A chiral, oxidatively cleavable auxiliary in β-lactam synthesis - Double diastereocontrol with p-methoxyphenethyl-substituted imines

Article abstract of DOI:10.1055/s-1999-3440

A new chiral, oxidatively removable auxiliary for the Staudinger reaction is presented. When diazo ketones 1-3 prepared from suitably protected amino acids reacted with p-methoxyphenethyl (PMPE)-substituted imines, the corresponding trans-substituted β-lactams 7 and 8a-h were formed. With the (S)-configured imine 5, an improvement of the selectivities is observed in comparison with achiral p-methoxybenzyl (PMB)-substituted imines by double stereoselection; consequently, the ratio of isomers decreased with the (R)-imine 4. The auxiliary could be removed with cerium ammonium nitrate (CAN).

Full text of DOI:10.1055/s-1999-3440

650
PAPER
A Chiral, Oxidatively Cleavable Auxiliary in b-Lactam Synthesis – Double
Diastereocontrol with p-Methoxyphenethyl-Substituted Imines
Joachim Podlech,* Steffen Steurer
Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany
Fax +49(711)6854269; E-mail: joachim.podlech@po.uni-stuttgart.de
Received 19 August 1998; revised 16 October 1998
Abstract: A new chiral, oxidatively removable auxiliary for the
Staudinger reaction is presented. When diazo ketones 1–3 prepared
from suitably protected amino acids reacted with p-methoxyphen-
ethyl (PMPE)-substituted imines, the corresponding trans-substi-
tuted b-lactams 7 and 8a–h were formed. With the (S)-configured
imine 5, an improvement of the selectivities is observed in compar-
ison with achiral p-methoxybenzyl (PMB)-substituted imines by
double stereoselection; consequently, the ratio of isomers decreased
with the (R)-imine 4. The auxiliary could be removed with cerium
ammonium nitrate (CAN).
Key words: protecting groups, double stereoinduction, b-lactam
synthesis, diazo ketones, imines
b-Lactams (2-azetidinones) are essential substructures of
natural products with antibiotic properties.1 The most fre-
quently used synthesis of b-lactams is the Staudinger re-
action, in which in situ generated ketenes, preferentially
Scheme 1
prepared from acid chlorides, are reacted with imines.2 b-
Lactams bearing no protection or substitution at the nitro-
gen are not accessible via this reaction; they can be ob-
The starting materials used herein, diazo ketones 1–3
were prepared from suitably protected amino acids (ala-
nine, valine and tert-leucine) in accordance with pub-
lished procedures.10 The imines 4–6 can be synthesized
without racemization and, above all, without tautomeriza-
tion using a method by Texier–Boullet starting from ben-
zaldehyde and the respective p-methoxybenzylamine.11
The chiral, enantiomerically pure amines can be obtained
by enzymatic resolution using lipases, e.g. candida
antarctica.12 In addition, (R)- and (S)-p-methoxypheneth-
ylamine, are commercially available.
tained through cleavage of the substituent introduced with
the imine. Recently, we presented a new variation of the
Staudinger reaction, in which ketenes A were prepared in
situ via a photochemical rearrangement of diazo ketones
prepared from amino acids, which react diastereoselec-
tively with imines to yield trans-substituted b-lactams.3
The diastereoselectivities can be additionally improved
when chiral, N-phenethyl-substituted imines are used.4
Nevertheless, this auxiliary which also acts as a protecting
group is, as well as the benzyl group, difficult to remove.5
We utilized the p-methoxybenzyl (PMB)-group6,7 in this
reaction,3b and we found that this auxiliary in the b-lac-
tams we used, cannot be removed with CAN.6 With these
conditions an over-oxidation to the corresponding p-
methoxybenzoyl-substituted b-lactam was observed.
While no cleavage of the PMB-group was observed with
2,3-dichloro-5,6-dicyano-1,4-quinone (DDQ),8 a reaction
to the deprotected b-lactams can be realized with potassi-
um peroxodisulfate in buffered media (Scheme 1).9
Photochemically induced rearrangement of diazo ketones
in the presence of PMPE-substituted imines led to the for-
mation of the corresponding b-lactams. Similar to prior
investigations, exclusively trans-substituted b-lactams
were observed (Scheme 2 and Table). As with phenethyl-
substituted imines, the selectivity decreased with the (R)-
configured imine 4; with the (S)-imine 5 an improvement
of the product ratio was observed. Rearrangement of the
diazo ketones with the achiral imine 6 led, as expected, to
diastereoselectivities in between. In all cases, the major
