SmI2-promoted intra- and intermolecular C-C bond formation with chiral N-acyl oxazolidinones

Article abstract of DOI:10.1016/j.tet.2008.09.044

The suitability of chiral oxazolidinones in the SmI₂-mediated C-C bond generation between the imide functionality of an N-acyl oxazolidinone unit and an olefinic radical acceptor, in both inter- and intramolecular reactions, was investigated. It was shown that the products from an Evans asymmetric alkylation can undergo direct carbon-carbon bond formation with an acrylamide providing chiral acyclic ketones in reasonable yields. These examples represent the first transformation of such N-acyl oxazolidinones where this chiral auxiliary is removed under the conditions for ketone formation. 5-exo-trig Cyclization studies were also undertaken with the same type of substrates, providing trans-2,5-disubstituted cyclopentanones in yields of approx. 50%. However, attempts to cyclize heteroatom-containing equivalents were less rewarding.

Full text of DOI:10.1016/j.tet.2008.09.044

Tetrahedron 64 (2008) 11884–11895
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
SmI2-promoted intra- and intermolecular C–C bond formation with chiral
N-acyl oxazolidinones
,
Rolf H. Taaning a, Laura Thim a, Jacob Karaffa a, Araceli G. Campan˜a a b, Anna-Mette Hansen a,
,
Troels Skrydstrup a
*
a Center for Insoluble Protein Structures, Department of Chemistry and Interdisciplinary Nanoscience Center, University of Aarhus, Langelandsgade 140, 8000 Aarhus C, Denmark
b Department of Organic Chemistry, Faculty of Sciences, University of Granada, E-18071 Granada, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
The suitability of chiral oxazolidinones in the SmI2-mediated C–C bond generation between the imide
functionality of an N-acyl oxazolidinone unit and an olefinic radical acceptor, in both inter- and in-
tramolecular reactions, was investigated. It was shown that the products from an Evans asymmetric
alkylation can undergo direct carbon–carbon bond formation with an acrylamide providing chiral
acyclic ketones in reasonable yields. These examples represent the first transformation of such N-acyl
oxazolidinones where this chiral auxiliary is removed under the conditions for ketone formation.
5-exo-trig Cyclization studies were also undertaken with the same type of substrates, providing trans-
2,5-disubstituted cyclopentanones in yields of approx. 50%. However, attempts to cyclize heteroatom-
containing equivalents were less rewarding.
Received 3 September 2008
Accepted 13 September 2008
Available online 24 September 2008
Ó 2008 Published by Elsevier Ltd.
1. Introduction
the mildness of the reaction conditions.5–7 This work led us to
consider the possibility of using such reactions with substrates
Evans chiral oxazolidinones are an important class of com-
pounds, which have been extensively employed as successful chiral
auxiliaries in an array of synthetic transformations including
asymmetric enolate alkylations, asymmetric aldol reactions, cy-
cloadditions, Michael additions, and others.1 Whereas there are
a variety of protocols for removing the chiral auxiliary direct car-
bon–carbon bond formation with expulsion of the oxazolidinone
requires a minimum of two steps. For example, an initial trime-
thylaluminum-mediated transamination of the N-acyl oxazolidi-
none with N,N-methoxymethylamine is required followed by the
C–C bond forming step in general with either organomagnesium or
-lithium reagents.2
bearing an Evans chiral oxazolidinone, as a short route for the
preparation of chiral -substituted ketones, where the C–C bond
formation occurs directly after the asymmetric alkylation step.
Thus in this paper, we report our studies on the application of chiral
N-acyl oxazolidinones in SmI2-mediated inter- and intramolecular
reactions with olefins.
a
CO2Trt
O
O
O
O
H
H
N
FmocHN
TrtO2C
N
+
N
H
N
O
OMe
Earlier, we have demonstrated the ability of N-acyl derivatives of
2-oxazolidinone to undergo direct C–C bond formation with acry-
lates and acrylamides promoted by the divalent lanthanide reagent,
O
Bn
Me
O
SmI2 (4-6 equiv)
H2O (8-12 equiv)
THF, -78 °C
samarium diiodide,3 leading to
g
-keto esters and amides.4 This
(62%)
reaction was exploited for the synthesis of ketomethylene isosteres
of peptides directly from N-peptidyl oxazolidinones without
epimerization at the stereogenic carbon center adjacent to the
keto-functionality in the final product (Scheme 1), which attests to
CO2Trt
O
O
O
H
H
N
FmocHN
TrtO2C
N
N
H
OMe
O
Bn
O
Me
* Corresponding author.
Scheme 1.
E-mail address: ts@chem.au.dk (T. Skrydstrup).
0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tet.2008.09.044

R.H. Taaning et al. / Tetrahedron 64 (2008) 11884–11895
11885
Table 1
2. Results and discussion
Radical addition of N-tert-butyl acrylamides to N-acyl derivatives of (4R,5S)-4-
methyl-5-phenyloxazolidin-2-one 1 promoted by SmI2/H2O
2.1. Intermolecular couplings
O
O
To investigate the suitability of this SmI2-mediated C–C bond
forming reaction coupled with Evans asymmetric alkylations for
the two-step preparation of chiral acyclic ketones, some simple
chiral N-acyl oxazolidinones were prepared according to the
literature procedures.8 The two commercially available chiral
auxiliaries, (4R,5S)-4-methyl-5-phenyl-2-oxazolidinone (1) and
5-(S)-4-benzyl-2-oxazolidinone (2), were deprotonated with butyl
lithium at ꢀ78 ꢁC and subjected to propanoyl chloride providing
N
O
R1
Ph
SmI2 (4 equiv)
H2O (8equiv)
O
R3
3,5 and 6
NHt-Bu
THF, -78 °C
R1 R2
O
R3
9-12
R2
NHt-Bu
O
the corresponding N-propionyl oxazolidinones
3 and 4, re-
spectively (Scheme 2). -Alkylation was then carried out by first
a
Entry
1
R1
R2
H
R3
H
Product
Yielda (%)
treatment of 3 and 4 with NaHMDS followed by the addition of
either allyl or benzyl bromide leading to the desired alkylated
products 5–8 with high diastereomeric excess.
O
O
NHt-Bu
NHt-Bu
NHt-Bu
H
9
67
O
O
O
O
1. n-BuLi
2
3
Bn
Bn
H
H
H
10
11
72
O
HN
Bn
O
HN
or
O
2.
Aux
Bn
O
O
3: from 1 91%
4: from 2 98%
Ph
Cl
1
2
Me
H
64 (dr¼1:1b)
Bn
O
O
1. NaHMDS
2. RX
1. NaHMDS
2. RX
O
NHt-Bu
4
Bn
Me
H
0
Bn
O
O
O
O
O
O
O
N
N
O
NHt-Bu
R
R
5
Allyl
H
12
65
Ph
Bn
7 R = Bn 59% (dr >95:5)
8 R = allyl 67% (dr >95:5)
5 R = Bn 64% (dr >95:5)
6 R = allyl 59% (dr >95:5)
a
Isolated yields after column chromatography.
Determined by 1H NMR.
Scheme 2.
b
Studies on the SmI2-promoted coupling of these chiral N-acyl
oxazolidinones derived from auxiliary 1 with acrylamides are
shown in Table 1. All reactions were performed according to our
previously reported procedure4a whereby SmI2 is added to a cooled
THF solution (ꢀ78 ꢁC) of the N-acyl oxazolidinone and the acryl-
amide with water as an additive.4,5 To examine the influence of an
additional substituent on the 2-oxazolidinone fragment on these
coupling reactions, 3 was first reacted with N-tert-butyl acrylamide.
Gratifyingly, this afforded the ethyl ketone 9 in a 67% yield (entry 1),
which is even better than that previously reported with the
unsubstituted 2-oxazolidinone.4a In agreement with this result, the
Table 2
Radical addition of N-tert-butyl acrylamides to N-acyl derivatives of (S)-4-benzy-
loxazolidin-2-one 2 promoted by SmI2/H2O
O
O
N
O
R
Bn
7 and 8
SmI2 (4 equiv)
H2O (8 equiv)
O
NHt-Bu
THF, -78 °C
desired chiral
obtained in good yields (entries 2 and 5). Even coupling to an
-substituted acrylamide such as the N-tert-butyl methacrylamide
a-substituted ketones 10 and 12 could also be
R
O
NHt-Bu
9,13 and 14
a
O
gave the ketone 11 in a 64% yield though without any control at the
new stereogenic carbon center formed under the coupling (entry
3). On the other hand, substitution in the b-position is detrimental
as shown with the crotyl derivative, resulting in no carbon–carbon
bond formation (entry 4).
Reactions performed with substrates bearing the alternative
chiral auxiliary 2 proved also feasible (Table 2) leading to ketones 9,
13, and 14. But in general slightly reduced yields were obtained,
which can be attributed to the greater sterical bulk of the 2-oxa-
zolidinone side chain adjacent to the reacting C]O center (benzyl
vs methyl). In contrast to what was generally observed in coupling
reactions with the simple 2-oxazolidinone, some reduction prod-
Entry
1
R
Product
Yielda (%)
53
O
O
NHt-Bu
H
9
O
NHt-Bu
NHt-Bu
2
Bn
13
61
55
Bn
O
O
O
3
Allyl
14
ucts of the chiral a-substituted ketones to the corresponding sec-
ondary alcohol were isolated in up to 15%. This may likely be
a result of a premature collapse of the intermediate hemiaminal
a
Isolated yields after column chromatography.

11886
R.H. Taaning et al. / Tetrahedron 64 (2008) 11884–11895
after the C–C bond forming step and can possibly be attributed to
the increased bulk of the oxazolidinone.
O
1. PivCl, Et3N
THF -78 - 0 °C
O
OH
Aux
To further investigate the utility of the developed protocol, we
attempted the radical addition of substrates prepared from an
Evans asymmetric aldol reaction.9 The aldol substrates were pre-
pared by first Z-selective enolization with n-Bu2BOTf and Et3N
followed by subjection to the appropriate aldehyde. However,
when subjected to SmI2/H2O in the presence of acrylamide reduced
and dimerized acrylamide as well as unreacted starting material
was obtained (Scheme 3). A range of protecting groups on the
secondary alcohol were also tried, i.e., acetyl (Ac), methyl ether, and
tert-butyl dimethyl silyl ether, but again no coupling product was
detected and the starting material was recovered.
2. nBuLi
2-oxazolidinone,
1 or 2
15: from 2-oxazolidinone 89%
16: from 1 90%
THF, -78 °C
17: from 2 88%
Ph
Ph
O
Grubbs cat. 2nd
CH2Cl2
Ph
Aux
a
40 °C, 2 days
or MW, 80 °C, 3 h
a
18: from 15 65%
19: from 16 80%
20: from 17 80%
b
b
a
1. NaHMDS
2. RX
THF, -78 °C
O
O
O
OR
O
19
SmI2 (4 equiv)
H2O (8 equiv)
Ph
N
NHt-Bu
O
N
O
R
O
THF, -78 °C
Ph
Bn
21: R = Me 41%
22: R = Allyl 49%
23: R = Bn 46%
R= H, Ac
OR
1. NaHMDS
2. BnBr
THF, -78 °C
SmI2 (4 equiv)
H2O (8 equiv)
O
O
O
O
O
NHt-Bu
Ph
20
N
N
O
O
THF, -78 °C
Bn
Bn
Bn
R= Me, TBS
24: 50%
Scheme 4.
Scheme 3.
Also an intramolecular variant was attempted, the hydroxyl
being protected with an acryl moiety. It was contemplated that the
resulting acrylate would be reduced in the presence of SmI2/H2O
and add to the N-acyl carbonyl. However, recovery of a product
possessing a propanoyl functionalized hydroxyl group led us to
conclude that the resulting radical is not suitably oriented to add to
this carbonyl.
major isolated product (44% yield), which likely arises from radical
dimerization of the intermediate benzylic radical.11 Only traces of
the desired cyclopentanone 25 could be observed upon 1H NMR
analysis of the crude reaction mixture.
SmI2 (4 equiv)
H2O (8 equiv)
O
O
O
O
Ph
Ph
Ph
N
O
THF
2.2. Intramolecular additions
18
Ph
25
26
In previous work, we have found that N-acyl oxazolidinones
could indeed be reduced to the ketyl radical in the absence of ac-
rylates and acrylamides.4b The question therefore arose whether
such carbon centered radicals could be exploited for intramolecular
ketyl radical additions to an olefin for the preparation of chiral
cyclic aliphatic ketones, as well as the corresponding heterocyclic
systems. To test this possibility, the simple achiral substrate 15 was
first synthesized by standard imide formation between 2-oxazoli-
dinone and the commercially available hex-5-enoic acid (Scheme
4). Subsequent installment of the C6-phenyl group in 18 was con-
veniently accomplished via cross-metathesis with cis-stilbene us-
ing Grubbs second generation catalyst in dichloromethane.10
Although the reaction was slow and required a period of 2 days, it
was nevertheless clean affording the trans-styrene derivative in
a 65% yield. The reaction time could be lowered to 3 h by running
the reaction in a microwave at 80 ꢁC as was achieved in the for-
mation of 19 (Scheme 4).
The N-acyl oxazolidinone 18 was then tested for its ability to
undergo 5-exo-trig cyclization at various reaction temperatures
using the combination of SmI2/H2O in THF, as illustrated in Scheme
5. This ring closure event proved particularly rewarding at 20 ꢁC
where an 80% yield of 2-benzylpentanone (25) could be isolated
after column chromatography. Lowering the reaction temperature
had an adverse effect on the isolated yields of 25, but at ꢀ78 ꢁC, it
was surprising to observe the formation of the dimer 16 as the
O
25
26
44 %
Temp.
trace
44 %
80 %
-78 °C
0 °C
20 °C
not determ.
not determ.
Scheme 5.
With these results in hand, we then turned to examine the re-
activity of the corresponding chiral N-acyl oxazolidinones 19 and
20, where it was anticipated that the C5-substitutent of the
2-oxazolidinone moiety would direct the selective facial attack of
the ketyl radical onto the olefinic radical acceptor. These
compounds were prepared in an analogous manner as that for
compound 18 (Scheme 4).
Although both N-acyl oxazolidinones 19 and 20 were consumed
upon treatment with SmI2, 19 provided only a moderate 40% yield
of the cyclopentanone 25, whereas the cyclic precursor 20 led to 25
in a poorer yield (Scheme 6). Considerable efforts were undertaken
in an attempt to improve the efficiency of this transformation by
varying the reaction temperature, as well as the nature of the
additives, however, all in vain. In analogy to the intermolecular
coupling reactions, the cyclizations were then examined with
substrates subjected to an initial asymmetric alkylation. It was our
expectation that introduction of this C2-substituent could induce

