Ruthenium-catalyzed allylic alkylations of chelated enolates using vinyl dioxolanon-2-ones

Article abstract of DOI:10.1021/jo501877q

4-Vinyl-substituted 1,3-dioxolan-2-ones are found to be good substrates for Ru-catalyzed allylic alkylations of chelated amino acid ester enolates. cis-1,3-Dioxolan-2-ones are more reactive than the corresponding trans-isomers. The attack occurs preferentially with regioretention at the position of the leaving group with perfect chirality transfer. Therefore, this protocol is a good complement to the Pd-catalyzed processes, which give only linear products with this type of substrate.

Full text of DOI:10.1021/jo501877q

Note
pubs.acs.org/joc
Ruthenium-Catalyzed Allylic Alkylations of Chelated Enolates Using
Vinyl Dioxolanon-2-ones
Anton Bayer and Uli Kazmaier*
Institut fur Organische Chemie, Universitat des Saarlandes, Campus, Geb. C4.2, D-66123 Saarbruecken, Germany
̈
̈
S
* Supporting Information
ABSTRACT: 4-Vinyl-substituted 1,3-dioxolan-2-ones are found to be good substrates for Ru-catalyzed allylic alkylations of
chelated amino acid ester enolates. cis-1,3-Dioxolan-2-ones are more reactive than the corresponding trans-isomers. The attack
occurs preferentially with regioretention at the position of the leaving group with perfect chirality transfer. Therefore, this
protocol is a good complement to the Pd-catalyzed processes, which give only linear products with this type of substrate.
ransition metal-catalyzed allylic alkylations play a
dominant role in organometallic chemistry, and besides
but also the Ru-complex CpRuCl(PPh3)2 with a wide range of
nucleophiles.10 The results described previously by Trost could
be confirmed also for this class of substrates. In the presence of
the Pd-catalyst attack occurred exclusively at the distal position
giving rise to the (E)-configured products. In contrast, the Ru-
catalyst gave rise to a mixture of the two regioisomers as an
almost 1:1 mixture (Scheme 2).
Ru-catalysts in general show a high flexibility with respect to
the nucleophile used. Besides stabilized carbanions, a wide
range of heteronucleophiles such as thiols,11 amines12 or
alcohols,13 can be applied. In general, Pd- and Ru-catalysts give
access to different regioisomeric substitution products, as
illustrated in Scheme 2, but in case of Ru the regioselectivity
strongly depends on the catalyst used. [Cp*Ru(NCCH3)3]PF6,
a catalyst intensively used by Trost14 and Bruneau15 et al.
generates a π-allyl-Ru-complex,16 such as the Pd-catalysts do,
resulting in a mixture of regioisomers. In contrast, [(p-
cymene)RuCl2]2 gives rise to products with excellent
regioretention and perfect chirality transfer.17
T
Pd, which is by far the most applied metal,1 a wide range of
other transition metal complexes can be used as catalysts.2
Besides Rh3 and Ir,4 especially Ru became more and more
interesting during the past few years.5 In general, allyl acetates,
carbonates or phosphates are used as substrates,1,2 but for the
introduction of functionalized allylic side chains also vinyl
epoxides6 or 4-vinyl 1,3-dioxolan-2-ones7 are suitable candi-
dates, at least for Pd-catalyzed reactions. Both classes of
substrates have been investigated in detail by Trost et al., using
soft nucleophiles such as disulfones.8 One might expect the
same product (ratio) from equivalent substrates, but significant
differences have been observed (Scheme 1). Although in both
Scheme 1. Allylic Alkylations Using Vinyl Epoxides and
Vinyl 1,3-Dioxolan-2-ones
Our group is also investigating transition metal-catalyzed
allylic alkylations using chelated amino acid esters as
nucleophiles.18 This approach gives direct access to γ,δ-
unsaturated amino acids and peptides.19 Although the same
structural motif can also be obtained via Claisen rearrange-
ment,20 the transition metal-catalyzed approach gives rise to the
opposite diastereomer.21 By far the most investigations have
been carried out with Pd-catalysts,22 but several other transition
metals such as Rh23 and Ir got into our focus during the past
years. Recently, we reported on Ru-catalyzed allylic alkylations
(Scheme 3) proceeding with excellent regioselectivity (rs) and
cases the nucleophile attacked at the sterically least hindered
position, distal to the remaining OH-functionality, the E/Z-
ratio depended on the substrate used. In the presence of
suitable chiral ligands symmetric 4,5-divinyl-dioxolan-2-one
(D/L or meso) react with several nucleophiles providing the
expected substitution products with excellent ee’s.9
Kang et al. investigated not only reactions of 4,5-
disubstituted dioxolan-2-ones in the presence of Pd(PPh3)4
Received: August 14, 2014
Published: August 18, 2014
© 2014 American Chemical Society
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Note
Scheme 2. Transition Metal-Catalyzed Allylations Using Vinyl 1,3-Dioxolan-2-ones
products (4−6) can be expected: the linear product 4 from
an attack of the nucleophile at the sterically least hindered
position of the allyl intermediate, the branched product 5, and
if the alcoholate intermediate formed attacks the ester
functionality, also the five-membered lactone 6 (Table 1).
First experiments were carried out with the catalyst used by
Trost14 and Bruneau.15 Indeed, with 3 a reaction could be
observed. Under standard conditions a mixture of the linear
product 418b and the lactone 6 was formed, while 6 was the
major product (entry 1), although the yield of the combined
products was moderate. The anti-product was formed
preferentially, and the linear product was (E)-configured. The
reaction started at a temperature of −60 °C, and therefore we
run the reaction also at −50 °C to suppress the lactonization
and to obtain the branched product 5 (entry 2). The
selectivities observed under these mild conditions were similar
to the first experiment, but the yield was even worse. Therefore,
we switched to [(p-cymene)RuCl2]2, the catalyst we used
successfully in our previous work (entries 3 and 4).24 The
regioselectivities were comparable, but the yield, especially
under standard conditions (entry 3) was excellent. Also here,
the cyclization could be suppressed almost completely if the
reaction was carried out at low temperature (entry 4). For
comparison, we also investigated the Pd-catalyzed allylation
(entries 5 and 6). As expected, here the linear product was
formed almost exclusively as a ∼ 4:1 (E)/(Z)-mixture,
independent of the reaction conditions used. In contrast, with
Wilkinson’s catalyst no allylation product could be obtained,
although the starting material was consumed (entry 7). A
complex mixture of side products was formed, which was not
further analyzed.
Scheme 3. Ru-Catalyzed Allylic Alkylations of Chelated
Enolates
chirality transfer (ct).24 The reactions perform smoothly
isomerization-free probably via an σ−π-allyl intermediates.
This would explain the perfect selectivities obtained. This
protocol also allows us to convert (Z)-allylic substrates to (Z)-
substitution products selectively
The last example clearly indicates that also functionalized
allylic substrates can be used, and one might expect the
corresponding branched products starting from an analogous
functionalized allylic substrate such as 1. But surprisingly, not
the desired allylated product was formed, but the acylated
product 2,25 resulting from a nucleophilic attack of the enolate
on one of the benzoates (Scheme 4). The situation was similar
with the corresponding diacetate, although the yield in this case
was lower (45%).
Scheme 4. Reaction of Chelated Enolates with Dibenzoate 1
These first experiments clearly indicate that especially the
cymene-Ru-complex is a good catalyst for these types of allylic
substrates, providing products that are not available by other
transition metal catalysts. Therefore, we next investigated 4,5-
disubstituted divinyldioxolan-2-ones (7). The introduction of a
second substituent on the heterocyclic ring should influence the
coordination properties of the catalyst, and therefore, one
might expect a different reaction behavior of the cis and trans
isomers.
The required substrates were obtained according to a
protocol described by Trombini et al. using a Zn-mediated
Barbier reaction (Scheme 5).26 The required disubstituted
dioxolan-2-ones were obtained in acceptable yield as cis/trans
mixtures. While the cis products were formed preferentially for
R = alkyl, the trans product was preferred in case of the aryl-
substituted carbonates. While the arylated substrates could
easily be separated by flash chromatography, this was not
always the case for the alkylated ones. In some cases a fraction
of a cis/trans mixture was obtained. To make this portion also
utilizable, we subjected it to a Pd-catalyzed isomerization
toward the thermodynamically more stable trans isomer, as
It should be mentioned that such side reactions have never
been observed under Pd-catalyzed reactions, which provide
selectively the linear, (E)-configured substitution product as
expected.18 Obviously, the direct nucleophilic attack of the
enolate on the allylbenzoate is faster than the attack on the
allyl-Ru-complex, if this complex is formed at all. This result
was completely unexpected, since terminal allyl benzoates in
general react fast and under mild conditions (see also Scheme
3). We assumed that the problems might be caused by the
second benzoate group, which might be able to coordinate to
the allyl-Ru-intermediate formed, generating a stable, inactive
bidentate Ru-complex.