isomers 7a–h were first eluted in chromatography. The
relative configuration of all isomers could be assigned by
comparison with similar compounds.3 In the Staudinger
reaction of chiral ketenes with chiral imines, the latter has
generally no great influence on the asymmetric induc-
tion.13 Nevertheless, the effects we found significantly
In this paper we describe a chiral, oxidatively removable
auxiliary as an alternative to the phenethyl group. We
combined the positive influence of the phenethyl group on
the diastereoselectivity with the facile removability of the
PMB group. We used the resulting p-methoxyphenethyl
(PMPE) group as an N-substituent in imines for the
Staudinger reaction.
Synthesis 1999, No. 4, 650–654 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
A Chiral, Oxidatively Cleavable Auxiliary in b-Lactam Synthesis
651
Scheme 2
show a match-mismatch relationship. Besides the better
diastereoselectivities, which can be obtained when the
(S)-configured imine 5 was used in our reaction, a much
easier separation of the products can be achieved. The two
isomers, e.g. 7 and 8a, bearing a PMB-group with no cen-
tre of chirality, could not be separated, either by HPLC, or
by MPLC. The isomers 7 and 8b with a PMPE-group,
with an additional stereogenic centre, can be easily sepa-
rated by chromatography (a-value indicating the separa-
tion: 1.4).
Several methods for the cleavage of the PMPE-group in
7b were tested: While oxidation with N-
bromosuccinimide14 led to decomposition of the sub-
strate, no reaction was observed with triphenylcarbenium
tetrafluoroborate,15 m-chloroperbenzoic acid (mCPBA),16
or dimethyldioxirane (prepared in situ from oxone/ace-
tone)17 or under electrolytical conditions.18 Oxidation
with ammonium peroxodisulfate/silver nitrate (catalytic
amount)19 gave the deprotected b-lactam product, but due
to the formation of a side product, whose identity could
not be solved, the yields were unsatisfactory (46%). Since
no over-oxidation (vide supra) is possible with the PMPE
group, even stronger oxidising agents can be used. Conse-
quently, we tested CAN as oxidant, which gave best re-
sults. Nevertheless, in comparison with published
procedures,6,14,20 longer reaction times have to be accept-
ed. The unprotected b-lactam 9 could be isolated after 4 h
in 75% yield (Scheme 3). The auxiliary was liberated as
4-methoxyacetophenone (59%).
Scheme 3
Solvents for chromatography and for workup, e.g. EtOAc and light
petroleum (PE) were distilled prior to use, Et2O was distilled over
KOH/FeSO4. Et2O used for the reactions was distilled over Na/ben-
zophenone. The diazo ketones 1–310a,21 and the imines 4–611 were
prepared according to literature procedures, the parent chiral amines
can be purchased from Lancaster. Photochemically induced rear-
rangements were performed in a UV reactor system (Heraeus) with
a quartz filter. An immersion UV lamp TQ 150 (Philips) was used.
Flash column chromatography: Merck silica gel 60 (230 – 400
mesh). TLC: precoated sheets, Alugram SIL G/UV254 Macherey-
Nagel; detection by UV extinction, by cerium molybdate soln
[phosphomolybdic acid (25 g), Ce(SO4)2·H2O (10 g), concd H2SO4
(60 mL), H2O (940 mL)]. MPLC: detection with a UV detector.
HPLC: Analyses of diastereoisomer distribution were carried out
with a Pharmacia LKB, RSD 2140 apparatus with a Pharmacia
LKB, RSD 2249 mixer and diode-array detection (Pharmacia RSD
2140) on a LiChrosorb Si 60, Merck (hexane/ EtOAc, flow: 2.0 mL/
min) chromatographic column. 1H and 13C NMR spectra: d in ppm
relative to internal TMS (0 ppm) or to resonances of the solvent (1H:
CHCl3, 7.25 ppm; 13C: CDCl3, 77.0 ppm); in spectra of higher order,
d and J values are not corrected. Assignment of the 13C signals was
made with DEPT spectra. Mass spectra were recorded using FAB
or CI (CH4 or NH3) techniques. IR spectra were recorded with a
FTIR instrument. Elemental analyses were performed by the service
of the Institut für Organische Chemie, University of Stuttgart. Mps
are uncorrected.
In the present paper, we have demonstrated the versatility
of a new chiral, oxidatively removable auxiliary in the
preparation of b-lactams. Of course, this auxiliary is not
restricted to usage in b-lactam chemistry. It may also find
useful applications in all fields of diastereoselective syn-
thesis. Work in this direction is currently ongoing in our
laboratories.
Synthesis 1999, No. 4, 650–654 ISSN 0039-7881 © Thieme Stuttgart · New York

