.6; FT-IR (film) 2965, 1780,
(m, 1H), 4.51 (s, 2H), 4.23e4.12 (m, 2H), 3.49 (t, J¼6.7 Hz, 2H), 3.29
(dd, J¼13.3, 3.5 Hz, 1H), 3.05e2.84 (m, 2H), 2.76 (dd, J¼13.3, 9.6 Hz,
1H), 1.78e1.61 (m, 4H), 1.54e1.44 (m, 2H); 13C NMR (100 MHz,
1682, 1635, 1481, 1361, 1394, 1199, 1164, 1108, 958, 922, 823 cmꢀ1
.
ESI-MS m/z 236.0 ([MþNa]þ); ESI-HRMS calcd for C10H15NO2SNa
([MþNa]þ) 236.0716, found 236.0727.
CDCl3)
d 173.2, 153.4, 138.6, 135.3, 129.4, 128.9, 128.3, 127.6, 127.4,
Data for 10k (a yellowish wax, 96% yield): ½a D26
ꢃ
ꢀ184.0 (c 0.50,
127.3, 72.9, 70.1, 66.1, 55.1, 37.9, 35.4, 29.5, 25.7, 24.0; FT-IR (film)
3062, 2934, 2860, 1783, 1698, 1386, 1329, 1209, 1097, 738 cmꢀ1. ESI-
MS m/z 404.3 ([MþNa]þ); ESI-HRMS calcd for C23H27NO4Na
([MþNa]þ) 404.1832, found 404.1836.
CHCl3). 1H NMR (400 MHz, CDCl3)
d 7.74e7.65 (m, 1H), 7.43e7.25
(m, 5H), 7.08e6.96 (m, 1H), 5.68 (dd, J¼8.7, 4.4 Hz, 1H), 4.81 (dd,
J¼9.0, 8.7 Hz, 1H), 4.43 (dd, J¼9.0, 4.4 Hz, 1H), 1.95 (dd, J¼7.0, 1.4 Hz,
3H); 13C NMR (100 MHz, CDCl3)
d
185.8, 165.7, 146.8, 138.3, 129.2,
Data for 11d (a white solid, 100% yield): mp 41e41 ꢁC ½a D26
ꢀ42.1
ꢃ
128.8, 126.0, 123.3, 74.1, 62.3, 18.5; FT-IR (film) 3065, 3030, 2967,
2914, 1687, 1634, 1367,1346, 1321,1298,1280, 1194,1161, 1068, 1018,
956, 919, 762, 699, 603, 572 cmꢀ1. ESI-MS m/z 270.1 ([MþNa]þ);
(c 1.10, CHCl3). 1H NMR (400 MHz, CDCl3)
d 7.37e7.18 (m, 5H),
4.72e4.62 (m, 1H), 4.24e4.13 (m, 2H), 3.29 (dd, J¼13.4, 3.1 Hz, 1H),
3.03e2.84 (m, 2H), 2.76 (dd, J¼13.4, 9.7 Hz, 1H), 2.23 (t, J¼7.2 Hz,

850
S.-G. Li et al. / Tetrahedron 68 (2012) 846e850
2H), 1.76e1.65 (m 2H), 1.59e1.49 (m, 2H), 1.49e1.34 (m, 4H), 0.15 (s,
9H); 13C NMR (100 MHz, CDCl3)
173.3, 153.4, 135.3, 129.4, 128.9,
Data for 11k (a white solid, 64% yield): mp 74e76 ꢁC ½a D26
ꢀ82.4
ꢃ
d
(c 1.10, CHCl3). 1H NMR (400 MHz, CDCl3)
d 7.45e7.22 (m, 5H), 5.69
127.3,107.5, 84.4, 66.1, 55.1, 37.9, 35.4, 28.6, 28.5, 28.4, 24.1, 19.8, 0.1;
FT-IR (KBr) 2925, 2854, 2171, 1789, 1704, 1455, 1378, 1248, 1211,
842 cmꢀ1. ESI-MS m/z 408.4 ([MþNa]þ); ESI-HRMS calcd for
C22H31NO3SiNa ([MþNa]þ) 408.1965, found 408.1971.
