Novel N-(2,2-dimethyl-2H-azirin-3-yl)-L-prolinates as Aib-Pro synthons

Article abstract of DOI:10.1002/hlca.200690178

The syntheses of phenacyl N-(2,2-dimethyl-2H-azirin-3-yl)-L-prolinate and allyl N-(2,2-dimethyl-2H-azirin-3-yl)-L-prolinate are reported. Reactions of these 2H-azirin-3-amine derivatives with Z-protected amino acids have shown them to be suitable synthons

Full text of DOI:10.1002/hlca.200690178

Helvetica Chimica Acta – Vol. 89 (2006)
1841
Novel N-(2,2-Dimethyl-2H-azirin-3-yl)-L-prolinates as Aib-Pro Synthons
by Simon Stamm1) and Heinz Heimgartner*
Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich
(phone: +41446354280; fax: +41446356836; e-mail: heimgart@oci.unizh.ch)
The syntheses of phenacyl N-(2,2-dimethyl-2H-azirin-3-yl)-L-prolinate and allyl N-(2,2-dimethyl-
2H-azirin-3-yl)-L-prolinate are reported. Reactions of these 2H-azirin-3-amine derivatives with Z-pro-
tected amino acids have shown them to be suitable synthons for the Aib-Pro unit in peptide synthesis.
After incorporation into the peptide by means of the ꢀazirine/oxazolone methodꢁ, the C-termini of the
resulting peptides were deprotected selectively with Zn in AcOHor by a mild Pd 0-promoted procedure,
respectively.
1.Introduction. – Peptides that contain a,a-disubstituted a-amino acids are of inter-
est because the rigidity of their backbones leads to a stabilization or even a promotion
of secondary structures, such as b-turns or helices [1–4]. Moreover, a group of peptide
antibiotics, the ꢀpeptaibolsꢁ, contain a high proportion of a,a-disubstituted a-amino
acids, in particular a-aminoisobutyric acid (Aib) [5]. A valuable and convenient
method for the introduction of these sterically demanding a,a-disubstituted a-amino
acids is the ꢀazirine/oxazolone methodꢁ [6–8]. Thus, the reaction of 2H-azirin-3-amines
1, which represent the amino acid synthons, with amino or peptide acids leads to pep-
tide amides, the terminal amide bonds of which can be hydrolyzed selectively to give
the extended peptide acids. This method has been applied successfully in the introduc-
tion of a variety of a,a-disubstituted a-amino acids into peptides, and it has found appli-
cation in the synthesis of some peptaibols or segments thereof [9–18].
Recently, we adapted the ꢀazirine/oxazolone methodꢁ to solid-phase conditions, in
order to additionally profit from their benefits [19]. Moreover, it was shown that,
1
)
Part of the Ph.D. thesis of S. S., Universität Zürich, 2006.
ꢂ 2006 Verlag Helvetica Chimica Acta AG, Zürich

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Helvetica Chimica Acta – Vol. 89 (2006)
also on solid phase, the method is not limited to the Aib synthon 1a, and it was extended
successfully to the 1-aminocyclopentane-1-carboxylic acid, the 4-amino-3,4,5,6-tetrahy-
dro-2H-pyran-4-carboxylic acid, and the a-methylphenylalanine synthons (see 1b–1d)
[20].
Since the Aib-Pro motif is widespread in peptaibols – in fact, 266 out of the 309 so
far known peptaibol sequences contain the Aib-Pro unit [21] – it was of great interest to
introduce this unit directly. In solution-phase chemistry, the introduction of the Aib-Pro
unit was accomplished with the use of dipeptide synthon 2 [22]. Unexpectedly, its use
on solid phase was not successful due to the incompatibility of the linker and the strong
basic media, which is required for the saponification of the methyl ester [23]. In the
course of working out a new strategy for the introduction of the Aib-Pro motif on
solid phase, a 2H-azirin-3-amine with an easily removable carboxy-protecting group
was required.
Herein, we present the synthesis, chemical characterization, and, briefly, the use in
solution-phase peptide synthesis of the novel Aib-Pro synthons 3a and 3b. After intro-
duction into the peptide, the C-termini of the resulting extended peptides can be depro-
0
tected with Zn in AcOHor by a mild Pd -promoted procedure, respectively.
2.Results and Discussion. – Since the synthesis of 2H-azirin-3-amines 1 is per-
formed under acidic conditions, the range of carboxy-protecting groups is limited to
those which are base-labile, which can be removed by reduction, or which are labile
towards transition-metal complexes, but feature a good stability towards acids. The
(9H-fluoren-9-yl)methyl (Fm) [24][25] and 2-[(4-nitrophenyl)sulfonyl]ethyl [26] pro-
tecting groups, which can be cleaved by treatment with secondary amines, should fulfill
these prerequisites. Hence, we aimed at the synthesis of the 2H-azirin-3-amines 4a and
4b as outlined in Scheme 1. After saponification of methyl prolinate 5 with LiOHand
subsequent carbodiimide-induced coupling of acid 6 with the corresponding alcohols,
the obtained amides 7a and 7b were converted to the thioamides 8a and 8b, respec-
tively, by thionation with Lawesson reagent. A procedure slightly modified2) compared
to that of Wipf [27] did not lead to the desired 2H-azirin-3-amines 4a and 4b. Conse-
quently, we headed for 4b via the 2-[(4-nitrophenyl)sulfanyl]ethyl-protected 2H-
azirin-3-amine 4c. This route comprises the ꢀsafety catch principleꢁ, since the activation
for the b-elimination is realized after the azirine synthesis by an oxidation of the sul-
fanyl group3). However, the synthesis of 4c failed too.
The phenacyl (=2-oxo-2-phenylethyl) and allyl ester protecting groups, which can
be removed by treatment with Zn/AcOH[28] and [Pd(Ph 3P)4]/PhSiH3 [29], respec-
G
tively, were the next promising candidates for proline protection. The synthesis of
the phenacyl and allyl ester-protected dipeptide synthons 3a and 3b started with the
preparation of the esters 9a and 9b by alkylation of 6 with phenacyl bromide and
allyl bromide, respectively (Scheme 2). A direct access from L-proline was accom-
plished for 9b. For this purpose, L-proline was esterified with allyl alcohol and then acy-
lated with isobutyryl (=2-methylpropanoyl) chloride. After thionation of the amides 9a
2
)
)
To prevent an early b-elimination, EtN(i-Pr)2 was used instead of 1,4-diaza[2.2.2]octane (DABCO).
A preliminary test showed that 2 is stable under mild oxidative conditions (tetrapropylammonium
perruthenate (TRAP), N-methylmorpholine N-oxide (NMO)).
3

Helvetica Chimica Acta – Vol. 89 (2006)
1843
Scheme 1
a) LiOH·H2O, THF, MeOH, H2O, r.t. b) For 7a: (9H-fluoren-9-yl)methanol, N,N’-dicyclohexylcarbo-
diimide (DCC), 4-(pyrrolidin-1-yl)pyridine (PPY), CH2Cl2, r.t.; for 7b: 2-[(4-nitrophenyl)sulfonyl]-
ethanol, 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride (EDCI), 4-(dimethylamino)-
pyridine (DMAP), CH2Cl2, r.t.; for 7c: 2-[(4-nitrophenyl)sulfanyl]ethanol, DCC, PPY, CH2Cl2, r.t. c)
Lawesson reagent, PhMe, ca. 908. d) 1. COCl2, PhMe, CH2Cl2, DMF (cat.), 08; 2. for 4a and 4b:
EtN(i-Pr)2, THF, r.t.; for 4c: 1,4-diazabicyclo[2.2.2]octane (DABCO), THF, r.t., 3. NaN3, TH F
(DMF), r.t.
and 9b with Lawesson reagent, the synthesis of 3a and 3b was accomplished by consec-
utive treatment of the obtained thioamides 10a and 10b, and catalytic amounts of DMF
in CH2Cl2 with COCl2, evaporation of the solvent, addition of THF and 1,4-diazabicy-
clo[2.2.2]octane (DABCO), filtration, and treatment with NaN3 (cf. [27]). After chro-
matographic workup, the 2H-azirin-3-amines 3a and 3b were obtained in 58 and 62%
yield, respectively, as pale yellow oils.
For a chemical characterization and for the examination of the reactivity of the
novel 2H-azirin-3-amines 3a and 3b, they were treated with PhCOSH( Scheme 3).
The reactions proceeded smoothly, and the thiopeptides 11 were obtained in high
yield (93 and 94%, resp.). In the case of 11a, crystals suitable for an X-ray crystal-struc-
ture determination were obtained (Fig.). Compound 11a in the crystal is enantiomeri-
cally pure, and the absolute configuration of the molecule has been determined inde-
pendently by the diffraction experiment. The molecule has the expected (S)-configura-
tion. The amide group forms an intermolecular H-bond with the S-atom of an adjacent
molecule and thereby links the molecules into extended chains, which run parallel to
the [0 1 0] direction and can be described by the graph set motif [30] of C(5).

