Chemoselective Rh-catalyzed allylic alkylations of chelated enolates using dienylcarbonates

Article abstract of DOI:10.1002/ejoc.201100350

Wilkinson's catalyst, RhCl(PPh₃)₃, was found to be an excellent catalyst not only for highly regio- but also chemoselective allylic alkylations of chelated enolates. In contrast to Pd-catalyzed reactions, the Rh-catalyzed version sho

Full text of DOI:10.1002/ejoc.201100350

FULL PAPER
DOI: 10.1002/ejoc.201100350
Chemoselective Rh-Catalyzed Allylic Alkylations of Chelated Enolates using
Dienylcarbonates
Saskia Hähn[a] and Uli Kazmaier*[a]
Dedicated to Professor Barry M. Trost on the occasion of his 70th birthday
Keywords: Allylic compounds / Alkylation / Amino acids / Chemoselectivity / Rhodium
Wilkinson’s catalyst, RhCl(PPh3)3, was found to be an excel-
lent catalyst not only for highly regio- but also chemoselec-
tive allylic alkylations of chelated enolates. In contrast to Pd-
catalyzed reactions, the Rh-catalyzed version shows also a
high degree of regioretention and proceeds without isomer-
ization. Allylic substrates with competitive allylic subunits re-
act selectively at the sterically least hindered allylic position,
in comparison to Ru-catalyzed processes.
plex C generates conformation I, which on recoordination
provides complex K. This explains why under certain cir-
cumstances cis-configured linear products L can also be ob-
tained. On the other hand, rotation of σ complex D results
in an epimerization, providing the products H and ent-H as
a racemic mixture.
Introduction
The transition metal catalyzed allylation of C- and het-
eronucleophiles has developed into one of the most popular
coupling reactions.[1] Although palladium is the by far dom-
inating metal, several other noble metals have been devel-
oped into suitable catalysts during the last years.[2] This sig-
nificantly enlarges the potential of this reaction, because
each metal has its own characteristics.
The inverted π-allyl complex ent-B can also directly be
obtained from the enantiomeric substrate ent-A. The re-
gioselectivity of the nucleophilic attack also depends on the
reaction mechanism, and therefore the outcome can be in-
fluenced, e.g. by proper choice of the ligands used. In Pd-
catalyzed reactions, the nucleophile attacks phosphane
complexes preferentially at the sterically least hindered po-
sition (G) in an SN2-type fashion.[1,2] In the presence of
electron-withdrawing ligands such as phosphites, the
mechanism can be shifted towards SN1, favoring the forma-
tion of the branched product.[5] The different metals used in
allylic alkylations differ in their preference for allyl complex
formation, the type of allyl complex (σ-, π- or σ-enyl) and
the mode of nucleophilic substitution (SN1 or SN2). While
Pd complexes show a high tendency towards the sterically
least hindered product G (SN2-type), others such as Ir,[6]
Mo[7] or W complexes[8] provide the branched product H
preferentially (SN1-type).[2] For all these metals, π-allyl
complexes are discussed as intermediates, which undergo
fast isomerization. On one hand, this results in the forma-
tion of racemic products from enantiomerically pure start-
ing material A, but on the other hand this allows the control
of the configuration (in branched products H) by using chi-
ral ligands.[1b] In comparison, metals such as Rh[4] and Ru[9]
are thought to form σ-enyl complexes in an SN2Ј-type fash-
ion, and do not (or slowly) undergo isomerization. There-
fore, these metal complexes show a high degree of regio-
retention (2ϫSN2Ј) and excellent chirality transfer.
The possible mechanistic scenarios are summarized in
Scheme 1. The reactions start either via coordination of a
low-valent transition metal complex ([M]) towards the
double bond, followed by the cleavage of the leaving group
X via nucleophilic attack of the nucleophilic metal. If chiral
substrates such as A are used, this process gives rise to π-
allyl complex B under inversion of the configuration. This
is the generally accepted mechanism for Pd-catalyzed reac-
tions.[1,2] Alternatively, the nucleophilic metal can directly
replace the leaving group, providing σ-allyl complexes C or
D. In principle, σ-allyl–metal complexes are also accessible
via oxidative addition.[3] The metal then can coordinate
with the double bond, forming σ-enyl complexes E or F,
which can isomerize to the π-allyl complex B. Such interme-
diates are proposed, for example, for Rh-catalyzed pro-
cesses.[4] In the next step, the nucleophile can attack the π-
allyl complex B at the two different allylic positions, or the
σ-enyl complexes E and F (in general in a SN2Ј-fashion),
giving rise to the regioisomeric products G and H. The σ-
allyl complexes can easily undergo rotation around the σ-
bond, resulting in further isomerizations. Rotation in com-
[a] Institute of Organic Chemistry, Saarland University
P. O. Box 151150, 66041 Saarbrücken, Germany
Fax: +49-681-302-2409
E-mail: u.kazmaier@mx.uni-saarland.de
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S. Hähn, U. Kazmaier
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Scheme 1. Mechanistic scenarios for transition-metal-catalyzed allylic alkylations. [M]: low-valent transition-metal complex.
Our group has been involved in allylic alkylations for sev- verted into cis-configured substitution products with com-
eral years, using chelated enolates as nucleophiles.[10] The plete retention of the olefin geometry.[13] Nevertheless, sub-
high reactivity of these enolates allows alkylation reactions strates forming terminal π-allyl complexes are critical candi-
to occur at very low temperature (–78 °C).[11] Under these dates. For example, if chiral allylic substrates such as 1 are
conditions, isomerization processes, as discussed in used, a complete epimerization is observed, and the linear
Scheme 1, can be suppressed nearly completely, even under product 2 is formed preferentially as a racemic mixture
Pd-catalyzed conditions.[12] Therefore, under optimized (Scheme 2). This forced us to investigate other transition
conditions, cis-configured allylic substrates can be con- metals as potential catalysts.
Scheme 2. Transition-metal-catalyzed allylic alkylations. rs: regioselectivity, ds: diastereoselectivity.
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Chemoselective Rh-Catalyzed Allylic Alkylations of Chelated Enolates
We observed that Rh[14] and Ru complexes[15] also give a product 7b with the completely conjugated π-system. In this
clean reaction at –78 °C, showing a high degree of regio- case, the substituted double bond was not attacked at all.
retention and excellent chirality transfer.
For comparison, we also subjected the regioisomeric allylic
The diastereoselectivities obtained for 3 with Wilkinson’s substrates 4Јa and 4ЈЈa to the same reaction conditions.
catalyst were slightly higher (94%ds) than with the Ru cata- Interestingly, no reaction was observed at all (Table 1, En-
lyst (83%ds), and it seems that the Rh complex is slightly tries 3 and 4). Clearly, RhCl(PPh3)3 reacts nearly exclusively
more sensitive towards steric hindrance. Both catalysts ob- with terminal double bonds.
viously react without isomerization. This is also illustrated
This led us to investigate substrates having two dif-
in reactions of dienyl substrates such as 4. While the Ru- ferently substituted allyl subunits such as 8. The aim was
catalyzed reaction provided only two products, 5 and 6, to selectively convert one without affecting the other. The
with a high degree of regioretention,[15] the comparable Pd- substrates 8 were obtained by standard reactions as dia-
catalyzed process gave a mixture of all three regioisomeric stereomeric mixtures (Scheme 3). The methyl-substituted
products.[16] Obviously, here both double bonds form π-allyl double bond resulted from a propenylmagnesium bromide
complexes and/or the complexes isomerize rapidly, even at addition to the corresponding aldehyde, providing the sub-
–78 °C. On the other hand, in the Ru-catalyzed reaction, stituted allyl alcohol as a 2:1 Z/E mixture. The carbonate
only the substituted double bond underwent allyl complex leaving group was introduced with Boc2O after deproton-
formation, because no linear product was formed. This ob- ation of the alcohol with nBuLi. This protocol proved supe-
servation raised the question of whether it might also be rior to other acylation reactions.
possible to selectively ionize the terminal double bond, for
example with sterically sensitive complexes such as Wilkin-
son’s catalyst.
Results and Discussion
We began our investigation with the methyl-substituted
diene 4a, and we observed nearly exclusive allyl complex
formation at the unsubstituted double bond (Table 1, En-
try 1). Only 4% of the β-branched product 6a was found.
As in our previous reactions, a high degree of regioretention
was observed, favoring the branched product 5a over the
linear one (7a) with conjugated double bonds. No signifi-
cant diastereoselectivity was observed, but this is not sur-
prising, considering the high similarity of the two allylic
substituents. Comparable reaction behavior was observed
with the phenyl-substituted derivative 4b (Table 1, Entry 2),
which showed a slightly higher preference for the linear
Table 1. Rhodium-catalyzed allylic alkylations using dienoates.
Scheme 3. Preparation of aliphatic diallyl substrates 8.
The substrates 8 with different spacers between the allyl
moieties were subjected to our standard reaction conditions
(Table 2). Interestingly, no reaction was observed with the
smallest substrate 8a (Table 2, Entry 1). Apparently, the two
allyl fragments interact with each other or stabilize a poten-
tial Rh complex formed in situ. The situation changed sig-
nificantly after introduction of only one additional CH2
group (Table 2, Entry 2). The linear substitution product 9b
was formed in acceptable yield and excellent regioselectivity
(rs). The corresponding branched product was formed only
in traces. It is worth mentioning, that the reaction is also
highly chemoselective, reacting at the sterically least hin-
dered position. The substituted double bond remains un-
touched, and the Z/E-ratio was identical to the starting ma-
terial 8b. An analogous behavior was observed with sub-
strates 8c and 8d, with a larger spacer between the allylic
Entry Substrate
R
Yield
[%]
Ratio
5/6/7
ds (5)
ds (6)
[%]
[%]
1
2
3
4
4a
4b
4Јa
4ЈЈa
Me
Ph
Me
Me
84
61
–
78:4:18
67:0:24
66
66
–
84
–
–
–
–
–
–
–
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S. Hähn, U. Kazmaier
FULL PAPER
leaving groups (Table 2, Entries 3 and 4). The only differ-
ence was the yield, which dropped with increasing chain
length.
Table 2. Rhodium-catalyzed allylic alkylations using diallyl sub-
strates 8.
Scheme 5. Rhodium-catalyzed allylic alkylations using diallyl sub-
strate 10. Before flash chromatography 11a/11b = 78:22; after flash
chromatography 11a/11b = 12:88.