R.H. Taaning et al. / Tetrahedron 64 (2008) 11884–11895
11887
a geometric constraint that might favor the reactive conformation
for cyclization. The asymmetric alkylations of 19 and 20 were
performed with NaHMDS and with an alkyl halide providing
compounds 21–24 (Scheme 4).
analogy with the previous studies on the ketyl–olefin radical cy-
clizations performed by Molander and McKie,13 it can be expected
that our ring closures proceed through an envelope transition state
with a trans-relationship between the ketyl oxygen and the olefin,
as depicted with conformers A and C. This is explained by electronic
repulsion between the anionic oxygen and the forming methylene
radical as would occur with conformer B. Moreover, A has the
benefit of having the R substituent in a pseudo-equatorial position
as opposed to B, which places R in a pseudo-axial orientation. For
all cases, we assume that the olefin prefers to approach the ketyl
from the side opposite to the protruding C5-substituent presented
on the oxazolidinone ring. As conformer C would lead to the
product of cis-selectivity, we therefore and counter intuitively
suggest that our samarium diiodide mediated ketyl–olefin cycli-
zations proceed through a monodentate coordinated samarium
species A based on the observed stereoselectivity. This suggestion is
in agreement with that proposed by Badone and coworkers on the
radical cyclizations of chiral oxazoldinone-derived 2-alkeneamides.14
O
O
O
SmI2 (2.2 equiv)
H2O (4.4 equiv)
THF, 20 °C, 5 min
Ph
Ph
Ph
N
N
O
19
25: 40%
Ph
O
O
O
SmI2 (2.2 equiv)
H2O (4.4 equiv)
THF, 20 °C, 5 min
Ph
O
Bn
20
25: 22%
Scheme 6.
Gratifyingly, cyclization of the N-acyl oxazolidinone 24 with
SmI2 increased the ring closing yield to 53%, providing 27 as a single
diastereomer according to 1H NMR analysis (Scheme 7). The rela-
tive configuration between the two benzyl substituents on the
cyclopentanone ring was assigned to the trans-relationship as
a high optical activity was observed for this product. In a similar
manner, the enantiomerically pure cyclopentanones 28, 30, and 32
could also be secured from the starting N-acyl oxazolidinones
21–23 in yields from 46 to 50%. However, a second product was
isolated from these reactions, identified to possess the [3.1.0]
bicyclic ring system, as illustrated with compounds 29, 31, and 33 in
Scheme 7. The isolation of these products is not entirely surprising,
as the intermediary benzylic anion bears a striking resemblance to
the intermediate samarium carbanion of the Simmons–Smith type
cyclopropanation of samarium enolates developed by Imamoto and
Takiyama.12 This in turn implies that there is partial collapse of the
hemiaminal to the ketone, after ketyl radical addition to the alkene,
which may be due to the increased sterical bulk of the more
functionalized oxazolidinone. Such cyclopropane containing
products were not observed with the simple 2-oxazolidinone.
SmIII
Ph
SmIII
O
SmIII
O
R
O
O
O
H
H
N
Ph
H
Ph
O
N
N
Ph
R
R
O
O
O
A
B
C
Ph
Ph
O
H
R
Ph
H
H
H
Ph
H
H
O
O
R
R
Ph
O
O
R
R
Ph
Scheme 8.
Ph
O
SmI2 (4 equiv)
Ph
O
H2O (8 equiv)
24
THF, 20 °C,18 h
Ph
R
Attempts were also undertaken to examine whether the product
from 4-exo-trig cyclization could also be feasible using these
reaction conditions. However, subjecting N-acyl oxazolidinone 34
to SmI2/H2O did not lead to any ring closing products (Scheme 9).
Nonetheless, several by-products derived from reduction of the
imide functionality were found including a substantial amount of
starting material (38%).
27
SmI2 (2.5 equiv)
H2O (10 equiv)
THF, 20 °C, 10 min
OH
21: R = Me
22: R = All
23: R = Bn
R
Ph
Ph
R = Me 28: 46 %
R = All 30: 48 %
R = Bn 32: 50%
29: 14%
31: 19%
33: 14%
O
O
SmI2 (2.5 equiv)
H2O (10 equiv)
THF, 20 °C, 10 min
27%
8%
Scheme 7.
Ph
OH
O
Ph
N
O
The effect of different proton donor additives was investigated on
the cyclization of the N-acyl oxazolidinone 23. When MeOH
(10 equiv) was used as an additive, the results were the same as with
H2O, producing the cyclopentanone and the cyclopropanol by-prod-
uct in 51 and 14% yield, respectively. On the other hand, with PhOH
(10 equiv) the isolated yield waslowered to 22%, while the addition of
t-BuOH (10 equiv) only gave a 7% yield of the desired cyclopentanone.
Inthislattercase, thecyclopropanolwasisolatedin25%,thehighyield
ofwhich mayoriginate froma slowerprotonation of the intermediary
benzylic anion with this less acidic proton source.
34
Ph
Ph
OH
Ph
Ph
6%
OH
Scheme 9.
Finally, a small study was initiated to investigate the application
A rational for the trans-selectivity observed for the cyclizations
of the chiral N-acyl oxazolidinones 21–24 is given in Scheme 8. In
of these SmI2 cyclizations with cyclic precursors possessing a het-
eroatom in the chain, under the assumption that the rate constant

11888
R.H. Taaning et al. / Tetrahedron 64 (2008) 11884–11895
for 5-exo cyclization substrates containing a nitrogen or oxygen is
higher than that for the corresponding all carbon chain and
therefore cyclization yields were expected to be greater. For this
purpose, the carboxylic acids 35–37 containing either an NBoc, NTs,
or an oxygen in the chain were prepared using standard synthetic
transformations (Scheme 10). Subsequent conversion to their PFP-
esters 38–40 and imide formation with 2-oxazolidinone in the
presence of isopropyl magnesium bromide then led to the desired
N-acyl oxazolidinones 41–43.5
can undergo direct C–C bond formation with an acrylamide pro-
viding chiral acyclic ketones in reasonable yields. This represents
the first example of a transformation of such N-acyl oxazolidinones
where this chiral auxiliary is removed under the conditions for
ketone formation. Finally, cyclization studies were also examined
with the same type of substrates, providing trans-2,5-disubstituted
cyclopentanones in yields of approx. 50%. However, attempts to
cyclize heteroatom-containing equivalents were less successful.
4. Experimental section
4.1. General methods
1. TsCl, Et3N, 92%
O
O
O
2. Cinnamyl bromide,
K2CO3, 95%
Ts
N
H2N
H2N
Ph
O
O
OH
3. NaOH, 98%
Unless otherwise noted all reactions were carried out under
inert atmosphere. Solvents were dried according to standard pro-
cedures and reactions were monitored by thin-layer chromato-
graphic (TLC) analysis. All other chemicals were used as-received
from the appropriate suppliers. Flash chromatography was carried
out on silica gel 60 (230–400 mesh). SmI2 was prepared according
to a literature method.15
35
1. Cinnamyl chloride
Et3N, 50%
2. Boc2O, I2, 96%
O
O
Boc
N
Ph
Ph
3. NaOH, 94%
OH
OH
36
The 1H NMR spectra were recorded at 400 MHz and 13C NMR
spectra were recorded at 100 MHz. The chemical shifts are reported
in parts per million downfield to TMS (
O
Cinnamyl alcohol
NaH
O
Cl
OH
O
d
¼0) and referenced using
37
the residual CHCl3 resonance (
d
¼7.26) for 1H NMR and the central
CDCl3 resonance (
d
¼77.16) for 13C NMR. 1H NMR spectra are
O
1. PFPOH, EDC.HCl
DMAP
2. oxazolidin-2-one
iPrMgCl
O
reported as follows: s¼singlet, d¼doublet, t¼triplet, q¼quartet,
qn¼quintet, sx¼sextet, sp¼septet, br¼broad; coupling constant(s)
in hertz; integration.
Ph
X
Ph
X
OH
N
O
1. 38: X = NTs 66%
39: X = NBoc 71%
2. 41: X = NTs 99%
42: X = NBoc 88%
4.2. (4R,5S)-4-Methyl-3-((S)-2-methyl-3-phenylpropanoyl)-5-
phenyloxazolidin-2-one (5). General procedure for the
asymmetric alkylation of chiral N-acyl oxazolidinones8
40: X = O
30%
43: X = O
40%
Scheme 10.
N-Acyl oxazolidinone 3 (2.405 g, 10.31 mmol) was dissolved in
THF (35 mL) and cooled to ꢀ78 ꢁC, and then NaHMDS (1.0 M in THF,
12.0 mL, 12.0 mmol) was added dropwise to the solution and stir-
red for 30 min at ꢀ78 ꢁC. Then benzyl bromide (3.7 mL, 31 mmol)
was added, and the solution was allowed to warm to 0 ꢁC over
60 min, and finally quenched with water (50 mL). The reaction
mixture was concentrated in vacuo, and extracted with CH2Cl2
(3ꢂ50 mL), dried over MgSO4, filtered, and concentrated in vacuo,
obtaining a pale yellow oil. The pure product was obtained by
column chromatography (10% EtOAc in pentane as eluant), which
gave compound 5 (2.049 g, 6.475 mmol, 64%) as a colorless wax. 1H
The substrates 41–43 were cyclized according to the same
procedure as their carbon analogs, but the yields of the cyclic
ketones 44–46 were disappointingly low for all three cases
(Scheme 11). Considerable efforts were made to optimize the re-
actions and a slight improvement was found when the substrate
42 was added slowly over a 20 min period by syringe pump to
the ethereal solution of SmI2 and H2O, leading to a 31% yield of the
cyclized product 45. As observed earlier in the cyclization of the
simple N-acyl oxazolidinone 18 where also the product 26 of di-
merization was observed when the reaction was performed at low
temperature, the same series of products 47–49 could also be noted
for these cyclization studies promoted by SmI2.
NMR (400 MHz, CDCl3)
d (ppm) 4.41–4.16 (m, 10H), 5.63 (d,
J¼7.4 Hz, 1H), 4.75 (m, 1H), 4.20–4.09 (m, 1H), 3.11 (dd, J¼13.3,
6.7 Hz, 1H), 2.66 (dd, J¼13.3, 8.0 Hz, 1H), 1.19 (d, J¼6.7 Hz, 3H), 0.73
(d, J¼6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d (ppm) 175.4, 152.7,
137.8, 134.9, 128.8 (4C), 128.3 (4C), 126.4 (2C), 78.4, 54.7, 40.2, 37.7,
15.1, 14.9.
X
Ph
O
O
SmI2 (2.2 equiv)
H2O (4.4 equiv)
THF, 20 °C, 5 min
41: X = NTs
42: X = NBoc
43: X = O
Ph
+
O
Ph
X
X
4.2.1. (4R,5S)-4-Methyl-3-((S)-2-methylpent-4-enoyl)-5-
X = NTs: 44: 15%
X = NBoc: 45: 31%
47: 15%
48: not determ.
49: 14%
phenyloxazolidin-2-one (6)
The reaction was conducted according to the general procedure
for asymmetric alkylation of chiral N-acyl oxazolidinones: N-acyl
oxazolidinone 3 (500 mg, 2.15 mmol), NaHMDS (1.0 M in THF,
2.63 mL, 2.63 mmol), and allyl bromide (0.22 mL, 2.6 mmol). The
pure product was obtained by column chromatography (5% EtOAc
in pentane as eluant), which gave compound 6 (393 mg, 1.4 mmol,
67%) as a white solid. Mp 64–65 ꢁC (EtOAc/hexanes). 1H NMR
X = O:
46: 17%
Scheme 11.
3. Conclusion
In summary, we have examined the suitability of chiral oxazo-
lidinones in the SmI2-mediated carbon–carbon bond generating
reactions between the imide functionality of an N-acyl oxazolidi-
none unit with olefinic radical acceptors. Quite pleasingly, we have
demonstrated that products from an Evans asymmetric alkylation
(400 MHz, CDCl3) d (ppm) 7.41–7.25 (m, 5H), 5.83–5.73 (m, 1H),
5.64 (d, J¼7.3 Hz, 1H), 5.06–4.99 (m, 2H), 4.80–4.73 (m, 1H), 3.91–
3.82 (m, 1H), 2.51–2.44 (m, 1H), 2.36–2.16 (m, 1H), 1.18 (d, J¼6.8 Hz,
3H), 0.84 (d, J¼6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d (ppm)
175.9, 152.9, 134.9, 134.4, 129.7 (2C), 129.2 (2C), 126.9, 116.8, 78.4,