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Helvetica Chimica Acta – Vol. 89 (2006)
Scheme 2
a) For 9a: PhCOCH2
N
N
H2O, 08 ! r.t. b) 1. SOCl2, allyl alcohol, ꢀ208 ! 658; 2. isobutyryl chloride, Et3N, AcOEt, 08 ! r.t.
U
c) Lawesson reagent, PhMe, ca. 908. d) 1. COCl2, PhMe, CH2Cl2, DMF (cat.), 08; 2. DABCO, THF,
r.t.; 3. NaN3, THF, r.t.
Scheme 3
To examine the use of 3a and 3b in peptide synthesis, reactions with N-protected
amino acids were performed. The Aib-Pro synthon 3a was reacted with Z-Ile-OH
and Z-Phe-OHto give the tripeptides 12a and 13, respectively, while the reaction of
3b with Z-Ile-OHyielded the tripeptide 12b (Scheme 4). All reactions gave the prod-
ucts in high purity and in very good yields (90–94%, after chromatographic workup).
Then, the selective deprotection of the C-terminus of 13 was accomplished with Zn
powder in AcOH, and yielded peptide acid 14. Deprotection of the phenacyl esters
with Bu
which is the ultimate use of the new azirine. Therefore, 12a and 13 were subjected to
Bu4
N+Fꢀ (3 equiv.) in DMF and THF, respectively, but in none of the experiments a
peptide acid 14 or 15, respectively, could be isolated.
G
AHCTREUNG

Helvetica Chimica Acta – Vol. 89 (2006)
1845
Figure. ORTEP Plot [31] of the molecular structure of 11a (50% probability ellipsoids; arbitrary
numbering of atoms)
The deprotection of the C-terminus can be performed under milder conditions if
synthon 3b is used in the peptide chain extension. This was illustrated with the
model peptide 12b, in which the allyl ester group was smoothly removed by treatment
with [Pd(Ph3P)4] and PhSiH3 in CH2Cl2 to give the peptide acid 15. Moreover, these
A
deprotecting conditions should be applicable in solid phase.
3.Conclusions. – The novel 2H-azirin-3-amines 3a and 3b, which contain a phenacyl
ester and an allyl ester group, respectively, as carboxy-protecting group, have been syn-
thesized. These azirines represent Aib-Pro synthons, and this dipeptide unit can be
introduced conveniently into peptides by the ꢀazirine/oxazolone methodꢁ. The C-termi-
nus of the resulting peptide esters can be deprotected under non-basic conditions, i.e.,
by treatment with Zn/AcOHand [Pd(Ph 3P)4]/PhSiH3. The use of 3a and 3b as building
A
blocks for the ꢀazirine/oxazolone methodꢁ in solid phase are being investigated.
We thank PD Dr. A. Linden for the X-ray crystal-structure determination, Dr. Daniel Obrecht, Poly-
phorLtd. , CH-Allschwil, for continous advice and valuable discussions, as well as the analytical sections
of our institute for spectra and analyses. Financial support of the Swiss National Science Foundation and
F. Hoffmann-La Roche AG, Basel, is gratefully acknowledged.
Experimental Part
1. General. – Reagents were obtained from commercial suppliers and were used without further puri-
fication. Solvents were purified by standard procedures. Compound 5 was prepared according to [22].
TLC: Merck TLC aluminum sheets, silica gel 60 F254. Prep. TLC: Merck PLC plates (glass), silica gel
60 F254. Column chromatography (CC): Uetikon-Chemie, silica gel C-560. M.p.: Büchi Melting Point
B-450 apparatus; uncorrected. IR Spectra: Perkin-Elmer, Spectrum One FT-IR spectrophotometer;
unless otherwise stated in KBr, absorptions in cmꢀ1. NMR Spectra: Bruker ARX-300, Bruker AV-600,
or Bruker AV-700 instruments; in CDCl3, d in ppm, TMS as internal standard, coupling constants J in
Hz 2D-NMR. Experiments were performed for assignment of the signals. In 1H- and 13C-NMR spectra

1846
Helvetica Chimica Acta – Vol. 89 (2006)
Scheme 4
where two conformers were observed, only the signals of the major conformer are shown. The ratio of the
two conformers is given in parentheses. MS (m/z (rel.%)): Bruker ESQUIRE-LC quadrupole ion-trap
instrument. Abbreviations: Aib: ꢀa-aminoisobutyric acidꢁ; DABCO: 1,4-diazabicyclo[2.2.2]octane;
DCC: N,N’-dicyclohexylcarbodiimide; DMAP: 4-(dimethylamino)pyridine; EDCI: 1-ethyl-3-[3-(dime-
thylamino)propyl]carbodiimide hydrochloride; PPY: 4-(pyrrolidin-1-yl)pyridine.
2. Synthesis of 2H-Azirin-3-amine Derivatives 3a and 3b. N-(2-Methyl-1-oxopropyl)-L-proline (6). A
soln. of methyl N-(2-methyl-1-oxopropyl)-L-prolinate (5; 2.000 g, 10.04 mmol) and LiOH·H2O (0.843 g,
20.11 mmol) in THF/MeOH/H2O 3 :1:1 (100 ml) was stirred at r.t. overnight. The org. solvents were
removed under reduced pressure, and the residue was washed with Et2O. At 08, the aq. phase was acidi-
A
fied with 1M HCl and saturated with NaCl. After extraction with CH2Cl2, the combined org. layers were
washed with brine, dried (MgSO4), and concentrated i.v. to give 6 (1.775 g, 96%). Colorless powder. M.p.
122.6–123.78. IR: 2969s, 2942s, 2879s, 2771m, 2606m, 1721vs, 1600vs, 1509w, 1478s, 1446vs, 1332m, 1266m,
1
1254s, 1228vs, 1191s, 1167m, 1154m, 1092s, 1042w, 968w, 914m, 838w, 808w, 752w. H-NMR (300 MHz;
conformers 95 :5): 10.9–9.6 (br. s, CO2H); 4.61–4.57 (m, CH a()(Pro)); 3.66–3.61, 3.58–3.50 (2m,
CH2(d)(Pro)); 2.72 (sept., J=6.8, Me2
C

Helvetica Chimica Acta – Vol. 89 (2006)
1847
(t, CH2(d)(Pro)); 32.5 (d, Me2CH); 27.4, 24.9 (2t, CH2(b)(Pro), CH2(g)(Pro)); 19.0, 18.5 (2q, 2 Me). ESI-
MS (MeOH): 208 (100, [M+Na]+). Anal. calc. for C9H15NO3 (185.22): C 58.36, H8.16, N 7.56; found: C
58.51, H8.06, N 7.77.
2-Oxo-2-phenylethyl N-(2-Methyl-1-oxopropyl)-L-prolinate (9a). A mixture of 6 (0.801 g, 4.32
mmol), Et
N
N
at r.t. overnight. The mixture was filtered, and the soln. was concentrated i.v. CC (SiO2; AcOEt/hexane
6 :4) yielded 9a (1.280 g, 98%). Colorless oil. IR (film): 3488m, 3391w, 3270w, 3063s, 2974vs, 2935vs,
2876vs, 1755vs, 1701vs, 1644vs, 1598vs, 1582vs, 1470vs, 1449vs, 1426vs, 1376vs, 1364vs, 1318vs, 1279vs,
1230vs, 1173vs, 1092vs, 1043s, 1001vs, 973vs, 953vs, 921m, 886m, 851m, 810s, 753vs, 735vs. 1H-NMR
(300 MHz; conformers 85 :15): 7.90–7.87, 7.63–7.57, 7.52–7.45 (3m, 5 arom. H); 5.55, 5.21 (AB,
J=16.5, CH2CO); 4.68–4.62 (m, CH a( )(Pro)); 3.76–3.67, 3.62–3.54 (2m, CH2(d)(Pro)); 2.69 (sept.,
J=6.8, Me2CH); 2.42–2.13, 2.10–1.97 (2m, CH2(b)(Pro), CH2(g)(Pro)); 1.15, 1.14 (2d, J=6.8, 2 Me).
G
13C-NMR (75 MHz): 192.2 (s, PhCO); 175.9 (s, CO(amide)); 171.8 (s, CO(ester)); 134.1 (s, arom. C);
133.8, 128.8, 127.6 (3d, 5 arom. CH); 60.0 (t, CH2CO); 58.5 (d, CH a( )(Pro)); 46.7 (t, CH2(d)(Pro));
32.2 (d, Me2CH); 29.1, 24.8 (2t, CH2(b)(Pro), CH2(g)(Pro)); 18.7, 18.6 (2q, 2 Me). ESI-MS (MeOH,
NaI): 326 (100, [M+Na]+). Anal. calc. for C17H21NO4 (303.35): C 67.31, H6.98, N 4.62; found: C
67.11, H6.61, N 4.62.
Prop-2-enyl N-(2-Methyl-1-oxopropyl)-L-prolinate (9b). From 6. A soln. of CH2=CHCH2Br (22.8 ml,
269.50 mmol) and ꢀAliquot 336ꢁ (21.6 g) in CH2Cl2 (75 ml) was added to a soln. of 6 (10.004 g, 54.01
mmol) and NaHCO3 (4.539 g, 54.03 mmol) in H2O (75 ml) at 08. The mixture was vigorously stirred at
r.t. for 3 d, then H2O (50 ml) was added, and the suspension was extracted with CH2Cl2. The combined
org. layers were dried (MgSO4) and concentrated i.v. CC (SiO2, AcOEt/hexane 4 :6 ! 1:1) yielded 9b
(11.328 g, 93%). Colorless liquid.
From L-Proline. At ꢀ208, SOCl2 (1.70 ml, 23.36 mmol) was added to CH2=CHCH2OH(12 ml,
176.45 mmol), then L-proline (2.000 g, 17.37 mmol) was added, and the mixture was slowly heated to
658 and stirred at 658 for 1 h. The mixture was concentrated i.v., the residue was dissolved in AcOEt
(60 ml), and Et3N (5.05 ml, 36.23 mmol) and isobutyryl chloride (1.85 ml, 17.52 mmol) were added at
U
08. The mixture was stirred at r.t. overnight, H2O (20 ml) was added, and the mixture was extracted
with AcOEt. The combined org. layers were dried (MgSO4) and concentrated i.v. CC (AcOEt/hexane
1:1) yielded 9b (3.164 g, 81%).
Data of 9b. Colorless liquid. IR (film): 3568w, 3479w, 3085w, 2973vs, 2935s, 2877s, 1745vs, 1650vs,
1741vs, 1426vs, 1377s, 1362s, 1318vs, 1274s, 1242s, 1177vs, 1091s, 1044m, 990s, 954m, 930s, 882w, 819w,
754m. 1H-NMR (300 MHz; conformers 85 :15): 5.97–5.84 (m, CH2=CH); 5.37–5.20 (m, CH2=CH);
4.68–4.60 (m, CH2O); 4.53–4.48 (m, CH a()(Pro)); 3.73–3.64, 3.62–3.53 (2m, CH2(d)(Pro)); 2.68
(sept., J=6.8, Me
2CH); 2.29–1.90 (m, CH2(b)(Pro), CH2(g)(Pro)); 1.16, 1.13 (2d, J=6.8, 2 Me). 13C-
H
NMR (75 MHz): 176.0 (s, CO(amide)); 172.3 (s, CO(ester)); 132.2 (d, CH2=CH); 118.4 (t, CH2=CH);
65.7 (t, CH2O); 58.9 (d, CH a()(Pro)); 46.9 (t, CH2(d)(Pro)); 32.4 (d, Me2CH); 29.3, 25.1 (2t,
CH2(b)(Pro),
CH2(g)(Pro));
19.0,
18.8
(2q,
2 Me).
ESI-MS
(MeOH):
298
(13,
[M+Na+MeOH+H2O]+), 248 (100, [M+Na]+). Anal. calc. for C12H19NO3 (225.28): C 63.98, H8.50,
N 6.22; found: C 63.71, H8.45, N 6.13.
2-Oxo-2-phenylethyl N-(2-Methyl-1-thioxopropyl)-L-prolinate (10a). A suspension of Lawesson
reagent (dried i.v., 444 mg, 1.10 mmol) and 9a (600 mg, 1.98 mmol) in toluene (20 ml) was heated at
908 (oil bath) for 1 h. After cooling to r.t., the mixture was filtered, and the solvent was evaporated.
CC (SiO2; CH2Cl2/MeOH200 :1 ! 100 :1) yielded 10a (571 mg, 90%). Colorless solid. M.p.
83.9–84.98. IR: 2976m, 2946w, 2928w, 2868w, 1749vs, 1701vs, 1596m, 1579w, 1468s, 1445vs, 1419m,
1373m, 1356m, 1345m, 1309w, 1263m, 1255m, 1237vs, 1192vs, 1173s, 1156s, 1130m, 1013s, 1000w, 967m,
910w, 815w, 757m, 735w, 690s. 1H-NMR (600 MHz; conformers 87:13): 7.90–7.88, 7.65–7.59,
7.52–7.47 (3m, 5 arom. H); 5.54, 5.25 (AB, J=16.4, CH2CO); 5.27–5.25 (m, CH (a)(Pro)); 3.97–3.93,
3.79–3.75 (2m, CH2(d)(Pro)); 3.07 (sept., J=6.6, Me2CH); 2.56–2.50, 2.40–2.31, 2.21–2.14 (3m,
N
CH2(b)(Pro), CH2(g)(Pro)); 1.26, 1.23 (2d, J=6.6, 2 Me). 13C-NMR (150 MHz): 209.9 (s, CS); 192.2 (s,
PhCO); 170.0 (s, CO(ester)); 134.1 (s, 1 arom. C); 134.0, 128.9, 127.7 (3d, 5 arom. CH); 66.3 (t,