Entry
Substrate
n
Product Yield [%]
rs [%]
1
2
3
4
8a
8b
8c
8d
1
2
3
4
9a
9b
9c
9d
–
–
Conclusions
57
48
29
96
94
94
In conclusion, we showed that Rh-catalyzed allylic alk-
ylations are an interesting alternative to other transition-
metal-catalyzed allylations, showing different reaction char-
acteristics. In contrast to Pd-catalyzed processes, the Rh-
catalyzed version shows a high degree of regioretention and
proceeds without isomerization. Compared to Ru-catalyzed
processes, the Rh complexes show a higher sensitivity
towards steric hindrance, allowing regio- and chemoselec-
tive reactions of substrates with otherwise comparable reac-
tion centers. Further mechanistic details and synthetic ap-
plications are currently under investigation.
To explore a second type of diallylic substrate, we also
subjected the aromatic dicarbonate 10 to our reaction con-
ditions. This substrate was obtained in a comparable man-
ner as described before (Scheme 4).
Experimental Section
General Remarks: All air- or moisture-sensitive reactions were car-
ried out in oven-dried glassware (70 °C). Dried solvents were dis-
tilled before use: THF was distilled from LiAlH4, CH2Cl2 was dried
with CaH2 before distillation. The products were purified by flash
chromatography on silica gel columns (Macherey–Nagel 60, 0.063–
0.2 mm). Analytical TLC was performed on pre-coated silica gel
plates (Macherey–Nagel, Polygram SIL G/UV254). Visualization
was accomplished with UV-light, KMnO4 solution or iodine. Melt-
ing points were determined with a Dr. Tottoli (Büchi) melting point
1
apparatus. H and 13C NMR spectra were recorded with a Bruker
Scheme 4. Preparation of aromatic diallyl substrate 10.
AC-400 [400 MHz (1H) and 100 MHz (13C)] spectrometer in
CDCl3. Chemical shifts are reported in ppm (δ) with respect to
TMS, and CHCl3 was used as the internal standard. Mass spectra
were recorded with a Finnigan MAT 95 spectrometer using the
CI technique. Elemental analyses were performed at the Saarland
University.
This reaction also occurred preferentially at the sterically
less hindered monosubstituted allyl position. But in con-
trast to the aliphatic substrates 8, in this case the branched
product 11a was formed preferentially as a 1:1 dia-
stereomeric mixture with excellent regioselectivity. The lin-
ear product and the product obtained from a nucleophilic
attack on the substituted double bond were not observed.
Interestingly, in this case an isomerization of the substituted
double bond to allyl carbonate 11b was observed
(Scheme 5). This isomerization was catalyzed by the silica
gel used during purification, and was faster for the (E)-
than for the (Z)-isomer.
Obviously, the phenyl ring activates the allylic substrates.
The preferred formation of the branched product might re-
sult from the σ-enyl mechanism, as discussed for regioreten-
tion (double SN2Ј), or is an indication for a SN1-type all-
ylation mechanism. This might also explain the migration
of the double bond in this aromatic substrate.
General Procedure for the Formation of tert-Butyl Carbonates
(GP 1): N-Butyllithium (1.6 m in hexane, 1.1 equiv.) was added
slowly at –78 °C to the alcohol (1 equiv.) dissolved in THF (2.0 mL/
mmol). After stirring for 30 min, a solution of di-tert-butyl dicar-
bonate (1.1 equiv.) in THF (1 mmol/mL) was added. The mixture
was warmed to room temperature. After full conversion, 1 n
KHSO4 was added. After separation of the layers, the aqueous
layer was extracted three times with diethyl ether, and the combined
organic layers were dried with Na2SO4. The solvent was evaporated
in vacuo, and the crude product was purified by flash chromatog-
raphy.
General Procedure for the Allylic Alkylations (GP 2): A solution of
hexamethyldisilazane (223 mg, 1.38 mmol) in THF (1.0 mL) under
argon was prepared in a Schlenk flask. After the solution had been
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Chemoselective Rh-Catalyzed Allylic Alkylations of Chelated Enolates
cooled to –20 °C, a solution of n-butyllithium (1.6 m in hexane,
0.78 mL, 1.25 mmol) was added slowly. The cooling bath was re-
moved, and stirring was continued for an additional 10 min. In a
second Schlenk flask, TFAGlyOtBu (114 mg, 0.50 mmol) was dis-
solved in THF (1.0 mL). The solution was cooled to –78 °C before
the freshly prepared LHMDS solution was added. After 10 min, a
solution of dried ZnCl2 (76 mg, 0.55 mmol) in THF (1.0 mmol) was
added, and stirring was continued for 30 min at –78 °C. A solution
prepared from Wilkinson’s Catalyst (5.8 mg, 6.25 μmol) and tri-
ethyl phosphite (4.3 μL, 25 μmol) in THF (1 mL) was stirred for
5 min, during which time it turned yellow. The allyl substrate
(0.25 mmol) was added to the solution, and the resulting solution
was added slowly to the chelated enolate at –78 °C. The mixture
was warmed to room temperature overnight. The solution was di-
luted with diethyl ether before 1 n KHSO4 was added. After sepa-
ration of the layers, the aqueous layer was extracted three times
with diethyl ether, and the combined organic layers were dried with
Na2SO4. The solvent was evaporated in vacuo, and the crude prod-
uct was purified by flash chromatography.
1.1 mmol, 1.1 equiv.). After evaporation of the solvent in vacuo and
flash chromatography (hexanes/EtOAc, 7:3), the desired product
was isolated in 88% yield (174 mg, 878 μmol) as a yellowish liquid.
1
Rf (hexanes/EtOAc, 7:3) = 0.59. H NMR (400 MHz, CDCl3): δ =
3
3
1.47 (s, 9 H, 1-H), 1.75 (d, J9,8 = 6.7 Hz, 3 H, 9-H), 4.55 (d, J4,5
3
3
= 6.7 Hz, 2 H, 4-H), 5.62 (dt, J5,6 = 15.2, J5,4 = 6.7 Hz, 1 H, 5-
H), 5.74 (dq, 3J8,7 = 15.0, 3J8,9 = 6.7 Hz, 1 H, 8-H), 6.04 (ddd, 3J6,5
= 15.0, 3J6,7 = 10.5, 4J6,8 = 1.7 Hz, 1 H, 6-H), 6.25 (dd, 3J7,8 = 15.2,
3J7,6 = 10.5 Hz, 1 H, 7-H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 18.1 (q, C-9), 27.8 (q, C-1), 67.4 (t, C-4), 82.0 (s, C-2), 123.4 (d,
C-8), 130.4 (d, C-6), 131.3 (d, C-5), 135.1 (d, C-7), 153.4 (s, C-3)
ppm.
(E)-tert-Butyl Hexa-3,5-dien-2-yl Carbonate (4ЈЈa): Following GP 1,
4ЈЈa was obtained from (E)-hexa-3,5-dien-2-ol (982 mg, 10 mmol,
1.0 equiv.), n-butyllithium (1.6 m in hexane, 6.88 mL, 11 mmol,
1.1 equiv.) and di-tert-butyl dicarbonate (2.40 g, 11 mmol,
1.1 equiv.). After evaporation of the solvent in vacuo and flash
chromatography (hexanes/EtOAc, 7:3), the desired product was iso-
lated in 94% yield (1.86 g, 9.38 mmol) as a yellowish liquid. Rf
(hexanes/EtOAc, 7:3) = 0.60. 1H NMR (400 MHz, CDCl3): δ =
(E)-tert-Butyl Hexa-1,4-dien-3-yl Carbonate (4a): Following GP 1,
4a was obtained from hexa-1,4-dien-3-ol (1.47 g, 15 mmol, 1.36 (d, 3J9,8 = 6.5 Hz, 3 H, 9-H), 1.48 (s, 9 H, 1-H), 5.11–5.26 (m,
3
3
1.0 equiv.), n-butyllithium (1.6 m in hexane, 10.3 mL, 16.5 mmol,
1.1 equiv.) and di-tert-butyl dicarbonate (3.60 g, 16.5 mmol,
1.1 equiv.). After evaporation of the solvent in vacuo and flash
chromatography (hexanes/EtOAc, 8:2), the desired product was iso-
lated in 93% yield (2.78 g, 14.0 mmol) as a yellowish liquid. Rf
(hexanes/EtOAc, 8:2) = 0.56. 1H NMR (400 MHz, CDCl3): δ =
3 H, 4-H, 8-H), 5.69 (dd, J5,6 = 14.4, J5,4 = 6.7 Hz, 1 H, 5-H),
6.21–6.35 (m, 2 H, 6-H, 7-H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 20.3 (q, C-9), 27.8 (q, C-1), 73.5 (d, C-4), 81.9 (s, C-2), 118.4
(t, C-8), 132.3 (d, C-6), 132.5 (d, C-5), 136.0 (d, C-7), 152.8 (s, C-3)
ppm. HRMS (CI): calcd. for C11H18O3 [M + H]+ 199.1334; found
199.1337.
3
4
1.47 (s, 9 H, 1H), 1.71 (dd, J7,6 = 6.5, J7,5 = 1.5 Hz, 3 H, 7-H),
(E)-tert-Butyl 2-(2,2,2-Trifluoroacetamido)-3-vinylhex-4-enoate (5a):
According to GP 2, 5a was obtained as the major product from
allylic carbonate 4a (50 mg, 0.25 mmol) in an overall yield
(mixture of isomers) of 84% (64 mg, 0.21 mmol) as a colourless
crystalline solid after flash chromatography [hexanes/EtOAc
3
2
4
5.19 (ddd, J9trans,8 = 10.5, J9trans,9cis = J9trans,4 = 1.1 Hz, 1 H, 9-
Htrans), 5.28 (ddd, 3J9cis,8 = 17.2, 2J9cis,9trans = 4J9cis,4 = 1.2 Hz, 1 H,
3
3
3
9-Hcis), 5.41 (dd, J4,5 = J4,8 = 6.7 Hz, 1 H, 4-H), 5.50 (ddq, J5,6
= 15.1, J5,4 = 7.2, 4J5,7 = 1.5 Hz, 1 H, 5-H), 5.79 (dq, 3J6,5 = 15.2,
3
3J6,7 = 6.5 Hz, 1 H, 6-H), 5.85 (ddd, 3J8,9cis = 17.3, 3J8,9trans = 10.5,
3J8,4 = 6.5 Hz, 1 H, 8-H) ppm. 13C NMR (100 MHz, CDCl3): δ =
17.8 (q, C-7), 27.8 (q, C-1), 78.2 (d, C-4), 82.0 (s, C-2), 117.0 (t, C-
9), 127.9 (d, C-6), 130.3 (d, C-5), 135.6 (d, C-8), 152.7 (s, C-3)
ppm. HRMS (CI): calcd. for C11H18O3 [M + H]+ 199.1334; found
199.1335.