R.H. Taaning et al. / Tetrahedron 64 (2008) 11884–11895
11889
55.3, 41.8, 37.8, 17.1, 14.1. HRMS C16H19NO3 [MþNaþ] calculated:
mixture was added satd NH4Cl(aq) (4 mL) at ꢀ78 ꢁC followed by
warming to room temperature. HCl(aq) (1 M, 5 mL) was added
followed by extraction with EtOAc (3ꢂ10 mL). The combined or-
ganic phases were washed with Na2S2O3(aq) (10 mL), dried over
MgSO4, filtered, and then evaporated in vacuo. The pure product
was obtained by column chromatography (15% EtOAc in pentane as
eluant), which gave compound 9 (37 mg, 0.198 mmol, 53%) as
a colorless solid. Mp 51–52 ꢁC (EtOAc/hexanes). 1H NMR (400 MHz,
296.1263, found: 296.1271.
4.2.2. (S)-4-Benzyl-3-((R)-2-methyl-3-phenylpropanoyl)-
oxazolidin-2-one (7)
The reaction was conducted according to the general procedure
for asymmetric alkylation of chiral N-acyl oxazolidinones: N-acyl
oxazolidinone 4 (500 mg, 2.15 mmol), NaHMDS (1.0 M in THF,
2.63 mL, 2.63 mmol) and benzyl bromide (0.31 mL, 2.6 mmol). The
pure product was obtained by column chromatography (10% EtOAc
in pentane as eluant), which gave compound 7 (444 mg, 1.4 mmol,
64%) as a white solid. Mp 91–92 ꢁC (EtOAc/hexanes). 1H NMR
CDCl3)
d
(ppm) 5.47 (br s, 1H), 2.74 (t, J¼6.0 Hz, 2H), 2.58 (m, 4H),
1.30 (s, 9H), 1.09 (t, J¼6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
(ppm) 210.7, 172.3, 51.7, 37.5, 35.4, 30.8, 29.2 (3C), 7.6. HRMS
C10H19NO2 [MþNaþ] calculated: 208.1313, found: 208.1310.
(400 MHz, CDCl3)
d (ppm) 7.34–7.05 (m, 10H), 4.70–4.64 (m, 1H),
4.19–4.07 (m, 3H), 3.19 (dd, J¼13.2, 7.2 Hz, 1H), 3.08 (dd, J¼13.4,
4.3.1. (S)-N-tert-Butyl-5-methyl-4-oxo-6-phenylhexanamide (10)
The title compound was prepared using the general method for
the SmI2-promoted coupling with acrylamides, with N-acyl oxa-
zolidinone 5 (179 mg, 0.555 mmol) and N-tert-butylacrylamide
(48 mg, 0.375 mmol). The pure product was obtained by column
chromatography (15% EtOAc in pentane as eluant), which gave
3.2 Hz, 1H), 2.71 (dd, J¼13.2, 7.2 Hz, 1H), 2.59 (dd, J¼13.4, 9.1 Hz,
1H), 1.22 (d, J¼6.7 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d (ppm)
176.6, 153.3, 139.5, 135.4, 129.6 (2C), 129.1 (4C), 128.6 (2C), 127.5,
126.6, 66.1, 55.2, 40.1, 39.8, 37.9, 17.1. HRMS C20H21NO3 [MþNaþ]
calculated: 346.1419, found: 346.1411.
compound 10 (74 mg, 0.27 mmol, 72%) as a colorless amorphous
ꢀ9.3 (c 1.1, CHCl3). 1H NMR (400 MHz, CDCl3)
d (ppm)
23
4.2.3. (S)-4-Benzyl-3-((R)-2-methylpent-4-enoyl)-
oxazolidin-2-one (8)
solid. [
a
]
D
7.30–7.24 (m, 2H), 7.22–7.16 (m, 1H), 7.16–7.11 (m, 2H), 5.50 (s, 1H),
3.00 (dd, J¼13.5, 6.9 Hz, 1H), 2.93–2.77 (m, 2H), 2.65–2.52 (m, 2H),
2.39–2.21 (m, 2H), 1.32 (s, 9H), 1.10 (d, J¼6.9 Hz, 3H). 13C NMR
Reaction was conducted according to the general procedure for
asymmetric alkylation of chiral N-acyl oxazolidinones: N-acyl
oxazolidinone 4 (500 mg, 2.15 mmol), NaHMDS (1.0 M in THF,
2.63 mL, 2.63 mmol) and allyl bromide (0.22 mL, 2.6 mmol). The
pure product was obtained by column chromatography (5% EtOAc
in pentane as eluant), which gave compound 8 (346 mg, 1.3 mmol,
(100 MHz, CDCl3) d (ppm) 213.5, 171.3, 139.7, 129.0 (2C), 128.5 (2C),
126.4, 51.2, 48.2, 39.1, 37.2, 30.9, 28.9 (3C), 16.5. HRMS C17H25NO2
[MþNaþ] calculated: 298.1783, found: 298.1774.
59%) as a colorless wax. 1H NMR (400 MHz, CDCl3)
d
(ppm) 7.29–
4.3.2. (5S)-N-tert-Butyl-2,5-dimethyl-4-oxo-6-
7.16 (m, 5H), 5.84–5.71 (m, 1H), 5.08–5.00 (m, 2H), 4.66–4.60 (m,
1H), 4.15–4.07 (m, 2H), 3.81 (dqn, J¼13.5, 6.7 Hz, 1H), 3.22 (dd,
J¼13.3, 2.8 Hz, 1H), 2.66 (dd, J¼13.3, 9.7 Hz, 1H), 2.51–2.44 (m, 1H),
2.22–2.15 (m, 1H), 1.14 (d, J¼6.7 Hz, 3H). 13C NMR (100 MHz, CDCl3)
phenylhexanamide (11)
The title compound was prepared using the general method for
the SmI2-promoted coupling with acrylamides, with N-acyl oxa-
zolidinone 5 (179 mg, 0.555 mmol) and N-tert-butylmethacryla-
mide (53 mg, 0.375 mmol). The pure product was obtained by
column chromatography (15% EtOAc in pentane as eluant), which
gave compound 11 (69 mg, 0.240 mmol, 64%) as a colorless solid. 1H
d
(ppm) 176.6, 153.3, 135.6, 135.5, 129.6 (2C), 129.1 (2C), 127.5, 117.4,
66.1, 55.5, 38.3, 38.2, 37.3, 16.6. HRMS C16H19NO3 [MþNaþ] calcu-
lated: 296.1263, found: 296.1257.
NMR (400 MHz, CDCl3)
d (ppm) 7.27–7.13 (m, 5H), 5.53 (br s, 1H),
4.2.4. (E)-N-tert-Butylbut-2-enamide
3.02–2.41 (m, 5H), 2.13 (dd, J¼18.0, 4.3 Hz, 1H), 1.30 (s, 9H), 1.09 (d,
Ethyl trans-2-butenoate (125 mg, 1.1 mmol) is dissolved in EtOH
(5 mL) followed by addition of NaOH(aq) (2 M, 1.3 mL, 2.6 mmol)
and stirred for 4 h, followed by addition of HCl(aq) (2 M, 1.5 mL,
3 mmol). The solution is extracted with CH2Cl2 (4ꢂ10 mL) and
concentrated in vacuo. The crude oil is used without further puri-
fication, dissolved in CH2Cl2 (10 mL), and cooled to 0 ꢁC followed by
addition of NMM (1.7 mL, 1.6 mmol), tert-butylamine (117 mg,
1.6 mmol), and EDC (0.3 g, 1.6 mmol). The solution was stirred at
room temperature for 6 h, and then washed with water (3ꢂ5 mL)
and brine (5 mL) and concentrated in vacuo. The pure product was
obtained by column chromatography (5% EtOAc in pentane as el-
uant), which gave the title compound (141 mg, 1.0 mmol, 91%) as
J¼7.1 Hz, 3H), 1.06 (d, J¼6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
(ppm) 213.6, 175.0, 139.8, 129.1 (2C), 128.6 (2C), 126.4, 51.1, 48.4,
46.6, 39.2, 36.4, 28.9 (3C), 17.9, 16.3. HRMS C18H27NO2 [MþNaþ]
calculated: 312.1939, found: 312.1942.
4.3.3. (S)-N-tert-Butyl-5-methyl-4-oxooct-7-enamide (12)
The title compound was prepared using the general method for
the SmI2-promoted coupling with acrylamides, with N-acyl oxa-
zolidinone 6 (151 mg, 0.555 mmol) and N-tert-butylacrylamide
(48 mg, 0.375 mmol). The pure product was obtained by column
chromatography (20% EtOAc in pentane as eluant), which gave
compound 12 (55 mg, 0.243 mmol, 65%) as a colorless oil. 1H NMR
a colorless solid. 1H NMR (400 MHz, CDCl3)
1H), 5.70 (d, J¼15.0 Hz, 1H), 5.23 (br s, 1H), 1.82 (dd, J¼6.8, 1.6 Hz,
d
(ppm) 6.81–6.72 (m,
(400 MHz, CDCl3) d (ppm) 5.77–5.64 (m, 1H), 5.48 (br s, 1H), 5.07–
4.94 (m, 2H), 2.87–2.61(m, 3H), 2.42–2.30 (m, 3H), 2.11–2.04 (m,
3H), 1.37 (s, 9H). 13C NMR (100 MHz, CDCl3)
d
(ppm) 165.6, 141.2,
1H), 1.30 (s, 9H), 1.04 (d, J¼6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3)
123.1, 51.9, 29.4 (3C), 18.7. HRMS C8H15NO [MþNaþ] calculated:
d (ppm) 211.2, 172.7, 132.9, 115.9, 52.2, 46.1, 35.7, 35.2, 31.0, 29.7
164.1051, found: 164.1042.
(3C), 16.7. HRMS C13H23NO2 [MþNaþ] calculated: 248.1626, found:
248.1620.
4.3. N-tert-Butyl-4-oxohexanamide (9). General procedure for
coupling with acrylamides4a
4.3.4. (R)-N-tert-Butyl-5-methyl-4-oxo-6-phenylhexanamide (13)
The title compound was prepared using the general method for
the SmI2-promoted coupling with acrylamides, with N-acyl oxa-
zolidinone 7 (179 mg, 0.555 mmol) and N-tert-butylacrylamide
(48 mg, 0.375 mmol). The pure product was obtained by column
chromatography (15% EtOAc in pentane as eluant), which gave
compound 13 (63 mg, 0.228 mmol, 61%) as a colorless amorphous
Water (54 mL, 3 mmol) was added to a solution of N-acyl oxa-
zolidinone 3 (129 mg, 0.555 mmol) and N-tert-butylacrylamide
(48 mg, 0.375 mmol) in THF (5.0 mL), and then the solution was
cooled to ꢀ78 ꢁC. A solution of SmI2 (0.1 M, 15 mL, 1.5 mmol) was
added dropwise over 1 h. The reaction mixture was then left stir-
ring at ꢀ78 ꢁC for 24 h. Excess SmI2 was oxidized by flushing the
mixture with oxygen from a balloon. To the now yellow reaction
solid. 1H NMR (400 MHz, CDCl3)
7.15 (m, 1H), 7.15–7.10 (m, 2H), 5.47 (s, 1H), 2.99 (dd, J¼13.5, 6.9 Hz,
d (ppm) 7.29–7.23 (m, 2H), 7.21–