(dd, J¼8.5, 2.1 Hz, 1H), 4.78 (dd, J¼9.0, 8.5 Hz, 1H), 4.44 (dd, J¼9.0,
2.1 Hz, 1H), 3.37e3.16 (m, 2H), 1.74e1.55 (m, 2H), 0.92 (t, J¼7.7 Hz,
3H); 13C NMR (100 MHz, CDCl3)
d 185.6, 173.5, 138.8, 129.2, 128.8,
126.0, 74.0, 62.1, 39.4, 17.8, 13.5; FT-IR (KBr) 2962, 2927, 2874, 1705,
1455, 1366, 1339, 1311, 1189, 1152, 946, 762, 698 cmꢀ1. ESI-MS m/z
271.9 ([MþNa]þ); ESI-HRMS calcd for C13H15NO2SNa ([MþNa]þ)
272.0716, found 272.0716.
Data for 11e (a white solid, 96% yield): mp 63e64 ꢁC ½a D23
þ41.9
ꢃ
(c 1.00, CHCl3). 1H NMR (400 MHz, CDCl3)
d 7.40e7.17 (m, 5H),
4.71e4.62 (m, 1H), 4.24e4.13 (m, 2H), 3.95 (s, 4H), 3.29 (dd, J¼13.3,
2.6 Hz, 1H), 3.07e2.88 (m, 2H), 2.76 (dd, J¼13.3, 9.8 Hz, 1H),
Data for 11l (a white solid, 94% yield): mp 105e105 ꢁC (very
1.87e1.70 (m, 4H), 1.33 (s, 3H); 13C NMR: (100 MHz, CDCl3)
d
173.0,
sharp). ½a 2D5
ꢃ
þ79.5 (c 1.10, CHCl3). 1H NMR (400 MHz, CDCl3)
153.4, 135.2, 129.3, 128.9, 127.3, 109.7, 66.1, 64.6, 55.0, 38.1, 37.8,
35.3, 23.8, 18.7; FT-IR (KBr) 2980, 2952, 1781, 1698, 1479, 1387, 1351,
1211, 1099, 1062, 762, 703 cmꢀ1. ESI-MS m/z 356.1 ([MþNa]þ); ESI-
HRMS calcd for C18H23NO5Na ([MþNa]þ) 356.1468, found 356.1455.
d 7.38e7.18 (m, 5H), 4.98e4.88 (m, 1H), 4.37e4.23 (m, 2H),
3.47e3.34 (m, 1H), 3.34e3.20 (m, 2H), 2.76 (dd, J¼14.1, 10.0 Hz, 1H),
1.84e1.53 (m, 7H), 1.41e1.09 (m, 4H), 1.04e0.87 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 185.4, 174.5, 135.3, 129.4, 129.0, 127.4, 70.2, 59.9,
Data for 11f (a yellowish oil, 78% yield): ½a D23
ꢃ
ꢀ25.3 (c 1.20,
37.6, 37.1, 35.1, 33.1, 33.0, 31.5, 26.5, 26.2; FT-IR (KBr) 3027, 2919,
2849,1698,1450,1400,1367,1352,1319,1287,1270,1195,1155,1017,
964, 740, 701 cmꢀ1. ESI-MS m/z 354.0 ([MþNa]þ); ESI-HRMS calcd
for C19H25NO2SNa ([MþNa]þ) 354.1498, found 354.1507.
CHCl3). 1H NMR (300 MHz, CDCl3)
d 7.38e7.18 (m, 5H), 6.06 (s, 1H),
5.75 (s, 1H), 4.72e4.63 (m, 1H), 4.25e4.14 (m, 2H), 3.31 (dd, J¼13.1,
3.2 Hz, 1H), 3.03e2.94 (m, 2H), 2.78 (dd, J¼13.1, 9.8 Hz, 1H), 2.40
(dd, J¼13.8, 5.8 Hz, 1H), 2.20 (dd, J¼13.8, 7.7 Hz, 1H), 1.95e1.74 (m,
2H), 1.58e1.44 (m, 1H), 0.94 (d, J¼6.5 Hz, 3H); 13C NMR (100 MHz,
Acknowledgements
CDCl3)
d 173.2, 153.4, 135.2, 129.4, 128.9, 127.3, 126.8, 111.3, 66.2,
55.2, 52.2, 37.9, 33.1, 31.8, 30.0, 18.4; FT-IR (film) 2956, 2921, 1781,
1699, 1386,1352, 1211, 896, 702 cmꢀ1. ESI-MS m/z 450.1 ([MþNa]þ);
ESI-HRMS calcd for C18H22NO3INa ([MþNa]þ) 450.0534, found
450.0544.
