First stereoselective synthesis of a Tyr-Tyr E-alkene isostere

Article abstract of DOI:10.1055/s-2006-956456

A stereoselective synthesis of a tyrosine-tyrosine E-alkene isostere is described. Starting from N-Fmoc-O-(tert-butyl)tyrosine as N-terminal component, the E double bond was generated by a Julia-Kocieński olefination. An enantioselective aldol reaction wa

Full text of DOI:10.1055/s-2006-956456

LETTER
99
First Stereoselective Synthesis of a Tyr-Tyr E-Alkene Isostere
Synthesisof
a
Tyr
i
E
-
n
A
lkene Isost
a
ere G. Bandur, Klaus Harms, Ulrich Koert*
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße, 35043 Marburg, Germany
Fax +49(6421)2825677; E-mail: koert@chemie.uni-marburg.de
Received 21 August 2006
Herein we present a convergent synthesis of a Tyr-Tyr E-
alkene isostere that is already protected for an application
in SPPS. As an entrance to the synthesis a protected L-ty-
rosine derivative was chosen as a versatile chiral pool ma-
Abstract: A stereoselective synthesis of a tyrosine-tyrosine E-alk-
ene isostere is described. Starting from N-Fmoc-O-(tert-butyl)ty-
rosine as N-terminal component, the E double bond was generated
by a Julia–Kocieński olefination. An enantioselective aldol reaction
was applied to synthesize the required aldehyde. The configuration terial. A stereoselective aldol reaction using an Evans
auxiliary4 to introduce the second stereocenter and a
of the new stereocenter was determined by X-ray crystallography.
Julia–Kocieński olefination5 to generate the E double
bond were applied as key steps.
Key words: tyrosine, E-alkene, dipeptide isostere, aldol reaction,
Julia–Kocieński olefination
Starting point of the route to sulfone 4 was the com-
mercially available protected tyrosine derivative 1
(Scheme 1). For the Julia–Kocieński olefination a 1-phen-
yl-1H-tetrazolyl (PT) sulfonyl moiety was introduced.5
Therefore acid 1 was first converted into the correspond-
ing alcohol via reduction of an in situ generated mixed
carbonic acid anhydride with sodium borohydride. The
PT-thioether 2 was generated from the alcohol following
the Mitsunobu protocol. Since the Fmoc protecting group
turned out to be unstable towards the olefination condi-
tions it was replaced by the trifluoroacetyl (TFA) group.
Fmoc deprotection under standard conditions followed by
TFA protection of the free amine yielded thioether 3 that
was oxidized to the sulfone 4 with 3-chloroperoxybenzoic
acid (MCPBA).6
In the past twenty years, there has been a substantial inter-
est in the synthesis of dipeptide analogues for the back-
bone modification of peptides for several reasons. These
backbone modifications generally consist in the isosteric
or isoelectronic exchange of the amide unit in the peptide
chain, possibly combined with the introduction of addi-
tional functional groups. Since biodegradation is a great
limitation for the in vivo application of many peptides,
isosteric amide bond replacements are often used to stabi-
lize biologically active peptides towards enzymatic degra-
dation and they may also alter other pharmacokinetics in
a favorable manner.1 In addition, incorporation of amide
bond isosteres is a convenient way to elucidate the role of
selected amide bonds in receptor binding, as well as their
influence on the secondary structure of peptides.
O
O
In this context, dipeptide isosteres in which the amide
bond featuring the ability of serving both as a hydrogen-
bond donor and acceptor is replaced by an E-alkene,
which is incapable of hydrogen bonding, are well suited
replacements. This is because they show a high degree of
structural rigidity and therefore closely resemble the
amide bond with respect to bond lengths and angles.2
However, hitherto this concept has been rarely realized
particularly due to the difficulties associated with the ste-
reoselective synthesis of E-alkene isosteres. Though vari-
ous syntheses of E-alkene dipeptide isosters have been
published to date,3 most of them are limited to specific
amino acids and are lacking of general applicability. The
synthesis of such dipeptide isosteres consisting of amino
acids with functionalized side chains is an even greater
challenge since it requires a more complex protecting
group strategy especially if a specific protecting group
pattern is needed, e.g. for the incorporation in a peptide by
Fmoc-based solid-phase peptide synthesis (SPPS).