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Helvetica Chimica Acta – Vol. 89 (2006)
CH2CO); 65.2 (d, CH a( )(Pro)); 50.4 (t, CH2(d)(Pro)); 38.7 (d, Me2CH); 29.0, 24.7 (2t, CH2(b)(Pro),
CH2(g)(Pro)); 22.7, 22.4 (2q, 2 Me). ESI-MS (MeOH, NaI): 342 (100, [M+Na]+). Anal. calc. for
C17H21NO3S (319.42): C 63.92, H6.63, N 4.39, S 10.04; found: C 64.07, H6.37, N 4.30, S 10.08.
Prop-2-enyl N-(2-Methyl-1-thioxopropyl)-L-prolinate (10b). A suspension of Lawesson reagent
(dried i.v., 5.584 g, 13.81 mmol) and 9b (5.618 g, 24.94 mmol) in toluene (70 ml) was heated at 958 (oil
bath) for 1 h. After cooling to r.t., the mixture was filtered, and the solvent was evaporated. CC (SiO2;
CH2Cl2/MeOH400 :1 ! 100 :1) yielded 10b (5.439 g, 90%). Pale yellow oil. IR (film): 3084w, 2973vs,
2931s, 2878s, 1742vs, 1648w, 1440vs, 1381s, 1360s, 1333vs, 1268vs, 1227vs, 1191vs, 1170vs, 1126s, 1088m,
1046m, 1016vs, 989s, 969s, 930s, 874m, 784w. 1H-NMR (700 MHz; conformers 83 :17): 5.94–5.88 (m,
CH2=CH); 5.37–5.23 (m, CH2=CH); 5.13–5.11 (m, CH a( )(Pro)); 4.67–4.60 (m, CH2O); 3.93–3.88,
3.78–3.74 (2m, CH2(d)(Pro)); 3.05 (sept., J=6.6, Me2CH); 2.30–2.25, 2.23–2.17, 2.14–2.09 (3m,
G
CH2(b)(Pro), CH2(g)(Pro)); 1.25, 1.24 (2d, J=6.6, 2 Me). 13C-NMR (175 MHz): 209.9 (s, CS); 170.5 (s,
CO); 132.1 (d, CH2=CH); 118.7 (t, CH2=CH); 66.0 (t, CH2O); 65.4 (d, CH a()(Pro)); 50.4 (t,
CH2(d)(Pro)); 38.9 (d, Me2CH); 29.0, 24.9 (2t, CH2(b)(Pro), CH2(g)(Pro)); 22.9, 22.5 (2q, 2 Me). ESI-
MS (MeOH): 264 (100, [M+Na]+). Anal. calc. for C12H19NO2S (241.35): C 59.72, H7.93, N 5.80, S
13.29; found: C 59.80, H7.65, N 5.58, S 13.07.
2-Oxo-2-phenylethyl N-(2,2-Dimethyl-2H-azirin-3-yl)-L-prolinate (3a). A soln. of COCl2 in toluene
(20%, 1.8 ml, 3.47 mmol) was added to a soln. of 10a (1.001 g, 3.13 mmol) and 3 drops of DMF in
CH2Cl2 (10 ml) at 08, the mixture was stirred for 30 min at 08, and the volatiles were removed i.v. TH F
(15 ml) and DABCO (0.351 g, 3.13 mmol) were added under vigorous stirring to the residue, and the mix-
ture was stirred at r.t. for 30 min. The solid was removed by filtration under N2 and washed with THF. To
the filtrate, NaN3 (0.617 g, 9.49 mmol) was added, and the resulting mixture was stirred at r.t. for 4 d.
After addition of Et
ACHTREUNG
removed i.v. CC (SiO2, AcOEt/hexane 6 :4, Et3
AHCTREUNG
(film): 3434w, 3388w, 3063w, 2976s, 2942s, 2879m, 1771vs, 1703vs, 1598m, 1581w, 1450s, 1417m, 1369s,
1
1345m, 1277s, 1233vs, 1174vs, 1095m, 1001w, 964s, 911w, 846w, 819w, 758m, 690s. H-NMR (300 MHz):
7.91–7.88, 7.65–7.59, 7.52–7.47 (3m, 5 arom. H); 5.47–5.32 (m, CH2CO); 4.50 (br. s, CH a( )(Pro));
3.74–3.67, 3.62–3.54 (2m, CH2(d)(Pro)); 2.50–2.04 (m, CH2(b)(Pro), CH2(g)(Pro)); 1.35, 1.31 (2s, 2
Me). 13C-NMR (75 MHz): 191.5 (s, PhCO); 171.7 (s, CO(ester)); 165.5 (s, C(3)); 134.1 (d, 1 arom.
CH); 134.0 (s, 1 arom. C); 129.0, 127.7 (2d, 4 arom. CH); 66.4 (t, CH2CO); ca. 60.9 (br. d, CH (a)(Pro));
ca. 46.9 (br. t, CH2(d)(Pro)); 39.2 (s, C(2)); 30.6 (t, CH2(b)(Pro)); 25.2 (q, 2 Me); 24.0 (t, CH2(g)(Pro)).
ESI-MS (MeOH): 323 (100, [M+Na]+). Anal. calc. for C17H20N2O3 (300.35): C 67.98, H6.71, N 9.33;
found: C 67.73, H6.53, N 9.35.
Prop-2-enyl N-(2,2-Dimethyl-2H-azirin-3-yl)-L-prolinate (3b). A soln. of COCl2 in toluene (20%, 2.6
ml, 5.02 mmol) was added to a soln. of 10b (1.008 g, 4.14 mmol) and 3 drops of DMF in CH2Cl2 (10 ml) at
08, the mixture was stirred for 30 min at 08, and the volatiles were removed i.v. The residue was dissolved
in THF (15 ml), DABCO (0.465 g, 4.15 mmol) was added, and the mixture was stirred at r.t. for 30 min.
The solid was removed by filtration under N2 and washed with THF. To the filtrate, NaN3 (0.810 g, 12.46
mmol) was added, and the resulting mixture was stirred at r.t. for 4 d. After addition of Et
suspension was filtered over a Celite pad, and the solvent was removed i.v. CC (SiO2; AcOEt/hexane 6 :4,
Et3N (1%)) yielded 3b (0.575 g, 63%). Pale yellow oil. IR (film): 3458w, 3087w, 2976s, 2943s, 2879s,
2O, the resulting
AHCTREUNG
1770vs, 1745vs, 1649w, 1454s, 1413m, 1368s, 1352m, 1272s, 1235s, 1177vs, 1093m, 1043w, 1015m, 987s,
933m. 1H-NMR (300 MHz): 5.97–5.84 (m, CH2=CH); 5.36–5.24 (m, CH2=CH); 4.67–4.61 (m,
CH2O); 4.35–4.34 (m, CH a()(Pro)); 3.70–3.52 (m, CH2(d)(Pro)); 2.39–1.99 (m, CH2(b)(Pro),
CH2(g)(Pro)); 1.32, 1.29 (2s, 2 Me). 13C-NMR (75 MHz): 171.6 (s, CO); 165.2 (s, C(3)); 131.4 (d,
CH2=CH); 118.8 (t, CH2=CH); 65.8 (t, CH2O); ca. 60.8 (br. d, CH2(d)(Pro)); ca. 46.9 (br. t,
CH2(d)(Pro)); 39.0 (s, C(2)); 30.2 (t, CH2(b)(Pro)); 25.0 (q, 2 Me); 23.9 (t, CH2(g)(Pro)). ESI-MS
(MeOH): 255 (23, [M+H+MeOH]+), 245 (100, [M+Na]+), 223 (29, [M+H]+), 196 (25). Anal. calc.
for C12H18N2O2·0.2 H2O (225.88): C 63.81, H8.21, N 12.40; found: C 63.85, H8.12, N 12.32.
3. Reactions of 2H-Azirin-3-amine Derivatives 3a and 3b with PhCOSH. 2-Oxo-2-phenylethyl N-[2-
(Benzoylamino)-2-methyl-1-thioxopropyl]-L-prolinate (11a). A soln. of PhCOSH(20 mg, 0.145 mmol) in
CH2Cl2 (2 ml) was added to a soln. of 3a (40 mg, 0.133 mmol) in CH2Cl2 (2.5 ml) at 08. The mixture was
stirred at r.t. overnight, the solvent was evaporated, and the crude product was purified by prep. TLC