To tackle this issue, we decided to switch to the
corresponding cyclic carbonate 3, which should not be able
to form such a bidentate complex. The influence of several
transition metal catalysts on the outcome of the reaction has
been investigated (Table 1). In principle, three different
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Note
Table 1. Transition Metal-Catalyzed Allylic Alkylations Using Carbonate 3
a
a
b
ratio
ratio (5,6)
yield (%)
entry
catalyst (mol %)
T (°C)
4:5:6
anti:syn
4
5/6
1
2
3
4
5
6
7
[Cp*Ru(MeCN)3]PF6 (2)
[Cp*Ru(MeCN)3]PF6 (2)
[(p-cymene)RuCl2]2 (2) PPh3 (4)
[(p-cymene)RuCl2]2 (2) PPh3 (4)
[allylPdCl]2 (2) PPh3 (9)
−78 to rt
−50
−78 to rt
−50
−78 to rt
−50
−78 to rt
37:0:63
31.65:4
35:0:65
41:54:5
96:4:0
96:4:0
−−
82:18
81:19
65:35
68:32
−−
19
11
12
25
33 (6)
25 (5)
65 (6)
52 (5)
−−
62 (E) 13 (Z)
59 (E) 18 (Z)
−−
[allylPdCl]2 (2) PPh3 (9)
n.d.
−−
−−
RhCl(PPh3)3 (2.5) P(OEt)3 (10)
−−
a
b
Determined by GC (L-Chirasil-Val). Isolated yields
5). This is a clear indication that also with these substrates no
isomerization occurs on the Ru-allyl intermediates.
Scheme 5. Synthesis of 4,5-Disubstituted 1,3-Dioxolan-2-
ones 7
The aryl-substituted derivatives 7f and 7g were found to be
significantly less suitable (entries 6 and 7). They showed also a
preference for the all-cis-lactone, but the regioselectivities and
also the yields were worse compared to the alkyl derivatives
7a−e. In addition, a range of not identified side reactions
occurred with 7g, which makes it impossible to determine the
product ratio by GC. Therefore, in Table 2 only the isolated
yield is shown.
Quite different was the situation with the corresponding
trans-configured carbonates. These derivatives are significantly
less reactive. With the linear alkyl-substituted carbonates trans-
7a and 7b also a good regioselectivity toward the lactone and
an excellent diastereoselectivity for the all-trans-product was
obtained (Scheme 6). No allylation product could be isolated
from reactions of the sterically more demanding derivatives
trans-7c and 7d and the aryl-substituted carbonates 7f and 7g.
The configuration of the allylation products could be confirmed
by H,H-NOESY spectra of the different isomers.
described by Garcia et al.27 According to these procedures, both
required isomers could be obtained in sufficient amounts.
The alkyl-substituted cis-dioxolan-2-ones were found to be
suitable substrates for the investigated Ru-catalyzed alkylations
(Table 2, entries 1−4). With the [(p-cymene)RuCl2]2 complex
the lactones were formed preferentially under standard
conditions (warm-up to room temperature overnight) in
good yields and high diastereoselectivity for the all-cis-product.
If enantioenriched carbonates such as (4S,5R)-7e were used, a
perfect chirality transfer into the product was observed (entry
The differences in the reaction behavior of the cis and trans
dioxolanones can be explained by different steric interactions in
the ionization step (Figure 1). The attack of the sterically
Table 2. Allylic Alkylations Using syn-4,5-Disubstituted Carbonates 7
a
b
ratio
yield (%)
entry
7
R
8+9:10
8:9
8
9
10
1
2
3
4
5
6
7
( )-7a
( )-7b
( )-7c
( )-7d
Et
89:11
90:10
82:18
86:14
95:5
>98:<2
86:14
96:4
70
60
69
62
76
47
34
n-Pent
i-Pr
8
7
10
c-Hex
n-Bu
Ph
>98:<2
93:7
(4S,5R)-7e (92% ee)
( )-7f
93:7
96:4
( )-7g
p-BrPh
n.d.
n.d.
a
b
Determined by GC (L-Chirasil-Val). Isolated yields
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Note
butyl-lithium in hexanes (1.6M, 1.17 mL, 1.88 mmol) was added
slowly. The cooling bath was removed, and stirring was continued for
further 10 min. The solution was cooled to −78 °C, and the TFA-
protected tert-butyl glycinate (171 mg, 0.75 mmol) dissolved in THF
(1 mL) was added to the freshly prepared LHMDS solution. After 10
min a solution of dried ZnCl2 (123 mg, 0.90 mmol) in THF (1.0 mL)
was added, and stirring was continued for 30 min at −78 °C. A second
solution was prepared from [(p-cymene)RuCl2]2 (6.4 mg, 0.01 mmol)
and triphenylphosphine (5.2 mg, 0.02 mmol) in THF (1 mL). The
solution was stirred for 5 min at room temperature while turning red.
The allylic substrate (0.50 mmol) was added, and the resulting
solution was slowly transferred to the chelated enolate at −78 °C. The
mixture was allowed to warm to room temperature overnight. The
solution was diluted with diethyl ether before 1 M KHSO4 was added.
After separation of the layers, the aqueous layer was extracted twice
with diethyl ether, and the combined organic layers were dried over
Na2SO4. The solvent was evaporated in vacuo, and the crude product
was purified by flash chromatography (SiO2).
Scheme 6. Allylic Alkylations Using anti-4,5-Disubstituted
Carbonates 7
tert-Butyl 3-hydroxymethyl-2-trifluoroacetylamino-4-pente-
noate (5). Following a slightly modified GP1 (reaction temperature:
−50 °C, 16 h) the reaction of 3 (114 mg, 1.00 mmol) with tert-butyl
N-trifluoroactyl-glycinate (342 mg 1.50 mmol) gave rise to a separable
mixture of the branched alcohol 5 (155 mg, 0.52 mmol, 52%) (ratio
anti:syn 68:32) and the linear (E)-configured alcohol (E)-418b (83 mg,
0.25 mmol, 25%) as colorless oils. anti-5 (68%): 1H NMR (400 MHz,
CDCl3) δ = 1.47 (s, 9 H), 2.96 (tdd, J = 9.5, 5.4, 3.1 Hz, 1 H), 3.11
(sbr, 1 H), 3.41 (dd, J = 12.1, 9.4 Hz, 1 H), 3.59 (dd, J = 12.1, 5.5 Hz, 1
H), 4.80 (dd, J = 7.9, 3.0 Hz, 1 H), 5.19 (d, J = 17.1 Hz, 1 H), 5.23 (d,
J = 10.4 Hz, 1 H), 5.48 (ddd, J = 17.1, 10.5, 8.8 Hz, 1 H), 7.23 (sbr, 1
H); 13C NMR (100 MHz, CDCl3) δ = 28.0, 49.1, 52.9, 61.9, 83.9,
115.6 (J = 287 Hz), 120.5, 131.2, 158.3 (J = 38.0 Hz), 169.0. syn-5
(32%): 1H NMR (400 MHz, CDCl3) δ = 1.48 (s, 9 H), 2.27 (sbr, 1 H),
2.76 (dq, J = 9.0, 5.1 Hz, 1 H), 3.79 (d, J = 5.1 Hz, 2 H), 4.65 (dd, J =
8.1, 5.2 Hz, 1 H), 5.23 (d, J = 17.1 Hz, 1 H), 5.26 (d, J = 10.3 Hz, 1
H), 5.74 (ddd, J = 17.1, 10.5, 8.4 Hz, 1 H), 7.49 (sbr, 1 H); 13C NMR
(100 MHz, CDCl3) δ = 27.9, 47.3, 54.5, 63.1, 83.7, 115.7 (J = 287 Hz),
119.6, 133.6, 157.1 (J = 37.4 Hz), 168.7; GC (L-ChiraSilVal, 80 °C, 10
min, 80 to 180 °C, 1 °C/min) tR(2R,3R)-5 (anti) = 50.76′, tR(2S,3S)-5
(anti) = 54.68′, tR(2R,3S)-5 (syn) = 65.98′, tR(2S,3R)-5 (syn) = 68.89′,
tR(E,2R)-4 = 72.85′, tR(E,2S)-4 = 75.88′; HRMS (CI) for
C12H19F3NO4 [M + H]+ calcd 298.1261, found 298.1273.