c, d
a, b
89%
Fmoc
S
74%
N
N
Fmoc
OH
N
N
H
N
H
N
O
Ph
1
2
O
O
e
O
O
TFA
S
TFA
S
87%
N
N
N
N
N
H
N
N
H
N
N
N
Ph
Ph
3
4
Scheme 1 Reagents and conditions: (a) i. ClCO2Et, NMM, THF,
–20 °C; ii. NaBH4, H2O, 0 °C; (b) PPh3, DIAD, PTSH, 0 °C to r.t.;
(c) piperidine, DMF; (d) TFAA, pyridine, CH2Cl2, 0 °C to r.t.; (e)
MCPBA, CH2Cl2, 0 °C to r.t.
For the synthesis of the aldehyde 8 (Scheme 2) acyloxazo-
lidinone 5 which was available from 3-(4-hydroxyphen-
yl)propionic acid7 was converted into the corresponding
titanium enolate and allowed to react with 1,3,5-trioxane8
as formaldehyde equivalent to the aldol adduct 6 with a
SYNLETT 2007, No. 1, pp 0099–0102
Advanced online publication: 20.12.2006
DOI: 10.1055/s-2006-956456; Art ID: G27806ST
© Georg Thieme Verlag Stuttgart · New York
0
4.
0
1.
2
0
0
7

100
N. G. Bandur et al.
LETTER
diastereoselectivity of >98:2.9,10 Transformation into the separation of E- and Z-isomer was also carried out on the
Weinreb amide in the presence of the free primary alcohol alcohol stage. The configuration of the double bond was
followed by THP protection furnished compound 7. After assigned by 1H NMR coupling constants.12 In order to in-
changing the protecting group on the phenol from a tert- troduce the N-Fmoc protecting group for solid-phase syn-
butyl(diphenyl)silyl ether to a tert-butyl ether, the Wein- thesis, the TFA amide was cleaved with K2CO3 in
reb amide was reduced to aldehyde 8.
MeOH–H2O followed by protection of the free amine us-
ing Fmoc-N-hydroxysuccinimide (FmocOSu). Oxidation
with iodobenzene diacetate (IBDA) and 2,2,6,6-tetra-
methyl-1-piperidinyloxy free radical (TEMPO) in the last
step furnished the b,g-unsaturated acid 11.13,14
O
O
O
O
HO
N
a
O
N
O
85%
Bn
TBDPSO
Bn
O
TBDPSO
O
5
6
a
O
O
b
TFA
N
OTHP
O
TFA
S
53%
92%
H
N
H
PT
THPO
O
THPO
N
b, c
d–f
68%
4
9
O
O
73%
(E/Z 2.3:1)
O
TBDPSO
O
O
7
8
O
Scheme 2 Reagents and conditions: (a) i. TiCl4, CH2Cl2, 0 °C; ii.
DIPEA; iii. 1,3,5-trioxane, TiCl4; (b) AlMe3, Me(MeO)NH·HCl,
CH2Cl2, –10 °C; (c) DHP, PPTS, CH2Cl2, 0 °C to r.t.; (d) TBAF,
AcOH, THF, 0 °C to r.t.; (e) t-BuOTCA, PPTS, CH2Cl2, 0 °C to r.t.;
(f) DIBAL-H, THF, –78 °C to –50 °C.
c–e
TFA
Fmoc
N
OH
N
OH
73%
H
H
O
O
10
11
Scheme 3 Reagents and conditions: (a) NaHMDS, DME, –78 °C,
then 8, –78 °C to r.t.; (b) p-TsOH, MeOH; (c) K2CO3, MeOH–H2O,
50 °C; (d) FmocOSu, NaHCO3, acetone, H2O, 0 °C to r.t.; (e) IBDA,
TEMPO, CH2Cl2.
Since the TBDPS-protected phenol 6 was not crystalline
the Me-protected derivative 6a was prepared and used to
obtain a crystal structure analysis in order to assign the
configuration of the aldol-adduct (Figure 1).11
In conclusion, a convergent method for the synthesis of E-
alkene dipeptide isosteres that is generally applicable also
for side-chain-functionalized amino acids was developed.
Tyr-Tyr isostere 11 was synthesized with a protecting
group pattern suitable for the use in Fmoc-based SPPS to-
wards the synthesis of corresponding peptide analogues.
Acknowledgment
This work was supported by the Deutsche Forschungsgemeinschaft
(Forschergruppe 475).