1
(95:5)]. Rf (hexanes/EtOAc, 9:1) = 0.33. M.p. 41–42 °C. H NMR
3
(400 MHz, CDCl3): δ = 1.46 (s, 9 H, 1-H), 1.70 (dd, J10,9 = 6.5,
3
4J10,8 = 1.4 Hz, 3 H, 10-H), 3.23 (m, 1 H, 7-H), 4.51 (dd, J4,NH
=
3
3
8.6, J4,7 = 5.8 Hz, 1 H, 4-H), 5.11 (ddd, J12cis,11 = 17.1,
2J12cis,12trans = 4J12cis,7 = 1.3 Hz, 1 H, 12-Hcis), 5.17 (ddd, 3J12trans,11
2
4
= 10.3, J12trans,12cis = J12trans,7 = 1.2 Hz, 1 H, 12-Htrans), 5.35 (m,
1 H, 8-H), 5.56 (m, 1 H, 9-H), 5.76 (ddd, 3J11,12cis = 17.4, 3J11,12trans
(E)-tert-Butyl 1-Phenylpenta-1,4-dien-3-yl Carbonate (4b): Follow-
ing GP 1, 4b was obtained from 1-phenylpenta-1,4-dien-3-ol
(801 mg, 5 mmol, 1.0 equiv.), n-butyllithium (1.6 m in hexane,
3.44 mL, 5.5 mmol, 1.1 equiv.) and di-tert-butyl dicarbonate
(1.20 g, 5.5 mmol, 1.1 equiv.). After evaporation of the solvent in
vacuo and flash chromatography (hexanes/EtOAc, 9:1), the desired
product was isolated in 85% yield (1.10 g, 4.23 mmol) as a yellow-
ish liquid. Rf (hexanes/EtOAc, 8:2) = 0.34. 1H NMR (400 MHz,
= 10.3, J11,7 = 7.4 Hz, 1 H, 11-H), 6.72 (br. s, 1 H, NH) ppm. 13C
3
NMR (100 MHz, CDCl3): δ = 18.0 (q, C-10), 28.0 (q, C-1), 49.6/
49.7 (2d, C-7), 55.9/56.0 (2d, C-4), 83.4 (s, C-2), 115.7 (q, J6,F
=
287.9 Hz, C-6), 117.9/118.0 (2t, C-12), 126.8/126.9 (2d, C-8), 129.7
(d, C-9), 135.3/135.4 (d, C-11), 156.9 (q, J5,F = 37.2 Hz, C-5), 168.4/
168.5 (2s, C-3) ppm. GC [Chirasil-l-Val, T0 (30 min) = 80 °C, 1 °C/
min to T = 180 °C]: tR (5a) = 51.53 min, tR (5aЈ) = 51.83 min,
tR (5a) = 52.50 min, tR (5aЈ) = 52.75 min. HRMS (CI): calcd. for
CDCl3): δ = 1.50 (s, 9 H, 1-H), 5.23 (ddd, 3J6trans,5 = 10.5, 2J6trans,6cis
3
=
4J6trans,4 = 1.2 Hz, 1 H, 6-Htrans), 5.39 (ddd, J6cis,5 = 17.2, C14H20F3NO3 [M + H]+ 308.1474; found 308.1428. C14H20F3NO3
2J6cis,6trans = 4J6cis,4 = 1.2 Hz, 1 H, 6-Hcis), 5.65 (m, 1 H, 4-H), 5.96 (307.31): calcd. C 54.72, H 6.56, N 4.56; found C 55.04, H 6.75, N
(ddd, 3J5,6cis = 17.1, 3J5,6trans = 10.4, J5,4 = 6.1 Hz, 1 H, 5-H), 6.20
4.33.
3
(dd, 3J7,8 = 16.0, 3J7,4 = 7.0 Hz, 1 H, 7-H), 6.67 (d, 3J8,7 = 15.9 Hz,
(E)-tert-Butyl 3-Methyl-2-(2,2,2-trifluoroacetamido)hepta-4,6-dien-
oate (6a): Ester 6a was obtained as one of the minor products in
3
3
1 H, 8-H), 7.26 (t, J12,11 = 7.2 Hz, 1 H, 12-H), 7.32 (dd, J11,10
=
3J11,12 = 7.0 Hz, 2 H, 11-H), 7.39 (d, J10,11 = 7.0 Hz, 1 H, 10-H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 27.8 (q, C-1), 78.0 (d, C-
4), 82.3 (s, C-2), 117.6 (t, C-6), 125.9 (d, C-7), 126.7 (d, C-10),
128.1 (d, C-12), 128.6 (d, C-11), 133.2 (d, C-8), 135.2 (d, C-5), 136.2
(s, C-9), 152.6 (s, C-3) ppm. HRMS (CI): calcd. for C16H20O3
(M)+ 260.1412; found 260.1367.
3
1
the allylic alkylation using 4a. anti-6a (selected signals): H NMR
3
(400 MHz, CDCl3): δ = 1.10 (d, J12,7 = 6.9 Hz, 3 H, 12-H), 1.46
3
3
(s, 9 H, 1-H), 2.87 (m, 1 H, 7-H), 6.11 (dd, J9,8 = 15.0, J9,10
=
3
3
3
10.2 Hz, 1 H, 9-H), 6.29 (ddd, J10,11cis = 16.9, J10,11trans = J10,9
= 10.3 Hz, 1 H, 10-H), 6.72 (br. s, 1 H, NH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 16.0 (q, C-12), 28.0 (q, C-1), 39.5 (d, C-7),
57.1 (d, C-4), 83.4 (s, C-2), 117.5 (t, C-11), 132.1 (d, C-8), 133.2 (d,
C-9), 136.2 (d, C-10), 168.8 (s, C-3) ppm. syn-6a (selected signals):
1H NMR (400 MHz, CDCl3): δ = 1.13 (d, 3J12,7 = 7.0 Hz, 3 H, 12-
tert-Butyl (2E,4E)-Hexa-2,4-dienyl Carbonate (4Јa): Following
GP 1, 4Јa was obtained from (2E,4E)-hexa-2,4-dienol (98 mg,
1 mmol, 1.0 equiv.), n-butyllithium (1.6 m in hexane, 688 μL,
1.1 mmol, 1.1 equiv.) and di-tert-butyl dicarbonate (240 mg,
3
H), 1.46 (s, 9 H, 1-H), 2.75 (m, 1 H, 7-H), 6.11 (dd, J9,8 = 15.0,
Eur. J. Org. Chem. 2011, 4931–4939
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4935

S. Hähn, U. Kazmaier
FULL PAPER
3J9,10 = 10.2 Hz, 1 H, 9-H), 6.29 (ddd, J10,11cis = 16.9, J10,11trans
3J10,9 = 10.3 Hz, 1 H, 10-H), 6.72 (br. s, 1 H, NH) ppm. 13C
NMR (100 MHz, CDCl3): δ = 16.0 (q, C-12), 28.0 (q, C-1), 39.6
15-H), 7.32 (dd, J14,13
=
3J14,15 = 7.3 Hz, 2 H, 14-H), 7.39 (dd,
3
3
3
4
=
3J13,14 = 7.3, J13,15 = 1.3 Hz, 2 H, 13-H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 28.0 (q, C-1), 35.1 (t, C-7), 52.8 (d, C-4),
(d, C-7), 57.1 (d, C-4), 83.4 (s, C-2), 117.5 (t, C-11), 132.0 (d, C- 83.6 (s, C-2), 115.6 (q, J6,F = 287.7 Hz, C-6), 125.9 (d, C-9), 126.4
8), 133.2 (d, C-9), 136.2 (d, C-10), 168.8 (s, C-3) ppm. GC [Chirasil-
(d, C-13), 127.7 (d, C-10), 127.9 (d, C-15), 128.6 (d, C-14), 132.5
l-Val, T0 (30 min) = 80 °C, 1 °C/min to T = 180 °C]: tR (anti-6a) =
(d, C-8), 135.3 (d, C-11), 136.9 (s, C-12), 156.5 (q, J5,F = 37.6 Hz,
58.53 min, tR (anti-6a) = 59.38 min, tR (syn-6a) = 59.81 min, tR C-5), 169.2 (s, C-3) ppm. GC [Chirasil-l-Val, T0 (30 min) = 80 °C,
(syn-6a) = 60.69 min.
1 °C/min to T = 180 °C]: tR (7b) = 35.14 min.
Di-tert-butyl Octa-1,6-diene-3,5-diyl Dicarbonate (8a): Following
GP 1, 8a was obtained from octa-1,6-diene-3,5-diol (156 mg,
1.1 mmol, 1.0 equiv.), n-butyllithium (1.6 m in hexane, 1.51 mL,
2.42 mmol, 2.2 equiv.) and di-tert-butyl dicarbonate (528 mg,
2.42 mmol, 2.2 equiv.). After evaporation of the solvent in vacuo
and flash chromatography (hexanes/EtOAc, 9:1), the desired prod-
uct was isolated in 81% yield [305 mg, 891 μmol, 67% (Z)] as a
colourless oil. Rf (hexanes/EtOAc, 9:1) = 0.34. (Z)-8a (dia-
stereomer I): 1H NMR (400 MHz, CDCl3): δ = 1.44 (s, 9 H, 1Ј-H),
1.45 (s, 9 H, 1-H), 1.70 (m, 3 H, 7-H), 1.75 (m, 1 H, 11-Ha), 2.15
(4E,6E)-tert-Butyl
(7a): Ester 7a was obtained as one of the minor products in the
allylic alkylation using 4a. H NMR (400 MHz, CDCl3): δ = 1.46
(s, 9 H, 1-H), 1.73 (d, J12,11 = 6.7 Hz, 3 H, 12-H), 2.59 (m, 1 H,
2-(2,2,2-Trifluoroacetamido)octa-4,6-dienoate
1
3
7-Ha), 2.63 (m, 1 H, 7-Hb), 4.55 (dd, J4,NH = 8.6, J4,7 = 3.4 Hz,
1 H, 4-H), 5.33 (m, 1 H, 8-H), 5.64 (m, 1 H, 11-H), 6.00–6.08 (m,
2 H, 9-H, 10-H), 6.89 (br. s, 1 H, NH) ppm. 13C NMR (100 MHz,
CDCl3): δ = 18.0 (q, C-10), 28.0 (q, C-1), 34.8 (t, C-7), 52.8 (d, C-
4), 83.4 (s, C-2), 115.7 (q, J6,F = 287.9 Hz, C-6), 122.4 (d, C-8),
3
3
129.7 (d, C-11), 130.6 (d, C-10), 135.4 (d, C-9), 156.9 (q, J5,F
=
3
3
(m, 1 H, 11-Hb), 5.01 (dt, J4,5 = J4,11 = 7.1 Hz, 1 H, 4-H), 5.19
37.2 Hz, C-5), 169.2 (s, C-3) ppm. GC [Chirasil-l-Val, T0 (30 min)
= 80 °C, 1 °C/min to T = 180 °C]: tR (7a) = 72.21 min, tR (7a) =
72.90 min.