11890
R.H. Taaning et al. / Tetrahedron 64 (2008) 11884–11895
1H), 2.92–2.75 (m, 2H), 2.64–2.51 (m, 2H), 2.37–2.19 (m, 2H),1.31 (s,
pivaloyl chloride (0.95 mL, 7.7 mmol) were added. The reaction
mixture was left stirring for 15 min at ꢀ78 ꢁC, 1 h at 0 ꢁC, and then
re-cooled to ꢀ78 ꢁC. In a separate flask, oxazolidinone 1 (1.435 g,
8.095 mmol) was dissolved in THF (23 mL) under an inert atmo-
sphere of argon. The solution was cooled to ꢀ78 ꢁC and n-butyl
lithium (1.6 M in hexane, 5.1 mL, 8.2 mmol) was added dropwise.
After 1 h of stirring at ꢀ78 ꢁC, the solution was transferred to the
first solution via cannula and the resulting reaction mixture was left
stirring overnight at ꢀ78 ꢁC. Quenching of excess base was ach-
ieved by adding AcOH (2.2 mL) and the solution was allowed to
reach room temperature over 2 h. Then NH4Cl(aq) (23 mL) and
water were added followed by extraction with diethyl ether
(3ꢂ30 mL). The organic phases were washed with NaHCO3(aq)ꢂ3
and brine, and subsequently dried over Na2SO4, filtered, and then
concentrated in vacuo. The pure product was obtained by column
chromatography (10% EtOAc in pentane as the eluant), which gave
compound 16 (1.795 g, 6.569 mmol, 90%) as a colorless oil. 1H NMR
9H), 1.08 (d, J¼6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d (ppm)
213.5, 171.4, 139.8, 129.1 (2C), 128.6 (2C), 126.5, 51.3, 48.3, 39.2, 37.3,
31.0, 29.1, 29.0 (3C), 16.6. HRMS C17H25NO2 [MþNaþ] calculated:
298.1783, found: 298.1774.
4.3.5. (R)-N-tert-Butyl-5-methyl-4-oxooct-7-enamide (14)
The title compound was prepared using the general method for
the SmI2-promoted coupling with acrylamides, with N-acyl oxa-
zolidinone 8 (151 mg, 0.555 mmol) and N-tert-butylacrylamide
(48 mg, 0.375 mmol). The pure product was obtained by column
chromatography (20% EtOAc in pentane as eluant), which gave
compound 14 (46 mg, 0.206 mmol, 55%) as a colorless oil. 1H NMR
(400 MHz, CDCl3)
d (ppm) 5.73–5.62 (m, 1H), 5.51 (br s, 1H), 5.98–
5.03 (m, 2H), 2.84–2.57 (m, 3H), 2.41–2.30 (m, 3H), 2.12–2.03 (m,
1H), 1.30 (s, 9H), 1.07 (d, J¼6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
(ppm) 211.4, 172.4, 133.1, 115.7, 52.0, 46.4, 35.2, 34.9, 31.5, 29.2
(3C), 17.0. HRMS C13H23NO2 [MþNaþ] calculated: 248.1626, found:
(400 MHz, CDCl3)
d
(ppm) 7.45–7.23 (m, 5H), 5.80 (ddt, J¼16.9, 10.2,
248.1620.
6.7 Hz, 1H), 5.64 (d, J¼7.3 Hz, 1H), 5.03 (ddd, J¼17.1, 3.6, 1.6 Hz, 1H),
5.00–4.95 (m, 1H), 4.74 (dq, J¼13.3, 6.6 Hz, 1H), 2.94 (qdd, J¼17.0,
8.0, 6.9 Hz, 2H), 2.18–2.07 (m, 2H), 1.84–1.70 (m, 2H), 0.87 (d,
4.4. (S)-4-Benzyl-3-hex-5-enoyloxazolidin-2-one (17).16
General procedure for the synthesis of N-acyl oxazolidinones
J¼6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d (ppm) 172.9, 153.1,137.9,
133.5, 128.8, 128.7 (2C), 125.7 (2C), 115.4, 79.0, 54.8, 35.0, 33.1, 23.5,
14.6. HRMS C16H19NO3 [MþNaþ] calculated: 296.1257, found:
296.1263.
Hex-5-enoic acid (0.5 mL, 4.2 mmol) was dissolved in THF
(17 mL) and cooled to ꢀ78 ꢁC. Triethylamine (0.75 mL, 5.4 mmol)
and subsequently pivaloyl chloride (0.54 mL, 4.4 mmol) were
added and the mixture was stirred for 15 min before it was allowed
to warm up to 0 ꢁC. After 1 h at 0 ꢁC, the mixture was cooled to
ꢀ78 ꢁC again. Then a solution of (S)-4-benzyloxazolidin-2-one
(815 mg, 4.6 mmol) deprotonated by treatment with n-BuLi (2.9 mL
of 1.6 M in hexane, 4.6 mmol) in THF (13 mL) at ꢀ78 ꢁC for 1 h was
added via cannula with N2 pressure. The mixture was stirred for
20 h at ꢀ78 ꢁC and then the reaction was quenched with concen-
trated acetic acid (1.3 mL, 20 mmol) and allowed to warm up to
room temperature. After 3 h, the mixture was poured into
NH4Cl(aq) (13 mL) and extracted three times with Et2O (50 mL).
The combined organic portions were washed two times with
NaHCO3(aq) (100 mL) and two times with brine (100 mL), and then
dried over MgSO4 and filtered. The solvent was removed in vacuo
and purification by flash column chromatography (increasing po-
larity from 5 to 10% EtOAc in pentane as eluant) provided the de-
sired product 17 as a colorless oil (1.01 g, 3.7 mmol, 88%). 1H NMR
4.4.3. (E)-3-(6-Phenylhex-5-enoyl)oxazolidin-2-one (18)
The title compound was prepared by the same method as
described for 20 using terminal alkene 15 (110 mg, 0.60 mmol), cis-
stilbene (0.22 mL, 1.2 mmol), and Grubbs’ second generation cata-
lyst (3 mg, 0.5 mol %). Flash column chromatography (10% EtOAc in
pentane as eluant) gave the desired product 18 as a colorless oil
(101 mg, 0.39 mmol, 65%). 1H NMR (400 MHz, CDCl3)
d (ppm) 7.35–
7.27 (m, 4H), 7.21–7.17 (m, 1H), 6.41 (d, J¼15.6 Hz, 1H), 6.20 (dt,
J¼15.6, 7.2 Hz, 1H), 4.33 (t, J¼8.0 Hz, 2H), 3.96 (t, J¼8.0 Hz, 2H), 2.99
(t, J¼7.2 Hz, 2H), 2.30 (qd, J¼7.2, 1.2 Hz, 2H), 1.98 (qn, J¼7.2 Hz, 2H).
13C NMR (100 MHz, CDCl3)
d (ppm) 173.6, 153.8, 137.8, 130.9, 130.0,
128.7 (2C), 127.2, 126.2 (2C), 62.2, 42.7, 34.6, 32.6, 24.1. HRMS
C15H17NO3 [MþNaþ] calculated: 282.1106, found: 282.1113.
4.4.4. (4R,5S)-4-Methyl-5-phenyl-3-((E)-6-phenylhex-5-
enoyl)oxazolidin-2-one (19)
(400 MHz, CDCl3)
d
(ppm) 7.35–7.20 (m, 5H), 5.82 (ddt, J¼16.8, 10.0,
Grubbs’ second generation catalyst (5.5 mg, 0.0065 mmol) was
placed in a 5 mL microwave tube under an inert atmosphere of
argon. N-Acyl oxazolidinone 16 (299.5 mg, 1.096 mmol) and cis-
stilbene (0.59 mL, 3.3 mmol) were dissolved in CH2Cl2 (2.2 mL) and
transferred to the microwave tube. The reaction mixture was
heated to 80 ꢁC in a Biotage InitiatorÔ microwave for 3 h. Finally, it
was concentrated with silica in vacuo and transferred directly for
column chromatography (increasing polarity from 2 to 40% EtOAc
in pentane), which gave 19 (307.3 mg, 0.8795 mmol, 80%) as a col-
6.8 Hz, 1H), 5.06 (dq, J¼16.8, 1.2 Hz, 1H), 5.00 (ddt, J¼10.0, 2.0,
1.2 Hz, 1H), 4.67 (ddt, J¼9.6, 7.2, 3.2 Hz, 1H), 4.22–4.17 (m, 2H), 3.30
(dd, J¼13.2, 3.2 Hz, 1H), 3.03–2.88 (m, 2H), 2.77 (dd, J¼13.2, 9.6 Hz,
1H), 2.15 (qt, J¼7.2, 1.2 Hz, 2H), 1.87–1.77 (m, 2H).
4.4.1. 3-Hex-5-enoyloxazolidin-2-one (15)17
The title compound was prepared according to the general
method for N-acyl oxazolidinones using hex-5-enoic acid (392 mg,
3.43 mmol), triethylamine (0.62 mL, 4.5 mmol) and pivaloyl chlo-
ride (0.51 mL, 4.1 mmol) in THF (17 mL). Oxazolidin-2-one (329 mg,
3.78 mmol), n-BuLi (1.6 M in hexane, 2.47 mL, 4.6 mmol) in THF
(13 mL). Flash column chromatography (20% EtOAc in pentane as
eluant) gave the desired product 15 as a colorless oil (561 mg,
orless oil. 1H NMR (400 MHz, CDCl3)
d (ppm) 7.51–7.15 (m, 10H),
6.45 (d, J¼15.9 Hz, 1H), 6.24 (dt, J¼15.8, 6.9 Hz, 1H), 5.52 (d,
J¼7.3 Hz, 1H), 4.72 (qn, J¼6.7 Hz, 1H), 3.03 (t, J¼7.2 Hz, 2H), 2.42–
2.26 (m, 2H), 1.93 (qn, J¼7.3 Hz, 2H), 0.89 (d, J¼6.6 Hz, 3H). 13C NMR
(100 MHz, CDCl3)
d (ppm) 173.0, 153.1, 137.7, 133.4, 130.8, 129.9,
3.06 mmol, 89%). 1H NMR (400 MHz, CDCl3)
d
(ppm) 5.79 (ddt,
128.8, 128.8 (2C), 128.6 (2C), 127.1, 126.1 (2C), 125.7 (2C), 79.0, 54.8,
35.0, 32.5, 24.0, 14.6. HRMS C22H23NO3 [MþNaþ] calculated:
372.1570, found: 372.1569.
J¼16.8, 10.0, 7.2 Hz, 1H), 5.03 (dd, J¼16.8, 1.2 Hz, 1H), 4.98 (dd,
J¼10.0, 1.2 Hz, 1H), 4.41 (t, J¼9.2 Hz, 2H), 4.02 (t, J¼9.2 Hz, 2H), 2.95
(t, J¼7.2 Hz, 2H), 2.15 (q, J¼7.2 Hz, 2H), 1.77 (qn, J¼7.2 Hz, 2H).
4.4.5. (S)-4-Benzyl-(E)-3-(6-phenylhex-5-enoyl)-
4.4.2. (4R,5S)-3-Hex-5-enoyl-4-methyl-5-phenyloxazolidin-
2-one (16)
5-Hexenoic acid (0.87 mL, 7.3 mmol) was dissolved in THF
(30 mL) under an inert atmosphere of argon. The solution was
cooled to ꢀ78 ꢁC. Subsequently, Et3N (1.3 mL, 9.4 mmol) and
oxazolidin-2-one (20)
A solution of terminal alkene 17 (300 mg, 1.09 mmol) in CH2Cl2
(2 mL) was transferred by syringe to Grubbs’ second generation
catalyst (5 mg, 0.5 mol %). cis-Stilbene (0.38 mL, 2.19 mmol) was
added and the mixture was heated to reflux for 48 h. The solvent