This work was supported by the National Basic Research Pro-
gram of China (the 973 Program, 2010CB833200), the National
Natural Science Foundation of China (21172247, 21032002,
20921091, 20672129, 20621062, 20772143), and the Chinese
Academy of Sciences.
Data for 11g (a white solid, 94% yield): mp 84e85 ꢁC (lit.12 mp
86e88 ꢁC). ½a 2D3
ꢃ
þ41.2 (c 1.00, CHCl3) (lit.11
½
a 2D0
ꢃ
þ92 (no concen-
tration/solvent information)). 1H NMR (400 MHz, CDCl3)
d
7.38e7.18 (m, 5H), 4.71e4.63 (m, 1H), 4.24e4.12 (m, 2H), 3.29 (dd,
Supplementary data
J¼13.3, 3.0 Hz, 1H), 3.04e2.86 (m, 2H), 2.78 (dd, J¼13.3, 9.7 Hz, 1H),
1.80e1.54 (m, 7H),1.35e1.10 (m, 4H),1.00e0.86 (m, 2H); FT-IR (KBr)
3059, 3027, 2921, 2850, 1782, 1699, 1386, 1352, 1211, 1107, 740,
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2011.11.038. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
702 cmꢀ1
.
Data for 11h (a white solid, 94% yield): mp 101e102 ꢁC ½a D25
ꢃ
þ67.4 (c 0.98, CHCl3). 1H NMR (400 MHz, CDCl3)
d 7.39e7.13 (m,
10H), 4.70e4.60 (m, 1H), 4.20e4.10 (m, 2H), 3.37e3.17 (m, 3H),
3.09e2.95 (m, 2H), 2.74 (dd, J¼13.3, 9.6 Hz,1H); 13C NMR (100 MHz,
References and notes
CDCl3)
d 172.3, 153.4, 140.4, 135.2, 129.4, 128.9, 128.5, 128.4, 127.3,
126.2, 66.1, 55.0, 37.7, 37.1, 30.2; FT-IR (KBr) 3083, 3063, 2956, 2930,
1779, 1698, 1496, 1454, 1389, 1376, 1353, 1210, 1113, 762, 747,
700 cmꢀ1. ESI-MS m/z 332.2 ([MþNa]þ); MALDI-HRMS calcd for
C19H19NO3Na ([MþNa]þ) 332.1257, found 333.1259.
1. (a) Evans, D. A.; Bartoli, J.; Shih, T. L. J. Am. Chem. Soc. 1981, 103, 2127e2129; (b)
For a review, see: Ager, D. J. I.; Schaad, D. R. Chem. Rev. 1996, 96, 835e875.
2. (a) Schindler, C. S.; Forster, P. M.; Carreira, E. M. Org. Lett. 2010, 12, 4103e4105;
(b) Gage, J. R.; Evans, D. A. Org. Synth. 1990, 68, 83e91; (c) Gage, J. R.; Evans, D.
A. Org. Synth. 1990, 68, 77e82; (d) Ho, G.-J.; Mathre, D. J. J. Org. Chem. 1995, 60,
2271e2273; (e) Andrade, C. K. Z.; Rocha, R. O.; Vercillo, O. E.; Silva, W. A.; Matos,
R. A. F. Synlett 2003, 2351e2352; (f) Ager, D. J.; Allen, D. R.; Schaad, D. R. Syn-
thesis 1996, 1283e1285; (g) Davies, S. G.; Doisneau, G. J.-M. Tetrahedron:
Asymmetry 1993, 4, 2513e2516; (h) Gaul, C.; Schweizer, B. W.; Seiler, P.; See-
bach, D. Helv. Chim. Acta 2002, 85, 1546e1566; (i) Evans, D. A.; Gage, J. R.;
Leighton, J. L. J. Am. Chem. Soc. 1992, 114, 9434e9453; (j) Evans, D. A.; Gage, J. R.