References and Notes
(1) Reviews on peptidomimetics: (a) Giannis, A.; Kolter, T.
Angew. Chem., Int. Ed. Engl. 1993, 32, 1244. (b) Gante, J.
Angew. Chem., Int. Ed. Engl. 1994, 33, 1699.
(c) Venkatesan, N.; Kim, B. H. Curr. Med. Chem. 2002, 9,
2243. (d) Tourwe, D. Synthesis of Peptides and
Peptidomimetics, In Methods of Organic Chemistry
(Houben-Weyl), Vol. E22c; Goodman, M.; Felix, A.;
Moroder, L.; Toniolo, C., Eds.; Thieme Verlag: Stuttgart,
New York, 2004.
Figure 1 Crystal structure analysis of 6a11
Now the stage was set for the Julia–Kocieński olefination
to connect the N-terminal sulfone 4 and the C-terminal al-
dehyde 8 (Scheme 3). To this end sulfone 4 was deproto-
nated with NaHMDS and upon addition of aldehyde 8 the
desired alkene 9 was formed with modest E/Z selectivity
of 2.3:1 determined by NMR after deprotection of the
THP acetal leading to alcohol 10.12 The chromatographic
(2) (a) Hann, M. M.; Sammes, P. G.; Kennewell, P. D.; Taylor,
J. B. J. Chem. Soc., Chem. Commun. 1980, 234. (b) Hann,
M. M.; Sammes, P. G.; Kennewell, P. D.; Taylor, J. B. J.
Chem. Soc., Perkin Trans. 1 1982, 307. (c) Kranz, M.;
Kessler, H. Tetrahedron Lett. 1996, 37, 5359.
Synlett 2007, No. 1, 99–102 © Thieme Stuttgart · New York

LETTER
Synthesis of a Tyr-Tyr E-Alkene Isostere
101
(3) For recent examples, see: (a) Otaka, A.; Katagiri, F.;
Kinoshita, T.; Odagaki, Y.; Oishi, S.; Tamamura, H.;
Hamanaka, N.; Fujii, N. J. Org. Chem. 2002, 67, 6152.
(b) Oishi, S.; Kamano, T.; Niida, A.; Odagaki, Y.;
H), 4.03 (dd, J = 9.1, 2.1 Hz, 1 H), 3.90–3.70 (m, 2 H), 3.83
(dd, J = 8.2, 8.2 Hz, 1 H), 3.23 (dd, J = 13.5, 3.3 Hz, 1 H),
2.86 (dd, J = 13.4, 7.6 Hz, 1 H), 2.76 (dd, J = 13.4, 5.3 Hz, 1
H), 2.73 (dd, J = 13.3, 3.7 Hz, 1 H), 2.26 (br s, 1 H), 1.08 (s,
9 H). 13C NMR (75 MHz, CDCl3): d = 175.5, 154.3, 153.2,
135.5 (4 C), 135.2, 133.0, 133.0, 132.9, 130.5, 129.9 (2 C),
129.8 (2 C), 129.5 (2 C), 128.9 (2 C), 127.7 (2 C), 127.4,
119.6 (2 C), 66.0, 63.0, 55.5, 47.1, 37.9, 34.0, 26.5 (3 C),
19.4. IR (KBr): n = 3506 (m, br), 3029 (w), 2930 (m), 2857
(m), 1780 (s), 1697 (s), 1510 (s), 1390 (m), 1350 (w), 1255
(s), 1210 (m), 1112 (m), 917 (m), 701 (s), 501 (m) cm–1.
HRMS (ESI): m/z calcd for C28H35NSiNaO4 [M + Na+]:
500.2228; found: 500.2229.
Hamanaka, N.; Yamamoto, M.; Ajito, K.; Tamamura, H.;
Otaka, A.; Fujii, N. J. Org. Chem. 2002, 67, 6162.
(c) Tamamura, H.; Hiramatsu, K.; Miyamoto, K.; Omagari,
A.; Oishi, S.; Nakashima, H.; Yamamoto, N.; Kuroda, Y.;
Nakagawa, T.; Otaka, A.; Fujii, N. Bioorg. Med. Chem. Lett.
2002, 12, 923. (d) Vasbinder, M. M.; Miller, S. J. J. Org.