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1849
(CH2Cl2/MeOH50 :1, 2”dev.; CH 2Cl2/MeOH30 :1, 1”dev.) to give 11a (54 mg, 93%). Colorless crys-
tals. M.p. 189.1–190.28. IR: 3361m, 3301m, 3059w, 2984m, 2932m, 2881w, 1749vs, 1702vs, 1642vs, 1598s,
1579s, 1524vs, 1486s, 1449vs, 1419vs, 1385s, 1362s, 1341m, 1301s, 1288s, 1264s, 1226vs, 1186vs, 1160vs,
1
1092m, 1074m, 1043s, 1028m, 1001m, 965s, 911w, 884w, 803w, 754s, 720s, 690vs. H-NMR (600 MHz):
8.51 (s, NH); 7.90–7.86, 7.63–7.60, 7.51–7.48, 7.45–7.43 (4m, 10 arom. H); 5.53, 5.27 (AB, J=16.4,
CH2CO); 5.38–5.36 (m, CH (a)(Pro)); 4.12–4.08, 3.96–3.92 (2m, CH2(d)(Pro)); 2.51–2.48, 2.39–2.31,
2.14–2.10 (3m, CH2(b)(Pro), CH2(g)(Pro)); 1.95, 1.89 (2s, 2 Me). 13C-NMR (150 MHz): 205.9 (s, CS);
192.1 (s, PHCO); 169.8 (s, CO(ester)); 164.9 (s, CO(amide)); 135.0 (s, 1 arom. C); 134.0 (d, 1 arom.
CH); 134.0 (s, 1 arom. C); 131.4, 128.9, 128.5, 127.7, 127.0 (5d, 9 arom. CH); 69.1 (d, CH a( )(Pro));
66.3 (t, CH2CO); 61.2 (s, C(a)(Aib)); 53.6 (t, CH2(d)(Pro)); 28.0 (t, CH2(b)(Pro)); 26.0 (t,
CH2(g)(Pro)); 25.8, 24.9 (2q, 2 Me). ESI-MS (MeOH): 461 (100, [M+Na]+). Anal. calc. for
C24H26N2O4S (438.54): C 65.73, H5.98, N 6.39, S 7.31; found: C 65.33, H5.72, N 6.24, S 7.02. Suitable crys-
tals for the X-ray crystal-structure determination were grown from CDCl3/Et2O.
G
Prop-2-enyl N-[2-(Benzoylamino)-2-methyl-1-thioxopropyl]-L-prolinate (11b). A soln. of PhCOSH
(27 mg, 0.195 mmol) in CH2Cl2 (3 ml) was added to a soln. of 3b (40 mg, 0.180 mmol) in CH2Cl2 (2 ml)
at 08. The mixture was stirred at r.t. overnight, the solvent was evaporated, and the crude product was
purified by prep. TLC (CH2Cl2/MeOH40 :1, Et 3N (0.5%), 2”dev.) to give 11b (61 mg, 94%). Colorless
E
powder. M.p. 46.5–48.08. IR: 3303m, 3059w, 2984m, 2925s, 2880m, 2853m, 1741vs, 1639vs, 1602m, 1578m,
1530vs, 1488s, 1461s, 1419vs, 1385s, 1362s, 1340m, 1301s, 1292s, 1271s, 1245m, 1187vs, 1160vs, 1086w,
1075w, 1046s, 1028w, 988m, 969m, 931m, 885w, 803w, 717s, 694m. 1H-NMR (300 MHz): 8.66 (br. s,
NH); 7.89–7.85, 7.52–7.40 (2m, 5 arom. H); 5.99–5.86 (m, CH2=CH); 5.39–5.20 (m, CH2=CH,
CH(a)(Pro)); 4.65–4.63 (m, CH2O); 4.08–3.91 (m, CH2(d)(Pro)); 2.34–2.15, 2.10–2.00 (2m,
CH2(b)(Pro), CH2(g)(Pro)); 1.95, 1.89 (2s, 2 Me). 13C-NMR (75 MHz): 205.8 (s, CS); 170.0, 164.7 (2s, 2
CO); 135.1 (s, 1 arom. C); 131.7, 131.2, 128.4, 126.9 (4d, 5 arom. CH, CH2=CH); 118.6 (t, CH2=CH);
68.9 (d, CH a()(Pro)); 65.8 (t, CH2O); 61.0 (s, C(a)(Aib)); 53.4 (t, CH2(d)(Pro)); 27.8 (t,
CH2(b)(Pro)); 25.8 (t, CH2(g)(Pro)); 25.5, 24.7 (2q, 2 Me(Aib)). ESI-MS (MeOH): 383 (100,
[M+Na]+), 367 (17, [M(S ! O)+Na]+). Anal. calc. for C19H24N2O3S (360.47): C 63.31, H6.71, N
7.77, S 8.90; found: C 63.25, H6.45, N 7.68, S 8.67.
4. Synthesis of Model Peptides. 2-Oxo-2-phenylethyl N-{2-[((2S,3S)-2-{[(Benzyloxy)carbonyl]ami-
no}-3-methyl-1-oxopentyl)amino]-2-methyl-1-oxopropyl}-L-prolinate (12a). A soln. of 3a (65 mg, 0.216
mmol) in CH2Cl2 (2.5 ml) was added to a soln. of Z-Ile-OH(57 mg, 0.215 mmol) in CH Cl2 (2.5 ml) at
2
08. The mixture was stirred at r.t. overnight, the solvent was evaporated, and the crude product was puri-
fied by CC (SiO2; CH2Cl2/MeOH60 :1) to give 12a (105 mg, 86%). Colorless solid. M.p. 70.1–71.58. IR:
3318s, 3064w, 3034w, 2966s, 2936m, 2877m, 1753vs, 1702vs, 1660vs, 1633vs, 1599m, 1531vs, 1468s, 1451s,
1
1409vs, 1378s, 1363s, 1286s, 1230vs, 1167vs, 1096m, 1042m, 1028m, 1001w, 977m, 754s, 693s. H-NMR
(600 MHz): 7.89–7.88, 7.62–7.59, 7.50–7.47, 7.37–7.31 (4m, 10 arom. H); 6.97 (s, NH(Aib)); 5.57,
5.21 (AB, J=16.4, CH2CO); 5.41 (d, J=8.8, NH(Ile)); 5.12, 5.08 (AB, J=12.3, CH2(carbamate));
4.72–4.69 (m, CH a()(Pro)); 4.00–3.97 (m, CH a()(Ile)); 3.77–3.73, 3.57–3.54 (2m, CH2(d)(Pro));
2.32–2.30 (m, 1 Hof CH 2(b)(Pro)); 2.19–2.10 (m, 1 Hof CH 2(b)(Pro), 1 Hof CH 2(g)(Pro));
1.90–1.88 (m, 1 Hof CH (g)(Pro)); 1.83–1.82 (m, CH (b)(Ile)); 1.65, 1.61 (2s, 2 Me(Aib)); 1.53–1.48,
2
1.16–1.11 (2m, CH2(g)(Ile)); 0.92 (d, J=6.8, MeCH(b)(Ile)); 0.89 (t, J=7.4, MeCH2(g)(Ile)). 13C-
NMR (150 MHz): 192.2 (s, PhCO); 172.2 (s, CO(Aib)); 171.8 (s, CO(Pro)); 169.6 (s, CO(Ile)); 156.2
(s, CO(carbamate)); 136.3, 134.1 (2s, 2 arom. C); 134.0, 128.9, 128.5, 128.2, 128.0, 127.7 (6d, 10 arom.
CH); 66.9 (t, PhCH2); 66.2 (t, CH2CO); 60.9 (d, CH a()(Pro)); 59.7 (d, CH a()(Ile)); 57.1 (s,
C(a)(Aib)); 48.2 (t, CH2(d)(Pro)); 37.8 (d, CH (b)(Ile)); 27.9 (t, CH2(b)(Pro)); 25.8 (t, CH2(g)(Pro));
24.9 (t, CH2(g)(Ile)); 23.6, 23.2 (2q, 2 Me(Aib)); 15.4 (q, MeCH(b)(Ile)); 11.4 (q, MeCH2(g)(Ile)).
A
ESI-MS (MeOH): 588 (100, [M+Na]+). Anal. calc. for C31H39N3O7 (565.66): C 65.82, H6.95, N 7.43;
found: C 65.53, H7.06, N 7.27.
Prop-2-enyl N-{2-[((2S,3S)-2-{[(Benzyloxy)carbonyl]amino}-3-methyl-1-oxopentyl)amino]-2-meth-
yl-1-oxopropyl}-L-prolinate (12b). A soln. of 3b (60 mg, 0.270 mmol) in CH2Cl2 (3 ml) was added to a
soln. of Z-Ile-OH(79 mg, 0.297 mmol) in CH 2Cl2 (2 ml) at 08. The mixture was stirred at r.t. overnight,
the solvent was evaporated, and the crude product was purified by CC (SiO2; CH2Cl2/MeOH20 :1) to
give 12b (123 mg, 93%). Colorless powder. M.p. 135.0–136.18. IR: 3287s, 3256s, 3065m, 2964s, 2937m,