Figure 1. Formation of alkene-Ru-complexes as initial ionization step
demanding Ru-complex on the vinylcarbonate occurs from the
face opposite to the leaving group (stereoretention via double
inversion). In case of cis-7 this face is open, while severe
interactions occur for trans-7. Obviously, a linear alkyl chain is
accepted, but a sterically more demanding branched or
aromatic substituent blocks this face, and the coordination/
ionization is suppressed.
In conclusion, we could show that cis-4-vinyl-substituted 1,3-
dioxolan-2-ones are good substrates for Ru-catalyzed allylic
alkylations of chelated amino acid ester enolates. The attack
occurs preferentially with regioretention at the position of the
leaving group with perfect chirality transfer. Therefore this
protocol is a good complement to the Pd-catalyzed processes,
which give only linear products. In contrast, the corresponding
trans isomers are significantly less reactive.
trans-2-Trifluoroacetylamino-3-vinyl-butyro-1,4-lactone
(trans-6). Following GP1 the reaction of 4-vinyl-1,3-dioxolan-2-one 3
(570 mg, 5.00 mmol) and tert-butyl N-trifluoroactyl-glycinate (1.70 g,
7.50 mmol) provided a mixture of the linear product (E)-4 and the
lactone 6 as a diastereomeric mixture (cis/trans 35:65). Flash
chromatography gave rise to cis-6 (204 mg, 0.91 mmol, 18%), trans-
6 (525 mg, 2.35 mmol, 47%) and (E)-4 (178 mg 0.60 mmol, 12%) as
colorless oils. The lactones 6 crystallized slowly on standing. trans-6:
mp 82−85 °C; 1H NMR (400 MHz, CDCl3) δ = 3.27 (tt, J = 11.0, 8.1
Hz, 1 H), 4.08 (dd, J = 10.7, 9.4 Hz, 1 H), 4.51 (dd, J = 9.2, 8.2 Hz, 1
H), 4.66 (dd, J = 11.7, 8.4 Hz, 1 H), 5.28 (d, J = 10.3 Hz, 1 H), 5.30
(d, J = 17.1 Hz, 1 H), 5.80 (ddd, J = 17.1, 10.2, 8.0 Hz, 1 H), 7.22 (d, J
= 7.8 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ = 47.0, 53.9, 69.2,
115.5 (J = 287 Hz), 120.7, 131.8, 157.8 (J = 38.4 Hz), 172.8. cis-6: mp
EXPERIMENTAL SECTION
■
General Remarks. All air- or moisture-sensitive reactions were
carried out in dried glassware (>100 °C) under an atmosphere of
nitrogen. THF was distilled from Na/benzophenone. The products
were purified by flash chromatography on silica gel columns (0.063−
0.2 mm). Mixtures of ethyl acetate and hexanes were generally used as
eluents. Analytical TLC was performed on precoated silica gel plates.
Visualization was accomplished with UV-light and KMnO4 solution.
Melting points are uncorrected. 1H and 13C NMR spectra were
recorded with a 400 MHz (1H) and 100 MHz (13C) spectrometer in
CDCl3. Chemical shifts are reported in ppm relative to TMS, and
CHCl3 was used as the internal standard. The correct assignment of
signals was verified by H,H-COSY and C,H-COSY spectral data.
Selected signals for the minor regio- and diastereomers are extracted
from the spectra of the isomeric mixture. Regioisomeric and
diastereomeric ratios were determined by GC equipped with a L-
ChiraSilVal capillary column (25 m × 0.25 mm). Nitrogen was used as
carrier gas. Mass spectra were recorded with a high resolution
quadrupole spectrometer (CI) and with an ion trap spectrometer
(ESI). 3-Buten-1,2-diol and 4-vinyl-1,3-dioxolanone (2) were
purchased from commercial suppliers. cis-7c, cis-7d and cis/trans-7f
were prepared as described by Lombardo.26 (4S)-3,4-Dihydroxy-1-
octene was obtained by deprotection of (4S)-3-hydroxy-4-tert-
butyldimethylsilyloxy-1-octene28 with TBAF.
1
84−89 °C; H NMR (400 MHz, CDCl3) δ = 3.62 (ddd, J = 8.9, 8.4,
5.4 Hz, 1 H), 4.38 (d, J = 9.6 Hz, 1 H), 4.55 (dd, J = 9.6, 5.1 Hz, 1 H),
4.77 (t, J = 8.9 Hz, 1 H), 5.28 (d, J = 17.0 Hz, 1 H), 5.34 (d, J = 10.3
Hz, 1 H), 5.65 (ddd, J = 17.0, 10.3, 8.9 Hz, 1 H), 6.90 (sbr, 1 H); 13
C
NMR (100 MHz, CDCl3, selected signals) δ = 43.2, 52.5, 70.9, 121.5,
130.3, 172.8; GC (L-ChiraSilVal, 80 °C, 10 min, 80 to 180 °C, 1 °C/
min, 20 min) tR(2R,3S)-6 (cis) = 51.66′, tR(2S,3R)-6 (cis) = 51.88′,
tR(E,2R)-4 = 72.85′, tR(E,2S)-4 = 75.88′, tR(2R,3R)-6 (trans) = 83.94′,
tR(2S,3S)-6 (trans) = 84.55′; HRMS (CI) for C8H9F3NO3 [M + H]+
calcd 224.0529, found 224.0522.
General Procedure 2 (GP2): Synthesis of 5-Substituted 4-
Vinyl-1,3-dioxolan-2-ones.26 (a) Activiation of zinc powder: Zinc
powder was treated with 10% HCl for 2 min. Afterward it was washed
with water, then acetone and dried in a high vacuum overnight. (b)
Triethylamine on silica gel: 25 g of silica gel and 5 mL of triethylamine
General Procedure 1 (GP1): Ru-Catalyzed Allylic Alkylations
of Chelated Enolates. A solution of hexamethyldisilazane (335 mg,
2.07 mmol) in THF (2.0 mL) was prepared in a Schlenk flask under
nitrogen. After the solution was cooled to −20 °C, a solution of n-
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Note
were stirred in diethylether for 1 h, before the solvent was removed in
vacuo.
13.8, 22.3, 24.3, 31.2, 32.9, 81.9, 82.7, 121.2, 132.1, 154.3; GC (CP-
Chirasil-Dex-CB, 110 °C, 10 min, 110 to 180 °C, 5 °C/min)
tR(4R,5R)-7b = 20.25′, tR(4S,5S)-7b = 20.49′; HRMS (CI) for
C10H17O3 [M + H]+ calcd 185.1172, found 185.1171.
3-Bromopropenyl methyl carbonate26 (1.2 mmol) and activated
zinc powder (1.5 mmol) were added to a solution of the
corresponding aldehyde (1 mmol) in sat. NH4Cl solution/THF
(9:1; 5 mL). The heterogenic mixture was stirred at room temperature
for 2−4 h. The aqueous phase was extracted twice with diethyl ether,
and the unreacted aldehyde was removed by stirring for 2 h with 1 M
NaHSO3/Na2S2O5 solution. The organic phase was dried over
Na2SO4, and the solvent was removed in vacuo. The crude product
was dissolved in diethyl ether (10 mL) and stirred with Et3N/SiO2
(1.5 g) at room temperature for 16 h. The solvent was removed in
vacuo, and the product was purified by flash chromatography
(hexanes/ethyl acetate 9:1).
(4S,5R)-4-Butyl-5-vinyl-1,3-dioxolan-2-one [(4S,5R)-7e]. To a
0 °C cold solution of (4S,5R)-3,4-dihydroxy-1-octene29 (720 mg, 4.15
mmol) in THF (10 mL), triethylamine (809 mg, 8.0 mmol) and ethyl
chloroformate (651 mg, 6.0 mmol) were added. The reaction mixture
was allowed to warm up to room temperature and was stirred for 16 h.
