Aminomethylation of chiral silyl enol ethers: access to β2-homotryptophane and β2-homolysine derivatives

Article abstract of DOI:10.1016/j.tetlet.2008.05.131

We describe here the aminomethylation of chiral silyl enol ether derivatives using iminium ion. The choice of judicious precursors with adequate protecting groups for the silylation/aminomethylation step was required to achieve the synthesis of β²-homotryptophane in few steps. The same methodology was used to prepare a β²-homolysine derivative.

Full text of DOI:10.1016/j.tetlet.2008.05.131

Tetrahedron Letters 49 (2008) 4704–4707
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Aminomethylation of chiral silyl enol ethers: access to
b2-homotryptophane and b2-homolysine derivatives
*
Roba Moumné, Maud Larregola, Youcef Boutadla, Solange Lavielle, Philippe Karoyan
Université Pierre et Marie Curie-Paris 6, Institut de Chimie Moléculaire FR 2769, UMR-CNRS 7613 Synthèse, Structure et Fonction des Molécules Bioactives case 45,
4 place jussieu 75252 Paris cedex 05, France
a r t i c l e i n f o
a b s t r a c t
Article history:
We describe here the aminomethylation of chiral silyl enol ether derivatives using iminium ion. The
choice of judicious precursors with adequate protecting groups for the silylation/aminomethylation step
was required to achieve the synthesis of b2-homotryptophane in few steps. The same methodology was
used to prepare a b2-homolysine derivative.
Received 4 May 2008
Revised 26 May 2008
Accepted 28 May 2008
Available online 3 June 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
b2-Amino acids
Aminomethylation
Chiral silyl enol ether derivatives
Iminium ion
1. Introduction
scale-up. Anyway, there is still a need for methodologies allowing
access to functionalized compounds and easy to scale up.
The development of scalable syntheses of b-amino acids deriva-
We recently reported our preliminary results on the homolo-
tives is an important challenge since these homologues of
a
-amino
gation of a
-amino acids to b2-amino acids via a Reformatsky
acids have relevant roles in medicinal chemistry.1 Moreover, pio-
neering work by Seebach et al.2 and Gellman et al.3 has demon-
strated the folding propensity of oligomers of these compounds,
leading to secondary and tertiary structures very similar to that of
type reaction using highly reactive preformed iminium ions9 as
aminomethylating agents10 (Scheme 1).
We have shown that the mild conditions required for this reac-
tion allow its application to the preparation of some orthogonally
protected functionalized b2-amino acids. Though, if this methodo-
logy is efficient for the preparation of racemic compounds, the
application to asymmetric synthesis by use of chiral auxiliaries is
very limited as only amino acids bearing high steric hindrance on
their side chains gave good diastereoselectivities. The best de were
observed with Oppolzer’s sultam as chiral auxiliary in this reaction.
Anyway the replacement of zinc enolates by silyl enol ethers in the
aminomethylation step11 allowed the preparation of various enan-
tiomerically pure b2-amino acids by this method12 (Scheme 2).
Herein, we report the application of this methodology to sub-
strates bearing functional group on their side chains through the
synthesis of optically pure b2-homotryptophane and b2-homoly-
sine derivatives, representing two examples of various functional
substitutions.
a
-peptides, hence these are considered as excellent peptidomimet-
ics.4 One will distinguish between b2- and b3-amino acids regarding
the position of the side chain on the b-amino acid skeleton. b3-Ami-
no acids are readily available in enantiomerically pure form by
homologation strategies of
catalytic homologation of
a
-amino acids. For instance, a recent
a
-amino acids via the carbonylation of
enantiopure oxazolines using a silylcobalt precatalyst has been
reported by Coates et al.5 However the methodology describes only
the synthesis of non-functionalized b3-amino acids, that is, bearing
alkyl or phenyl chains. Noticeably, the Arndt–Eistert homologation
of a
-amino acids allows in few steps the preparation of b3-amino
acids bearing functional groups on their side chains.6 The prepara-
tion of b2-amino acids is much more challenging and many useful
strategies are reported for the synthesis of these compounds, allow-
ing access to b2-amino acids bearing trivial7 or functionalized8 side
chains. Traditionally, these syntheses involve low temperature
reaction (ꢀ30 °C to ꢀ78 °C), which can make them difficult to
2. Synthesis of b2-homotryptophane derivative
The synthesis of b2-homotryptophane was first reported by See-
bach et al. in 2002.13 Initially, a route involving a Curtius-degrada-
tion step was described, allowing the preparation of the compound
* Corresponding author. Tel.: +33 (1) 44273842; fax: +33 (1) 44273843.