R.H. Taaning et al. / Tetrahedron 64 (2008) 11884–11895
11891
was removed in vacuo and purification by flash column chroma-
tography (5% EtOAc in pentane as eluant) gave the product 20 as
a colorless oil (307 mg, 0.88 mmol, 80%). 1H NMR (400 MHz, CDCl3)
133.5, 130.5, 130.3, 129.5 (2C), 128.8 (2C), 128.6, 128.6 (2C), 128.4
(2C), 127.3, 126.5, 126.1 (2C), 125.7 (2C), 78.4, 54.7, 44.4, 39.6, 32.1,
30.8, 14.3.
d
(ppm) 7.37–7.35 (m, 7H), 7.22–7.18 (m, 3H), 6.45 (d, J¼15.6 Hz,
1H), 6.24 (dt, J¼15.6, 7.2 Hz, 1H), 4.64 (ddt, J¼9.6, 7.0, 3.2 Hz, 1H),
4.18–4.08 (m, 2H), 3.28 (dd, J¼13.2, 3.2 Hz, 1H), 3.02 (td, J¼7.2,
1.6 Hz, 2H), 2.74 (dd, J¼13.2, 9.6 Hz, 1H), 2.34 (q, J¼7.2 Hz, 2H), 1.92
4.4.9. (S)-4-Benzyl-3-((R,E)-2-benzyl-6-phenylhex-5-
enoyl)oxazolidin-2-one (24)
The preparation was conducted according to the general pro-
cedure for asymmetric alkylation of chiral N-acyl oxazolidinones:
N-acyl oxazolidinone 20 (162 mg, 0.464 mmol), NaHMDS (1 M in
THF, 0.56 mL, 0.56 mmol), and benzyl bromide (95 mg, 0.56 mmol).
The product was obtained by column chromatography (increasing
polarity from 0 to 5% Et2O in pentane as the eluant) (101 mg,
0.230 mmol, 50%), and subjected to the general method for SmI2-
promoted cyclization (vide infra).
(qn, J¼7.2 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d (ppm) 173.3, 153.6,
137.7, 135.4, 130.8, 129.8, 129.5 (2C), 129.1 (2C), 128.6 (2C), 127.5,
127.1, 126.1 (2C), 66.3, 55.3, 38.1, 35.0, 32.5, 24.0. HRMS C22H23NO3
[MþNaþ] calculated: 372.1576, found: 372.1577.
4.4.6. (4R,5S)-4-Methyl-3-((R,E)-2-methyl-6-phenylhex-5-enoyl)-
5-phenyloxazolidin-2-one (21)
The reaction was conducted according to the general procedure
for asymmetric alkylation of chiral N-acyl oxazolidinones, with
N-acyl oxazolidinone 19 (181.8 mg, 0.5203 mmol), NaHMDS (1 M in
4.4.10. 2-Benzylcyclopentane (25)18
N-Acyl oxazolidinone 18 (50 mg, 0.19 mmol) was dissolved in
THF, 0.62 mL, 0.62 mmol), and methyl iodide (97
mL, 1.6 mmol). The
THF (10 mL) and water (28
m
L, 1.54 mmol) at ꢀ20 ꢁC and SmI2 so-
pure product was obtained by column chromatography (increasing
polarity from 2 to 10% Et2O in pentane as the eluant), which gave
compound 21 (78.3 mg, 0.215 mmol, 41%) as a colorless oil. 1H NMR
lution (0.1 M in THF, 7.7 mL, 0.77 mmol) was added. After 4 h, the
excess SmI2 was quenched by flushing the flask with O2, and
NH4Cl(aq) (4 mL) and 1 M HCl(aq) (4 mL) were added. The mixture
was extracted three times with EtOAc (50 mL), and the combined
organic phase was washed with Na2S2O3(aq) (100 mL) and brine
(100 mL), dried over MgSO4, filtered, and the solvent was removed
in vacuo. Purification by flash column chromatography (10% EtOAc
in pentane as eluant) gave the desired product as a colorless oil
(400 MHz, CDCl3)
d (ppm) 7.41–7.27 (m, 7H), 7.25–7.20 (m, 1H),
7.16–7.08 (m, 2H), 6.40 (d, J¼15.9 Hz, 1H), 6.20 (ddd, J¼15.8, 8.3,
5.9 Hz, 1H), 4.99 (d, J¼7.2 Hz, 1H), 4.50 (qn, J¼6.7 Hz, 1H), 3.83–3.72
(m, 1H), 2.44–2.32 (m, 1H), 2.29–2.17 (m, 1H), 2.17–2.02 (m, 1H),
1.69–1.55 (m, 1H), 1.22 (d, J¼6.9 Hz, 3H), 0.80 (d, J¼6.6 Hz, 3H). 13C
NMR (100 MHz, CDCl3)
d
(ppm) 177.1, 152.8, 137.6, 133.5, 130.5,
(26 mg, 0.15 mmol, 80%). 1H NMR (400 MHz, CDCl3)
d (ppm) 7.30–
130.3, 128.8 (2C), 128.7 (2C), 127.3, 126.1 (2C), 125.7 (2C), 78.7, 55.0,
37.7, 32.9, 31.8, 18.1, 14.5. HRMS C23H25NO3 [MþNaþ] calculated:
386.1727, found: 386.1725.
7.26 (m, 2H), 7.23–7.16 (m, 3H), 3.15 (dd, J¼14.0, 4.0 Hz, 1H), 2.54
(dd, J¼14.0, 9.6 Hz, 1H), 2.39–2.30 (m, 2H), 2.13–2.04 (m, 1H), 2.11
(qn, J¼8.8 Hz, 1H), 2.00–1.91 (m, 1H), 1.79–1.68 (m, 2H), 1.61–1.51
(m, 2H). 13C NMR (100 MHz, CDCl3)
d (ppm) 220.4, 140.2, 129.1 (2C),
4.4.7. (4R,5S)-3-((S,E)-2-Allyl-6-phenylhex-5-enoyl)-4-methyl-5-
phenyloxazolidin-2-one (22)
128.6 (2C), 126.4, 51.3, 38.4, 35.8, 29.4, 20.8. HRMS C12H11O
[MþNaþ] calculated: 197.0942, found: 197.0937.
The reaction was conducted according to the general procedure
for the asymmetric alkylation of chiral N-acyl oxazolidinones, with
N-acyl oxazolidinone 19 (176.0 mg, 0.5037 mmol), NaHMDS (1 M in
THF, 0.6 mL, 0.6 mmol), and allyl bromide (0.13 mL, 1.5 mmol). The
pure product was obtained by column chromatography (increasing
polarity from 2 to 10% Et2O in pentane as the eluant), which gave
compound 22 (96.9 mg, 0.249 mmol, 49%) as a colorless oil. 1H NMR
4.4.11. 2,20-(1,2-Diphenylethane-1,2-diyl)dicyclopentanone (26)
The protocol was followed as for 25, with the exception that the
reaction was run at ꢀ78 ꢁC yielding the dimer of 25. 1H NMR
(400 MHz, CDCl3)
d (ppm) 7.09–6.88 (m, 10H), 3.96 (s, 2H), 3.11 (t,
J¼9.9 Hz, 2H), 2.30–2.10 (m, 4H), 1.95–1.78 (m, 2H), 1.69–1.48 (m,
6H). 13C NMR (100 MHz, CDCl3)
d (ppm) 223.1, 142.1, 129.4 (br),
(400 MHz, CDCl3)
d
(ppm) 7.43–7.30 (m, 7H), 7.27–7.22 (m, 1H),
128.1, 126.3, 50.1, 49.9, 41.2, 28.7, 21.2. HRMS C24H26O2 [MþNaþ]
7.13–7.07 (m, 2H), 6.42 (d, J¼15.9 Hz, 1H), 6.20 (ddd, J¼15.8, 8.6,
5.6 Hz, 1H), 5.84 (ddt, J¼17.2, 10.1, 7.2 Hz, 1H), 5.12–4.99 (m, 2H),
4.81 (d, J¼7.3 Hz, 1H), 4.49 (p, J¼6.6 Hz, 1H), 4.02–3.93 (m, 1H),
2.50–2.37 (m, 2H), 2.37–2.18 (m, 2H), 2.11 (dtd, J¼13.7, 9.3, 6.7 Hz,
1H), 1.74 (dddd, J¼13.6, 6.8, 5.1, 3.7 Hz, 1H), 0.77 (d, J¼6.6 Hz, 3H).
calculated: 369.1825, found: 369.1833.
4.4.12. (R,R)-2,5-Dibenzylcyclopentanone (27)
N-Acyl oxazolidinone 24 (100 mg, 0.23 mmol) was dissolved in
THF (2.3 mL), after which water (33 mg, 1.82 mmol) was added.
SmI2 (1.00 mmol) in THF (0.1 M) was added dropwise over 30 min.
The mixture was stirred at room temperature for 18 h, and then the
flask was flushed with O2 to remove excess SmI2. NH4Cl(aq) (5 mL)
was added and the mixture was poured into 0.5 M HCl(aq) (10 mL)
before extraction with EtOAc (3ꢂ15 mL). The combined organic
portions were washed with Na2S2O3(aq) (2ꢂ15 mL), dried over
MgSO4, filtered, and evaporated in vacuo. Pure product obtained by
13C NMR (100 MHz, CDCl3)
d (ppm) 176.0, 152.8, 137.5, 135.0, 133.5,
130.5, 130.3, 128.8 (C2), 128.7, 128.6 (C2), 127.3, 126.1 (C2), 125.7
(C2), 117.4, 78.5, 54.9, 42.2, 37.9, 32.1, 30.9, 14.6. HRMS C25H27NO3
[MþNaþ] calculated: 412.1883, found: 412.1885.
4.4.8. (4R,5S)-3-((S,E)-2-Benzyl-6-phenylhex-5-enoyl)-4-methyl-
5-phenyloxazolidin-2-one (23)
The reaction was conducted according to the general procedure
for asymmetric alkylation of chiral N-acyl oxazolidinones, with
N-acyl oxazolidinone 19 (691.5 mg, 1.979 mmol), NaHMDS (1 M in
THF, 2.4 mL, 2.4 mmol), and benzyl bromide (0.71 mL, 5.9 mmol).
The pure product was obtained by column chromatography (in-
creasing polarity from 2 to 10% Et2O in pentane as the eluant),
which gave compound 23 (399.1 mg, 0.9080 mmol, 46%) as a col-
flash column chromatography (2% EtOAc/pentane) gave the title
23
compound (32 mg, 0.12 mmol, 53%) as a colorless oil. [
a
]
þ180.4
D
(c 0.9, CH2Cl2). 1H NMR (400 MHz, CDCl3)
d
(ppm) 7.29–7.15 (m,
10H), 3.18 (dd, J¼14.0, 4.4 Hz, 2H), 2.62 (dd, J¼14.0, 9.2 Hz, 2H),
2.35–2.27 (m, 2H), 2.03–1.97 (m, 2H), 1.47–1.36 (m, 2H). 13C NMR
(100 MHz, CDCl3)
d (ppm) 220.0, 140.0, 129.0, 128.2, 126.0, 52.0,
36.0, 27.0. HRMS C19H20O [MþNaþ] calculated: 287.1412, found:
orless oil. 1H NMR (400 MHz, CDCl3)
d
(ppm) 7.44–7.16 (m, 13H),
287.1409.
7.06–7.00 (m, 2H), 6.41 (d, J¼15.9 Hz, 1H), 6.20 (ddd, J¼15.8, 8.6,
5.4 Hz, 1H), 4.76 (d, J¼7.3 Hz, 1H), 4.49–4.37 (m, 1H), 4.33–4.24 (m,
1H), 3.02 (dd, J¼13.3, 7.3 Hz, 1H), 2.78 (dd, J¼13.3, 7.9 Hz, 1H), 2.48–
2.32 (m, 1H), 2.29–2.04 (m, 2H), 1.80–1.70 (m,1H), 0.56 (d, J¼6.6 Hz,
4.4.13. (2S,5R)-2-Benzyl-5-methylcyclopentanone (28)
The reaction was conducted according to the general procedure
for SmI2-promoted cyclization: with chiral N-acyl oxazolidinone 21
3H). 13C NMR (100 MHz, CDCl3)
d
(ppm) 176.1, 152.7, 138.7, 137.5,
(128.6 mg, 0.3538 mmol), H2O (64 mL, 3.6 mmol) and SmI2 (0.1 M in