3
3
(d, J6trans,5 = 10.5 Hz, 1 H, 6-Htrans), 5.27 (d, J6cis,5 = 17.3 Hz, 1
H, 6-Hcis), 5.35 (m, 1 H, 9-H), 5.43 (m, 1 H, 10-H), 5.66 (m, 1 H,
8-H), 5.77 (m, 1 H, 5-H) ppm. 13C NMR (100 MHz, CDCl3): δ =
13.3 (q, C-7), 27.7 (q, C-1, C-1Ј), 38.7 (t, C-11), 69.1 (d, C-10), 73.8
(d, C-4), 81.8 (s, C-2), 82.0 (s, C-2Ј), 117.3 (t, C-6), 128.3 (d, C-9),
128.7 (d, C-8), 135.6 (d, C-5), 152.6 (s, C-3), 152.7 (s, C-3Ј) ppm.
(Z)-8a (diastereomer II): 1H NMR (400 MHz, CDCl3): δ = 1.44 (s,
9 H, 1Ј-H), 1.45 (s, 9 H, 1-H), 1.70 (m, 3 H, 7-H), 1.87 (m, 1 H,
(E)-tert-Butyl 5-Phenyl-2-(2,2,2-trifluoroacetamido)-3-vinylpent-4-
enoate (5b): Following GP 2, 5b was obtained as the major product
from allylic carbonate 4b (65 mg, 0.25 mmol) in an overall yield
(mixture of isomers) of 61% (56 mg, 152 μmol) as a colourless oil
after flash chromatography (hexanes/EtOAc, 95:5). Rf (hexanes/
EtOAc, 9:1) = 0.32. anti-5b: 1H NMR (400 MHz, CDCl3): δ = 1.47
3
11-Ha), 1.97 (m, 1 H, 11-Hb), 5.08 (m, 1 H, 4-H), 5.19 (d, J6trans,5
3
3
3
(s, 9 H, 1-H), 3.50 (m, 1 H, 7-H), 4.70 (dd, J4,NH = 8.3, J4,7
=
= 10.5 Hz, 1 H, 6-Htrans), 5.27 (d, J6cis,5 = 17.3 Hz, 1 H, 6-Hcis),
3
5.0 Hz, 1 H, 4-H), 5.21 (d, J9cis,8 = 17.1 Hz, 1 H, 9-Hcis), 5.27 (d,
5.35 (m, 1 H, 9-H), 5.43 (m, 1 H, 10-H), 5.66 (m, 1 H, 8-H), 5.77
(m, 1 H, 5-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.5 (q, C-
7), 27.7 (q, C-1, C-1Ј), 39.3 (t, C-11), 69.7 (d, C-10), 74.5 (d, C-4),
81.8 (s, C-2), 82.0 (s, C-2Ј), 117.6 (t, C-6), 128.4 (d, C-9), 128.9 (d,
C-8), 135.8 (d, C-5), 152.6 (s, C-3), 152.7 (s, C-3Ј) ppm. (E)-8a
(diastereomer I): 1H NMR (400 MHz, CDCl3): δ = 1.44 (s, 9 H,
1Ј-H), 1.45 (s, 9 H, 1-H), 1.70 (m, 3 H, 7-H), 1.75 (m, 1 H, 11-Ha),
3J9trans,8 = 10.4 Hz, 1 H, 9-Htrans), 5.82 (ddd, 3J8,9cis = 17.3, 3J8,9trans
3
3
3
= 10.2, J8,7 = 7.7 Hz, 1 H, 8-H), 6.17 (dd, J10,11 = 15.9, J10,7
=
7.6 Hz, 1 H, 10-H), 6.50 (d, 3J11,10 = 15.9 Hz, 1 H, 11-H), 6.91 (br.
3
s, 1 H, NH), 7.25 (t, J15,14 = 7.0 Hz, 1 H, 15-H), 7.30–7.37 (m, 4
H, 13-H, 14-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 28.0 (q,
C-1), 49.8 (d, C-7), 56.0 (d, C-4), 83.4 (s, C-2), 115.6 (q, J6,F
=
3
3
2.15 (m, 1 H, 11-Hb), 4.94 (td, J10,11 = 6.3, J10,9 = 5.6 Hz, 1 H,
287.7 Hz, C-6), 119.1 (t, C-9), 125.8 (d, C-10), 126.3 (d, C-13),
127.8 (d, C-15), 128.6 (d, C-14), 133.3 (d, C-11), 134.4 (d, C-8),
136.5 (s, C-12), 156.7 (q, J5,F = 37.8 Hz, C-5), 168.2 (s, C-3) ppm.
3
3
3
10-H), 5.01 (dt, J4,5 = J4,11 = 7.1 Hz, 1 H, 4-H), 5.19 (d, J6trans,5
= 10.5 Hz, 1 H, 6-Htrans), 5.27 (d, J6cis,5 = 17.3 Hz, 1 H, 6-Hcis),
3
1
syn-5b: H NMR (400 MHz, CDCl3): δ = 1.47 (s, 9 H, 1-H), 3.45
5.35 (m, 1 H, 9-H), 5.66 (m, 1 H, 8-H), 5.77 (m, 1 H, 5-H) ppm.
13C NMR (100 MHz, CDCl3): δ = 17.7 (q, C-7), 27.7 (q, C-1, C-
1Ј), 38.8 (t, C-11), 73.8 (d, C-4), 74.4 (d, C-10), 81.8 (s, C-2), 82.0
(s, C-2Ј), 117.3 (t, C-6), 127.8 (d, C-9), 129.7 (d, C-8), 135.6 (d, C-
3
3
(m, 1 H, 7-H), 4.67 (dd, J4,NH = 8.5, J4,7 = 5.8 Hz, 1 H, 4-H),
5.21 (d, 3J9cis,8 = 17.1 Hz, 1 H, 9-Hcis), 5.27 (d, 3J9trans,8 = 10.4 Hz,
3
3
3
1 H, 9-Htrans), 5.82 (ddd, J8,9cis = 17.3, J8,9trans = 10.2, J8,7
=
7.7 Hz, 1 H, 8-H), 6.17 (dd, 3J10,11 = 15.9, 3J10,7 = 7.6 Hz, 1 H, 10-
1
5), 152.6 (s, C-3), 152.7 (s, C-3Ј) ppm. (E)-8a (diastereomer II): H
3
H), 6.50 (d, J11,10 = 15.9 Hz, 1 H, 11-H), 6.99 (br. s, 1 H, NH),
NMR (400 MHz, CDCl3): δ = 1.44 (s, 9 H, 1Ј-H), 1.45 (s, 9 H, 1-
3
H), 1.70 (m, 3 H, 7-H), 1.87 (m, 1 H, 11-Ha), 1.95 (m, 1 H, 11-
7.25 (t, J15,14 = 7.0 Hz, 1 H, 15-H), 7.30–7.37 (m, 4 H, 13-H, 14-
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 28.0 (q, C-1), 49.8 (d,
C-7), 56.0 (d, C-4), 83.4 (s, C-2), 115.6 (q, J6,F = 287.7 Hz, C-6),
119.1 (t, C-9), 125.8 (d, C-10), 126.3 (d, C-13), 127.8 (d, C-15),
128.6 (d, C-14), 133.3 (d, C-11), 134.4 (d, C-8), 136.5 (s, C-12),
156.7 (q, J5,F = 37.8 Hz, C-5), 168.2 (s, C-3) ppm. GC [Chirasil-l-
Val, T0 (30 min) = 80 °C, 1 °C/min to T = 180 °C]: tR (anti-5b) =
92.57 min, tR (syn-5b) = 92.84 min, tR (anti-5b) = 95.05 min, tR
(syn-5b) = 95.57 min.
3
3
Hb), 4.94 (td, J10,11 = 6.3, J10,9 = 5.6 Hz, 1 H, 10-H), 5.08 (m, 1
3
3
H, 4-H), 5.19 (d, J6trans,5 = 10.5 Hz, 1 H, 6-Htrans), 5.27 (d, J6cis,5
= 17.3 Hz, 1 H, 6-Hcis), 5.35 (m, 1 H, 9-H), 5.66 (m, 1 H, 8-H),
5.77 (m, 1 H, 5-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 17.7
(q, C-7), 27.7 (q, C-1, C-1Ј), 39.2 (t, C-11), 74.4 (d, C-10), 74.7 (d,
C-4), 81.8 (s, C-2), 82.0 (s, C-2Ј), 117.6 (t, C-6), 127.8 (d, C-9),
129.7 (d, C-8), 135.8 (d, C-5), 152.6 (s, C-3), 152.7 (s, C-3Ј) ppm.
HRMS (CI): calcd. for C18H30O6 [M + H]+ 343.2121; found
343.2089. C18H30O6 (342.43): calcd. C 63.14, H 8.83; found C
62.95, H 8.86.