E-mail address: philippe.karoyan@upmc.fr (P. Karoyan).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.05.131

R. Moumné et al. / Tetrahedron Letters 49 (2008) 4704–4707
4705
NaNO2, "H+"
1/ Zn
H2N
CO2H
Br
CO2R'
2/
CH2 NBn2
CF3CO2
-
R
R
R'=H
R'=Me
α-amino acids
CO2Me
CO2H
Bn2N
BocHN
R
R
β2-amino acids
R= Me, Bn, i Bu, CH2CO2t Bu
Scheme 1. Synthesis of b2-amino acids by Reformatsky reaction using iminium trifluoroacetate salt.
CH2 NBn2
CF3CO2
TMSOTf
NEt3
R
-
S*
N
Bn2N
S*
R
R
S
O
OTMS
O
O
O
Scheme 2. Addition of chiral silyl ketene N,O-acetals on in situ generated iminium salt.
optically active in eleven steps. More recently, the failure of strat-
egies involving aminomethylation reaction for the synthesis of
b2-homotryptophane led the group of Seebach to propose an alter-
native route consisting of an aldol addition (with a 90/10 de)
followed by a deoxygenation step.8 The title compound was
obtained in nine steps.
chain of the amino acid, leading to good yields and diastereoselec-
tivities for the aminomethylation key step. In this synthesis, strong
Lewis acids were required to activate the poorly reactive ami-
nomethylating reagent, implying the use of robust protective
group, which needs to be removed and replaced by a more suitable
protecting group for solid phase peptide synthesis. This highly
lengthens the synthesis, and 11 linear steps were required for
the preparation of b2-homolysine. Gellman et al. reported the syn-
thesis of the b2-homolysine by Michael addition of a chiral amine
on an acrylate, providing a mixture of diastereoisomers that need
to be separated by chromatography.16 Recently, the same group re-
ported an organocatalytic aminomethylation reaction as a new
route to b2-amino acids.17 In the reported methodology, good
yields and selectivities are obtained when amino acids with hydro-
carbonic side chains are involved. However, if the selectivity re-
mains high in the case of functionalized b2-amino acids, such as
b2-homolysine, a drop of the yield is observed. Consequently, none
of these strategies appears to be efficient for the multi gram syn-
thesis of the target compounds.
In a first attempt to apply our strategy to the synthesis of b2-
homotryptophane, the camphorsultam was introduced on the
commercially available 3-indolylpropanoic acid 1. The obtained
compound 2 bearing no protection on the indole moiety was tested
toward aminomethylation conditions (Scheme 3).
However, compound 2 failed to react with the iminium salt and
only the starting material was isolated from the reaction mixture.
Noticeably, we previously observed that a red coloration appears
through the formation of silyl enol ether derivatives. This red col-
oration was not observed in silylation attempts involving com-
pound 2, suggesting that silylation did not occurred. As it seemed
necessary to protect the indole ring, we firstly investigated the
use of formate as protecting group and compound 3 was prepared
from alkanoylsultam 2. But again, the red coloration was not ob-
served during silylation attempts and as expected, the aminome-
thylation failed. The protection of the indole moiety was yet
considered using a benzyl group on the nitrogen of 3-indolylprop-
anoic acid 1 leading to compound 4. After introduction of Oppol-
zer’s Sultam, compound 5 was obtained and engaged in the
silylation/aminomethylation reaction. In that case, although the
red coloration was observed, only partial conversion occurred, giv-
ing the b2-homotryptophane derivative 6 in a poor yield of 26%, the
major product being the starting material. Fortunately, increasing
the amount of TMSTf to 2 equiv allowed to rise up the conversion
and compound 6 was obtained in a good yield of 88% as a single
diastereoisomer (NMR analysis) (Scheme 3).