The solution was washed with 1 M HCl, sat. NaHCO3 solution and
brine. The organic phase was dried over Na2SO4 and concentrated in
vacuo. The residue was taken up in diethyl ether and was stirred for 4
h with NEt3/SiO2 (see GP2b). After filtration the solvent was removed
in vacuo, and the residue was purified by column chromatography
(hexanes/ethyl acetate = 75:25) giving rise to cyclic carbonate (4S)-7e
(666 mg, 3.92 mmol, 92%, cis:trans = 63:37) as colorless oil. The
diastereomeric mixture was further purified by column chromatog-
raphy (hexanes/ethyl acetate = 85:15) providing pure (4S,5R)-7e (300
mg, 1.76 mmol, >99% cis, 92% ee). The minor trans-configured
diastereomer ((4S,5S)-7e) could not be obtained in diastereomeric
pure form: 1H NMR (400 MHz, CDCl3) δ = 0.91 (t, J = 7.2 Hz, 3 H),
1.28−1.40 (m, 3 H), 1.40−1.58 (m, 2 H), 1.65 (m, 1 H), 4.69 (ddd, J
= 9.8, 7.6, 3.8 Hz, 1 H), 5.07 (tt, J = 7.5, 1.0 Hz, 1 H), 5.45 (ddd, J =
10.6, 0.8, 0.8 Hz, 1 H), 5.49 (dt, J = 17.0, 1.0, 1.0 Hz, 1 H), 5.84 (ddd,
J = 17.2, 10.4, 7.1 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ = 13.8,
22.2, 27.5, 29.6, 80.0, 80.1, 121.5, 129.4, 154.4; GC (CP-Chirasil-Dex-
CB, 110 °C, 10 min, 110 to 180 °C, 5 °C/min) tR(4R,5R)-7e = 53.31′,
tR(4S,5S)-7e = 53.66′, tR(4S,5R)-7e = 65.22′, tR(4R,5S)-7e = 65.99′;
HRMS (CI) for C9H15O3 [M + H]+ calcd 171.1015, found 171.1000.
trans-4-(4-Bromophenyl)-5-vinyl-1,3-dioxolan-2-one (trans-
7g). According to GP2 trans-7g (1.13 g, 4.19 mmol, 42%) and cis-
7g (622 mg 2.31 mmol, 23%) were obtained as clear colorless oils
from 3-bromo-propenylmethylcarbonat (2.34 g, 12.0 mmol, 64% cis)
and 4-bromobenzaldehyde (1.84 g, 10.0 mmol): 1H NMR (400 MHz,
CDCl3) δ = 4.80 (ddt, J = 8.2, 7.1, 0.9 Hz, 1 H), 5.23 (d, J = 8.2 Hz, 1
H), 5.45 (d, J = 17.1 Hz, 1 H), 5.49 (d, J = 10.5 Hz, 1 H), 5.97 (ddd, J
= 17.4, 10.5, 7.2 Hz, 1 H), 7.23 (d, J = 8.4 Hz, 2 H), 7.57 (d, J = 8.5
Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ = 82.3, 84.6, 122.6, 123.8,
127.4, 130.9, 132.4, 133.6, 153.6; HRMS (CI) for C11H1079BrO3 [M +
H]+ calcd 268.9807, found 268.9806.
General Procedure 3 (GP3): cis-trans-Isomerization of 5-
Substituted 4-Vinyl-1,3-dioxolan-2-ones.27 A cis-configured or a
cis/trans mixture of 5-substituted 4-vinyl-1,3-dioxolan-2-one (5 mmol)
was dissolved in a 25 mL flask in CH2Cl2 (15 mL). Pd(PPh3)4 (280
mg, 5 mol%, 0.25 mmol) was added, and the flask was filled up with
CH2Cl2 and sealed to minimize the loss of CO2. The solution was
stirred at room temperature for 16−32 h. Then the reaction mixture
was quickly filtered through a short pad of silica to remove the catalyst.
After concentration of the filtrate in vacuo, the crude product was
purified by flash chromatography (hexanes/ether or hexanes/ ethyl
acetate).
cis-4-Ethyl-5-vinyl-1,3-dioxolan-2-one (cis-7a). Following GP2
cis-7a (536 mg, 3.77 mmol, 37%) and trans-7a (211 mg, 1.48 mmol,
15%) were obtained as clear colorless oils from 3-bromo-propenyl
methyl carbonate (2.34 g, 12.0 mmol, 64% cis) and propanal (581 mg,
1
10.0 mmol): H NMR (400 MHz, CDCl3) δ = 1.03 (t, J = 7.4 Hz, 3
H), 1.55 −1.75 (m, 2 H), 4.63 (ddd, J = 9.3, 7.6, 4.6 Hz, 1 H), 5.09 (tt,
J = 7.3, 1.0 Hz, 1 H), 5.45 (dt, J = 10.5, 1.0 Hz, 1 H), 5.50 (dt, J = 17.2,
1.0 Hz, 1 H), 5.84 (ddd, J = 17.2, 10.4, 7.2 Hz, 1 H); 13C NMR (100
MHz, CDCl3) δ = 9.8, 23.3, 80.0, 81.3, 121.5, 129.3, 154.4; GC (CP-
Chirasil-Dex-CB, 110 °C, 10 min, 110 to 180 °C, 5 °C/min)
tR(4S,5R)-7a = 15.51′, tR(4R,5S)-7a = 15.72′; HRMS (CI) for
C7H11O3 [M + H]+ calcd 143.0703, found 143.0724.
trans-4-Ethyl-5-vinyl-1,3-dioxolan-2-one (trans-7a). trans-7a
was obtained after chromatography as minor stereoisomer using GP2
or according to GP3 via cis-trans isomerization of the crude product
(711 mg, 3.85 mmol, 67% cis) as clear colorless oil (410 mg, 2.22
mmol, 58%, >99% trans): 1H NMR (400 MHz, CDCl3) δ = 1.05 (t, J
= 7.4 Hz, 3 H), 1.74−1.83 (m, 2 H), 4.26 (ddd, J = 7.1, 7.0, 5.9 Hz, 1
H), 4.65 (tt, J = 7.1, 0.9 Hz, 1 H), 5.42 (ddd, J = 10.5, 1.0, 1.0 Hz, 1
H), 5.48 (ddd, J = 17.4, 0.9, 0.9 Hz, 1 H), 5.87 (ddd, J = 17.3, 10.4, 7.1
Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ = 8.9, 26.0, 82.2, 82.9,
121.1, 132.2, 154.3; GC (CP-Chirasil-Dex-CB, 110 °C, 10 min, 110 to
180 °C, 5 °C/min) tR(4R,5R)-7a = 11.72′, tR(4S,5S)-7a = 12.31′;
HRMS (CI) for C7H11O3 [M + H]+ calcd 143.0703, found 143.0708.
cis-4-Pentyl-5-vinyl-1,3-dioxolan-2-one (cis-7b). Following
GP2 cis-7b (1.13, 6.12 mmol, 61%) and trans-7b (413 mg, 2.24
mmol, 22%) were obtained as clear colorless oils from 3-bromo-
propenyl methyl carbonate (2.34 g, 12.0 mmol, 64% cis) and hexanal
(1.00 g, 10.0 mmol): 1H NMR (400 MHz, CDCl3) δ = 0.89 (t, J = 7.1
Hz, 3 H), 1.25−1.44 (m, 5 H), 1.45−1.58 (m, 2 H), 1.58−1.73 (m, 1
H), 4.69 (ddd, J = 9.7, 7.6, 3.8 Hz, 1 H), 5.08 (tt, J = 7.5, 1.1 Hz, 1 H),
5.45 (ddd, J = 10.4, 0.9, 0.9 Hz, 1 H), 5.48 (ddd, J = 17.1, 0.9, 0.9 Hz,
1 H), 5.84 (ddd, J = 17.0, 10.5, 7.2 Hz, 1 H); 13C NMR (100 MHz,
CDCl3) δ = 13.8, 22.3, 25.1, 29.9, 31.3, 80.0, 80.1, 121.5, 129.4, 154.4;
GC (CP-Chirasil-Dex-CB, 110 °C, 10 min, 110 to 180 °C, 5 °C/min)
tR(4S,5R)-7b = 22.15′, tR(4R,5S)-7b = 22.36′; HRMS (CI) for
C10H17O3 [M + H]+ calcd 185.1172, found 185.1180.
cis-4-(4-Bromophenyl)-5-vinyl-1,3-dioxolan-2-one (cis-7g).