Chem. 2002, 67, 6240. (e) Tamamura, H.; Koh, Y.; Ueda,
S.; Sasaki, Y.; Yamasaki, T.; Aoiki, M.; Maeda, K.; Watai,
Y.; Arikuni, H.; Otaka, A.; Mitsuya, H.; Fujii, N. J. Med.
Chem. 2003, 46, 1764. (f) Wang, X. J.; Hart, S. A.; Xu, B.;
Mason, M. D.; Goodell, J. R.; Etzkorn, F. A. J. Org. Chem.
2003, 68, 2343. (g) Garbe, D.; Sieber, S.; Bandur, N. G.;
Koert, U.; Marahiel, M. A. ChemBioChem 2004, 5, 1000.
(h) Wipf, P.; Xiao, J. Org. Lett. 2005, 7, 103. (i) Bandur, N.
G.; Harms, K.; Koert, U. Synlett 2005, 773. (j) Fu, Y.;
Bieschke, J.; Kelly, J. W. J. Am. Chem. Soc. 2005, 127,
15366. (k) Reginato, G.; Gaggini, F.; Mordini, A.; Valacchi,
M. Tetrahedron 2005, 61, 6791.
(9) No other stereoisomer was detected in the NMR spectra. For
the assignment of the stereochemistry of 6, see Figure 1.
(10) (a) Evans, D. A.; Urpi, F.; Somers, T. C.; Clark, J. S.;
Bilodeau, M. T. J. Am. Chem. Soc. 1990, 112, 8215.
(b) Takacs, J. M.; Jaber, M. R.; Vellekoop, A. S. J. Org.
Chem. 1998, 63, 2742.
(11) The crystal data of compound 6a has been deposited in the
Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC 616493. Crystal data: C21H23NO5,
M = 369.40, orthorhombic, P212121, a = 7.0200(4) Å,
b = 13.4213(10) Å, c = 19.5897(12) Å, a = 90°, b = 90°,
g = 90°, V = 1845.7(2) Å3, Z = 4, Dcalcd = 1.329 g/cm3,
16972 collected reflections, 3696 independent
(4) Gage, J. R.; Evans, D. A. Org. Synth. 1989, 68, 77.
(5) Blakemore, P. R.; Cole, W. J.; Kocieński, P. J.; Morley, A.
Synlett 1998, 26.
(6) Analytical Data of Sulfone 4.
Rf = 0.11 (cHex–TBME, 2:1); [a]D27 –9.1 (c 1.23, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.67–7.53 (m, 5 H), 7.11–
7.03 (m, 2 H), 6.99–6.89 (m, 3 H), 4.84–4.67 (m, 1 H), 4.13
(dd, J = 15.3, 9.1 Hz, 1 H), 3.97 (dd, J = 15.3, 3.6 Hz, 1 H),
3.11 (dd, J = 13.8, 7.0 Hz, 1 H), 3.04 (dd, J = 13.8, 6.8 Hz, 1
H), 1.33 (s, 9 H). 13C NMR (75 MHz, CDCl3): d = 156.8 (q,
J = 38 Hz), 155.1, 153.6, 131.7, 129.75 (2 C), 129.72 (2 C),
129.3, 125.1 (2 C), 124.6 (2 C), 78.8, 57.5, 47.5, 38.7, 28.8
(3 C). IR (film): n = 3323 (m), 2982 (m), 2932 (w), 1703 (s),
1559 (m), 1508 (m), 1354 (s), 1220 (m), 1156 (s), 899 (w),
879 (w), 764 (m), 689 (w), 639 (m), 522 (m) cm–1. HRMS
(ESI): m/z calcd for C22H24F3N5NaO4S [M + Na+]: 534.1393;
found: 534.1401.
(Rint = 0.0390), R1 = 0.0265, wR2 = 0.0686 (all data).
(12) Preparation of Compound 9.
A solution of sulfone 4 (0.17 mmol, 85 mg) in 1,2-
dimethoxyethane (DME, 1 mL) was cooled to –78 °C and
NaHMDS (2 M in THF, 0.37 mmol, 0.18 mL) was added.
The resulting yellow solution was stirred at –78 °C for 30
min and aldehyde 8 dissolved in DME (0.5 mL) was added.