Different precursors that might give a straightforward access to
the targeted compound 16 were tested under our aminomethyla-
tion conditions. The simplest way would be in principle to start
from a compound that already contains the suitably protected
amine, in the aim of avoiding any replacement of protective group.
Thus, we investigated the synthesis starting from the commercially
available 6-amino hexanoic acid 9. The crucial choice of the pro-
tecting group on the e-amino function appears to be quite tricky
as this one has to be stable toward the Lewis acid conditions re-
quired for the aminomethylation step and orthogonal to the re-
moval of both the chiral auxiliary and the dibenzyl moiety. Thus,
the amine function of compound 9 was protected as Boc-carba-
mate 10 and after introduction of the chiral auxiliary, compound
11 was engaged in the aminomethylation process. However, the
reaction was unsuccessful as only deprotection of the amine moi-
ety was observed (Scheme 4).
Finally, deprotection of the dibenzylamine moiety was carried
out by hydrogenolysis catalysed by Pd(OH)2 on charcoal. After re-
moval of the Sultam by saponification and Boc-protection, the in-
dole’s nitrogen of compound 7 was deprotected under Birch
conditions. Thus, N-Boc-b2-homotryptophane 8 was obtained in
seven steps in 24% overall yield.14
We thereof decided to use for the aminomethylation step a
precursor of amine function that can be transformed later in the
synthesis (Scheme 5).
The synthesis was thus considered by aminomethylation of
derivative 14 bearing an amine masked as an azido group. This
compound was prepared starting from the commercially available
6-bromohexanoic acyl chloride 12, after introduction of the chiral
auxiliary and nucleophilic substitution of the halogeno compound
13. However, no reaction occurred in that case and the starting
3. Synthesis of b2-homolysine derivative
The synthesis of b2-homolysine was reported for the first time
by Seebach et al. in 2001.15 The reported methodology is based
on aminomethylation of a chiral compound that bears the side

4706
R. Moumné et al. / Tetrahedron Letters 49 (2008) 4704–4707
1/ iBuOCOCl, NMM
DME, -15 °C
2/ Sultam sodium salt
O
O
N
OH
83%
S
O
O
N
N
1
R
2
3
R
1/ NaH (2eq)
DMF, 0 °C
2/ PhCH2Br
75%
HCO2H, Δ
78%
4
1/ iBuOCOCl, NMM
1 : R = H
2 : R = H
3 : R = -CHO
4 : R = -Bn
DME, -15 °C
70%
2/ (+) Sultam sodium
salt
1/ TMSOTf, NEt3
2/ CH2=NBn2CF3CO2
3/ TBAF
O
O
N
Bn2N
N
N
S
S
88%
O
O
O
O
N
Bn
Bn
5
6
1/ H2, Pd(OH)2/C, THF-MeOH
2/ LiOH, MeCN-H2O
65%
3/ Boc2O, LiOH, H2O-dioxane
O
O
Na, NH3
BocHN
N
OH
BocHN
OH
THF, -50 °C
81%
N
H
8
Bn
7
Scheme 3. Synthesis of N-Boc-b2-homotryptophane.
Boc2O, K2CO3
dioxane-H2O
O
O
Sultam
(sodium salt)
DME
NaN3, DMF
O
O
BocHN
H2N
73%
OH
10
93%
OH
R
R
N
S
Cl
9
82%
12
O
1/ iBuOCOCl, NMM
DME, -15 °C
2/ Sultam sodium salt
13
14
O
1/ TMSOTf, NEt3, DCM
2/ CH2=NBn2CF3CO2, DCM
3/ TBAF
77%
76%
O
N
12 : R = Br
13 : R = Br
O
HN(Boc)2,NaH
DMF
14 : R = -N3
BocHN
11
S
Bn2N
N
15 : R = -Br
O
O
16 : R = -N(Boc)2
68%
S
O
R
O
Scheme 4. Attempt to prepare b2-homolysine from 6-amino hexanoic acid.