11892
R.H. Taaning et al. / Tetrahedron 64 (2008) 11884–11895
THF, 8.8 mL, 0.88 mmol). The pure product was obtained by column
chromatography (increasing polarity from 0 to 5% EtOAc in pentane
as the eluant), which gave compound 28 (30.8 mg, 0.164 mmol,
(400 MHz, CDCl3) d (ppm) 7.37–7.15 (m, 10H), 3.32–3.22 (m, 1H),
2.60–2.45 (m, 2H), 2.09 (d, J¼4.2 Hz, 1H), 1.98 (dtd, J¼4.5, 8.2,
12.5 Hz, 1H), 1.86 (t, J¼4.3 Hz, 1H), 1.63–1.50 (m, 3H), 1.42–1.28 (m,
23
46%) as a colorless oil. [
(400 MHz, CDCl3)
a
]
D
ꢀ213.3 (c 1.4, CHCl3). 1H NMR
2H). 13C NMR (100 MHz, CDCl3)
d (ppm) 141.7, 137.5, 129.5 (C2),
d
(ppm) 7.32–7.11 (m, 5H), 3.16 (dd, J¼13.8,
128.5 (C2), 128.4 (C2), 128.4 (C2), 126.1, 125.9, 70.8, 45.7, 36.6, 31.2,
30.8, 25.3, 24.7. LRMS C19H20O [MþNaþ] calculated: 287.3, found:
287.3.
4.2 Hz, 1H), 2.60 (dd, J¼13.8, 9.2 Hz, 1H), 2.39–2.28 (m, 1H), 2.20–
2.10 (m,1H), 2.09–1.97 (m, 2H),1.52–1.40 (m,1H),1.40–1.27 (m,1H),
1.12 (d, J¼7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d (ppm) 221.7,
140.1, 129.1 (2C), 128.5 (2C), 126.2, 50.9, 44.6, 36.3, 30.0, 27.4, 14.6.
4.4.19. (E)-2-(N-3-Phenylprop-2-enyl-para-
toluenesulfonamido)acetic acid (35)
HRMS C13H16O [MþNaþ] calculated: 211.1093, found: 211.1083.
Et3N (26 mL, 0.19 mol) and subsequently cinnamyl chloride
(4.50 mL, 32.0 mmol) were added to a stirring solution of glycine
methyl ester hydrochloride (20.0 g, 0.16 mol) in CH3CN. The
resulting mixture was heated at reflux for 3 h, and then poured into
water (150 mL) and extracted three times with CH2Cl2 (150 mL).
The combined organic portions were washed with water (200 mL),
NaHCO3(aq) (200 mL), and brine (200 mL), and then dried over
MgSO4, filtered, and the solvent was removed in vacuo. Purification
by flash column chromatography (25–60% EtOAc in pentane as el-
uant) afforded the cinnamyl amine as a pale yellow oil (3.28 g,
4.4.14. (1R,2R,5S,6S)-2-Methyl-6-phenylbicyclo[3.1.0]hexan-1-ol (29)
From the SmI2-promoted cyclization affording 28, a major by-
product 29 (9.4 mg, 0.050 mmol, 14%) was isolated. 1H NMR
(400 MHz, CDCl3) d (ppm) 7.33–7.24 (m, 2H), 7.23–7.15 (m, 3H), 2.32
(qn, J¼7.0 Hz, 1H), 2.17–2.08 (m, 1H), 2.07 (d, J¼4.2 Hz, 1H), 1.79 (t,
J¼4.3 Hz,1H),1.66–1.50 (m, 4H), 1.41 (dd, J¼12.7, 8.3 Hz,1H), 1.14 (d,
J¼7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d (ppm) 137.9, 128.5 (2C),
128.4 (2C), 125.9, 71.6, 38.4, 31.2, 30.5, 29.3, 24.6, 17.2. LRMS
C13H16O [MþNaþ] calculated: 211.3, found: 211.3.
16.0 mmol, 50%). 1H NMR (400 MHz, CDCl3)
d (ppm) 7.36–7.18 (m,
4.4.15. (2S,5S)-2-Allyl-5-benzylcyclopentanone (30)
The reaction was conducted according to the general procedure
for SmI2-promoted cyclization: with chiral N-acyl oxazolidinone 22
5H), 6.52 (d, J¼15.6 Hz, 1H), 6.23 (d, J¼15.6 Hz, 1H), 3.70 (s, 3H),
3.44 (s, 2H), 3.41 (dd, J¼6.4, 1.2 Hz, 2H) 1.84 (br s, 1H). 13C NMR
(100 MHz, CDCl3) d (ppm) 173.1, 137.1, 132.3, 128.8 (2C), 127.7, 127.5,
(97.6 mg, 0.251 mmol), H2O (45
mL, 2.5 mmol), and SmI2 (0.1 M in
126.5 (2C), 52.1, 51.5, 50.0. HRMS C12H15NO2 [MþHþ] calculated:
THF, 6.3 mL, 0.63 mmol). The pure product was obtained by column
chromatography (increasing polarity from 0 to 5% EtOAc in pentane
as the eluant), which gave compound 30 (25.9 mg, 0.121 mmol,
206.1181, found: 206.1186.
Cinnamyl amine (1.2 g, 5.8 mmol), Boc2O (1.4 g, 6.4 mmol), I2
(0.15 g, 0.58 mmol), and THF (2 mL) were mixed at 0 ꢁC and then
stirred for 2 h at room temperature before the reaction mixture was
poured into Et2O (100 mL). The organic phase was washed with
Na2S2O3(aq) (100 mL) and brine (100 mL). After that it was dried
over MgSO4, filtered, and the solvent was removed in vacuo. Puri-
fication by flash column chromatography (0–15% ethyl acetate in
pentane as eluant) gave the Boc-protected amine as a colorless oil
23
48%) as a colorless oil. [
(400 MHz, CDCl3)
a]
ꢀ243.4 (c 1.2, CHCl3). 1H NMR
D
d
(ppm) 7.20 (t, J¼7.4 Hz, 2H), 7.15–7.05 (m, 3H),
5.67 (ddt, J¼16.9, 10.1, 6.7 Hz, 1H), 5.02–4.90 (m, 2H), 3.09 (dd,
J¼13.8, 4.2 Hz, 1H), 2.52 (dd, J¼13.9, 9.2 Hz, 1H), 2.49–2.41 (m, 1H),
2.31–2.17 (m, 1H), 2.11–1.91 (m, 4H), 1.46–1.27 (m, 2H). 13C NMR
(100 MHz, CDCl3) d (ppm) 220.4, 140.0, 135.9, 129.1 (2C), 128.5 (2C),
126.3, 116.6, 51.6, 49.3, 36.1, 34.4, 27.3, 27.0. HRMS C15H18
O
(1.7 g, 5.6 mmol, 96%). 1H NMR (400 MHz, CDCl3)
d (ppm) 7.37–7.24
[MþNaþ] calculated: 237.1250, found: 237.1257.
(m, 5H), 6.49 (d, J¼15.2 Hz, (1⁄2 )ꢂ1H), 6.45 (d, J¼13.2 Hz, (1⁄2 )ꢂ
1H), 6.20–6.12 (m, 1H), 4.14 (d, J¼7.2 Hz, (1⁄2 )ꢂ2H), 4.06 (d,
J¼6.0 Hz, (1⁄2 )ꢂ2H), 4.00 (s, (1⁄2 )ꢂ2H), 3.88 (s, (1⁄2 )ꢂ2H), 3.71 (s,
3H), 1.49 (s, (1⁄2 )ꢂ9H), 1.45 (s, (1⁄2 )ꢂ9H). 13C NMR (100 MHz,
4.4.16. (1R,2S,5S,6S)-2-Allyl-6-phenylbicyclo[3.1.0]hexan-1-ol (31)
From the SmI2-promoted cyclization affording 30, a major by-
product 31 (10.1 mg, 0.0471 mmol, 19%) was isolated. 1H NMR
CDCl3)
d (ppm) 170.8, 155.8/155.4, 136.8, 133.3/132.5, 128.8 (2C),
(400 MHz, CDCl3)
d
(ppm) 7.34–7.27 (m, 2H), 7.24–7.16 (m, 3H), 5.89
127.9 (2C), 126.7, 125.4/125.3, 80.7, 52.2, 50.5/50.0, 48.0/47.8, 28.6/
28.5 (3C). LRMS C17H23NO4 [MþNaþ] calculated: 328.2, found:
328.2.
(dddd, J¼16.7, 10.1, 7.6, 6.5 Hz, 1H), 5.14–5.06 (m, 1H), 5.06–5.01 (m,
1H), 2.67–2.52 (m, 1H), 2.33–2.25 (m, 1H), 2.12–2.01 (m, 2H), 2.05
(d, J¼4.3 Hz, 1H), 1.82 (t, J¼4.3 Hz, 1H), 1.68–1.56 (m, 3H), 1.54–1.39
The methyl ester was hydrolyzed by the same method used in
the preparation of 36: Methyl ester (1.57 g, 5.1 mmol), 2 M NaO-
H(aq) (5 mL), and methanol (50 mL). This gave 35 as a colorless
(m, 1H). 13C NMR (100 MHz, CDCl3)
d (ppm) 138.2, 137.7, 128.5 (2C),
128.4 (2C), 126.0, 116.0, 70.8, 43.5, 35.4, 31.4, 31.0, 25.9, 25.0. LRMS
C15H18O [MþNaþ] calculated: 237.3, found: 237.3.
solid (1.39 g, 4.8 mmol, 94%). 1H NMR (400 MHz, CDCl3)
d (ppm)
10.96 (br s, 1H), 7.37–7.24 (m, 5H), 6.51–6.46 (m, 1H), 6.17–6.13 (m,
4.4.17. (2S,5S)-2,5-Dibenzylcyclopentanone (32)
The reaction was conducted according to the general procedure
for SmI2-promoted cyclization: with chiral N-acyl oxazolidinone 23
(99.8 mg, 0.227 mmol), H2O (41 mL, 2.3 mmol), and SmI2 (0.1 M in
THF, 5.7 mL, 0.57 mmol). The pure product was obtained by column
chromatography (increasing polarity from 1 to 5% EtOAc in pentane
1H), 4.12 (d, J¼6.0 Hz, 1H), 4.06 (m, 3H), 3.93 (s, (1⁄2 )ꢂ2H), 1.49 (s,
(1⁄2 )ꢂ9H), 1.46 (s, (1⁄2 )ꢂ9H). 13C NMR (100 MHz, CDCl3)
d (ppm)
176.1/175.6, 155.4/155.4, 136.7, 133.5/132.8, 128.8 (2C), 128.0, 126.7,
126.6, 125.1/124.9, 81.2, 50.6/50.0, 47.9, 28.6/28.5 (3C). LRMS
C16H21NO4 [MþNaþ] calculated: 314.1, found: 314.1.
as the eluant), which gave compound 32 (30.3 mg, 0.115 mmol,
4.4.20. N-tert-Butoxycarbonyl((E)-3-phenylprop-2-
enyl)aminoacetic acid (36)
A solution of triethylamine (5.0 mL, 35 mmol) and p-toluene-
sulfonyl chloride (3.7 g, 19 mmol) in CH2Cl2 (10 mL) was added to
23
50%) as a crystalline solid. Mp 62–63 ꢁC (EtOAc/Hexanes). [
a]
D
ꢀ211.5 (c 0.9, CHCl3). 1H NMR (400 MHz, CDCl3)
d
(ppm) 7.28 (tt,
J¼8.2, 1.5 Hz, 4H), 7.23–7.14 (m, 6H), 3.19 (dd, J¼13.9, 4.2 Hz, 2H),
2.63 (dd, J¼13.9, 9.1 Hz, 2H), 2.36–2.26 (m, 2H), 2.07–1.94 (m, 2H),
a
suspension of glycine methyl ester hydrochloride (2.00 g,
1.48–1.35 (m, 2H). 13C NMR (100 MHz, CDCl3)
d
(ppm) 220.1, 140.0,
15.9 mmol) in CH2Cl2, and the resulting mixture was refluxed for
24 h. Then it was poured into water (50 mL) and extracted three
times with Et2O. The combined organic phase was washed with
brine, dried over MgSO4, filtered, and the solvent was removed in
vacuo. Purification by flash column chromatography (increasing
polarity from 10 to 60% EtOAc in pentane as eluant) yielded the
tosylamide as a colorless solid (3.57 g, 14.7 mmol, 92%). 1H NMR
129.1 (2C), 128.5 (2C), 126.3, 51.6, 36.1, 27.2. HRMS C19H20
O
[MþNaþ] calculated: 287.1406, found: 287.1412.
4.4.18. (1R,2S,5S,6S)-2-Benzyl-6-phenylbicyclo[3.1.0]hexan-1-ol (33)
From the SmI2-promoted cyclization to obtain 32, a major by-
product 33 (8.6 mg, 0.033 mmol, 14%) was isolated. 1H NMR