J. Org. Chem. 1992, 57, 1958e1961.
Data for 11i (a gray-brownish oil, 94% yield): ½a D25
þ38.4 (c 0.65,
ꢃ
CHCl3). 1H NMR (400 MHz, CDCl3)
d 7.37e7.17 (m, 6H), 6.07 (dd,
J¼3.3, 3.3 Hz, 1H), 6.03e6.00 (m, 1H), 4.71e4.63 (m, 1H), 4.23e4.13
(m, 2H), 3.34e3.21 (m, 5H), 2.75 (dd, J¼13.3, 7.6 Hz, 1H), 1.60 (s,
9H); 13C NMR (100 MHz, CDCl3)
d 172.4, 153.4, 149.3, 135.3, 133.8,
129.4, 128.9, 127.3, 121.3, 111.8, 109.9, 83.5, 66.1, 55.1, 37.9, 35.1, 28.0,
23.6; FT-IR (film) 2979, 2932, 1783, 1738, 1699, 1371, 1335, 1212,
1125, 1064, 847, 808, 734, 703 cmꢀ1. ESI-MS m/z 421.2 ([MþNa]þ);
ESI-HRMS calcd for C22H26N2O5Na ([MþNa]þ) 421.1734, found
421.1729.
3. For a convenient synthesis of such chiral auxiliaries, see Wu, Y.-K.; Shen, X.
Tetrahedron: Asymmetry 2000, 11, 4359e4363.
4. For syntheses involving such species as 8, see (a) Shapiro, G.; Cai, C. Tetrahedron
Lett. 1992, 33, 2447e2450; (b) Evans, D. A.; Black, W. C. J. Am. Chem. Soc. 1992,
114, 2260e2262 For an example for use of 9 (derived through saturation of the
double bond in 8 by hydrogenation), cf Ref. 5a below.
5. For previous reports on 1,4-reduction of individual N-acyl oxazolidinones, see:
(a) Roush, W. R.; Brown, B. B. J. Org. Chem. 1993, 58, 2162e2172; (b) Evans, D. A.;
Fu, G. C. J. Org. Chem. 1990, 55, 5678e5680.
Data for 11j (a white solid, 77% yield): mp 39e41 ꢁC ½a D26
þ125.3
ꢃ
(c 1.10, CHCl3). 1H NMR (400 MHz, CDCl3)
d 4.73e4.76 (m,1H),
4.40e4.34 (m, 2H), 3.36 (ddd, J¼17.0, 7.9, 6.1 Hz, 1H), 3.18 (ddd,
J¼17.0, 8.5, 6.5 Hz, 1H), 2.40e2.27 (m, 1H), 1.80e1.63 (m, 2H), 0.98
(t, J¼7.3 Hz, 3H), 0.92 (t, J¼7.0 Hz, 3H), 0.87 (t, J¼7.0 Hz, 3H); 13C
6. Fortunato, J. M.; Ganem, B. J. Org. Chem. 1976, 41, 2194e2200.
7. Fukuda, T.; Sugiyama, K.; Arima, S.; Harigaya, Y.; Nagamitsu, T.; Omura, S. Org.
Lett. 2008, 10, 4239e4242.
8. Katayama, S.; Ae, N.; Nagata, R. J. Org. Chem. 2001, 66, 3474e3483.
9. Ashby, E. C.; Lin, J. J.; Kovar, R. J. Org. Chem. 1976, 41, 1939e1943.
10. Tsuda, T.; Hayashi, T.; Satomi, H.; Kawamoto, T.; Saegusa, T. J. Org. Chem. 1986,
51, 537e540.
11. Dias, L. C.; Melgar, G. Z.; Jardim, L. S. A. Tetrahedron Lett. 2005, 46, 4427e4432.
12. Edmonds, M. K.; Graichen, F. H. M.; Gardiner, J.; Abell, A. D. Org. Lett. 2008, 10,
885e887.
NMR (100 MHz, CDCl3) d 186.1,174.0, 67.5, 63.2, 39.3, 28.9,18.2,18.0,
14.9, 13.5; FT-IR (KBr) 2964, 2932, 2875, 1702, 1481, 1464, 1401,
1306, 1197, 1159, 1010, 957 cmꢀ1. ESI-MS m/z 238.1 ([MþNa]þ); ESI-
HRMS calcd for C10H17NO2SNa ([MþNa]þ) 238.0872, found
238.0883.