(4E,6E)-tert-Butyl 7-Phenyl-2-(2,2,2-trifluoroacetamido)hepta-4,6-
dienoate (7b): Ester 7b was obtained as the minor product in the
allylic alkylation using 4b. Rf (hexanes/EtOAc, 9:1) = 0.28. 1H
NMR (400 MHz, CDCl3): δ = 1.50 (s, 9 H, 1-H), 2.68 (m, 1 H, 7-
Di-tert-butyl Nona-1,7-diene-3,6-diyl Dicarbonate (8b): Following
GP 1, 8b was obtained from nona-1,7-diene-3,6-diol (312 mg,
2 mmol, 1.0 equiv.), n-butyllithium (1.6 m in hexane, 2.75 mL,
4.4 mmol, 2.2 equiv.) and di-tert-butyl dicarbonate (960 mg,
Ha), 2.77 (m, 1 H, 7-Hb), 4.58 (dt, J4,NH = 7.2, J4,7 = 5.4 Hz, 1
3
3
3
3
H, 4-H), 5.61 (dt, J8,9 = 15.1, J8,7 = 7.6 Hz, 1 H, 8-H), 6.27 (dd,
3J9,8 = 14.8, J9,10 = 10.4 Hz, 1 H, 9-H), 6.50 (d, J11,10 = 15.7 Hz, 4.4 mmol, 2.2 equiv.). After evaporation of the solvent in vacuo and
3
3
3
3
1 H, 11-H), 6.73 (dd, J10,11 = 15.7, J10,9 = 10.4 Hz, 1 H, 10-H),
6.98 (br. s, 1 H, NH), 7.23 (tt, J15,14 = 7.2, J15,13 = 1.2 Hz, 1 H,
flash chromatography (hexanes/EtOAc, 9:1) the desired product
was isolated in 85% yield [602 mg, 1.69 mmol, 67% (Z)] as a
3
4
4936
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4931–4939

Chemoselective Rh-Catalyzed Allylic Alkylations of Chelated Enolates
colourless oil. Rf (hexanes/EtOAc, 9:1) = 0.33. (Z)-8b: 1H NMR
(400 MHz, CDCl3): δ = 1.46 (s, 9 H, 1Ј-H), 1.47 (s, 9 H, 1-H), 1.54–
could be separated, and the desired product was isolated in 71%
yield [271 mg, 705 μmol, 83% (Z)] as a colourless oil. The NMR
spectra showed signals of the Z- and E-isomers in a (Z/E)-ratio of
3
4
1.65 (m, 4 H, 11-H, 12-H), 1.71 (dd, J7,8 = 7.1, J7,9 = 1.3 Hz, 3
3
2
H, 7-H), 5.00 (m, 1 H, 4-H), 5.18 (ddd, J6trans,5 = 10.5, J6trans,6cis 67:33 before flash chromatography. Rf (hexanes/EtOAc, 9:1) = 0.44.
3
1
=
4J6trans,4 = 1.0 Hz, 1 H, 6-Htrans), 5.26 (ddd, J6cis,5 = 17.3, (Z)-8c: H NMR (400 MHz, CDCl3): δ = 1.27–1.39 (m, 4 H, 12-
2J6cis,6trans = J6cis,4 = 1.0 Hz, 1 H, 6-Hcis), 5.32–5.35 (m, 2 H, 9-H,
H, 13-H), 1.46 (s, 9 H, 1Ј-H), 1.47 (s, 9 H, 1-H), 1.50–1.65 (m, 4
4
10-H), 5.64 (m, 1 H, 8-H), 5.76 (ddd, 3J5,6cis = 17.2, 3J5,6trans = 10.5, H, 11-H, 14-H), 1.71 (d, 3J7,8 = 7.6 Hz, 3 H, 7-H), 4.96 (dt, J4,5
=
=
3
3J5,4 = 6.7 Hz, 1 H, 5-H) ppm. 13C NMR (100 MHz, CDCl3): δ =
3J4,13 = 6.7 Hz, 1 H, 4-H), 5.17 (dd, J6trans,5 = 10.5, J6trans,6cis
3
2
3
2
13.5 (q, C-7), 27.8 (q, C-1, C-1Ј), 29.7 (t, C-12), 30.2 (t, C-11), 72.5 0.9 Hz, 1 H, 6-Htrans), 5.25 (dd, J6cis,5 = 17.3, J6cis,6trans = 1.0 Hz,
(d, C-10), 77.5 (d, C-4), 81.8 (s, C-2), 82.0 (s, C-2Ј), 117.3 (t, C-6),
3
1 H, 6-Hcis), 5.31–5.37 (m, 2 H, 9-H, 10-H), 5.63 (dq, J8,9 = 9.5,
128.5 (d, C-8), 128.6 (d, C-9), 136.0 (d, C-5), 152.8 (s, C-3), 152.9
3J8,7 = 7.0 Hz, 1 H, 8-H), 5.77 (ddd, 3J5,6cis = 17.2, 3J5,6trans = 10.5,
1
(s, C-3Ј) ppm. (E)-8b: H NMR (400 MHz, CDCl3): δ = 1.46 (s, 9 3J5,4 = 6.7 Hz, 1 H, 5-H) ppm. 13C NMR (100 MHz, CDCl3): δ =
H, 1Ј-H), 1.47 (s, 9 H, 1-H), 1.54–1.65 (m, 4 H, 11-H, 12-H), 1.68 13.5 (q, C-7), 24.8 (t, C-13), 24.9 (t, C-12), 27.8 (q, C-1, C-1Ј), 34.2
(dd, 3J7,8 = 6.5, 4J7,9 = 1.5 Hz, 3 H, 7-H), 4.94 (m, 1 H, 10-H), 5.00
(t, C-14), 34.5 (t, C-11), 73.0 (d, C-10), 77.8 (d, C-4), 81.7 (s, C-2),
81.9 (s, C-2Ј), 117.0 (t, C-6), 128.2 (d, C-8), 129.0 (d, C-9), 136.3
3
2
4
(m, 1 H, 4-H), 5.18 (ddd, J6trans,5 = 10.5, J6trans,6cis = J6trans,4
=
2
1.0 Hz, 1 H, 6-Htrans), 5.26 (ddd, 3J6cis,5 = 17.3, J6cis,6trans = 4J6cis,4 (d, C-5), 153.0 (s, C-3), 153.1 (s, C-3Ј) ppm. (E)-8c: 1H NMR
3
3
4
= 1.0 Hz, 1 H, 6-Hcis), 5.39 (ddt, J9,8 = 15.4, J9,10 = 7.7, J9,11
=
(400 MHz, CDCl3): δ = 1.27–1.39 (m, 4 H, 12-H, 13-H), 1.46 (s, 9
H, 1Ј-H), 1.47 (s, 9 H, 1-H), 1.50–1.68 (m, 7 H, 7-H, 11-H, 14-H),
1.6 Hz, 1 H, 9-H), 5.71–5.80 (m, 2 H, 5-H, 8-H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 17.7 (q, C-7), 27.8 (q, C-1, C-1Ј), 30.0 (t, 4.91 (dt, 3J10,9 = 3J10,11 = 7.1 Hz, 1 H, 10-H), 4.96 (dt, 3J4,5 = 3J4,14
3
C-12), 30.1 (t, C-11), 77.5 (d, C-4), 77.7 (d, C-10), 81.8 (s, C-2),
82.0 (s, C-2Ј), 117.3 (t, C-6), 129.0 (d, C-9), 129.9 (d, C-8), 136.0
(d, C-5), 152.8 (s, C-3), 152.9 (s, C-3Ј) ppm. HRMS (CI): calcd. for
C19H32O6 [M + H]+ 357.2277; found 357.2265. C19H32O6 (356.46):
calcd. C 64.02, H 9.05; found C 63.58, H 9.02.
= 6.7 Hz, 1 H, 4-H), 5.17 (dd, J6trans,5 = 10.5, 2J6trans,6cis = 0.9 Hz,
3
2
1 H, 6-Htrans), 5.25 (dd, J6cis,5 = 17.3, J6cis,6trans = 1.0 Hz, 1 H, 6-
Hcis), 5.40 (ddt, 3J9,8 = 15.3, 3J9,10 = 7.6, 4J9,11 = 1.5 Hz, 1 H, 9-H),
5.70–5.81 (m, 2 H, 5-H, 8-H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 17.7 (q, C-7), 24.8 (t, C-13), 24.9 (t, C-12), 27.8 (q, C-1, C-1Ј),
34.2 (t, C-14), 34.5 (t, C-11), 77.8 (d, C-4), 78.0 (d, C-10), 81.7 (s,
C-2), 81.9 (s, C-2Ј), 117.0 (t, C-6), 129.4 (d, C-9), 129.6 (d, C-8),
136.3 (d, C-5), 153.0 (s, C-3), 153.1 (s, C-3Ј) ppm. HRMS (CI):
calcd. for C21H36O6 [M + H]+ 385.2590; found 385.2591. C21H36O6
(384.51): calcd. C 65.60, H 9.44; found C 65.39, H 9.33.