1850
Helvetica Chimica Acta – Vol. 89 (2006)
2876w, 1751vs, 1715vs, 1666vs, 1619vs, 1547vs, 1497m, 1453s, 1419s, 1383s, 1366m, 1355m, 1285s, 1272s,
1243vs, 1208m, 1174vs, 1162vs, 1126m, 1095w, 1047m, 1028m, 987m, 949w, 923w, 877w, 853w, 778w,
1
751w, 738m, 700m. H-NMR (600 MHz): 7.37–7.29 (m, 5 arom. H); 6.97 (br. s, NH(Aib)); 5.94–5.87
(m, CH2=CH); 5.40 (d, J=8.5, NH(Ile)); 5.35–5.31, 5.25–5.23 (2m, CH2=CH); 5.11, 5.08 (AB,
J=12.3, CH2(carbamate)); 4.66–4.58 (m, CH2O); 4.58–4.55 (m, CH a()(Pro)); 4.00–3.97 (m,
CH(a)(Ile)); 3.72–3.69, 3.58–3.55 (2m, CH2(d)(Pro)); 2.11–2.07 (m, 1 Hof CH (b)(Pro)); 2.04–1.97
2
(m, 1 Hof CH (g)(Pro)); 1.91–1.82 (m, 1 Hof CH (b)(Pro), 1 Hof CH (g)(Pro), CH(b)(Ile)); 1.65,
2
2
2
1.62 (2s, 2 Me(Aib)); 1.53–1.49, 1.16–1.10 (2m, CH2(g)(Ile)); 0.92 (d, J=7.0, MeCH(b)(Ile)); 0.90 (t,
J=7.4, MeCH2(g)(Ile)). 13C-NMR (150 MHz): 172.0 (s, CO(Aib)); 172.0 (s, CO(Pro)); 169.6 (s,
CO(Ile)); 156.2 (s, CO(carbamate)); 136.4 (s, 1 arom. C); 131.9 (d, CH2=CH); 128.5, 128.2, 128.0 (3d,
5 arom. CH); 118.5 (t, CH2=CH); 66.9 (t, CH2(carbamate)); 65.7 (t, CH2O); 61.0 (d, CH a( )(Pro));
59.7 (d, CH a()(Ile)); 57.1 (s, C(a)(Aib)); 48.1 (t, CH2(d)(Pro)); 37.8 (d, CH b()(Ile)); 27.8 (t,
CH2(b)(Pro)); 25.8 (t, CH2(g)(Pro)); 24.9 (t, CH2(g)(Ile)); 23.5, 23.1 (2q, 2 Me(Aib)); 15.4 (q, MeCH(-
b)(Ile)); 11.4 (q, MeCH2(g)(Ile)). ESI-MS (MeOH): 510 (100, [M+Na]+). Anal. calc. for C26H37N3O6
(487.59): C 64.05, H7.65, N 8.62; found: C 63.89, H7.40, N 8.58.
2-Oxo-2-phenylethyl N-{2-[((S)-2-{[(Benzyloxy)carbonyl]amino}-3-phenyl-1-oxopropyl)amino]-2-
methyl-1-oxopropyl}-L-prolinate (13). A soln. of 3a (120 mg, 0.380 mmol) in CH2Cl2 (3 ml) was added
to a soln. of Z-Phe-OH(120 mg, 0.401 mmol) in CH 2Cl2 (3 ml) at 08. The mixture was stirred at r.t. over-
night, the solvent was evaporated, and the crude product was purified by CC (SiO2; CH2Cl2/MeOH80 :1
! 60 :1) to give 13 (213 mg, 94%). Colorless powder. M.p. 76.7–78.48. IR: 3311s, 3062m, 3031w, 2983m,
2940m, 2880w, 1752vs, 1703vs, 1670vs, 1625vs, 1532vs, 1498s, 1469s, 1451s, 1412vs, 1377s, 1364s, 1341m,
1286s, 1232vs, 1166vs, 1097w, 1084w, 1052m, 1028m, 1001w, 977m, 913w, 848w, 752s, 698s. 1H-NMR
(600 MHz): 7.88–7.87, 7.61–7.59, 7.49–7.46, 7.37–7.20 (4m, 15 arom. H); 6.57 (s, NH(Aib)); 5.55,
5.18 (AB, J=16.5, CH2CO); 5.39 (d, J=7.2, NH(Phe)); 5.10, 5.08 (AB, J=12.0, CH2(carbamate));
4.68–4.66 (m, CH a()(Pro)); 4.38–4.37 (m, CH a()(Phe)); 3.66–3.59, 3.46–3.42 (2m, CH2(d)(Pro));
3.11–3.08, 3.03–3.00 (2m, CH2(Phe)); 2.32–2.26, 2.19–2.13 (2m, CH2(b)(Pro)); 2.10–2.06, 1.92–1.84
(2m, CH2(g)(Pro)); 1.50, 1.42 (2s, 2 Me(Aib)). 13C-NMR (150 MHz): 192.2 (s, PhCO); 171.8 (s,
CO(Aib), CO(Pro)); 169.1 (s, CO(Phe)); 155.9 (s, CO(carbamate)); 136.3, 136.2, 134.1 (3s, 3 arom.
C); 134.0, 129.5, 128.9, 128.7, 128.6, 128.2, 128.0, 127.7, 127.1 (9d, 15 arom. CH); 67.0 (t,
CH2(carbamate)); 66.1 (t, CH2CO); 60.8 (d, CH (a)(Pro)); 56.9 (s, C(a)(Aib)); 56.4 (d, CH (a)(Phe));
48.1 (t, CH2(d)(Pro)); 38.7 (t, CH2(Phe)); 27.8 (t, CH2(b)(Pro)); 25.8 (t, CH2(g)(Pro)); 23.7, 23.4 (2q, 2
Me(Aib)). ESI-MS (MeOH): 622 (100, [M+Na]+). Anal. calc. for C34H37N3O7 (599.67): C 68.10, H
6.22, N 7.01; found: C 68.13, H6.27, N 6.90.
N-{2-[((S)-2-{[(Benzyloxy)carbonyl]amino}-3-phenyl-1-oxopropyl)amino]-2-methyl-1-oxopropyl}-
L-proline (14). Zn Powder (274 mg, 4.190 mmol) was added to a soln. of 13 (50 mg, 0.083 mmol) in AcOH
(100%, 2 ml), and the mixture was stirred at r.t. for 45 min. Additional Zn powder (136 mg, 2.080 mmol)
and AcOH(100%, 0.5 ml were added, and the mixture was stirred for further 45 min. The mixture was
filtered, the residue was washed with AcOH, and the filtrate was concentrated under reduced pressure.
Prep. TLC (CH2Cl2/MeOH10 :1, 2”dev.) yielded 14 (30 mg, 75%). Colorless powder. M.p. 94.4–96.38.
IR: 3305vs, 3063s, 3032s, 2984s, 2945s, 2879m, 1720vs, 1666vs, 1620vs, 1537vs, 1498vs, 1469s, 1454vs,
1419vs, 1383s, 1366s, 1341s, 1294(sh), 1245vs, 1217s, 1178s, 1152s, 1084w, 1053s, 1028m, 912w, 744s,
1
699vs. H-NMR (600 MHz): 7.37–7.21 (m, 10 arom. H); 6.58 (br. s, NH(Aib)); 5.43 (br. s, NH(Phe));
5.12, 5.07 (AB, J=12.1, CH2(carbamate)); 4.57–4.54 (m, CH a()(Pro)); 4.41 (q-like, Jꢁ7.4, CH(a)
(Phe)); 3.39–3.35 (m, 1 Hof CH 2(d)(Pro)); 3.07–3.05 (m, CH2(Phe)); 2.96–2.94 (m, 1 H of
CH2(d)(Pro)); 2.09–1.95 (m, CH2(b)(Pro)); 1.78–1.68 (m, CH2(g)(Pro)); 1.37 (s, 2 Me(Aib)); COOH
could not be detected. 13C-NMR (150 MHz): 173.0 (s, CO(Pro)); 172.7 (s, CO(Aib)); 170.4 (s,
CO(Phe)); 156.3 (s, CO(carbamate)); 136.0, 135.9 (2s, 2 arom. C); 129.5, 128.8, 128.6, 128.4, 128.1,
127.2 (6d, 10 arom. CH); 67.4 (t, CH2(carbamate)); 61.6 (d, CH (a)(Pro)); 56.9 (s, C(a)(Aib)); 56.1 (d,
CH(a)(Phe)); 48.2 (t, CH2(d)(Pro)); 37.4 (t, CH2(Phe)); 27.3 (t, CH2(b)(Pro)); 25.9 (t, CH2(g)(Pro));
24.8, 24.3 (2q, 2 Me(Aib)). ESI-MS (MeOH): 504 (100, [M+Na]+). Anal. calc. for C26H31N3O6 ·H2O
(499.56): C 62.51, H6.66, N 8.41; found: C 62.80, H6.47, N 8.27.
N-{2-[((2S,3S)-2-{[(Benzyloxy)carbonyl]amino}-3-methyl-1-oxopentyl)amino]-2-methyl-1-oxopropyl}-
L-proline (15). A soln. of [Pd(Ph3P)4] (ca. 4 mg, ca. 0.004 mmol) and PhSiH3 (70 ml, 0.567 mmol) in
A