16
15
Scheme 5. Synthesis of b2-homolysine derivative 16.
material was recovered. Again, this was expected since the red col-
oration of the reaction mixture was not observed. Fortunately,
when the reaction was carried out with the bromo derivative 13,
the corresponding aminomethylated compound 15 was obtained
in a good yield of 76% as a single diastereoisomer. Substitution of
the brome by the commercially available di-tert-butyl iminodi-
carboxylate gives access in three steps to the expected b2-homoly-
sine skeleton 16.18
a versatile methodology for the preparation of b2-amino acids
derivatives. Noticeably, low temperatures are avoided and multi-
gram scale syntheses are easily feasible.
Acknowledgment
Roba Moumné is grateful to Senn Chemicals for the financial
support of her PhD thesis.
In conclusion, the aminomethylation of chiral silyl enol ethers
with the very reactive dibenzylidene iminium ion appeared to be

R. Moumné et al. / Tetrahedron Letters 49 (2008) 4704–4707
4707
J = 6.3 Hz, 1H); 3.45 (d, J = 13.9 Hz, 1H); 3.42 (d, J = 13.9 Hz, 1H); 3.06–3.19 (m,
4H); 2.03–2.05 (m, 2H); 1.81–1.87 (m, 3H); 1.29–1.39 (m, 2H); 1.05 (s, 3H);
0.92 (s, 3H); 13C NMR (100 MHz, CDCl3): d 171.5; 137.7; 136.6; 128.7; 127.9;
127.4; 126.7; 125.8; 121.7; 119.1; 119.0; 113.8; 109.5; 65.2; 52.9; 49.8; 48.4;
47.7; 44.6; 38.5; 36.1; 32.8; 26.4; 20.7; 20.2; 19.8. Anal. Calcd for C28H32N2O3S:
C, 70.56; H, 6.77; N, 5.88. Found: C, 70.31; H, 6.98; N, 5.67. (1R)-N-(2-
Dibenzylaminomethyl-3-N-benzylindoyl propanoyl) camphorsultam 6: Rf (Cy/AE,
References and notes
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In Enantioselective Synthesis of b-Amino acids; Juaristi, E., Ed.; Wiley-VCH: New
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Beck, A. K.; Bierbaum, D. J. Chem. Biodiv. 2004, 1, 1111; For recent example in
medicinal chemistry see: Lukaszuk, A.; Demaegdt, H.; Szemenyei, E.; Tóth, G.;
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Tourwé, D. J. Med. Chem. 2008, 51, 2291.
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3. Horne, W. S.; Price, J. L.; Keck, J. L.; Gellman, S. H. J. Am. Chem. Soc. 2007, 129,
4178. and references cited therein.
4. For recent examples see: Lukaszuk, A.; Demaegdt, H.; Szemenyei, E.; Tóth, G.;
Tymecka, D.; Misicka, A.; Karoyan, Ph.; Vanderheyden, P.; Vauquelin, G.;
Tourwé, D. J. Med. Chem. 2008, 51, 2291; Petersson, E. J.; Schepartz, A. J. Am.
Chem. Soc. 2008, 130, 821; Schmitt, M. A.; Weisblum, B.; Gellman, S. H. J. Am.
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Gellman, S. H. J. Am. Chem. Soc. 2007, 129, 139; Kritzer, J. A.; Stephens, O. M.;
Guarracino, D. A.; Reznik, S. K.; Schepartz, A. Bioorg. Med. Chem. 2005, 13, 11;
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Am. Chem. Soc. 2005, 127, 13126.