The solution allowed to warm to r.t. overnight. Then
phosphate buffer (1 M, 2 mL) and TBME (4 mL) were
added. After the layers were separated the aqueous layer was
extracted with additional TBME (3 × 4 mL). The combined
organic extracts were dried with Na2SO4 and after
evaporation of solvents the residue was purified by flash
column chromatography (8 g, TBME–pentane, 1:10)
followed by a second chromatography (8 g, acetone–
pentane, 1:10). The pure product 9 was obtained as a
colorless oil. The determination of the E/Z selectivity of
2.3:1 and the separation of the isomers was done after THP
deprotection affording compound 10.
(7) Compound 5 was prepared from 3-(4-hydroxyphenyl)prop-
ionic acid by the following sequence: 1. i. BnCl, KI, K2CO3,
acetone, reflux, 2 d; ii. NaOH, H2O, reflux, 2 d, 80%; 2. i.
PvCl, TEA, –20 °C, 2 h; ii. (R)-4-benzyl-1,3-oxazolidin-2-
one, LiCl, 12 h, r.t., 91%; 3. Pd(OH)2/C, H2 (1 atm), MeOH–
EtOAc (1:1), 3 h, 99%; 4. TBDPSCl, imidazole, DMF, 0 °C
to r.t., 12 h, 89%.
E-Isomer: Rf = 0.41 (c-Hex–EtOAc, 1:1); [a]D25 –31.2 (c
1.06, CHCl3). 1H NMR (300 MHz, CDCl3): d = 7.05–6.84
(m, 8 H), 6.23 (br d, J = 7.2 Hz, 1 H), 5.33 (dd, J = 15.2, 7.3
Hz, 1 H), 5.25 (dd, J = 15.4, 7.3 Hz, 1 H), 4.59 (ddd,
J = 13.8, 7.0, 6.8 Hz, 1 H), 3.51 (dd, J = 10.6, 4.6 Hz, 1 H),
3.34 (dd, J = 10.3, 7.3 Hz, 1 H), 2.80 (dd, J = 13.6, 6.4 Hz, 1
H), 2.75 (dd, J = 13.0, 7.7 Hz, 1 H), 2.64 (dd, J = 12.9, 5.8
Hz, 1 H), 2.54–2.34 (m, 1 H), 2.49 (dd, J = 12.7, 8.0 Hz, 1
H), 1.67 (br s, 1 H), 1.32 (s, 9 H), 1.31 (s, 9 H). 13C NMR (75
MHz, CDCl3): d = 156.3 (q, J = 37 Hz), 154.5, 153.7, 134.6,
134.1, 131.0, 129.9, 129.7 (2 C), 129.5 (2 C), 124.3 (2 C),
124.0 (2 C), 117.7, 78.5, 78.2, 64.9, 53.2, 47.1, 40.1, 36.7,
28.82 (3 C), 28.80 (3 C). HRMS (ESI): m/z calcd for
C29H38F3NNaO4 [M + Na+]: 544.2645; found: 544.2655.
Z-Isomer: Rf = 0.42 (c-Hex–EtOAc, 1:1); [a]D24 +25.2 (c
1.04, CHCl3). 1H NMR (300 MHz, CDCl3): d = 7.07–6.82
(m, 8 H), 6.39 (br d, J = 6.0 Hz, 1 H), 5.41 (dd, J = 10.8, 10.4
Hz, 1 H), 5.31 (dd, J = 10.8, 9.0 Hz, 1 H), 4.59 (ddd,
J = 14.4, 7.9, 7.0 Hz, 1 H, 5-H), 3.70 (dd, J = 10.5, 4.4 Hz, 1
H), 3.41 (dd, J = 10.1, 9.5 Hz, 1 H), 3.06–2.92 (m, 1 H), 2.63
(dd, J = 13.4, 5.1 Hz, 1 H), 2.37 (dd, J = 13.9, 7.3 Hz, 1 H),
2.30 (dd, J = 13.9, 6.0 Hz, 1 H), 2.25 (dd, J = 13.5, 9.2 Hz,
(8) Preparation of Compound 6.
A solution of 5 (7.02 mmol, 3.96 g) in CH2Cl2 (40 mL) was
cooled to 0 °C and TiCl4 (7.72 mmol, 0.85 mL) was added
dropwise. After 5 min, diisopropylethyl amine (DIPEA, 8.01
mmol, 1.4 mL) was added whereupon the solution turned
dark purple. After the mixture was stirred at 0 °C for 1 h a
solution of 1,3,5-trioxane (8.01 mmol, 0.72 g) in CH2Cl2 (5
mL) was added, followed by TiCl4 (7.37 mmol, 0.81 mL).