R.H. Taaning et al. / Tetrahedron 64 (2008) 11884–11895
11893
(400 MHz, CDCl3)
d
(ppm) 7.75 (d, J¼8.0 Hz, 2H), 7.31 (dd, J¼8.0,
4.4.23. Pentafluorophenyl N-tert-butoxycarbonyl((E)-(3-
phenylprop-2-enyl)amino)acetate (39)
0.8 Hz, 2H), 4.09 (br s, 1H), 3.78 (d, J¼5.6 Hz, 2H), 3.64 (s, 3H), 2.43
(s, 3H).19
The title compound 39 was prepared using the same method for
the preparation of compound 38: carboxylic acid 36 (1.30 g,
4.46 mmol), pentafluorophenol (0.90 g, 4.90 mmol), EDC (1.74 g,
8.9 mmol), and DMAP (0.11 g, 0.89 mmol) in CH2Cl2 (60 mL). Flash
column chromatography (25–75% CH2Cl2 in pentane as eluant)
gave the pentafluorophenyl ester 39 as a colorless oil (1.45 g,
Oven dried K2CO3 (1.77 g, 12.8 mmol) and cinnamyl bromide
(1.9 mL, 12.8 mmol) in THF (5 mL) were added to a solution of the
tosylamide (1.56 g, 6.4 mmol) in acetone (60 mL). The resulting
mixture was heated at reflux for 18 h and then allowed to cool
before water (30 mL) was added. The acetone was removed by
rotary evaporation, and Et2O (50 mL) was added and a colorless
solid remained undissolved. Filtration yielded the methyl ester as
a colorless solid (2.19 g, 6.09 mmol, 95%). 1H NMR (400 MHz, CDCl3)
3.27 mmol, 71%). 1H NMR (400 MHz, CDCl3)
d (ppm) major rotamer:
7.39–7.24 (m, 5H), 6.56 (d, J¼15.6 Hz, 1H), 6.18 (dt, J¼15.6, 6.8 Hz,
1H), 4.25 (s, 2H), 4.19 (d, J¼6.8 Hz, 2H), 1.49 (s, 9H); minor rotamer
inter alia: 6.52 (m, 1H), 4.36 (s, 2H), 4.12 (d, J¼6.0 Hz, 2H), 1.50 (s,
d
(ppm) 7.77 (d, J¼8.4 Hz, 2H), 7.32 (d, J¼8.4 Hz, 2H), 7.30–7.23 (m,
5H), 6.45 (d, J¼15.6 Hz, 1H), 6.03 (dt, J¼15.6, 6.8 Hz, 1H), 4.06 (s,
2H), 4.04 (d, J¼0.8 Hz, 2H), 3.61 (s, 3H), 3.32 (s, 3H).
9H). 13C NMR (100 MHz, CDCl3)
d (ppm) 166.6/166.5, 155.6/155.0,
142.4 (br), 141.1 (br), 140.1 (br), 139.3 (br), 138.6 (br), 136.9 (br),
136.5, 134.1/133.4, 128.8 (2C), 128.2, 126.7 (2C), 124.5/124.5, 81.7/
81.5, 50.6/50.0, 47.4, 28.5/28.3 (3C).
NaOH(aq) (2 M, 5 mL) was added to a suspension of the methyl
ester (1.01 g, 2.81 mmol) in methanol (50 mL). The resulting mix-
ture was heated at reflux for 1 h, and then it was poured into
a mixture of water (50 mL) and CH2Cl2 (50 mL). This mixture was
extracted three times with water (70 mL), and the combined
aqueous portions were acidified with concentrated aq HCl and
subsequently extracted four times with CH2Cl2 (100 mL). The
combined organic portions were dried over MgSO4, filtered, and the
solvent was removed in vacuo. This afforded the carboxylic acid 36
as a colorless solid (0.947 mg, 2.74 mmol, 98%). 1H NMR (400 MHz,
4.4.24. Pentafluorophenyl (E)-3-phenylprop-2-enyloxyacetate (40)
The crude of 37 (1 g), pentafluorophenol (1.93 g, 10.5 mmol),
EDC (3.71 g, 19 mmol), and DMAP (230 mg, 1.9 mmol) were dis-
solved in CH2Cl2 (30 mL) and stirred for 18 h. The mixture was then
poured into NaHCO3(aq) and extracted three times with CH2Cl2
(50 mL). The combined organic portions were washed with NaH-
CO3(aq) (100 mL) and brine (100 mL), and then dried over MgSO4
and filtered. The solvent was removed in vacuo and flash column
chromatography (increasing polarity from 10 to 30% CH2Cl2 in
pentane) gave the desired product 40 as a pale yellow oil (999 mg,
CDCl3)
d
(ppm) 7.76 (d, J¼8.4 Hz, 2H), 7.33–7.23 (m, 7H), 6.47 (d,
J¼15.6 Hz, 1H), 6.01 (dt, J¼15.6, 6.8 Hz, 1H), 4.07 (s, 2H), 4.04 (dd,
J¼6.8, 0.8 Hz, 2H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3)
d (ppm)
175.1, 144.1, 136.8, 136.1, 135.4, 130.0 (2C), 128.9 (2C), 128.5, 127.6
(2C), 126.8 (2C), 123.1, 50.8, 47.1, 21.8. LRMS C16H21NO4 [MþNaþ]
calculated: 368.4, found: 368.4.
2.8 mmol, 30% over two steps). 1H NMR (400 MHz, CDCl3)
d (ppm)
7.42–7.27 (m, 5H), 6.68 (d, J¼16.0 Hz, 1H), 6.31 (dt, J¼16.0, 6.4 Hz,
1H), 4.51 (s, 2H), 4.36 (dd, J¼6.4, 0.8 Hz, 2H). 13C NMR (100 MHz,
CDCl3)
d (ppm) 167.1, 142.5 (br), 141.3 (br), 140.0 (br), 139.4 (br),
4.4.21. (E)-3-Phenylprop-2-enyloxyacetic acid (37)20
138.7 (br), 136.9 (br), 136.2, 135.3, 128.8 (2C), 128.4, 126.8 (2C),
123.6, 72.7, 66.1.
Cinnamyl alcohol (3.19 g, 23.8 mmol) in THF (20 mL) was added
slowly to a suspension of NaH (33.3 mmol, 1.33 g of 60% NaH in oil,
the oil had previously been removed by washing with pentane) in
THF (20 mL) at 0 ꢁC. After stirring for 45 min, 2-chloroacetic acid
(900 mg, 9.5 mmol) in THF (15 mL) was added over 20 min. The
resulting mixture was heated at reflux for 18 h. The volume was
reduced by rotary evaporation and Et2O (100 mL) was added. The
organic phase was extracted three times with NaHCO3(aq) (80 mL).
The combined aqueous portions were acidified with concentrated
aq HCl and extracted three times with Et2O (200 mL). The com-
bined organic portions were dried over MgSO4, filtered, and the
solvent was removed in vacuo yielding 1.0 g of crude product,
which was used without further purification. 1H NMR (400 MHz,
4.4.25. (E)-N-3-Phenylprop-2-enyl-N-(2-oxo-2-(2-oxooxazolidin-
3-yl)ethyl)-para-toluenesulfonamide (41)
i-PrMgCl (2 M in THF, 1.6 mL, 3.2 mmol) was added to a stirred
solution of oxazolidin-2-one (280 mg, 3.2 mmol) in THF (20 mL) at
ꢀ15 ꢁC, and after 20 min the PFP-ester 38 (829 mg, 1.60 mmol) in
THF (20 mL) was added over 20 min. The resulting mixture was
stirred for 3 h at ꢀ15 ꢁC and then poured into NaHCO3(aq) (50 mL).
Next it was extracted three times with EtOAc (50 mL), and the
combined organic portions were washed with NaHCO3(aq)
(100 mL) and brine (100 mL). The organic phase was dried over
MgSO4, filtered, and the solvent was removed in vacuo. The crude
product was purified by flash column chromatography (increasing
polarity from 20 to 40% EtOAc in pentane as eluant) to give N-acyl
oxazolidinone 41 as a colorless solid (657 mg, 1.58 mmol, 99%). Mp
CDCl3)
d
(ppm) 7.40–7.20 (m), 6.64 (d, J¼16.0 Hz, 1H), 6.28 (dt,
J¼16.0, 6.4 Hz, 1H), 4.29 (d, J¼6.4 Hz, 2H), 4.18 (s, 2H).
4.4.22. Pentafluorophenyl (E)-(N-3-phenylprop-2-enyl-para-
toluenesulfonamido)acetate (38)
58–60 ꢁC (CH2Cl2). 1H NMR (400 MHz, CDCl3)
d (ppm) 7.78 (d,
J¼8.0 Hz, 2H), 7.32 (d, J¼8.0 Hz, 2H), 7.29–7.23 (m, 5H), 6.40 (d,
J¼15.6 Hz, 1H), 5.99 (dt, J¼15.6, 6.8 Hz, 1H), 4.63 (s, 2H), 4.37 (t,
J¼8.4 Hz, 2H), 4.05 (dd, 6.8, 1.2 Hz, 2H), 3.94 (t, J¼8.4 Hz, 2H), 2.43
The carboxylic acid 35 (785 mg, 2.28 mmol), pentafluorophenol
(460 mg, 2.50 mmol), EDC (870 mg, 4.6 mmol), and DMAP (55 mg,
0.46 mmol) were dissolved in CH2Cl2 (60 mL), and stirred at room
temperature for 16 h. The mixture was poured into NaHCO3(aq)
(50 mL) and extracted three times with CH2Cl2 (50 mL). The com-
bined organic portions were washed two times with NaHCO3(aq)
(100 mL) and once with NaCl(aq) (50 mL) before it was dried over
MgSO4 and filtered. The solvent was removed in vacuo and the crude
productwaspurified byflashcolumn chromatography(0–50%CH2Cl2
in pentane as eluant). This gave the desired product as a colorless oil
(s, 3H). 13C NMR (100 MHz, CDCl3)
d (ppm) 169.1, 153.8, 143.8, 137.3,
136.2, 134.7, 129.9, 128.8 (2C), 128.3 (2C), 127.7 (2C), 126.7, 123.8,
63.1, 51.1, 49.6, 42.5, 21.8. HRMS C21H21N2O4S [MþNaþ] calculated:
437.1147, found: 437.1155.
4.4.26. tert-Butyl 2-oxo-2-(2-oxooxazolidin-3-yl)((E)-3-
phenylprop-2-enylethyl)carbamate (42)
The title compound 42 was prepared using the method de-
scribed for the preparation of compound 41: i-PrMgCl (2 M in THF,
3.0 mL), oxazolidin-2-one (521 mg, 6.0 mmol), and 39 (1.37 g,
2.99 mmol) in THF (50 mL). Flash column chromatography (15–40%
ethyl acetate in pentane as eluant) gave the N-acyl oxazolidinone
42 as a colorless solid (950 mg, 2.64 mmol, 88%). Mp 148–149 ꢁC
(0.775 g,1.52 mmol, 66%). 1H NMR (400 MHz, CDCl3)
d (ppm) 7.78 (d,
J¼8.0 Hz, 2H), 7.33–7.26 (m, 7H), 6.52 (d, J¼15.6 Hz, 1H), 6.06 (dt,
J¼15.6, 6.8 Hz,1H), 4.47 (s, 2H), 4.10 (d, J¼6.8 Hz, 2H), 2.43 (s, 3H).13C
NMR (100 MHz, CDCl3)
d (ppm) 165.3, 144.0, 139.7 (br), 139.2 (br),
139.0 (br), 138.4 (br), 136.6 (br), 136.3, 135.8, 135.6, 129.8 (2C), 128.6
(2C), 128.3, 127.4 (2C), 126.6 (2C), 122.3, 50.2, 46.2, 21.5.
(CH2Cl2). 1H NMR (400 MHz, CDCl3)
d (ppm) major rotamer