8/2) 0.35; mp 80–81 °C; ½a D20
ꢁ
25 (c 1. CHCl3); 1H NMR (400 MHz, CDCl3): d
7.78–7.80 (m, 1H); 7.09–7.34 (m, 16H); 6.99–7.01 (m, 2H); 6.85 (s, 1H); 5.20 (s,
2H); 3.88 (m, 2H); 3.42–3.52 (m, 6H); 3.21 (dd, J = 14.4 Hz, 3.8 Hz, 1H); 2.94
(dd, J = 12.4 Hz, 10.3 Hz, 1H); 2.86 (dd, J = 14.4 Hz, 9.1 Hz, 1H); 2.56 (dd,
J = 12.6 Hz, 4.5 Hz, 1H); 2.06–2.15 (m, 2H); 1.85–1.87 (m, 3H); 1.30–1.37 (m,
2H); 1.23 (s, 3H); 0.96 (s, 3H); 13C NMR (100 MHz, CDCl3): d 174.7; 138.7;
137.9; 136.6; 129.1; 128.6; 128.4; 127.9; 127.0; 126.7; 126.6; 121.6; 119.6;
112.4; 109.4; 65.4; 57.5; 55.8; 53.2; 49.8; 48.3; 47.7; 44.7; 38.6; 32.8; 26.5;
25.8; 21.0; 19.9. Anal. Calcd for C43H47N3O3S: C, 75.29; H, 6.91; N, 6.13. Found:
C, 75.45; H, 7.20; N, 5.81. (R)-(N-tert-butyloxycarbonylaminomethyl)-3-N-
benzylindolylpropanoic acid 7: 1H NMR (400 MHz, CDCl3): d 7.62–6.98 (m,
10H); 6.62 (br, 0.5H); 5.27 (s, 2H); 4.96 (br, 0.5H); 3.43–3.30 (m, 2H); 3.21–
2.84 (m, 3H); 1.43 and 1.25 (2s, 9H); 13C NMR (100 MHz, CDCl3): d 179.95;
178.65; 158.16; 156.08; 137.73; 136.85; 136.66; 129.17; 128.85; 128.36;
128.14; 127.99; 127.64; 127.07; 126.76; 126.61; 125.43; 121.99; 119.34;
118.96; 111.69; 111.42; 109.92; 81.10; 79.70; 50.00; 46.81; 46.56; 42.67;
41.35; 28.49; 28.16; 25.78; 25.21. MS: calcd for C24H29N2O4 [M+H] 409, found
409. (R)-(N-tert-Butyl oxycarbonylaminomethyl)-3-indoyl-propanoic acid 8:
5. Byrne, C. M.; Church, T. L.; Kramer, J. W.; Coates, G. W. Angew. Chem., Int. Ed.
2008, 47, 1.
6. Ellmerer-Müller, E. P.; Brössner, D.; Maslouh, N.; Tako, A. Helv. Chim. Acta 1998,
81, 59.
mp 56 °C; ½a 2D0
ꢁ
8.5 (c 1, CHCl3); 1H NMR (400 MHz, CDCl3): d 8.02 (br, 1H); 7.61–
7.04 (m, 5H); 6.47 (br, 0.5H); 4.99 (br, 0.5H); 3.43–3.34 (m, 2H); 3.21–2.86 (m,
3H); 1.44 and 1.28 (2s, 9H); 13C NMR (100 MHz, CDCl3): d 179.91; 178.86;
158.06; 156.26; 136.43; 136.28; 129.17; 128.36; 127.40; 125.43; 122.97;
122.55; 122.08; 119.50; 118.64; 112.32; 112.03; 111.38; 81.21; 79.88; 46.76;
46.43; 42.70; 41.29; 28.51; 28.20; 25.65; 25.15. MS: calcd for C17H23N2O4
[M+H] 319, found 319.