1H NMR (400 MHz, CDCl3) δ = 5.15−5.30 (m, 2 H), 5.34 (dd, J
= 7.9, 6.1 Hz, 1 H), 5.42 (ddd, J = 17.1, 9.9, 6.2 Hz, 1 H), 5.75 (d, J =
7.9 Hz, 1 H), 7.10 (d, J = 8.4 Hz, 2 H), 7.54 (d, J = 8.5 Hz, 2 H); 13C
NMR (100 MHz, CDCl3) δ = 79.9, 80.8, 121.6, 123.4, 127.8, 129.8,
132.0, 132.1, 154.1; HRMS (CI) for C11H1079BrO3 [M + H]+ calcd
268.9807, found 268.9819.
all-cis-4-Ethyl-2-trifluoroacetylamino-3-vinyl-butyro-1,4-lac-
tone (8a). According to GP1 the all-cis-lactone 8a (84 mg, 0.35 mmol,
70%) was obtained as colorless solid from cis-7a (71 mg, 0.50 mmol)
and tert-butyl N-trifluoroactyl-glycinate (170 mg, 0.75 mmol): mp
117−120 °C; 1H NMR (400 MHz, CDCl3) δ = 1.01 (t, J = 7.4 Hz, 3
H), 1.58 (m, 1 H), 1.82 (m, 1 H), 3.56 (ddd, J = 10.4, 7.0, 4.3 Hz, 1
H), 4.48 (ddd, J = 7.7, 6.7, 4.3 Hz, 1 H), 4.78 (t, J = 6.5 Hz, 1 H), 5.29
(dd, J = 16.4, 1.9 Hz, 1 H), 5.38 (dd, J = 10.2, 1.7 Hz, 1 H), 5.48 (ddd,
J = 16.2, 10.2, 10.2 Hz, 1 H), 6.90 (sbr, 1 H); 13C NMR (100 MHz,
CDCl3) δ = 13.9, 23.8, 48.4, 54.0, 82.9, 115.5 (J = 287 Hz), 123.5,
127.1, 157.2 (J = 38.6 Hz), 172.6; GC (L-ChiraSilVal, 80 °C, 10 min,
80 to 180 °C, 1 °C/min) tR(2R,3S,5S)-8a = 61.41′, tR(2S,3R,5R)-8a =
62.40′, tR(E,2R,6R)-10a = tR(E,2R,6S)-10a = 79.33′, tR(E,2S,6S)-10a =
tR(E,2S,6R)-10a = 82.09′; HRMS (CI) for C10H13F3NO3 [M + H]+
calcd 252.0842, found 252.0849.
trans-4-Pentyl-5-vinyl-1,3-dioxolan-2-one (trans-7b). Follow-
ing GP3 trans-7b (602 mg, 3.27 mmol, 79%, > 99% trans) was
obtained as clear colorless oil from cis-7b (770 mg, 4.15 mmol, 85%
cis): 1H NMR (400 MHz, CDCl3) δ = 0.89 (t, J = 7.1 Hz, 3 H), 1.28−
1.35 (m, 4 H), 1.40 (m, 1 H), 1.48 (m, 1 H), 1.63−1.80 (m, 2 H), 4.30
(td, J = 7.6, 5.0 Hz, 1 H), 4.63 (tt, J = 7.3, 0.9 Hz, 1 H), 5.42 (ddd, J =
10.4, 0.8, 0.8 Hz, 1 H), 5.48 (ddd, J = 17.3, 0.9, 0.9 Hz, 1 H), 5.86
(ddd, J = 17.3, 10.4, 7.1 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ =
all-cis-4-Pentyl-2-trifluoroacetylamino-3-vinyl-butyro-1,4-
lactone (8b). Following GP1 all-cis-lactone 8b (176 mg, 0.60 mmol,
60%), trans,cis-lactone 9b (31 mg, 0.08 mmol, 8%) and the linear, (E)-
configured allylation product 10b (54 mg, 0.10 mmol, 10%) were
obtained as colorless solid, respectively, as colorless oils from cis-7b
(184 mg, 1.00 mmol) and tert-butyl N-trifluoroactyl-glycinate (341
1
mg, 1.50 mmol): mp 72−76 °C; H NMR (400 MHz, CDCl3) δ =
0.82 (t, J = 7.0 Hz, 3 H), 1.18−1.28 (m, 4 H), 1.28−1.52 (m, 3 H),
8502
dx.doi.org/10.1021/jo501877q | J. Org. Chem. 2014, 79, 8498−8504

The Journal of Organic Chemistry
Note
1.70 (m, 1 H), 3.48 (ddd, J = 10.4, 7.0, 4.3 Hz, 1 H), 4.49 (ddd, J =
8.2, 5.8, 4.3 Hz, 1 H), 4.70 (t, J = 6.4 Hz, 1 H), 5.21 (dd, J = 16.6, 1.7
Hz, 1 H), 5.31 (dd, J = 10.2, 1.8 Hz, 1 H), 5.41 (ddd, J = 16.4, 10.2,
10.2 Hz, 1 H), 6.72 (sbr, 1 H); 13C NMR (100 MHz, CDCl3) δ = 13.9,
22.4, 24.8, 30.5, 31.4, 48.7, 54.0, 81.7, 115.4 (J = 287 Hz), 123.4, 127.3,
157.2 (J = 38.3 Hz), 172.7; GC (L-ChiraSilVal, 80 °C, 10 min, 80 to
180 °C, 1 °C/min) tR(2R,3S,4S)-8b = 85.91′, tR(2S,3R,4R)-8b =
86.72′, tR(E)-10b = 103.23′, tR(E)-10b = 104.91′, tR(2R,3R,4R)-9b =
117.48′, tR(2S,3S,4S)-9b = 117.85′; HRMS (CI) for C13H19F3NO3 [M
+ H]+ calcd 294. 1312, found 294.1320.
1.30−1.60 (m, 5 H), 1.76 (m, 1 H), 3.54 (ddd, J = 10.6, 7.0, 4.3 Hz, 1
H), 4.55 (ddd, J = 8.2, 5.9, 4.3 Hz, 1 H), 4.78 (t, J = 6.5 Hz, 1 H), 5.28
(dd, J = 16.6, 1.6 Hz, 1 H), 5.38 (dd, J = 10.2, 1.7 Hz, 1 H), 5.48 (ddd,
J = 16.4, 10.3, 10.3 Hz, 1 H), 6.91 (sbr, 1 H); 13C NMR (100 MHz,
CDCl3) δ = 13.8, 22.3, 27.2, 30.2, 48.7, 54.0, 81.7, 115.3 (J = 287 Hz),
123.4, 127.2, 157.2 (J = 38.3 Hz), 172.7; GC (L-ChiraSilVal, 80 °C, 10
min, 80 to 180 °C, 1 °C/min) tR(2R,3S,4S)-8e = 77.05′, tR(2S,3R,4R)-
8e = 77.72′, tR(2R,6S)-10e = 94.62′, tR(2S,6S)-10e = 96.24′,
tR(2R,3R,4R)-9e = 107.98′, tR(2S,3S,4S)-9e = 108.42′. Analysis calcd
for C12H16F3NO3 (279.26): C 51.61, H 5.78, N 5.02. Found: C 51.38,
H 5.54, N 5.21.