11894
R.H. Taaning et al. / Tetrahedron 64 (2008) 11884–11895
7.36–7.28 (m, 4H), 7.26–7.23 (m, 1H), 6.46 (br d, J¼16.0 Hz, 1H),
6.21–6.13 (m, 1H), 4.57 (s, 2H), 4.41 (t, J¼8.0 Hz, 2H), 4.05 (d,
J¼6.0 Hz, 1H), 4.00 (t, J¼8.0 Hz, 2H), 1.49 (s, 9H). Minor rotamer
inter alia: 4.51 (s, 2H), 4.40 (t, J¼8.0 Hz, 2H), 4.11 (d, J¼6.4 Hz, 2H),
3.97 (t, J¼8.0 Hz, 2H), 1.44 (s, 9H). 13C NMR (100 MHz, CDCl3)
chromatography (5% Et2O in pentane/CH2Cl2 1:1 as eluant) afforded
the title compound 45 as a colorless amorphous solid (16 mg,
0.06 mmol, 32%). 1H NMR (400 MHz, CDCl3)
d (ppm) 7.31–7.21 (m,
3H), 7.17–7.15 (m, 2H), 3.95–3.88 (m, 2H), 3.66 (br d, J¼19.0 Hz, 1H),
3.33 (dd, J¼11.6, 8.8 Hz, 1H), 3.18 (dd, J¼14.0, 4.0 Hz, 1H), 2.91–2.84
(m, 1H), 2.67 (dd, J¼14.0, 9.6 Hz, 1H), 1.45 (s, 9H). 13C NMR
d
(ppm) 169.7/169.6, 155.6/155.2, 153.6/153.6, 136.6, 132.8/132.1,
128.6/128.5 (2C), 127.7 (2C), 126.4/126.4, 125.6/125.6, 80.7/80.5,
63.1, 51.0/50.5, 50.1/50.0, 42.5, 28.6/28.5 (3C). HRMS C19H24N2O5
[MþNaþ] calculated: 383.1583, found: 383.1577.
(100 MHz, CDCl3) d (ppm) 212.1 (br), 154.2, 138.1, 128.7 (4C), 126.7,
80.4, 53.1, 49.3, 47.8, 34.4, 28.4 (3C). HRMS C16H21NO3 [MþNa]
calculated: 298.1419, found: 298.1426.
4.4.27. (E)-(3-Phenylprop-2-enyloxyacetyl)oxazolidin-2-one (43)
i-PrMgCl (2 M in THF, 2.8 mL) was added to a solution of oxa-
zolidin-2-one (486 mg, 5.58 mmol) in THF (20 mL) at ꢀ15 ꢁC. After
30 min the PFP-ester 40 (0.992 g, 2.79 mmol) in THF (25 mL) was
added over 20 min and the resulting mixture was stirred for 3 h at
ꢀ15 ꢁC. It was then poured into NaHCO3(aq) (50 mL) and extracted
three times with Et2O (50 mL). The combined organic portions
were washed with NaHCO3(aq) (100 mL) and brine (100 mL), dried
over MgSO4, filtered and the volume reduced in vacuo. Purification
by flash column chromatography (increasing polarity from 20 to
40% EtOAc in pentane as eluant) gave the N-acyl oxazolidinone 43
as a colorless solid. (294 mg, 1.13 mmol, 40%). Mp 113–114 ꢁC
4.5.3. 4-Benzyldihydrofuran-3(2H)-one (46)21
The dihydrofuranone 46 was prepared according to the general
method for SmI2-promoted cyclizations using N-acyl oxazolidinone
43 (60 mg, 0.23 mmol), water (18 mL, 1.0 mmol) and SmI2 (0.1 M in
THF, 5 mL, 0.5 mmol) at 20 ꢁC. Purification by flash column chro-
matography (5% Et2O in pentane:CH2Cl2 1:1 as eluant) afforded of
the title compound as
a
colorless amorphous solid. (7 mg,
(ppm) 7.32–7.21 (m,
0.04 mmol, 17%). 1H NMR (400 MHz, CDCl3)
d
3H), 7.17 (m, 2H), 4.31 (br.t, J¼8.8 Hz,1H), 4.07(dt, J¼17.2, 0.4 Hz,1H),
3.85 (d, J¼17.2 Hz,1H), 3.85 (d, J¼8.8 Hz,1H), 3.16 (dd, J¼14.0, 4.0 Hz,
1H), 2.79 (ddt, J¼10.0, 8.8, 4.0 Hz, 1H), 2.66 (dd, J¼10.0, 8.8 Hz, 1H).
HRMS C11H12O2 [MþNaþ] calculated: 199.0735, found: 199.0740.
(CH2Cl2). 1H NMR (400 MHz, CDCl3)
d (ppm) 7.40–7.37 (m, 2H),
7.33–7.29 (m, 2H), 7.26–7.22 (m, 1H), 6.64 (d, J¼16.0 Hz, 1H), 6.31
4.5.4. 4,40-(1,2-Diphenylethane-1,2-diyl)bis(1-tosylpyrrolidin-3-
one) (47)
Subjecting N-acyl oxazolidinone 41 (75 mg, 0.18 mmol) to the
general procedure for SmI2-promoted cyclizations using water
(dt, J¼16.0, 6.4 Hz, 1H), 4.44 (t, J¼8.0 Hz, 2H), 4.29 (dd, J¼6.4, 1.2 Hz,
2H), 4.01 (t, J¼8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d
(ppm) 170.2,
153.4, 136.3, 133.5, 128.5 (2C), 127.8, 126.5 (2C), 124.9, 72.1, 69.1,
63.1, 41.9. HRMS C14H15NO4 [MþNaþ] calculated: 284.0899, found:
284. 0905.
(14
ded apart from 44 (7 mg, 0.021 mmol, 12%) also by-product 47
(18 mg, 0.027 mmol, 15%). 1H NMR (400 MHz, CDCl3)
(ppm) 7.41
mL, 0.8 mmol) and SmI2 (0.1 M in THF, 4.0 mL, 0.4 mmol) affor-
d
4.5. General procedure for SmI2 cyclizations
(d, J¼8.4 Hz, 4H), 7.20–7.14 (m, 10H), 7.12–7.07 (m, 4H), 3.87 (s, 2H),
3.67 (t, J¼9.6 Hz, 2H), 3.42 (d, J¼17.2 Hz, 2H), 2.92 (t, J¼9.6 Hz, 2H),
2.63 (d, J¼17.2 Hz, 2H), 2.46 (t, J¼9.6 Hz, 2H), 2.40 (s, 6H). 13C NMR
A mixture of the N-acyl oxazolidinone (0.18 mmol) and water
(0.8 mmol) in THF (20 mL) was added dropwise (1 mL/min) to
a solution of SmI2 in THF (0.1 M, 4 mL, 0.40 mmol) at the temper-
ature in question. Immediately after addition was complete excess
SmI2 was quenched with O2. Then NH4Cl(aq) (4 mL) and 1 M aq HCl
(4 mL) were added and the mixture was extracted three times with
EtOAc (50 mL). The combined organic portions were washed with
Na2S2O3(aq) (100 mL) and brine (100 mL). The organic phase was
then dried over MgSO4, filtered, and the solvent was removed in
vacuo. The crude product was purified by flash column chromato-
graphy with the stated solvent system.
(100 MHz, CDCl3)
d (ppm) 210.0 (2C), 144.0 (2C), 138.4 (2C), 131.4
(2C), 129.7 (4C), 129.0 (4C), 127.7 (4C), 127.6 (6C), 55.0 (2C), 48.6
(2C), 48.4 (2C), 46.9 (2C), 21.5 (2C). HRMS C36H36N2O6S2 [MþNaþ]
calculated: 679.1912, found: 679.1938.
4.5.5. 4,40-(1,2-Diphenylethane-1,2-diyl)bis(dihydrofuran-3-
(2H)-one) (49)
The title compound was a by-product of the general procedure
for SmI2-promoted cyclizations using oxazolidinone 43 (11 mg,
0.03 mmol, 14%). 1H NMR (400 MHz, CDCl3)
d (ppm) 7.38–7.27 (m,
10H), 4.21 (t, J¼8.8 Hz, 2H), 4.10 (t, J¼1.6 Hz, 2H), 3.73 (t, J¼8.8 Hz,
4.5.1. 4-Benzyl-1-para-toluenesulfonylpyrrolidin-3-one (44)
The N-tosyl pyrrolidinone 44 was prepared by the general
procedure for SmI2-promoted cyclizations using N-acyl oxazolidi-
2H), 3.71 (d, J¼16.8 Hz, 2H), 3.28 (d, J¼16.8 Hz, 1H), 2.52 (td,
J¼8.8 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d (ppm) 216.5 (2C), 139.6
(2C), 129.0 (6C), 127.7 (4C), 72.3 (2C), 70.3 (2C), 47.6 (2C), 46.2 (2C).
none 41 (100 mg, 0.24 mmol), water (22
mL, 1.2 mmol), and SmI2
HRMS C22H22O4 [MþNaþ] calculated: 373.1416, found: 373.1414.
(0.1 M in THF, 6.0 mL, 0.6 mmol) at room temperature. Purification
by flash column chromatography (5% Et2O in pentane/CH2Cl2 1:1 as
eluant) yielded the product 44 as a colorless amorphous solid
Acknowledgements
(12 mg, 0.036 mmol, 15%). 1H NMR (400 MHz, CDCl3)
d (ppm) 7.67
We deeply appreciative the generous financial support from the
Danish National Research Foundation, the Lundbeck Foundation,
the Carlsberg Foundation, the iNANO and OChem Graduate Schools,
and the University of Aarhus.
(d, J¼8.0 Hz, 2H), 7.35 (dd, J¼8.0, 0.8 Hz, 2H), 7.31–7.21 (m, 3H), 7.08
(d, J¼6.8 Hz, 2H), 3.75 (d, J¼18.0 Hz, 1H), 3.72 (t, J¼9.2 Hz, 1H),
3.37(d, J¼18.0 Hz, 1H), 3.12 (dd, J¼14.0 Hz, 1H), 3.02 (t, J¼9.2 Hz,
1H), 2.81 (ddt, J¼10.0, 9.6, 4.0 Hz, 1H), 2.54 (dd, J¼14.0, 10.0 Hz, 1H),
2.45 (s, 3H). 13C NMR (100 MHz, CDCl3)
d (ppm) 209.2, 144.4, 137.7,
References and notes
131.6, 130.0 (2C), 128.9 (2C), 128.6 (2C), 127.9 (2C), 127.2, 54.0, 50.2,
33.8, 28.4, 21.6. HRMS C18H19NO3 [MþNaþ] calculated: 352.0983,
found: 352.0981.
1. For comprehensive reviews on the use of substituted 2-oxazolidinones as chiral
auxiliaries in organic synthesis, see: (a) Ager, D. J.; Prakash, I.; Schaad, D. R.
Chem. Rev. 1996, 96, 835–876; (b) Taaning, R.; Skrydstrup, T. (S)-4-Benzyl-2-
oxazolidinone. In Encyclopedia on Reagents for Organic Synthesis; Wiley: 2007.
2. For an example, see: Wender, P. A.; Rice, K. D.; Schnute, M. E. J. Am. Chem. Soc.
1997, 119, 7897–7898.
3. For some recent reviews on the use of SmI2 in organic synthesis, see: (a) Go-
palaiah, K.; Kagan, H. B. New J. Chem. 2008, 32, 607–637; (b) Jung, D. Y.; Kim,
Y. H. Synlett 2005, 3019–3032; (c) Edmonds, D. J.; Johnston, D.; Procter, D. J.
Chem. Rev. 2004, 104, 3371–3403; (d) Kagan, H. B. Tetrahedron 2003, 59,
4.5.2. tert-Butyl 3-benzyl-4-oxopyrrolidine-1-carboxylate (45)
The N-Boc pyrrolidinone 45 was prepared by the general pro-
cedure for SmI2-promoted cyclizations using N-acyl oxazolidinone
42 (65 mg, 0.18 mmol), water (14
mL, 0.80 mmol), and SmI2 (0.1 M
in THF, 4.0 mL, 0.40 mmol) at 20 ꢁC. Purification by flash column

R.H. Taaning et al. / Tetrahedron 64 (2008) 11884–11895
11895
10351–10372; (e) Agarwal, S.; Greiner, A. J. Chem. Soc., Perkin Trans. 1 2002,
2033–2042; (f) Steel, P. G. J. Chem. Soc., Perkin Trans. 1 2001, 2727–2751; (g)
Krief, A.; Laval, A.-M. Chem. Rev. 1999, 99, 745–777; (h) Molander, G. A.;
Harris, C. R. Tetrahedron 1998, 54, 3321–3354; (i) Skrydstrup, T. Angew. Chem.,
Int. Ed. 1997, 36, 345–347; (j) Molander, G. A.; Harris, C. R. Chem. Rev. 1996,
96, 307–338.
4. (a) Jensen, C. M.; Lindsay, K. B.; Taaning, R. H.; Karaffa, J.; Hansen, A. M.;
Skrydstrup, T. J. Am. Chem. Soc. 2005, 127, 6544–6545; (b) Hansen, A. M.;
Lindsay, K. B.; Sudhadevi Antharjanam, P. K.; Karaffa, J.; Daasbjerg, K.; Flowers,
R. A., II; Skrydstrup, T. J. Am. Chem. Soc. 2006, 128, 9616–9617; (c) Lindsay, B. K.;
Ferrando, F.; Christensen, K. L.; Overgaard, J.; Roca, T.; Bennasar, M.-L.;
Skrydstrup, T. J. Org. Chem. 2007, 72, 4181–4188.
Chem. 2006, 4, 3553–3564; (b) Croft, A.; Lindsay, K. B.; Renaud, P.; Skrydstrup, T.
Chimia 2008, 62, 735–741.
8. Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem. Soc. 1982, 104, 1737–1739.
9. Evans, D. A.; Bartroli, J.; Shih, T. L. J. Am. Chem. Soc. 1981, 103, 2127–2129.
10. For some recent reviews on olefin metathesis, see: (a) Trnka, T. M.; Grubbs,
R. H. Acc. Chem. Res. 2001, 34, 18–29; (b) Connon, S. J.; Blechert, S. Angew. Chem.,
Int. Ed. 2003, 42, 1900–1923; (c) Chatterjee, A. K.; Choi, T. L.; Sanders, D. P.;
Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 11360–11370; (d) Astruc, D. New J.
Chem. 2005, 29, 42–56.
11. Molander, G. A.; McKie, J. A. J. Org. Chem. 1992, 57, 3132–3139.
12. Imamoto, T.; Takiyama, N. Tetrahedron Lett. 1987, 28, 1307–1308.
13. Molander, G. A.; McKie, J. A. J. Org. Chem. 1995, 60, 872–882.
14. Badone, D.; Bernassau, J.-M.; Cardamone, R.; Guzzi, U. Angew. Chem., Int. Ed.
Engl. 1996, 35, 535–538.
15. Samarium(II) diiodide was prepared according to a literature procedure. Girard,
P.; Namy, J. L.; Kagan, H. B. J. Am. Chem. Soc. 1980, 102, 2693–2698.
16. Xiao, D.; Vera, M. D.; Liang, B.; Joullie´, M. M. J. Org. Chem. 2001, 66, 2734–2742.
17. Wu, M.-J.; Yeha, J.-Y. Tetrahedron 1994, 50, 1073–1082.
18. Reich, H. J.; Renga, J. M.; Reich, I. L. J. Am. Chem. Soc. 1975, 97, 5434–5447.
19. Yip, K.-T.; Li, J.-H.; Lee, O.-Y.; Yang, D. Org. Lett. 2005, 7, 5717–5719.
20. Benati, L.; Calestani, G.; Leardini, R.; Minozzi, M.; Nanni, D.; Spagnolo, P.;
Strazzari, S. Org. Lett. 2003, 5, 1313–1316.
5. (a) Karaffa, J.; Lindsay, K. B.; Skrydstrup, T. J. Org. Chem. 2006, 71, 8219–8226;
(b) Mittag, T.; Christensen, K. L.; Lindsay, K. B.; Nielsen, N. C.; Skrydstrup, T.
J. Org. Chem. 2008, 73, 1088–1092.
6. For related work on SmI2 promoted coupling reactions with amino acid thio-
esters, see: (a) Blakskjær, P.; Høj, B.; Riber, D.; Skrydstrup, T. J. Am. Chem. Soc.
2003, 125, 4030–4031; (b) Mikkelsen, L. M.; Jensen, C. M.; Høj, B.; Blakskjær, P.;
Skrydstrup, T. Tetrahedron 2003, 59, 10541–10549; (c) Jensen, C. M.; Lindsay,
K. B.; Andreasen, P.; Skrydstrup, T. J. Org. Chem. 2005, 70, 7512–7519; (d)
Lindsay, K. B.; Skrydstrup, T. J. Org. Chem. 2006, 71, 4766–4777.
7. For a couple of reviews on this work, see: (a) Ebran, J. P.; Jensen, C. M.; Jo-
hannesen, S. A.; Karaffa, J.; Lindsay, K. B.; Taaning, R.; Skrydstrup, T. Org. Biomol.
21. Crich, D.; Yao, Q. J. Org. Chem. 1996, 61, 3566–3570.