7. Juaristi, E.; Soloshonok, V. A. In Enantioselective Synthesis of Beta-Amino Acids,
2nd ed.; John Wiley & Sons, 2005; Lelais, G.; Seebach, D. Biopolymers (Peptides
Science) 2004, 76, 206; For examples, of syntheses of b2-amino acids bearing
hydrocarbonic side chains see: Juaristi, E.; Quintana, D.; Lamatsch, B.; Seebach,
D. J. Org. Chem. 1991, 56, 2553; Juaristi, E.; Quintana, D.; Balderas, M.; Garcia-
Perez, E. Tetrahedron: Asymmetry 1996, 7, 2233; Seebach, D.; Boog, A.;
Schweizer, W. B. Eur. J. Org. Chem. 1999, 335; Ponsinet, R.; Chassaing, G.;
Vaissermann, J.; Lavielle, S. Eur. J. Org. Chem. 2000, 83; Gutiérez-Garcia, V. M.;
Reyes-Rangel, G.; Lopez-Ruiz, H.; Juaristi, E. Tetrahedron 2001, 57, 6487;
Nagula, G.; Huber, V. J.; Lum, C.; Goodman, B. A. Org. Lett. 2000, 2, 3527; Bedow,
J. E.; Davies, S. G.; Smith, A. D.; Russel, A. J. J. Chem. Soc., Chem. Comm. 2004,
2778; Rimkus, A.; Sewald, N. Org. Lett. 2003, 5, 79; Eilitz, U.; Lessmann, F.;
Seidelmann, O.; Wendisch, V. Tetrahedron: Asymmetry 2003, 14, 189; Dursma,
A.; Minard, A. J.; Feringa, B. L. J. Am. Chem. Soc. 2003, 125, 3700; Bower, J. F.;
Williams, J. M. J. Synlett 1996, 685; Bower, J. F.; Jumnah, R.; Williams, J. M. J. J.
Chem. Soc., Perkin Trans. 1 1997, 1411; Davies, H. M. L.; Venkataramani, C.
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2005, 88, 2235.
9. Millot, N.; Piazza, C.; Avolio, S.; Knochel, P. Synthesis 2000, 7, 941.
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15. Gademann, K.; Ernst, M.; Seebach, D. J. Med. Chem. 2001, 44, 2460; Gessier, F.;
Schaeffer, L.; Kimmerlin, T.; Flögel, O.; Seebach, D. Helv. Chim. Acta 2005, 88,
2235.
16. Lee, H. S.; Park, J. S.; Kim, B. M.; Gellman, S. H. J. Org. Chem. 2003, 68,
1575.
17. Chi, Y.; Gellman, S. H. J. Am. Chem. Soc. 2006, 128, 6804; Chi, Y.; English, E. P.;
Pomerantz, W. C.; Horne, W. S.; Joyce, L. A.; Alexander, L. R.; Fleming, W. S.;
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18. (1R)N-(6-Bromohexanoyl) camphorsultam 13: Rf (Cy/AE: 8/2) 0.49; mp 54–
55 °C; ½a 2D0
ꢁ
88 (c 1, CHCl3); 1H NMR (400 MHz, CDCl3): d 3.86 (dd, 1H, J = 7.4 Hz,
5.3 Hz); 3.50 (d, J = 13.6 Hz, 1H); 3.43 (d, J = 13.6 Hz, 1H); 3.40 (t, 2H,
J = 6.8 Hz); 2.71–2.75 (m, 2H); 2.04–2.12 (m, 2H); 1.85–1.92 (m, 5H); 1.65–
1.74 (m, 2H); 1.33–1.53 (m, 4H); 1.15 (s, 3H); 0.97 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 171.6; 65.2; 52.9; 48.4; 47.7; 44.6; 38.5; 35.1; 33.5; 32.8; 32.4; 27.5;
26.4; 23.5; 20.8; 19.9; Anal. Calcd for C16H26NO4SBr: C, 48.98; H, 6.68; N, 3.57.