(2S,3S,4S)-4-Butyl-2-trifluoroacetylamino-3-vinyl-butyro-
1,4-lactone (9e). trans,cis-Lactone (2S,3S,4S)-9e (21 mg, 0.07 mmol,
7%) was obtained as minor stereoisomer from (4S,5R)-7e (170 mg,
1.00 mmol, 92% ee) and tert-butyl N-trifluoroactyl-glycinate (342 mg,
1.50 mmol) as colorless oil: 1H NMR (400 MHz, CDCl3) δ = 0.91 (t,
J = 7.0 Hz, 3 H), 1.30−1.80 (m, 6 H), 3.31 (ddd, J = 12.1, 8.4, 3.4 Hz,
1 H), 4.61 (ddd, J = 10.7, 8.2, 3.5 Hz, 1 H), 4.82 (dd, J = 12.2, 8.6 Hz,
1 H), 5.29 (d, J = 17.0 Hz, 1 H), 5.29 (d, J = 10.3 Hz, 1 H), 5.81 (ddd,
J = 17.3, 9.9, 8.6 Hz, 1 H), 7.26 (d, J = 8.4 Hz, 1 H); 13C NMR (100
MHz, CDCl3) δ = 13.8, 22.2, 27.7, 30.5, 49.7, 52.1, 81.3, 115.5 (J =
288 Hz), 121.1, 131.0, 157.2 (J = 38.3 Hz), 172.9; HRMS (CI) for
C12H17F3NO3 [M + H]+ calcd 280.1154, found 280.1129.
trans,cis-4-Pentyl-2-trifluoroacetylamino-3-vinyl-butyro-1,4-
lactone (9b). trans,cis-Lactone 9b was the minor diastereomer
1
obtained in the preparation of 8b: H NMR (400 MHz, CDCl3) δ
= 0.89 (t, J = 6.0 Hz, 3 H), 1.22−1.40 (m, 4 H), 1.42−1.70 (m, 4 H),
3.31 (ddd, J = 12.0, 8.4, 8.4 Hz, 1 H), 4.61 (ddd, J = 10.6, 8.5, 3.4 Hz,
1 H), 4.81 (dd, J = 12.1, 8.7 Hz, 1 H), 5.28 (d, J = 16.4 Hz, 1 H), 5.29
(d, J = 10.7 Hz, 1 H), 5.80 (ddd, J = 17.2, 9.8, 8.4 Hz, 1 H), 7.16 (d, J
= 8.3 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ = 13.9, 22.4, 25.3,
30.8, 31.3, 49.5, 52.0, 81.3, 115.5 (J = 287 Hz), 121.0, 131.0, 157.8 (s, J
= 38.1 Hz), 173.0; HRMS (C) for C13H19F3NO3 [M + H]+ calcd 294.
1312, found 294.1340.
(E)-tert-Butyl 6-hydroxy-2-(2,2,2-trifluoroacetamido)undec-
4-enoate [(E)-10b]. Linear allylation product (E)-10b was the
1
minor regioisomer obtained in the preparation of 8b: H NMR (400
all-cis-4-Phenyl-2-trifluoroacetylamino-3-vinyl-butyro-1,4-
lactone (8f). Following GP1 all-cis-lactone 8f (135 mg, 0.47 mmol,
47%) was obtained from cis-7f (190 mg, 1.00 mmol) and tert-butyl N-
trifluoroactyl-glycinate (342 mg, 1.50 mmol) as colorless solid: mp
MHz, CDCl3) δ = 0.87 (t, J = 6.7 Hz, 3 H), 1.21−1.35 (m, 4 H),
1.40−1.55 (m, 4 H), 1.48 (s, 9 H), 1.69 (sbr, 1 H) 2.51 (m, 1 H), 2.67
(m, 1 H), 4.04 (td, J = 6.3, 6.3 Hz, 1 H), 4.52 (dt, J = 7.3, 5.5 Hz, 1 H),
5.47 (dt, J = 15.4, 6.8 Hz, 1 H), 5.58 (dd, J = 15.3, 6.3 Hz, 1 H), 7.01
(d, J = 7.3 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ = 13.9, 22.5,
25.0, 27.8, 31.6, 34.4, 37.0, 52.6, 72.3, 83.6, 115.6 (J = 288 Hz), 123.2,
138.7, 156.6 (J = 37.3 Hz), 169.3; HRMS (CI) for C17H29F3NO4 [M +
H]+ calcd 368.2042, found 368.2032.
1
168−172 °C; H NMR (400 MHz, CDCl3) δ = 3.88 (ddd, J = 10.5,
7.1, 4.6 Hz, 1 H), 5.03 (t, J = 6.6 Hz, 1 H), 5.05 (dd, J = 17.0, 1.4 Hz, 1
H), 5.12 (dd, J = 10.3, 1.4 Hz, 1 H), 5.27 (ddd, J = 16.7, 10.4, 10.4 Hz,
1 H), 5.78 (d, J = 4.7 Hz, 1 H), 6.88 (sbr, 1 H), 7.20−7.44 (m, 5 H);
13C NMR (100 MHz, CDCl3) δ = 50.5, 54.2, 81.4, 115.3 (J = 287 Hz),
all-cis-4-Isopropyl-2-trifluoroacetylamino-3-vinyl-butyro-
1,4-lactone (8c). Following GP1 the all-cis-lactone 8c (176 mg, 0.69
mmol, 69%) was obtained as colorless solid from cis-7c (156 mg, 1.00
mmol) and tert-butyl N-trifluoroactyl-glycinate (341 mg, 1.50 mmol):
123.3, 125.2, 127.3, 128.4, 128.6, 134.2, 157.2 (J = 38.5 Hz), 172.3;
GC (L-ChiraSilVal, 80 °C, 10 min, 80 to 180 °C, 1 °C/min)
tR(2R,3S,4S)-8f = 107.24′, tR(2S,3R,4R)-8f = 108.28′, tR(E)-10f =
134.09′, tR(E)-10f = 137,43′, tR(2R,3R,4R)-9f = 155.77′, tR(2S,3S,4S)-
9f = 157.07′; HRMS (CI) for C14H13F3NO3 [M + H]+ calcd 300.0842,
found 300.0841. Analysis calcd for C14H12F3NO3 (299.25): C 56.19, H
4.04, N, 4.68. Found: C 56.00, H 4.01, N, 4.56.
all-cis-4-(4-Bromphenyl)-2-trifluoroacetylamino-3-vinyl-bu-
tyro-1,4-lacton (8g). Following GP1 the all-cis-lactone 8g (65 mg,
0.17 mmol, 34%) was obtained from cis-7g (135 mg, 0.50 mmol) and
tert-butyl N-trifluoroactyl-glycinate (170 mg, 0.75 mmol) as colorless
solid: mp 152−156 °C; 1H NMR (400 MHz, CDCl3) δ = 3.87 (ddd, J
= 9.9, 7.0, 4.7 Hz, 1 H), 5.01 (t, J = 6.6 Hz, 1 H), 5.07 (dd, J = 16.1,
2.0 Hz, 1 H), 5.15 (dd, J = 10.1, 1.9 Hz, 1 H), 5.22 (ddd, J = 16.2, 10.2,
10.2 Hz, 1 H), 5.72 (d, J = 4.6 Hz, 1 H), 6.85 (sbr, 1 H) 7.14 (d, J = 8.5
Hz, 2 H), 7.52 (d, J = 8.5 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ =
50.3, 54.2, 80.7, 115.3 (J = 288 Hz), 122.5,123.8, 26.9, 127.0, 131.9,
133.3, 157.2 (J = 38.3 Hz) 172.0; GC (L-ChiraSilVal, 80 °C, 10 min,
80 to 180 °C, 1 °C/min) tR(2R,3S,4S)-8g = 96.98′, tR(2S,3R,4R)-8g =
97.35′. Analysis calcd for C14H11BrF3NO3 (378.14): C 44.47, H 2.93,
N 3.70. Found: C 44.68, H 3.15, N 3.76.
all-trans-4-Ethyl-2-trifluoroacetylamino-3-vinyl-butyro-1,4-
lactone (11a). Following GP1 the all-trans-lactone 11a (121 mg 0.48
mmol, 50%) was obtained as colorless oil from trans-7a (136 mg, 0.95
mmol) and tert-butyl N-trifluoroactyl-glycinate (343 mg, 1.50 mmol):
1H NMR (400 MHz, CDCl3) δ = 1.49 (m, 3 H), 1.67 (ddq, J = 14.8,
7.8, 7.4 Hz, 1 H), 1.86 (dqd, J = 15.0, 7.5, 3.6 Hz, 1 H), 2.85 (dt, J =
11.5, 9.4 Hz, 1 H), 4.19 (ddd, J = 9.9, 8.0, 3.6 Hz, 1 H), 4.75 (dd, J =
11.8, 8.6 Hz, 1 H), 5.27 (d, J = 17.0 Hz, 1 H), 5.27 (d, J = 10.6 Hz, 1
H), 5.76 (ddd, J = 17.2, 10.0, 8.5 Hz, 1 H), 7.29 (sbr, 1 H); 13C NMR
(100 MHz, CDCl3) δ = 9.6, 25.8, 52.7, 54.9, 83.0, 115.5 (J = 288 Hz),
121.1, 132.2, 157.7 (J = 38.3 Hz), 172.5; GC (L-ChiraSilVal, 80 °C, 10
min, 80 to 180 °C, 1 °C/min) tR(E,2R,6R)-10a = tR(E,2R,6R)-10a =
75.91′, tR(E,2S,6S)-10a = tR(E,2S,6R)-10a = 78.36′, tR(2R,3S,5S)-11a
= 94.99′, tR(2S,3R,5R)-11a = 96.23′; HRMS (CI) for C10H13F3NO3
[M + H]+ calcd 252.0842, found 252.0856.