Di-tert-butyl Deca-1,8-diene-3,7-diyl Dicarbonate (8c): Following
GP 1, 8c was obtained from deca-1,8-diene-3,7-diol (426 mg,
2.5 mmol, 1.0 equiv.), n-butyllithium (1.6 m in hexane, 3.44 mL,
5.5 mmol, 2.2 equiv.) and di-tert-butyl dicarbonate (1.20 g,
5.5 mmol, 2.2 equiv.). After evaporation of the solvent in vacuo and
flash chromatography (hexanes/EtOAc, 9:1), the desired product
was isolated in 79% yield [730 mg, 1.97 mmol, 67% (Z)] as colour-
(4E)-tert-Butyl 8-(tert-Butoxycarbonyloxy)-2-(2,2,2-trifluoroacet-
amido)undeca-4,9-dienoate (9b): By following to GP 2, 9b was ob-
less oil. Rf (hexanes/EtOAc, 9:1) = 0.35. (Z)-8c: 1H NMR tained from allylic carbonate 8b (89 mg, 0.25 mmol) with TFA-pro-
(400 MHz, CDCl3): δ = 1.37 (m, 2 H, 12-H), 1.46 (s, 9 H, 1Ј-H),
tected tert-butyl glycinate (62 mg, 275 μmol) in 57% yield (66 mg,
142 μmol, 96% rs) as a colourless oil after flash chromatography
3
1.47 (s, 9 H, 1-H), 1.49–1.66 (m, 4 H, 11-H, 13-H), 1.70 (d, J7,8
=
3
3
6.9 Hz, 3 H, 7-H), 4.96 (td, J4,13 = 7.0, J4,5 = 6.6 Hz, 1 H, 4-H), (hexanes/EtOAc, 95:5). Rf (hexanes/ EtOAc, 9:1) = 0.20. (Z)-9b: 1H
3
2
4
5.17 (ddd, J6trans,5 = 10.5, J6trans,6cis = J6trans,4 = 1.0 Hz, 1 H, 6- NMR (400 MHz, CDCl3): δ = 1.46 (s, 9 H, 18-H), 1.47 (s, 9 H, 1-
H
trans), 5.25 (ddd, 3J6cis,5 = 17.3, 2J6cis,6trans = 4J6cis,4 = 1.2 Hz, 1 H,
H), 1.55 (m, 1 H, 11-Ha), 1.70 (m, 3 H, 15-H), 1.76 (m, 1 H, 11-
6-Hcis), 5.31–5.34 (m, 2 H, 9-H, 10-H), 5.63 (dq, J8,9 = 9.6, J8,7 Hb), 2.03 (dt, J10,9 = J10,11 = 7.2 Hz, 2 H, 10-H), 2.51 (m, 1 H,
3
3
3
3
= 7.0 Hz, 1 H, 8-H), 5.76 (m, 1 H, 5-H) ppm. 13C NMR (100 MHz,
7-Ha), 2.59 (m, 1 H, 7-Hb), 4.50 (m, 1 H, 4-H), 5.26 (dt, J8,9
=
3
3
CDCl3): δ = 13.4 (q, C-7), 20.6 (t, C-12), 27.8 (q, C-1, C-1Ј), 34.0 15.1, J8,9 = 7.4 Hz, 1 H, 8-H), 5.31–5.34 (m, 2 H, 12-H, 13-H),
(t, C-13), 34.3 (t, C-11), 72.8 (d, C-10), 77.7 (d, C-4), 81.7 (s, C-2),
3
3
5.53 (dt, J9,8 = 15.2, J9,10 = 7.2 Hz, 1 H, 9-H), 5.64 (m, 1 H, 14-
81.9 (s, C-2Ј), 117.0 (t, C-6), 128.3 (d, C-8), 128.7 (d, C-9), 136.2
H), 6.94 (br. s, 1 H, NH) ppm. 13C NMR (100 MHz, CDCl3): δ =
(d, C-5), 153.0 (s, C-3), 153.1 (s, C-3Ј) ppm. (E)-8c: 1H NMR 13.5 (q, C-15), 27.8 (q, C-18), 28.0 (q, C-1), 28.1 (t, C-10), 34.1 (t,
(400 MHz, CDCl3): δ = 1.37 (m, 2 H, 12-H), 1.46 (s, 9 H, 1Ј-H),
C-11), 34.7 (t, C-7), 52.6 (d, C-4), 72.4 (d, C-12), 81.8 (s, C-17),
83.2 (s, C-2), 115.6 (q, J6,F = 287.4 Hz, C-6), 123.1 (d, C-8), 128.5
3
1.47 (s, 9 H, 1-H), 1.49–1.66 (m, 4 H, 11-H, 13-H), 1.68 (d, J7,8
6.6 Hz, 3 H, 7-H), 4.92 (dt, J10,9 = 6.9, J10,11 = 6.6 Hz, 1 H, 10- (d, C-14), 128.7 (d, C-13), 135.0 (d, C-9), 153.0 (s, C-16), 156.5 (q,
=
3
3
3
3
H), 4.96 (td, J4,13 = 7.0, J4,5 = 6.6 Hz, 1 H, 4-H), 5.17 (ddd,
J5,F = 37.3 Hz, C-5), 169.2 (s, C-3) ppm. (E)-9b: 1H NMR
(400 MHz, CDCl3): δ = 1.46 (s, 9 H, 18-H), 1.47 (s, 9 H, 1-H), 1.55
3J6trans,5 = 10.5, J6trans,6cis = J6trans,4 = 1.0 Hz, 1 H, 6-Htrans), 5.25
2
4
(ddd, 3J6cis,5 = 17.3, 2J6cis,6trans = 4J6cis,4 = 1.2 Hz, 1 H, 6-Hcis), 5.40 (m, 1 H, 11-Ha), 1.70 (m, 3 H, 15-H), 1.76 (m, 1 H, 11-Hb), 2.03
(ddt, 3J9,8 = 15.3, 3J9,10 = 7.7, J9,11 = 1.5 Hz, 1 H, 9-H), 5.70–5.81
(dt, J10,9 = J10,11 = 7.2 Hz, 2 H, 10-H), 2.51 (m, 1 H, 7-Ha), 2.59
4
3
3
(m, 2 H, 5-H, 8-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 17.7
(q, C-7), 20.8 (t, C-12), 27.8 (q, C-1, C-1Ј), 33.9 (t, C-13), 34.2 (t,
C-11), 77.7 (d, C-4), 77.8 (d, C-10), 81.7 (s, C-2), 81.9 (s, C-2Ј),
117.0 (t, C-6), 129.2 (d, C-9), 129.7 (d, C-8), 136.2 (d, C-5), 153.0
(m, 1 H, 7-Hb), 4.50 (m, 1 H, 4-H), 4.94 (td, J12,11
=
3J12,13
=
3
3
3
7.4 Hz, 1 H, 12-H), 5.26 (dt, J8,9 = 15.1, J8,9 = 7.4 Hz, 1 H, 8-
H), 5.40 (ddt, 3J13,14 = 15.3, J13,12 = 7.6, J13,11 = 1.7 Hz, 1 H, 13-
3
4
3
3
H), 5.53 (dt, J9,8 = 15.2, J9,10 = 7.2 Hz, 1 H, 9-H), 5.74 (m, 1 H,
(s, C-3), 153.1 (s, C-3Ј) ppm. HRMS (CI): calcd. for C20H34O6 [M 14-H), 6.97 (br. s, 1 H, NH) ppm. 13C NMR (100 MHz, CDCl3):
+ H]+ 371.2434; found 371.2395. C20H34O6 (370.49): calcd. C
64.84, H 9.25; found C 64.38, H 9.42.
δ = 17.7 (q, C-15), 27.8 (q, C-18), 28.0 (q, C-1), 28.1 (t, C-10), 34.1
(t, C-11), 34.7 (t, C-7), 52.6 (d, C-4), 77.2 (d, C-12), 81.8 (s, C-17),
83.2 (s, C-2), 115.6 (q, J6,F = 287.4 Hz, C-6), 123.1 (d, C-8), 129.1
(d, C-13), 129.8 (d, C-14), 135.0 (d, C-9), 153.0 (s, C-16), 156.5 (q,
J5,F = 37.3 Hz, C-5), 169.2 (s, C-3) ppm. HRMS (CI): calcd. for
C22H34F3NO6 [M + H]+ 466.2416; found 466.2416.
Di-tert-butyl Undeca-1,9-diene-3,8-diyl Dicarbonate (8d): Following
GP 1, 8d was obtained from undeca-1,9-diene-3,8-diol (184 mg,
1 mmol, 1.0 equiv.), n-butyllithium (1.6 m in hexane, 1.38 mL,
2.2 mmol, 2.2 equiv.) and di-tert-butyl dicarbonate (480 mg,
2.2 mmol, 2.2 equiv.). After evaporation of the solvent in vacuo
and flash chromatography (hexanes/EtOAc, 9:1), the (E/Z)-isomers
(4E)-tert-Butyl 9-(tert-Butoxycarbonyloxy)-2-(2,2,2-trifluoroacet-
amido)dodeca-4,10-dienoate (9c): According to GP 2, 9c was ob-
Eur. J. Org. Chem. 2011, 4931–4939
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4937

S. Hähn, U. Kazmaier
FULL PAPER
tained from allylic carbonate 8c (93 mg, 0.25 mmol) with TFA-pro-
tected tert-butyl glycinate (62 mg, 275 μmol) in 48% yield (58 mg,
121 μmol, 94% rs) as a colourless oil after flash chromatography
(hexanes/EtOAc, 95:5). Rf (hexanes/ EtOAc, 9:1) = 0.21. (Z)-9c: 1H
CDCl3): δ = 17.7 (q, C-17), 23.3 (t, C-12), 24.5 (t, C-11), 27.8 (q,
C-20), 28.0 (q, C-1), 32.3 (t, C-10), 34.5 (t, C-13), 34.7 (t, C-7),
52.7 (d, C-4), 78.1 (d, C-14), 81.7 (s, C-19), 83.2 (s, C-2), 115.7 (q,
J6,F = 287.8 Hz, C-6), 122.3 (d, C-8), 129.0 (d, C-15), 129.4 (d, C-
NMR (400 MHz, CDCl3): δ = 1.36 (m, 2 H, 11-H), 1.46 (s, 9 H, 16), 136.2 (d, C-9), 153.1 (s, C-18), 156.4 (q, J5,F = 37.6 Hz, C-5),
19-H), 1.47 (s, 9 H, 1-H), 1.51 (m, 1 H, 12-Ha), 1.63 (m, 1 H, 12- 169.3 (s, C-3) ppm. HRMS (CI): calcd. for C24H38F3NO6 [M –
3
3
3
Hb), 1.71 (d, J16,15 = 7.3 Hz, 3 H, 16-H), 2.00 (dt, J10,9 = J10,11
C5H8O3]+ 377.2178; found 377.2204.