The mixture was stirred for 3 h at 0–10 °C. Then, sat. NH4Cl
solution (50 mL) was added and the layers were separated.
After extraction with additional CH2Cl2 (3 × 50 mL) the
organic layers were pooled and washed subsequently with
H2O (2 × 25 mL) and brine (50 mL). After drying with
Na2SO4 and evaporation of solvents the residue was purified
by flash column chromatography on silica (300 g, TBME–
pentane 1:2 to 1:1) to give compound 6 as a colorless oil
(5.97 mmol, 3.55 g, 85%). Rf = 0.37 (c-Hex–EtOAc, 1:1);
[a]D24 –75.0 (c 0.98, CHCl3). 1H NMR (300 MHz, CDCl3):
d = 7.74–7.65 (m, 4 H), 7.43–7.26 (m, 9 H), 7.24–7.16 (m, 2
H), 6.96 (pd, J = 8.5 Hz, 2 H), 6.67 (pd, J = 8.5 Hz, 2 H),
4.44 (dddd, J = 9.4, 7.6, 3.5, 2.1 Hz, 1 H), 4.26–4.13 (m, 1
Synlett 2007, No. 1, 99–102 © Thieme Stuttgart · New York

102
N. G. Bandur et al.
LETTER
1 H), 1.70 (br s, 1 H), 1.29 (s, 9 H), 1.23 (s, 9 H). 13C NMR
(75 MHz, CDCl3): d = 156.8 (q, J = 37 Hz), 154.6, 153.7,
135.1, 134.3, 130.3, 129.7, 129.6 (2 C), 129.5 (2 C), 124.4
(2 C), 124.0 (2 C), 117.5, 78.5, 78.2, 65.9, 49.3, 43.8, 39.4,
37.2, 28.8 (3 C), 28.7 (3 C). HRMS (ESI): m/z calcd for
C29H38F3NNaO4 [M + Na+]: 544.2645; found: 544.2651.
6.83 (pd, J = 8.5 Hz, 2 H), 6.78 (pd, J = 8.5 Hz, 2 H), 5.57–
5.42 (m, 2 H), 4.28–4.17 (m, 2 H), 4.15–4.07 (m, 1 H), 4.14
(t, J = 6.8 Hz), 3.17–3.06 (m, 1 H), 2.90 (dd, J = 13.7, 7.6
Hz, 1 H), 2.69–2.57 (m, 3 H), 1.26 (s, 9 H), 1.22 (s, 9 H). 13C
NMR (500 MHz, 343 K, DMSO-d6): d = 177.4, 153.2, 153.1
(2 C), 143.61, 143.59, 140.4 (2 C), 133.1, 132.64, 132.58,
129.3 (2 C), 129.1 (2 C), 127.3, 127.1 (2 C), 126.6 (2 C),
124.7 (2 C), 122.7 (2 C), 122.6 (2 C), 119.6 (2 C), 77.2, 77.1,
65.1, 53.6, 49.6, 46.5, 37.0, 28.28 (3 C), 28.26 (3 C); one
benzylic carbon atom was not observed because of a
superposition with the DMSO-d6 signal. HRMS (ESI):
m/z calcd for C42H47NNaO6 [M + Na+]: 684.3296; found:
684.3313.
(13) De Mico, A.; Margarita, R.; Parlani, L.; Vescovi, A.;
Piancatelli, G. J. Org. Chem. 1997, 62, 6974.
(14) Analytical Data of Compound 11.
Rf = 0.24 (c-Hex–EtOAc, 1:1); [a]D19 –30.7 (c 0.32, CHCl3).
1H NMR (500 MHz, 343 K, DMSO-d6): d = 11.98 (br s,
1 H), 7.85 (pd, J = 7.6 Hz, 2 H), 7.63 (pd, J = 7.6 Hz, 2 H),
7.40 (pt, J = 7.4 Hz, 2 H), 7.31 (pt, J = 7.4 Hz, 2 H), 7.25–
7.11 (m, 1 H), 7.05 (pd, J = 8.3 Hz, 2 H), 7.03–6.97 (m, 2 H),
Synlett 2007, No. 1, 99–102 © Thieme Stuttgart · New York

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