1
mp 118−122 °C; H NMR (400 MHz, CDCl3) δ = 0.87 (d, J = 6.7
Hz, 3 H), 1.11 (d, J = 6.5 Hz, 3 H), 1.88 (dqq, J = 10.7, 6.6, 6.5 Hz, 1
H), 3.58 (ddd, J = 10.6, 6.9, 4.0 Hz, 1 H), 4.08 (dd, J = 10.7, 4.0 Hz, 1
H), 4.77 (t, J = 6.4 Hz, 1 H), 5.29 (dd, J = 16.7, 1.6 Hz, 1 H), 5.39 (dd,
J = 10.2, 1.7 Hz, 1 H), 5.49 (ddd, J = 16.5, 10.6, 10.3 Hz, 1 H), 6.87
(sbr, 1 H); 13C NMR (100 MHz, CDCl3) δ = 16.6, 19.8, 28.9, 47.9,
54.3, 86.9, 115.3 (J = 287 Hz), 123.5, 127.1, 157.2 (J = 38.6 Hz),
172.7; GC (L-ChiraSilVal, 80 °C, 10 min, 80 to 180 °C, 1 °C/min)
tR(2R,3S,4S)-8c = 64.50′, tR(2S,3R,4R)-8c = 65.56′, tR(E)-10c =
83.77′, tR(E)-10c = 84.13′, tR(E)-10c = 86.21′, tR(E)-10c = 86.66′,
tR(2R,3R,4R)-9c = 99.87′, tR(2S,3S,4S)-9c = 99.94′. Analysis calcd for
C11H14F3NO3 (265.23): C 49.81, H 5.32, N 5.28, found C 49.61, H
5.09, N 5.52.
all-cis-4-Cyclohexyl-2-trifluoroacetylamino-3-vinyl-butyro-
1,4-lactone (8d). Following GP1 all-cis-lactone 8d (189 mg, 0.62
mmol, 62%) was obtained as colorless solid from from cis-7d (196 mg,
1.00 mmol) and tert-butyl N-trifluoroactyl-glycinate (341 mg, 1.50
mmol): mp 118−122 °C; 1H NMR (400 MHz, CDCl3) δ = 0.70−1.09
(m, 2 H), 1.12−1.33 (m, 4 H), 1.53−1.81 (m, 4 H), 2.05−2.13 (m, 1
H), 3.59 (ddd, J = 10.5, 6.9, 4.0 Hz, 1 H), 4.16 (dd, J = 10.5, 4.0 Hz, 1
H), 4.72 (dd, J = 6.4, 6.4 Hz, 1 H), 5.29 (dd, J = 16.7, 1.6 Hz, 1 H),
5.40 (dd, J = 10.2, 1.7 Hz, 1 H), 5.49 (ddd, J = 16.5, 10.2, 10.2 Hz, 1
H), 6.71 (sbr, 1 H); 13C NMR (100 MHz, CDCl3) δ = 25.0, 25.1, 26.1,
26.6, 30.0, 37.8, 47.6, 54.1, 85.5, 115.3 (J = 287 Hz), 123.4, 127.1,
157.2 (J = 38.1 Hz), 172.6; GC (L-ChiraSilVal, 80 °C, 10 min, 80 to
180 °C, 1 °C/min) tR(2R,3S,4S)-8d = 101.36′, tR(2S,3R,4R)-8d =
102.30′, tR(E)-10d = 121,90′, tR(E)-10d = 124.18′; HRMS (CI) for
C14H19F3NO3 [M + H]+ calcd 306.1312, found 306.1328.
(2R,3S,4S)-4-Butyl-2-trifluoroacetylamino-3-vinyl-butyro-
1,4-lactone (8e). Following GP1 all-cis-lactone (2R,3S,4S)-8e (212
mg, 0.76 mmol, 76%) was obtained as colorless solid from (4S,5R)-7e
(170 mg, 1.00 mmol, 92% ee) and tert-butyl N-trifluoroactyl-glycinate
20
(342 mg, 1.50 mmol): mp 112−114 °C; [α]D = −145.9 ° (c = 1.0,
all-trans-4-Pentyl-2-trifluoroacetylamino-3-vinyl-butyro-1,4-
lactone (11b). Following GP3 the all-trans-lactone 11b (176 mg, 0.60
1
CHCl3); H NMR (400 MHz, CDCl3) δ = 0.91 (t, J = 7.1 Hz, 3 H),
8503
dx.doi.org/10.1021/jo501877q | J. Org. Chem. 2014, 79, 8498−8504

The Journal of Organic Chemistry
Note
mmol, 60%) was obtained as colorless oil from trans-7b (184 mg, 1.00
mmol) and tert-butyl N-trifluoroactyl-glycinate (343 mg, 1.50 mmol):
1H NMR (400 MHz, CDCl3) δ = 0.89 (t, J = 7.0 Hz, 3 H), 1.28−1.35
(m, 4 H), 1.35−1.60 (m, 2 H), 1.65 (m, 1 H), 1.78 (m, 1 H), 2.80 (dt,
J = 11.6, 8.6 Hz, 1 H), 4.23 (ddd, J = 9.9, 8.5, 3.3 Hz, 1 H), 4.73 (dd, J
= 11.8, 8.5 Hz, 1 H), 5.28 (d, J = 17.0 Hz, 1 H), 5.28 (d, J = 10.8 Hz, 1
H), 5.77 (ddd, J = 17.3, 10.0, 8.5 Hz, 1 H), 7.07 (d, J = 8.2 Hz, 1 H);
13C NMR (100 MHz, CDCl3) δ = 13.9, 22.4, 25.1, 31.4, 32.8, 53.4,
54.9, 81.8, 115.5 (J = 288 Hz), 121.1, 132.2, 157.6 (J = 38.5 Hz),
172.3; GC (L-ChiraSilVal, 80 °C, 10 min, 80 to 180 °C, 1 °C/min)
tR(E,2R,6R)-10b = tR(E,2R,6S)-10b = 103.38′, tR(E,2S,6S)-10b =
tR(E,2S,6R)-10b = 105.01′, tR(2R,3R,4S)-11b = 116.45′, tR(2S,3S,4R)-
11b = 118.18′; HRMS (CI) for C13H19F3NO3 [M + H]+ calcd 294.
1312, found 294.1318. Analysis calcd for C13H18F3NO3 (293.28): C
53.24, H 6.19, N 4.78. Found: C 53.22, H 6.27, N 4.75.
(10) (a) Kang, S.-K.; Park, D.-C.; Jeon, J.-H.; Rho, H.-S.; Yu, C.-M.
Tetrahedron Lett. 1994, 35, 2357−2360. (b) Kang, S.-K.; Kim, D.-Y.;
Hong, R.-K.; Ho, P.-S. Synth. Commun. 1996, 26, 3225−3235.
(c) Kang, S.-K.; Park, D.-C.; Rho, H.-S.; Yu, C.-M.; Hong, J.-H.
Synth. Commun. 1995, 25, 203−214.
(11) (a) Kondo, T.; Morisaki, Y.; Uenoyama, S.; Wada, K.; Mitsudo,
T. J. Am. Chem. Soc. 1999, 121, 8657−8658. (b) Zaitsev, A. B.;
Caldwell, H. F.; Pregosin, P. S.; Veiros, L. F. Chem.Eur. J. 2009, 15,
6468−6477.
(12) (a) Morisaki, Y.; Kondo, T.; Mitsudo, T. Organometallics 1999,
18, 4742−4746. (b) Kawatsura, M.; Ata, F.; Hirakawa, T.; Hayase, S.;
Itoh, T. Tetrahedron Lett. 2008, 49, 4873−4875.