= 7.0 Hz, 2 H, 10-H), 2.50 (m, 1 H, 7-Ha), 2.58 (m, 1 H, 7-Hb),
4.48 (m, 1 H, 4-H), 5.24 (dt, J8,9 = 15.2, J8,9 = 7.3 Hz, 1 H, 8-
H), 5.31–5.34 (m, 2 H, 13-H, 14-H), 5.51 (dt, J9,8 = 15.1, J9,10
1-(4-{1-[(tert-Butoxycarbonyl)oxy]but-2-en-1-yl}phenyl)prop-2-en-1-
yl tert-Butyl Carbonate (10): Following GP 1, 10 was obtained
from 1-(1-hydroxybut-2-en-1-yl)-4-(1-hydroxyprop-2-en-1-yl)benz-
ene (613 mg, 3 mmol, 1.0 equiv.), n-butyllithium (1.6 m in hexane,
4.20 mL, 6.6 mmol, 2.2 equiv.) and di-tert-butyl dicarbonate
(1.44 g, 6.6 mmol, 2.2 equiv.). After evaporation of the solvent in
vacuo and flash chromatography (hexanes/EtOAc, 9:1), the desired
product was isolated in 81% yield (989 mg, 2.44 mmol, 65% Z) as
a colourless solid. Rf (hexanes/EtOAc, 9:1) = 0.25. M.p. 119-
3
3
3
3
=
6.9 Hz, 1 H, 9-H), 5.63 (dq, 3J15,14 = 9.7, J15,16 = 7.0 Hz, 1 H, 15-
H), 6.86 (br. s, 1 H, NH) ppm. 13C NMR (100 MHz, CDCl3): δ =
13.4 (q, C-16), 24.6 (t, C-11), 27.8 (q, C-19), 28.0 (q, C-1), 32.2 (t,
C-10), 34.1 (t, C-12), 34.7 (t, C-7), 52.7 (d, C-4), 72.9 (d, C-13),
81.7 (s, C-18), 83.2 (s, C-2), 115.6 (q, J6,F = 287.8 Hz, C-6), 122.6
(d, C-8), 128.8 (d, C-15), 128.9 (d, C-14), 135.8 (d, C-9), 153.1 (s,
C-16), 156.4 (q, J5,F = 37.4 Hz, C-5), 169.3 (s, C-3) ppm. (E)-9c:
1H NMR (400 MHz, CDCl3): δ = 1.36 (m, 2 H, 11-H), 1.46 (s, 9
H, 19-H), 1.47 (s, 9 H, 1-H), 1.51 (m, 1 H, 12-Ha), 1.63 (m, 1 H,
12-Hb), 1.68 (d, 3J16,15 = 6.6 Hz, 3 H, 16-H), 2.00 (dt, 3J10,9 = 3J10,11
= 7.0 Hz, 2 H, 10-H), 2.50 (m, 1 H, 7-Ha), 2.58 (m, 1 H, 7-Hb),
3
1
120 °C. (Z)-10: H NMR (400 MHz, CDCl3): δ = 1.46 (s, 9 H, 1Ј-
3
H), 1.47 (s, 9 H, 1-H), 1.80 (d, J7,8 = 5.8 Hz, 3 H, 7-H), 5.24 (dd,
3J6trans,5 = 10.1, 2J6trans,6cis = 1.5 Hz, 1 H, 6-Htrans), 5.30 (dd, 3J6cis,5
2
= 15.7, J6cis,6trans = 1.1 Hz, 1 H, 6-Hcis), 5.63–5.70 (m, 2 H, 8-H,
3
9-H), 6.00–6.05 (m, 2 H, 4-H, 5-H), 6.34 (d, J10,9 = 8.1 Hz, 1 H,
3
3
4.48 (m, 1 H, 4-H), 4.91 (td, J12,11 = J12,13 = 7.1 Hz, 1 H, 13-H),
5.24 (dt, J8,9 = 15.2, J8,9 = 7.3 Hz, 1 H, 8-H), 5.40 (dd, J14,15
15.3, J14,13 = 7.7, J14,16 = 1.6 Hz, 1 H, 14-H), 5.51 (dt, J9,8
15.1, J9,10 = 6.9 Hz, 1 H, 9-H), 5.73 (dq, J15,14 = 15.3, J15,16
10-H), 7.33–7.37 (m, 4 H, 12-H, 13-H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 13.5 (q, C-7), 27.8 (q, C-1, C-1Ј), 74.0 (d, C-10), 78.9
(d, C-4), 82.2 (s, C-2), 82.4 (s, C-2Ј), 117.2 (t, C-6), 126.7 (d, C-13),
127.3 (d, C-12), 128.1 (d, C-8), 128.7 (d, C-9), 136.1 (d, C-5), 138.4
(s, C-14), 139.9 (s, C-11), 152.7 (s, C-3), 152.8 (s, C-3Ј) ppm. (E)-
3
3
3
=
=
=
3
4
3
3
3
3
6.5 Hz, 1 H, 15-H), 6.86 (br. s, 1 H, NH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 17.7 (q, C-16), 24.6 (t, C-11), 27.8 (q, C-
19), 28.0 (q, C-1), 32.2 (t, C-10), 34.1 (t, C-12), 34.7 (t, C-7), 52.7
(d, C-4), 77.9 (d, C-13), 81.7 (s, C-18), 83.2 (s, C-2), 115.6 (q, J6,F
= 287.8 Hz, C-6), 122.6 (d, C-8), 129.3 (d, C-14), 129.6 (d, C-15),
135.8 (d, C-9), 153.1 (s, C-16), 156.4 (q, J5,F = 37.4 Hz, C-5), 169.3
(s, C-3) ppm. C23H36F3NO6 (479.53): calcd. C 57.61, H 7.57, N
2.92; found C 57.86, H 7.42, N 2.93.
1
10: H NMR (400 MHz, CDCl3): δ = 1.46 (s, 9 H, 1Ј-H), 1.47 (s,
9 H, 1-H), 1.70 (dd, 3J7,8 = 6.5, 4J7,9 = 0.5 Hz, 3 H, 7-H), 5.24 (dd,
3J6trans,5 = 10.1, 2J6trans,6cis = 1.5 Hz, 1 H, 6-Htrans), 5.30 (dd, 3J6cis,5
2
= 15.7, J6cis,6trans = 1.1 Hz, 1 H, 6-Hcis), 5.67 (m, 1 H, 9-H), 5.77
3
4
(dqd, 3J8,9 = 15.3, J8,7 = 6.3, J8,10 = 0.7 Hz, 1 H, 8-H), 6.00–6.05
(m, 3 H, 4-H, 5-H, 10-H), 7.33–7.37 (m, 4 H, 12-H, 13-H) ppm.
13C NMR (100 MHz, CDCl3): δ = 17.7 (q, C-7), 27.8 (q, C-1, C-
1Ј), 74.3 (d, C-4), 79.0 (d, C-10), 82.2 (s, C-2), 82.4 (s, C-2Ј), 117.2
(t, C-6), 126.7 (d, C-13), 127.3 (d, C-12), 129.3 (d, C-9), 130.0 (d,
C-8), 136.1 (d, C-5), 138.4 (s, C-14), 139.9 (s, C-11), 152.7 (s, C-3),
152.8 (s, C-3Ј) ppm. C23H32O6 (404.50): calcd. C 68.29, H 7.97;
found C 68.71, H 8.18.
(4E)-tert-Butyl 10-(tert-Butoxycarbonyloxy)-2-(2,2,2-trifluoroacet-
amido)trideca-4,11-dienoate (9d): By following to GP 2, 9d was ob-
tained from allylic carbonate 8d (96 mg, 0.25 mmol) with TFA-pro-
tected tert-butyl glycinate (62 mg, 275 μmol) in 29% yield (36 mg,
73 μmol, 94% rs) as a colourless oil after flash chromatography
(hexanes/EtOAc, 95:5). Rf (hexanes/EtOAc, 9:1) = 0.25. (Z)-9d: 1H
NMR (400 MHz, CDCl3): δ = 1.23–1.39 (m, 4 H, 11-H, 12-H),
(E)-tert-Butyl 3-{4-[3-(tert-Butoxycarbonyloxy)but-1-enyl]phenyl}-2-
(2,2,2-trifluoroacetamido)pent-4-enoate (11a): By following to GP 2,
1.47 (s, 9 H, 20-H), 1.48 (s, 9 H, 1-H), 1.55 (m, 1 H, 12-Ha), 1.63 11b was obtained as the major product from allylic carbonate 10
(m, 1 H, 12-Hb), 1.74 (d, J17,16 = 7.3 Hz, 3 H, 17-H), 2.00 (dt, (286 mg, 707 μmol) with TFA-protected tert-butyl glycinate
3
3J10,9 = J10,11 = 6.7 Hz, 2 H, 10-H), 2.50 (m, 1 H, 7-Ha), 2.58 (m, (321 mg, 1.41 mmol) in an overall yield (mixture of isomers) of
3
1 H, 7-Hb), 4.48 (dt, J4,NH = 7.4, J4,7 = 5.4 Hz, 1 H, 4-H), 5.23
76% (277 mg, 539 μmol) as a colourless oil after flash chromatog-
(dt, J8,9 = 15.1, J8,9 = 7.3 Hz, 1 H, 8-H), 5.31–5.37 (m, 2 H, 14- raphy (hexanes/EtOAc, 95:5). The NMR spectra and HPLC
3
3
3
3
3
3
H, 15-H), 5.52 (dt, J9,8 = 15.2, J9,10 = 6.8 Hz, 1 H, 9-H), 5.63
showed a ds of 54%. Rf (hexanes/EtOAc, 9:1) = 0.15. Diastereomer
3
3
3
(dq, J16,15 = 9.8, J16,17 = 6.9 Hz, 1 H, 16-H), 6.85 (d, JNH,4
=
I: 1H NMR (400 MHz, CDCl3): δ = 1.38 (s, 9 H, 1-H), 1.45 (d,
6.9 Hz, 1 H, NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.4 (q, 3J17,16 = 6.5 Hz, 3 H, 17-H), 1.49 (s, 9 H, 20-H), 3.90 (dd, J7,8
=
3
C-17), 23.3 (t, C-12), 24.5 (t, C-11), 27.8 (q, C-20), 28.0 (q, C-1),
32.3 (t, C-10), 34.5 (t, C-13), 34.7 (t, C-7), 52.7 (d, C-4), 73.0 (d, 1 H, 4-H), 5.19 (ddd, J9cis,8 = 17.1, J9cis,9trans = J9cis,7 = 0.9 Hz,
C-14), 81.7 (s, C-19), 83.2 (s, C-2), 115.7 (q, J6,F = 287.8 Hz, C-6),
122.3 (d, C-8), 128.2 (d, C-16), 129.0 (d, C-15), 136.2 (d, C-9), 153.1
7.9, 3J7,4 = 6.0 Hz, 1 H, 7-H), 4.86 (dd, 3J4,NH = 8.7, 3J4,7 = 5.7 Hz,
3
2
4
3
2
1 H, 9-Hcis), 5.26 (ddd, J9trans,8 = 10.2, J9trans,9cis
=
4J9trans,7
=
=
3
4
0.8 Hz, 1 H, 9-Htrans), 5.31 (ddd, J16,15
=
3J16,17 = 6.7, J16,14
3
3
3
(s, C-18), 156.4 (q, J5,F = 37.6 Hz, C-5), 169.3 (s, C-3) ppm. (E)- 0.7 Hz, 1 H, 16-H), 6.04 (ddd, J8,9cis = 17.0, J8,9trans = 10.3, J8,7
9d: 1H NMR (400 MHz, CDCl3): δ = 1.23–1.39 (m, 4 H, 11-H, 12-
= 8.2 Hz, 1 H, 8-H), 6.19 (dd, J15,14 = 16.0, J15,16 = 6.9 Hz, 1 H,
15-H), 6.59 (d, 3J14,15 = 15.8 Hz, 1 H, 14-H), 6.63 (br. s, 1 H, NH),
7.17 (d, 3J11,12 = 8.2 Hz, 1 H, 11-H), 7.35 (d, 3J12,11 = 8.2 Hz, 1 H,
3
3
H), 1.47 (s, 9 H, 20-H), 1.48 (s, 9 H, 1-H), 1.55 (m, 1 H, 12-Ha),
1.63 (m, 1 H, 12-Hb), 1.69 (d, J17,16 = 6.6 Hz, 3 H, 17-H), 2.00
3
(dt, J10,9 = J10,11 = 6.7 Hz, 2 H, 10-H), 2.50 (m, 1 H, 7-Ha), 2.58 12-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.5 (q, C-17), 27.8
3
3
(m, 1 H, 7-Hb), 4.48 (dt, J4,NH = 7.4, J4,7 = 5.4 Hz, 1 H, 4-H),
(q, C-20), 27.9 (q, C-1), 51.5 (d, C-7), 56.4 (d, C-4), 74.0 (d, C-16),
82.1 (s, C-19), 83.6 (s, C-2), 115.6 (q, J6,F = 288.0 Hz, C-6), 118.9
(t, C-9), 126.9 (d, C-11), 128.4 (d, C-12), 129.0 (d, C-15), 131.2 (s,
C-13), 134.9 (d, C-14), 135.8 (s, C-10), 137.6 (d, C-8), 152.8 (s, C-
3
3
3
3
4.91 (td, J12,11
=
3J12,13 = 7.1 Hz, 1 H, 14-H), 5.23 (dt, J8,9
=
=
=
3
3
3
15.1, J8,9 = 7.3 Hz, 1 H, 8-H), 5.40 (ddq, J15,16 = 15.3, J15,14
4
3
3
7.7, J15,17 = 1.7 Hz, 1 H, 15-H), 5.52 (dt, J9,8 = 15.2, J9,10
6.8 Hz, 1 H, 9-H), 5.73 (dq, 3J16,15 = 15.3, 3J16,17 = 6.5 Hz, 1 H, 16- 18), 156.6 (q, J5,F = 37.4 Hz, C-5), 168.2 (s, C-3) ppm. Dia-
H), 6.85 (d, 3JNH,4 = 6.9 Hz, 1 H, NH) ppm. 13C NMR (100 MHz,
stereomer II: H NMR (400 MHz, CDCl3): δ = 1.26 (s, 9 H, 1-H),
1
4938
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4931–4939