Helvetica Chimica Acta – Vol. 89 (2006)
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CH2Cl2 (1 ml), was added to a soln. of 12b (70 mg, 0.144 mmol) in CH2Cl2 (1 ml), and the mixture was
stirred at r.t. under Ar and exclusion of light for 50 min. The mixture was concentrated i.v. and purified
by prep. TLC (CH2Cl2/MeOH10 :1, 3”dev.) to give 15 (54 mg, 84%). Colorless powder. M.p.
101.5–103.28. IR: 3426s, 3306vs, 3063s, 3035s, 2966vs, 2936s, 2878s, 1705vs, 1659vs, 1622vs, 1535vs,
1469s, 1454vs, 1416vs, 1384s, 1365s, 1342s, 1309s, 1288s, 1245vs, 1178s, 1128m, 1094m, 1042s, 1028m,
983w, 914w, 882w, 778w, 739m, 698s. 1H-NMR (600 MHz): 7.34–7.31 (m, 5 arom. H); 7.10 (br. s,
NH(Aib)); 5.69 (br. s, NH(Ile)); 5.11, 5.07 (AB, J=11.8, CH2(carbamate)); 4.55 (br. s, CH (a)(Pro));
3.97 (br. s, CH a( )(Ile)); 3.49 (br. s, CH2(d)(Pro)); 2.08–1.83 (m, CH2(b)(Pro), 1 Hof CH 2(g)(Pro),
CH(b)(Ile)); 1.75–1.67 (m, 1 Hof CH (g)(Pro)); 1.53, 1.51 (2s, 2 Me(Aib)); ca. 1.50, 1.67–1.09 (2m,
2
CH2(g)(Ile)); 0.92 (d, J=7.1, MeCH(b)(Ile)); 0.88 (t, J=7.1, MeCH2(g)(Ile)); COOHcould not be
detected. 13C-NMR (150 MHz): 173.9, 173.0, 171.1 (3s, 3 CO); 156.6 (s, CO(carbamate)); 136.2 (s, 1
arom. C); 128.6, 128.3, 128.0 (3d, 5 arom. CH); 67.1 (t, CH2(carbamate)); 61.7 (d, CH (a)(Pro)); 59.8
(d, CH a()(Ile)); 57.0 (s, C(a)(Aib)); 48.2 (t, CH2(d)(Pro)); 36.8 (d, CH b()(Ile)); 27.4 (t,
CH2(b)(Pro)); 25.9 (t, CH2(g)(Pro)); 24.8 (t, CH2(g)(Ile)); 24.5, 24.4 (2q, 2 Me(Aib)); 15.5 (q,
MeCH(b)(Ile)); 11.2 (q, MeCH2(g)(Ile)). ESI-MS (MeOH): 486 (19, [M+K]+), 470 (100, [M+Na]+),
305 (57, [MꢀProꢀCO]+). Anal. calc. for C23H33N3O6 ·H2O (465.54): C 59.34, H7.58, N 9.03; found: C
59.46, H7.41, N 8.69.
5. Synthesis of L-Prolinates 8a–8c. (9H-Fluoren-9-yl)methyl N-(2-Methyl-1-oxopropyl)-L-prolinate
(7a). At 08, DCC (1.227 g, 5.95 mmol) was added to a soln. of 6 (1.000 g, 5.40 mmol), (9H-fluoren-9-
yl)methanol (1.166 g, 5.94 mmol) and PPY (42 mg, 0.283 mmol) in CH2Cl2 (50 ml). After stirring at r.t.
for 4 h, the mixture was filtered, and the solvent was evaporated. CC (SiO2, AcOEt/hexane: 4 :6 !
6 :4) yielded 7a (1.786 g, 91%). Colorless powder. M.p. 104.4–107.38. IR: 2971m, 2951m, 2932m,
2892w, 2873m, 1750vs, 1707w, 1629vs, 1536w, 1471s, 1446s, 1432vs, 1381m, 1329s, 1320m, 1270m, 1196s,
1167vs, 1088m, 1035m, 1024w, 1003w, 955w, 945w, 903w, 752s, 741s. 1H-NMR (300 MHz; conformers
86 :14): 7.78–7.73, 7.64–7.54, 7.42–7.27 (3m, 8 arom. H); 4.64–4.59 (m, CH (a)(Pro)); 4.53–4.43 (m,
CH2(Fm)); 4.21 (t, J=6.3, CH(Fm)); 3.52–3.46 (m, CH2(d)(Pro)); 2.60 (sept., J=6.8, Me2CH);
U
2.11–2.01, 1.91–1.65 (2m, CH2(b)(Pro), CH2(g)(Pro)); 1.10, 1.06 (2d, J=6.8, 2 Me). 13C-NMR (75
MHz): 175.9, 172.4 (2s, 2 CO); 144.1, 143.7, 141.4, 141.4 (4s, 4 arom. C); 127.8, 127.2, 125.1, 125.0,
119.9 (5d, 8 arom. CH); 66.2 (t, CH2(Fm)); 58.8 (d, CH a()(Pro)); 47.1 (d, CH(Fm)); 46.7 (t,
CH2(d)(Pro)); 32.3 (d, Me2CH); 29.0, 24.7 (2t, CH2(b)(Pro), CH2(g)(Pro)); 18.8, 18.7 (2q, 2 Me). ESI-
MS (MeOH): 414 (19, [M+H+H2O+MeOH]+), 386 (100, [M+Na]+).
2-[(4-Nitrophenyl)sulfonyl]ethyl N-(2-Methyl-1-oxopropyl)-L-prolinate (7b). A soln. of 2-[(4-nitro-
phenyl)sulfonyl]ethanol (433 mg, 1.873 mmol), EDCI (474 mg, 2.473 mmol), DMAP (24 mg, 0.196
mmol), and 6 (381 mg, 2.057 mmol) in CH2Cl2 (30 ml) was stirred under N2 at r.t. for 1 d. Aq. AcOH
(5%, ca. 40 ml) was added, and the mixture was extracted with CH2Cl2. The combined org. layers
were dried (Na2SO4) and concentrated i.v. CC (SiO2; CH2Cl2/MeOH50 :1) yielded 7b (683 mg, 92%).
Colorless powder. M.p. 89.8–91.98. IR: 3463w, 3119w, 2975s, 2931m, 2879w, 1740vs, 1642vs, 1608m,
1530vs, 1467m, 1428vs, 1391m, 1351vs, 1330vs, 1312vs, 1302vs, 1270w, 1248m, 1210m, 1179vs, 1146vs,
1
1104m, 1089s, 1046w, 1010m, 994w, 919w, 857m, 840w, 805w, 757s, 739s, 703s. H-NMR (300 MHz; con-
formers 96 :4): 8.44–8.40, 8.20–8.15 (2m, 4 arom. H); 4.51–4.46 (m, CH
N
G
CH(a)(Pro)); 3.67–3.49 (m, CH2CH2O, CH2(d)(Pro)); 2.64 (sept., J=6.8, Me2
AHCTREUNG
CH2(b)(Pro), CH2(g)(Pro)); 1.12, 1.10 (2d, J=6.8, 2 Me). 13C-NMR (75 MHz): 176.0 (s, CO(amide));
171.8 (s, CO(ester)); 151.0, 144.8 (2s, 2 arom. C); 129.9, 124.6 (2d, 4 arom. CH); 58.5 (d, CH (a)(Pro));
57.5 (t, CH2CH2O); 55.1 (t, CH2CH2O); 46.8 (t, CH d()(Pro)); 32.2 (d, Me2CH); 28.8, 25.0 (2t,
CH2(b)(Pro), CH2(g)(Pro)); 18.8, 18.7 (2q, 2 Me). ESI-MS (MeOH, NaI): 421 (100, [M+Na]+).
2-[(4-Nitrophenyl)sulfanyl]ethyl N-(2-Methyl-1-oxopropyl)-L-prolinate (7c). At 08, DCC (513 mg,
2.486 mmol) was added to a soln. of 6 (420 mg, 2.268 mmol), 2-[(4-nitrophenyl)sulfanyl]ethanol (470
mg, 2.359 mmol), and PPY (38 mg, 0.256 mmol) in CH2Cl2 (20 ml). After stirring at r.t. for 5.5 h, the mix-
ture was filtered, and the solvent was evaporated. CC (SiO2; AcOEt/hexane 6 :4) yielded 7c (807 mg,
97%). Yellow oil. IR (film): 3469w, 3327w, 3100m, 3069w, 2972vs, 2933vs, 2876s, 1745vs, 1643vs, 1594vs,
1578vs, 1512vs, 1471vs, 1427vs, 1381vs, 1338vs, 1322(sh), 1274vs, 1243s, 1171vs, 1090vs, 1046s, 1009s,
966m, 953m, 916w, 886w, 853vs, 742vs. 1H-NMR (600 MHz; conformers 92 :8): 8.18–8.13, 7.44–7.40
(2m, 4 arom. H); 4.45–4.43 (m, CH a( )(Pro)); 4.39–4.30 (m, CH
N
N