Found: C, 48.93; H, 6.75; N, 3.57. (1R)N-(2-dibenzyl amino methyl 6-bromo
hexanoyl) camphorsultam 15: Rf (Cy/AE, 8/2) 0.47; mp 90 °C; ½a D20
ꢁ
57 (c 1,
CHCl3); 1H NMR (400 MHz, CDCl3): d 7.20–7.40 (m, 10H); 3.87 (dd, J = 7.3 Hz,
J = 5.3 Hz, 1H); 3.68 (d, J = 13.6 Hz, 2H); 3.51 (d, J = 13.9 Hz, 1H); 3.47 (d,
J = 13.6 Hz, 2H); 3.43 (d, J = 13.9 Hz, 1H); 3.31–3.37 (m, 3H); 2.77 (dd,
J = 12.6 Hz, 6.6 Hz 1H); 2.52 (dd, J = 12.6 Hz, 7.3 Hz, 1H); 2.03–2.07 (m, 2H);
1.86–1.90 (m, 3H); 1.77–1.81 (m, 2H); 1.56–1.60 (m, 2H); 1.33–1.42 (m, 4H);
1.21 (s, 3H); 0.97 (s, 3H); 13C NMR (100 MHz, CDCl3): d 174.4; 139.0; 129.0;
128.1; 126.9; 65.4; 58.2; 56.3; 53.2; 48.2; 47.7; 44.6; 44.0; 38.5; 33.5; 32.9;
32.8; 28.9; 26.4; 25.7; 21.0; 19.9; ESI+: [MH+] = 603. (1R)N-[2-dibenzyl
aminomethyl-6-N,N-di-(tert-Butyloxycarbonyl) amino hexanoyl] camphorsultam
13. Micuch, P.; Seebach, D. Helv. Chim. Acta 2002, 85, 1567.
14. (N-benzylindoyl) propanoic acid 4: Rf (Cy/AE: 8/2) 0.25; mp 117 °C; 1H NMR
(400 MHz, CDCl3):
d 7.60 (d, J = 7.6 Hz, 1H); 7.22–7.29 (m, 5H); 7.17 (t,
16: Rf (Cy/AE, 8/2) 0.44; ½a D20
ꢁ
40 (c 1, CHCl3); 1H NMR (250 MHz, CDCl3): d
J = 7.1 Hz, 1H); 7.11 (t, J = 7.6 Hz, 1H); 7.07 (d, J = 7.1 Hz, 1H); 6.93 (s, J = 1H);
5.24 (s, 2H); 3.71 (t, J = 7.6 Hz, 2H); 2.76 (t, J = 7.6 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d 179.5; 137.6; 136.7; 128.7; 127.7; 127.5; 126.7; 125.6; 121.9; 119.1;
118.8; 113.8; 109.7; 49.9; 34.8; 20.4. Anal. Calcd for C18H17NO2: C, 77.40; H,
6.13; N, 5.01. Found: C, 77.12; H, 6.37; N, 4.89. (1R)N-3-(N-
benzylindoylpropanoyl) camphorsultam 5: Rf (Cy/AE/NEt3: 8/2/0.1) 0.42; mp
7.18–7.32 (m, 10H); 3.86 (dd, J = 7.5 Hz, 5.0 Hz, 1H); 3.36–3.65 (m, 8H); 2.79
(dd, J = 12.5 Hz, 7.5 Hz, 1H); 2.52 (dd, J = 12.5 Hz, 5.0 Hz, 1H); 2.03–2.06 (m,
2H); 1.86–1.89 (m, 3H); 1.25–1.63 (m, 22H); 1.22 (m, 5H); 0.96 (s, 3H); 13C
NMR (62.5 MHz, CDCl3): d 174.5; 152.6; 129.1; 128.1; 126.9; 82; 65.4; 58.1;
56.5; 53.3; 48.2; 47.8; 46.4; 44.7; 38.6; 33; 29.9; 29.3; 28.1; 26.5; 24.6; 21.1;
20. Anal. Calcd for C41H59N3O7S: C, 66.73; H, 8.06; N, 5.69. Found: C, 67.10; H,
8.16; N, 5.59.
123 °C; ½a 2D0
ꢁ
57 (c 1. CHCl3); 1H NMR (400 MHz, CDCl3): d 7.63–7.65 (m, 1H);
7.20–7.28 (m, 4H); 7.07–7.16 (m, 4H); 6.97 (s, 1H); 5.23 (s, 2H); 3.85 (t,