Chemoselective Rh-Catalyzed Allylic Alkylations of Chelated Enolates
3
[2] Recent reviews: a) U. Kazmaier, M. Pohlman in Metal Cata-
lyzed C–C and C–N Coupling Reactions (Eds.: A. de Meijere,
F. Diederich), Wiley-VCH, Weinheim, 2004, pp. 531–583; b) G.
Helmchen, U. Kazmaier, S. Förster in Catalytic Asymmetric
Synthesis (Ed.: I. Ojima), Wiley-VCH, Weinheim, 2009, pp.
497–641 and references cited therein.
1.44 (d, J17,16 = 6.5 Hz, 3 H, 17-H), 1.49 (s, 9 H, 20-H), 3.66 (dd,
3J7,8 = J7,4 = 8.4 Hz, 1 H, 7-H), 4.77 (dd, J4,NH = 3J4,7 = 8.4 Hz,
1 H, 4-H), 5.17 (ddd, J9cis,8 = 15.7, J9cis,9trans = J9cis,7 = 0.9 Hz,
1 H, 9-Hcis), 5.21 (ddd, J9trans,8 = 9.5, J9trans,9cis
1.1 Hz, 1 H, 9-Htrans), 5.31 (ddd, J16,15
0.7 Hz, 1 H, 16-H), 6.02 (ddd, J8,9cis = 16.9, J8,9trans = 10.2, J8,7
= 8.9 Hz, 1 H, 8-H), 6.19 (ddd, J15,14 = 16.0, J15,16 = 6.9, J15,17
= 0.6 Hz, 1 H, 15-H), 6.59 (d, J14,15 = 15.9 Hz, 1 H, 14-H), 6.74
(d, JNH,4 = 8.5 Hz, 1 H, NH), 7.17 (d, J11,12 = 8.2 Hz, 1 H, 11-
H), 7.34 (d, 3J12,11 = 8.2 Hz, 1 H, 12-H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 20.4 (q, C-17), 27.7 (q, C-20), 27.8 (q, C-1), 53.4 (d,
C-7), 56.6 (d, C-4), 74.0 (d, C-16), 82.1 (s, C-19), 83.4 (s, C-2),
115.6 (q, J6,F = 288.0 Hz, C-6), 118.6 (t, C-9), 126.9 (d, C-11), 128.4
(d, C-12), 128.8 (d, C-15), 131.1 (s, C-13), 135.7 (d, C-14), 135.8 (s,
C-10), 137.9 (d, C-8), 152.8 (s, C-18), 156.6 (q, J5,F = 37.4 Hz, C-
5), 168.6 (s, C-3) ppm. HPLC (LiChrosorb, hexanes/EtOAc, 95:5,
1.0 mL/min): tR (11a, diast. I) = 17.12 min, tR (11a, diast. II) =
21.10 min. HRMS (CI): calcd. for C26H34F3NO6 [M – C5H9O3]+
396.1787; found 396.1775.
3
3
3
2
4
3
2
=
4J9trans,7
=
=
3
4
=
3J16,17 = 6.6, J16,14
3
3
3
[3] L. S. Hegedus in Organometallics in Synthesis (Ed.: M.
Schlosser), Wiley, Chichester 1994, pp. 427–444.
3
3
4
3
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3
3
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1329.
tert-Butyl
3-{4-[1-(tert-Butoxycarbonyloxy)but-2-enyl]phenyl}-2-
(2,2,2-trifluoroacetamido)pent-4-enoate (11b): Ester 11b was ob-
tained as minor product in the allylic alkylation using 10 as a dia-
stereomeric and (E/Z)-mixture. (Z)-11b (diastereomer I, selected
1
signals): H NMR (400 MHz, CDCl3): δ = 1.20 (s, 9 H, 1-H), 1.46
3
3
(s, 9 H, 20-H), 1.79 (d, J17,16 = 5.4 Hz, 1 H, 7-H), 3.62 (dd, J7,4
3
3
3
= J7,8 = 8.6 Hz, 1 H, 17-H), 4.76 (dd, J4,NH = J4,7 = 8.6 Hz, 1
3
H, 4-H), 5.61–5.74 (m, 2 H, 15-H, 16-H), 6.35 (d, J14,15 = 8.1 Hz,
1 H, 14-H), 7.20 (d, J11,12 = 8.1 Hz, 1 H, 11-H) ppm. 13C NMR
3
(100 MHz, CDCl3): δ = 13.5 (q, C-17), 27.8 (q, C-20), 27.9 (q, C-
1), 51.5 (d, C-7), 56.4 (d, C-4), 74.0 (d, C-14), 118.9 (t, C-9), 126.9
(d, C-11), 127.0 (d, C-16), 128.4 (d, C-12), 128.5 (d, C-17), 137.6 (d,
C-8), 152.8 (s, C-18), 168.2 (s, C-3) ppm. (Z)-11b (diastereomer II,
1
selected signals): H NMR (400 MHz, CDCl3): δ = 1.34 (s, 9 H, 1-
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.5 (q, C-17), 27.7 (q,
C-20), 27.8 (q, C-1), 53.4 (d, C-7), 56.6 (d, C-4), 74.0 (d, C-16),
118.6 (t, C-9), 126.9 (d, C-11), 127.0 (d, C-16), 128.4 (d, C-12),
128.5 (d, C-17), 128.8 (d, C-15), 137.9 (d, C-8), 152.8 (s, C-18),
168.6 (s, C-3) ppm. (E)-11b (diastereomer I, selected signals): 1H
NMR (400 MHz, CDCl3): δ = 1.21 (s, 9 H, 1-H), 1.46 (s, 9 H, 20-
3
4
H), 1.70 (dd, J17,16 = 6.1 Hz, J17,15 = 1.2 Hz, 1 H, 17-H), 5.61–
5.79 (m, 2 H, 15-H, 16-H), 5.95 (d, J14,15 = 7.3 Hz, 1 H, 14-H)
3
ppm. 13C NMR (100 MHz, CDCl3): δ = 17.7 (q, C-17), 27.8 (q, C-
20), 27.9 (q, C-1), 51.5 (d, C-7), 56.4 (d, C-4), 74.3 (d, C-14), 118.9
(t, C-9), 126.9 (d, C-11), 128.4 (d, C-12), 137.6 (d, C-8), 152.8 (s,
C-18), 168.2 (s, C-3) ppm. (E)-11b (diastereomer II, selected sig-
nals): 1H NMR (400 MHz, CDCl3): δ = 1.35 (s, 9 H, 1-H) ppm.
13C NMR (100 MHz, CDCl3): δ = 17.7 (q, C-17), 27.7 (q, C-20),
27.8 (q, C-1), 53.4 (d, C-7), 56.6 (d, C-4), 74.3 (d, C-16), 118.6 (t,
C-9), 126.9 (d, C-11), 128.4 (d, C-12), 137.9 (d, C-8), 152.8 (s, C-
18), 168.6 (s, C-3) ppm. HPLC (LiChrosorb, hexanes/EtOAc, 95:5,
1.0 mL/min): tR [(Z)-11b, diast. I] = 11.12 min, tR [(Z)-11b, diast.
II] = 11.93 min, tR [(E)-11b, diast. I] = 13.08 min, tR [(E)-11b, diast.
II] = 14.19 min.
[13] K. Krämer, U. Kazmaier, J. Org. Chem. 2006, 71, 8950–8953.
[14] a) U. Kazmaier, D. Stolz, Angew. Chem. 2006, 118, 3143–3146;
Angew. Chem. Int. Ed. 2006, 45, 3072–3075; b) D. Stolz, U.
Kazmaier, Synthesis 2008, 2288–2292.
[15] A. Bayer, U. Kazmaier, Org. Lett. 2010, 12, 4960–4963.
[16] a) S. Basak, U. Kazmaier, Org. Lett. 2008, 10, 501–504; b) S.
Basak, U. Kazmaier, Eur. J. Org. Chem. 2008, 4169–4177.
Received: March 11, 2011
Acknowledgments
Financial support by the Deutsche Forschungsgemeinschaft (Ka
880/9-2) is gratefully acknowledged.
Published Online: July 14, 2011
[1] Recent reviews: a) B. M. Trost, M. L. Crawley, Chem. Rev.
2003, 103, 2921–2943; b) Z. Lu, S. Ma, Angew. Chem. 2008,
120, 264–303; Angew. Chem. Int. Ed. 2008, 47, 258–297.
Eur. J. Org. Chem. 2011, 4931–4939
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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