1852
Helvetica Chimica Acta – Vol. 89 (2006)
CH); 2.21–2.16, 2.11–2.07, 2.02–1.93
CH2(d)(Pro)); 3.31–3.27 (m, CH2CH2O); 2.69 (sept., J=6.8, Me2
AHCTREUNG
(3m, CH2(b)(Pro), CH2(g)(Pro)); 1.16, 1.13 (2d, J=6.8, 2 Me). 13C-NMR (150 MHz): 176.0 (s, CO
(amide)); 172.3 (s, CO(ester)); 146.0, 145.4 (2s, 2 arom. C); 126.7, 124.1 (2d, 4 arom. CH); 62.5 (t,
CH2CH2O); 58.8 (d, CH (a)(Pro)); 46.8 (t, CH2(d)(Pro)); 32.3 (d, Me2CH); 30.3 (t, CH2CH2O); 29.1 (t,
CH2(b)(Pro)); 25.0 (t, CH2(g)(Pro)); 18.9, 18.7 (2q, 2 Me). ESI-MS (CH2Cl2, MeOH, NaI): 389 (100,
[M+Na]+).
(9H-Fluoren-9-yl)methyl N-(2-Methyl-1-thioxopropyl)-L-prolinate (8a). A suspension of Lawesson
reagent (dried i.v., 307 mg, 0.759 mmol) and 7a (499 mg, 1.373 mmol) in toluene (15 ml) was heated at
958 (oil bath) for 1 h. After cooling to r.t., the mixture was filtered, and the solvent was evaporated.
CC (SiO2; AcOEt/hexane 2 :8) yielded 8a (369 mg, 71%). Colorless powder. M.p. 174.1–176.38. IR:
2974m, 2964m, 2927m, 2873w, 1743vs, 1595w, 1554w, 1503w, 1461s, 1440vs, 1383s, 1359m, 1345s, 1336s,
1300w, 1270s, 1255m, 1229m, 1194vs, 1171vs, 1156vs, 1123s, 1020m, 1006s, 975m, 939m, 761s, 742vs,
716w. 1H-NMR (300 MHz; conformers 88 :12): 7.78–7.58, 7.42–7.27 (2m, 8 arom. H); 5.10–5.06 (m,
CH(a)(Pro)); 4.73 (dd, J=10.8, 5.6, 1 Hof CH (Fm)); 4.42 (dd, J=10.8, 6.4, 1 Hof CH (Fm)); 4.24
2
2
(t-like, J ꢁ 6.0, CH(Fm)); 3.68–3.63 (m, CH2(d)(Pro)); 2.94 (sept., J=6.6, Me2
ACHTREUNG
1.96–1.73 (2m, CH2(b)(Pro), CH2(g)(Pro)); 1.21, 1.11 (2d, J=6.5, 2 Me). 13C-NMR (CDCl3, 75 MHz):
209.7 (s, CS); 170.5 (s, CO); 144.0, 143.6, 141.4, 141.4 (4s, 4 arom. C); 127.8, 127.2, 125.2, 125.0, 119.9
(5d, 8 arom. H); 66.2 (t, CH2(Fm)); 65.3 (d, CH a( )(Pro)); 50.1 (t, CH2(d)(Pro)); 47.1 (d, CH(Fm));
38.7 (d, Me2CH); 28.7, 24.5 (2t, CH2(b)(Pro), CH2(g)(Pro)); 22.6, 22.4 (2q, 2 Me). ESI-MS (MeOH):
402 (100, [M+Na]+).
2-[(4-Nitrophenyl)sulfonyl]ethyl N-(2-Methyl-1-thioxopropyl)-L-prolinate (8b). A suspension of
Lawesson reagent (dried i.v., 374 mg, 0.925 mmol) and 7b (662 mg, 1.662 mmol) in toluene (20 ml) was
heated at 908 (oil bath) for 1 h. After cooling to r.t., the mixture was filtered, and the solvent was evapo-
rated. CC (SiO2; CH2Cl2/MeOH70 :1) yielded 8b (509 mg, 74%). Yellow powder. M.p. 174.1–176.38. IR:
3470w, 3109w, 3062w, 3033w, 2966s, 2924s, 2887m, 2864w, 1742vs, 1606m, 1524vs, 1475vs, 1458vs, 1402m,
1377s, 1350vs, 1327vs, 1303vs, 1264s, 1253s, 1226s, 1196vs, 1174vs, 1152vs, 1124s, 1106m, 1086s, 1070s,
1
1013s, 999m, 977m, 921w, 881w, 851s, 828w, 789w, 756vs, 738vs, 702vs. H-NMR (300 MHz; conformers
95 :5): 8.47–8.41, 8.20–8.14 (2m, 4 arom. H); 4.77–4.73 (m, CH (a)(Pro)); 4.61–4.44 (m, CH
N
G
4.13–3.85, 3.78–3.69 (2m, CH2(d)(Pro)); 3.63–3.46 (m, CH2CH2O); 3.02 (sept., J=6.6, Me2
AHCTREUNG
2.24–1.98 (m, CH2(b)(Pro), CH2(g)(Pro)); 1.21, 1.21 (2d, J=6.5, 2 Me). 13C-NMR (75 MHz): 209.9 (s,
CS); 169.8 (s, CO); 151.0, 144.8 (2s, 2 arom. C); 129.9, 124.6 (2d, 4 arom. CH); 65.0 (d, CH (a)(Pro));
57.6 (t, CH2CH2O); 55.1 (t, CH2CH2O); 50.3 (t, CH2(d)(Pro)); 38.7 (d, Me2CH); 28.5, 24.8 (2t,
CH2(b)(Pro), CH2(g)(Pro)); 22.7, 22.4 (2q, 2 Me). ESI-MS (MeOH, NaI): 437 (100, [M+Na]+), 206 (25).
2-[(4-Nitrophenyl)sulfanyl]ethyl N-(2-Methyl-1-thioxopropyl)-L-prolinate (8c). A suspension of
Lawesson reagent (dried i.v., 473 mg, 1.170 mmol) and 7c (773 mg, 2.110 mmol) in toluene (20 ml) was
heated at 908 (oil bath) for 1 h. After cooling to r.t., the mixture was filtered, and the solvent was evapo-
rated. CC (SiO2; CH2Cl2/MeOH300 :1 ! 100 :1) yielded 8c (599 mg, 74%). Yellow oil. IR (film): 3098w,
3067w, 2971vs, 2929s, 2878s, 1743vs, 1594vs, 1578vs, 1513vs, 1479vs, 1462vs, 1441vs, 1381vs, 1338vs, 1300s,
1268vs, 1257vs, 1227vs, 1188vs, 1166vs, 1125s, 1090vs, 1049m, 1016vs, 970s, 922w, 912w, 877w, 853vs, 841s,
779w, 742vs. 1H-NMR (300 MHz; conformers 93 :7): 8.16–8.13, 7.45–7.41 (2m, 4 arom. H); 5.05–5.01 (m,
CH(a)(Pro)); 4.41–4.30 (m, CH
N
G
CH2CH2O); 3.06 (sept., J=6.6, Me2
AHCTREUNG
J=6.6, 2 Me). 13C-NMR (75 MHz): 210.1 (s, CS); 170.5 (s, CO); 146.1, 145.6 (2s, 2 arom. C); 126.8,
124.3 (2d, 4 arom. CH); 65.4 (d, CH a()(Pro)); 62.8 (t, CH2CH2O); 50.5 (t, CH2(d)(Pro)); 38.9 (d,
Me2CH); 30.3 (t, CH2CH2O); 29.0, 25.0 (2t, CH2(b)(Pro), CH2(g)(Pro)); 22.9, 22.5 (2q, 2 Me). ESI-MS
(MeOH, NaI): 405 (100, [M+Na]+).
6. X-Ray Crystal-Structure Determination of 11a (Table and Fig.)4). A crystal of C24H26N2O4S,
obtained from CDCl3/Et2O, was used for a low-temp. X-ray crystal-structure determination. All measure-
G
4
)
CCDC-602724 contains the supplementary crystallographic data for this paper. These data can be
obtained free of charge from the Cambridge Crystallographic Data Center via http://www.ccdc.cam.
ac.uk/data_request/cif.