(13) (a) Mbaye, M. D.; Demerseman, B.; Renaud, J.-L.; Toupet, L.;
Bruneau, C. Adv. Synth. Catal. 2004, 346, 835−841. (b) Hermatsch-
́
weiler, R.; Fernandez, I.; Pregosin, P. S. Organometallics 2006, 25,
1440−1447. (c) Onitsuka, K.; Okuda, H.; Sasai, H. Angew. Chem.
2008, 120, 1476−1479; Angew. Chem., Int. Ed. 2006, 47, 1454−1457.
(d) Achard, M.; Derrien, N.; Zhang, H.-J.; Demerseman, B.; Bruneau,
C. Org. Lett. 2009, 11, 185−188.
ASSOCIATED CONTENT
* Supporting Information
■
S
Copies of NMR spectra and chromatograms. This material is
available free of charge via the Internet at http://pubs.acs.org.
(14) Trost, B. M.; Fraisse, P. L.; Ball, Z. T. Angew. Chem. 2002, 114,
1101−1103; Angew. Chem., Int. Ed. 2002, 41, 1059−1061.
(15) (a) Bruneau, C.; Renaud, J. L.; Demerseman, B. Chem.Eur. J.
2006, 12, 5178−5187. (b) Bruneau, C.; Renaud, J.-L.; Demerseman, B.
Pure Appl. Chem. 2008, 80, 861−871. (c) Zhang, H.-J.; Demerseman,
B.; Toupet, L.; Xi, Z.; Bruneau, C. Adv. Synth. Catal. 2008, 350, 1601−
1609.
AUTHOR INFORMATION
Corresponding Author
*E-mail: u.kazmaier@mx.uni-saarland.de.
■
(16) (a) Hermatschweiler, R.; Fernandez, I.; Pregosin, P. S.; Watson,
E. J.; Albinati, A.; Rizzato, S.; Veiros, L. F.; Calhorda, M. J.
Organometallics 2005, 24, 1809−1812. (b) Hermatschweiler, R.;
Fernandez, I.; Breher, F.; Pregosin, P. S.; Veiros, L. F.; Calhorda, M.
J. Angew. Chem. 2005, 117, 4471−4474; Angew. Chem., Int. Ed. 2005,
44, 4397−4400. (c) Fernandez, I.; Hermatschweiler, R.; Breher, F.;
Pregosin, P. S.; Veiros, L. F.; Calhorda, M. J. Angew. Chem. 2006, 118,
6535−6540; Angew. Chem., Int. Ed. 2006, 45, 6386−6391.
(17) Kawatsure, M.; Ata, F.; Hayase, S.; Itoh, T. Chem. Commun.
2007, 4283−4285.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Deutsche Forschungsgemein-
schaft (Ka 880/8-2).
REFERENCES
■
(1) Recent reviews: (a) Trost, B. M.; Crawley, M. L. Chem. Rev.
2003, 103, 2921−2943. (b) Lu, Z.; Ma, S. Angew. Chem. 2008, 120,
264−303; Angew. Chem., Int. Ed. 2008, 47, 258−297. (c) Transition
Metal Catalyzed Enantioselective Allylic Substitutions in Organic
Synthesis; Kazmaier, U., Ed.; Springer: Berlin, 2012.
(18) (a) Kazmaier, U.; Stolz, D.; Kramer, K.; Zumpe, F. Chem.Eur.
̈
J. 2008, 14, 1322−1329. (b) Thies, S.; Kazmaier, U. Synlett 2010,
2010, 137−141.
(19) (a) Kazmaier, U.; Deska, J.; Watzke, A. Angew. Chem. 2006, 118,
4973−4976; Angew. Chem., Int. Ed. 2006, 45, 4855−4858. (b) Deska,
J.; Kazmaier, U. Chem.Eur. J. 2007, 13, 6204−6211.
(20) (a) Kazmaier, U.; Maier, S. J. Org. Chem. 1999, 64, 4574−4575.
(b) Kazmaier, U.; Maier, S. Org. Lett. 1999, 1, 1763−1766.
(21) Kazmaier, U.; Zumpe, F. L. Eur. J. Org. Chem. 2001, 4067−4076.
(22) (a) Kazmaier, U.; Pohlman, M. Synlett 2004, 623−626.
(b) Pohlman, M.; Kazmaier, U.; Lindner, T. J. Org. Chem. 2004, 69,
6909−6912.
(2) Recent reviews: (a) Helmchen, G.; Kazmaier, U.; Forster S. In
̈
Catalytic Asymmetric Synthesis; Ojima I., Ed.; Wiley-VCH: Weinheim,
2009; pp 497−641. (b) Bandini, M.; Cera, G.; Chiarucci, M. Synthesis
2012, 44, 504−512. (c) Bayer, A.; Kazmaier U. In Metal-Catalyzed
Cross-Coupling Reactions and More; de Meijere, A., Brase, S., Oestreich,
̈
M., Eds.; Wiley-VCH: Weinheim, 2014; pp 926−994.
(3) Recent reviews: (a) Leahy, D. K.; Evans P. A. In Modern
Rhodium-Catalyzed Reactions; Evans P. A., Ed.; Wiley-VCH:
Weinheim, 2005; pp 191−214. (b) Miyabe, H.; Takemoto, Y. Synlett
2005, 1641−1655. (c) Norsikian, S.; Chang, C.-W. Curr. Org. Chem.
2009, 6, 264−289.
(4) Reviews: (a) Takeuchi, R. Synlett 2002, 1954−1965. (b) Take-
uchi, R.; Kezuka, S. Synthesis 2006, 3349−3366. (c) Helmchen, G.;
Dahnz, A.; Dubon, P.; Schelwies, M.; Weihofen, R. Chem Commun.
2007, 675−691.
(5) Kondo, T.; Mitsudo T. In Ruthenium in Organic Synthesis;
Murahashi, S.-I., Ed.; Wiley-VCH: Weinheim, 2004; pp 129−151 and
references cited therein.
(6) (a) Trost, B. M.; Molander, G. A. J. Am. Chem. Soc. 1981, 103,
5969−5972. (b) Tsuji, J.; Kataoka, H.; Kobayashi, Y. Tetrahedron Lett.
1981, 22, 2575−8. (c) Kimura, M.; Mukai, R.; Tamaki, T.; Horino, Y.;
Tamaru, Y. J. Am. Chem. Soc. 2007, 129, 4122−4123.
(7) Kang, S.-K.; Kim, S.-G.; Lee, J.-S. Tetrahedron: Asymmetry 1992,
3, 1139−1140.
(23) Kazmaier, U.; Stolz, D. Angew. Chem. 2006, 118, 3143−3146;
Angew. Chem., Int. Ed. 2006, 45, 3072−3075.
(24) (a) Bayer, A.; Kazmaier, U. Org. Lett. 2010, 12, 4960−4963.
(b) Bayer, A.; Kazmaier, U. Chem.Eur. J. 2014, 20, 10484−10491.
(25) Schultz, K.; Stief, L.; Kazmaier, U. Synthesis 2012, 4, 600−604.
(26) Lombardo, M.; Pasi, F.; Tiberi, C.; Trombini, C. Synthesis 2005,
2005, 2609−2614.
(27) Georges, Y.; Allenbach, Y.; Ariza, X.; Campagne, J.-M.; Garcia, J.
J. Org. Chem. 2004, 69, 7387−7390.
(28) Gawas, D.; Kazmaier, U. Org. Biomol. Chem. 2010, 8, 457−462.
(29) Habel, L. W.; De Keersmaecker, S.; Wahlen, J.; Jacobs, P. A.; De
Vos, D. E. Tetrahedron Lett. 2004, 45, 4057−4059.
(8) Trost, B. M.; Granja, J. R. Tetrahedron Lett. 1991, 32, 2193−2196.
(9) (a) Trost, B. M.; Aponick, A. J. Am. Chem. Soc. 2006, 128, 3931−
3933. (b) Trost, B. M.; Aponick, A.; Stanzl, B. N. Chem.Eur. J. 2007,
13, 9547−9560. (c) Trost, B. M.; O’Boyle, B. M.; Torres, W.; Ameriks,
M. K. Chem.Eur. J. 2011, 17, 7890−7903.
8504
dx.doi.org/10.1021/jo501877q | J. Org. Chem. 2014, 79, 8498−8504