Helvetica Chimica Acta – Vol. 89 (2006)
1853
Table. Crystallographic Data for Compound 11a
Crystallized from
CDCl3/Et2
24H26N2O4
438.54
colorless, needle
0.08”0.10”0.30
160(1)
A
Empirical formula
Formula weight [g molꢀ1
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
C
A
G
G
]
Crystal system
Space group
monoclinic
P21
Z
2
Reflections for cell determination
2q Range for cell determination [8]
30655
4–55
Unit cell parameters
a [Š]
b [Š]
c [Š]
b [8]
9.2417(3)
11.1230(4)
11.4726(4)
110.418(2)
1105.24(7)
1.318
0.180
f and w
55
V [Š3]
Dx [g cmꢀ3
]
m(MoKa) [mmꢀ1
Scan type
]
2q(max) [8]
Transmission factors (min; max)
Total reflections measured
Symmetry independent reflections
Reflections with I>2s(I)
0.799; 0.994
24199
5044
4212
Reflections used in refinement
Parameters refined; restraints
Final R(F) [I>2s(I) reflections]
wR(F2) (all data)
5044
287; 1
0.0391
0.0862
w=[s2(F2os2)+(0.0369P)2 +0.2109P]ꢀ1 where P=(Fo2 +2F2c ) /3
Weights:
Goodness-of-fit
Final Dmax/s
D1 (max; min) [e Š
1.030
0.001
0.19; ꢀ0.22
ꢀ3
]
ments were conducted on a Nonius KappaCCD area-detector diffractometer [33] using graphite-mono-
chromated MoKa radiation (l 0.71073 Š) and an Oxford Cryosystems Cryostream 700 cooler. The data
collection and refinement parameters are given in the Table, and a view of the molecule is shown in the
Figure. Data reduction was performed with HKL Denzo and Scalepack [34]. The intensities were cor-
rected for Lorentz and polarization effects, and an absorption correction based on the multi-scan method
[35] was applied. Equivalent reflections, other than Friedel pairs, were merged. The structure was solved
by direct methods using SIR92 [36], which revealed the positions of all non-H-atoms. The non-H-atoms
were refined anisotropically. The amide H-atom was placed in the position indicated by a difference elec-
tron density map, and its position was allowed to refine together with an isotropic displacement param-
eter. All remaining H-atoms were placed in geometrically calculated positions and refined using a riding
model where each H-atom was assigned a fixed isotropic displacement parameter with a value equal to
1.2 Ueq of its parent C-atom (1.5 Ueq for the Me groups). Refinement of the structure was carried out on
F2 using full-matrix least-squares procedures, which minimized the function Sw(Fo2 ꢀF2c )2. A correction
for secondary extinction was applied. Refinement of the absolute structure parameter [37] yielded a
value of ꢀ0.08(6), which confidently confirms that the refined coordinates represent the true enantio-
morph. Neutral atom scattering factors for non-Hatoms were taken from [38a], and the scattering factors

1854
Helvetica Chimica Acta – Vol. 89 (2006)
for H-atoms were taken from [39]. Anomalous dispersion effects were included in Fc [40]; the values for
f’ and f’’ were those of [38b]. The values of the mass attenuation coefficients are those of [38c]. All cal-
culations were performed using the SHELXL97 [41] program.
REFERENCES
[1] W. F. DeGrado, Adv. Protein Chem. 1988, 39, 51.
[2] J. Rizo, L. M. Gierasch, Annu. Rev. Biochem. 1992, 61, 387.
[3] V. J. Hruby, F. Al-Obeidi, W. Kazmierski, Biochem. J. 1990, 268, 249.
[4] M. Mutter, Angew. Chem., Int. Ed. 1985, 24, 639.
[5] H. Brückner, T. Kripp, M. Kiess, in ꢀPeptides 1990ꢁ, Eds. E. Giralt, D. Andreu, ESCOM, Leiden,
1991, p. 387; C. Auvin-Guette, S. Rebuffat, Y. Prigent, B. Bodo, J. Am. Chem. Soc. 1992, 114, 2170.
[6] H. Heimgartner, Angew. Chem., Int. Ed. 1991, 30, 238.
[7] J. M. Humphrey, A. R. Chamberlin, Chem. Rev. 1997, 97, 2243.
[8] P. Wipf, H. Heimgartner, Helv. Chim. Acta 1986, 69, 1153; 1987, 70, 354.
[9] N. Pradeille, A. Linden, K. Mçhle, O. Zerbe, H. Heimgartner, Chem. Biodivers. 2005, 2, 1127.
[10] S. A. Stoykova, Ph. D. thesis, Universität Zürich, 2005.
[11] R. T. N. Luykx, A. Linden, H. Heimgartner, Helv. Chim. Acta 2003, 86, 4093.
[12] N. Pradeille, H. Heimgartner, J. Pept. Sci. 2003, 9, 827.
[13] S. Stamm, A. Linden, H. Heimgartner, Helv. Chim. Acta 2003, 86, 1371.
[14] K. A. Brun, Ph. D. thesis, Universität Zürich, 2002.
[15] J. Lehmann, A. Linden, H. Heimgartner, Tetrahedron 1998, 54, 8721.
[16] C. B. Bucher, H. Heimgartner, Helv. Chim. Acta 1996, 79, 1903.
[17] W. Altherr, Ph. D. thesis, Universität Zürich, 1994.
[18] P. Wipf, H. Heimgartner, Helv. Chim. Acta 1990, 73, 13.
[19] S. Stamm, H. Heimgartner, Eur. J. Org. Chem.2004, 3820.
[20] S. Stamm, A. Linden, H. Heimgartner, Helv. Chim. Acta 2006, 89, 1.
[21] L. Whitmore, B. A. Wallace, Nucleic Acids Res. 2004, 32, D593–D594.
[22] R. T. N. Luykx, C. B. Bucher, A. Linden, H. Heimgartner, Helv. Chim. Acta 1996, 79, 527.
[23] S. Stamm, H. Heimgartner, Tetrahedron, in press.
[24] H. Kessler, R. Siegmeier, Tetrahedron Lett. 1983, 24, 281.
[25] M. A. Bednarek, M. Bodanszky, Int. J. Pept. Protein Res. 1983, 21, 196.
[26] D. A. Alonso, C. Nꢃjera, M. Varea, Synthesis 2003, 277.
[27] P. Wipf, Ph. D. thesis, Universität Zürich, 1987.
[28] J. B. Hendrickson, C. Kandall, Tetrahedron Lett. 1970, 11, 343.
[29] M. Dessolin, M.-G. Guillerez, N. Thieriet, F. Guibꢄ, A. Loffet, Tetrahedron Lett. 1995, 36, 5741.
[30] J. Bernstein, R. E. Davis, L. Shimoni, N.-L. Chang, Angew. Chem., Int. Ed. 1995, 34, 1555.
[31] C. K. Johnson, ORTEPII, Report ORNL-5138, Oak Ridge National Laboratory, Oak Ridge, Ten-
nessee, 1976.
[32] M. Namikoshi, B. Kundu, K. L. Rinehart, J. Org. Chem. 1991, 56, 5464.
[33] R. Hooft, KappaCCD Collect Software, Nonius BV, Delft, The Netherlands, 1999.
[34] Z. Otwinowski, W. Minor, in ꢀMethods in Enzymologyꢁ, Vol. 276, ꢀMacromolecular Crystallogra-
phyꢁ, Part A, Eds. C. W. Carter Jr., R. M. Sweet, Academic Press, New York, 1997, p. 307.
[35] R. H. Blessing, Acta Crystallogr., Sect A 1995, 51, 33.
[36] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M. C. Burla, G. Polidori, M. Camalli,
SIR92, J. Appl. Crystallogr. 1994, 27, 435.
[37] H. D. Flack, G. Bernardinelli, Acta Crystallogr., Sect A 1999, 55, 908; H. D. Flack, G. Bernardinelli,
J. Appl. Crystallogr. 2000, 33, 1143.
[38] a) E. N. Maslen, A. G. Fox, M. A. OꢁKeefe, in ꢀInternational Tables for Crystallographyꢁ, Ed. A. J.
C. Wilson, Kluwer Academic Publishers, Dordrecht, 1992, Vol. C, Table 6.1.1.1, p. 477; b) D. C.
Creagh, W. J. McAuley, in ꢀInternational Tables for Crystallographyꢁ, Ed. A. J. C. Wilson, Kluwer
Academic Publishers, Dordrecht, 1992, Vol. C, Table 4.2.6.8, p. 219; c) D. C. Creagh, J. H. Hubbell,

Helvetica Chimica Acta – Vol. 89 (2006)
1855
in ꢀInternational Tables for Crystallographyꢁ, Ed. A. J. C. Wilson, Kluwer Academic Publishers,
Dordrecht, 1992, Vol. C, Table 4.2.4.3, p. 200.
[39] R. F. Stewart, E. R. Davidson, W. T. Simpson, J. Chem. Phys. 1965, 42, 3175.
[40] J. A. Ibers, W. C. Hamilton, Acta Crystallogr. 1964, 17, 781.
[41] G. M. Sheldrick, ꢀSHELXL97, Program for the Refinement of Crystal Structuresꢁ, University of
Gçttingen, Germany, 1997.
Received March 28, 2006