652
J. Podlech, S. Steurer
PAPER
Table b-Lactam Synthesis with PMPE- and PMB-Substituted Imines.
c
Start-
ing
Diazo
Ket-
one
Start-
ing
Imine
Prod-
ucta
Yield
(ra-
[a]20
mp
IR
1 H NMRd
(500 MHz, CDCl3)
d (ppm), J (Hz)
13C NMRd
(126 MHz, CDCl3)
d (ppm)
D
(ºC)
(Et2O/
PE)
(KBr/film)
tiob)
n (cm–1)
1
6
7ae,f
63%
7 : 3
–6
128–
129
3270,
3020,
1721,1705
1.32 (d, 3 H, J = 6.9, H-2’), 3.11 (dd,
1 H, J = 2.4, 2.4, H-3), 3.67 (d, 1 H,
NCHaHb, partly covered), 3.68 (s, 3 H,
OCH3), 4.19 (m, 1 H, H-1’), 4.23 (br s,
1 H, H-4), 4.78 (d, 1 H, J = 14.9,
19.8 (q, C-2’), 43.8
(t, NCH2Ph), 45.1
(d, C-1’), 55.1,
56.6 (q, d, C-4,
OCH3), 65.0 (d, C-
3), 167.5 (s, C-2)
NCHaHb), 4.95 (d, 1 H, J = 8.9, NH)
1
5 (S)
7b
53%
4 : 1
–3
139–
140
3263,
2960,
2918, 1703
1.31 (d, 3 H, J = 6.9, H-2’), 1.70 (d, 3
H, J = 7.1, H-2”), 3.03 (dd, 1 H, J =
2.9, 2.9, H-3), 3.68 (s, 3 H, OCH3),
4.19 (br s, 2 H, H-4, H-1’), 4.24 (q, 1 H,
J = 7.3, H-1”), 4.97 – 4.99 (m, 1 H, NH,
covered)
19.7, 19.9 (2 q,
2 CHCH3), 45.1 (d,
C-1’), 53.8, 55.1,
56.6 (q, 2 d, C-4,
C-1”, OCH3), 64.2
(d, C-3), 167.6 (s,
C-2)
8b
7c
–20
+28
oil
oil
3320,
2974,1736
1.19 (d, 3 H, J = 6.7, H-2’), 1.28 (d,
3 H, J = 7.1, H-2”), 2.99 (dd, 1 H, J =
7.9, 2.2, H-3), 3.79 (s, 3 H, OCH3),
4.07 (sextet, 1 H, J = 7.3, H-1’), 4.18
(br s, 1 H, H-4), 4.84 (d, 1 H, J = 8.8,
NH), 4.93 (q, 1 H, J = 7.0, H-1”)
18.4, 19.9 (2 q,
C-2’, C-2”), 45.9
(d, C-1’), 51.5,
55.0, 57.7 (q, 2 d,
C-4, C-1”, OCH3),
64.5 (d, C-3),
167.6 (s, C-2)
2
4 (R)
73%
7 : 3
3317,
2962, 1736
0.89 [d, 3 H, J = 6.8, CH(CH3)2], 0.91
[d, 3 H, J = 6.8, CH(CH3)2], 1.25 (d,
3 H, J = 7.2, H-2”), 1.89 [m, 1 H,
H-2’], 3.20 (dd, 1 H, J = 2.7, 2.7, H-3),
3.71 (s, 3 H, OCH3), 3.78 (m, 1 H,
H-1’), 4.10 (d, 1 H, J = 2.2, H-4), 4.80
(d, 1 H, J = 10.2, NH), 4.91 (q, 1 H,
J = 7.2, H-1”)
18.9, 19.7 [2 q,
CH(CH3)2, C-2”,
partly covered],
31.8 (d, C-2’),
51.5, 54.9, 55.1,
57.4 (q, 3 d, C-4,
C-1’, C-1”,
OCH3), 61.5 (d, C-
3), 167.7 (s, C-2)
8c
–11
oil
3425,
2962, 1741
0.82 [d, 3 H, J = 6.9, CH(CH3)2], 0.90
[d, 3 H, J = 6.8, CH(CH3)2], 1.71 (d,
3 H, J = 7.1, H-2”), 2.21 (m, 1 H,
H-2’), 2.99 (dd, 1 H, J = 9.7, 2.2, H-3),
3.74 (s, 3 H, OCH3), 4.08 (ddd, 1 H,
J = 10.0, 10.0, 3.9, H-1’), 4.27 (d, 1 H,
J = 2.1, H-4), 4.31 (q, 1 H, J = 7.2,
H-1”), 4.55 (d, 1 H, J = 10.2, NH)
16.1, 19.8 [2 q,
CH(CH3)2, C-2”,
partly covered],
29.9 (d, C-2’),
53.6, 55.2, 55.7,
58.2 (q, 3 d, C-4,
C-1’, C-1”,
OCH3), 62.4 (d,
C-3), 167.2 (s,
C-2)
2
6
7de
50%
5 : 1
+14
oil
3315,
2961, 1739
0.93 [d, 3 H, J = 6.8, CH(CH3)2], 0.94
[d, 3 H, J = 6.7, CH(CH3)2], 1.93 [m,
1 H, H-2’], 3.25 (dd, 1 H, J = 2.6, 2.6,
H-3), 3.67 (d, 1 H, J = 15.3, NCHaHb),
3.68 (s, 3 H, OCH3), 3.85 (ddd, 1 H,
J = 10.5, 7.6, 3.0, H-1’), 4.19 (d, 1 H, J
= 2.2, H-4), 4.77 (d, 1 H, J = 14.8,
NCHaHb), 4.88, (d, 1 H, J = 10.3, NH)g
18.8, 19.7 [2 q,
CH(CH3)2], 31.7
(d, C-2’), 43.7
(t, NCH2), 54.9,
54.9, 57.1 (q, 2 d,
C-4, C-1, OCH3),
62.3 (d, C-3),
167.3 (s, C-2)g
2
5 (S)
7e
61%
9 : 1
+19
oil
3318,
2961, 1738
0.93 [d, 6 H, J = 6.8, CH(CH3)2], 1.68
(d, 3 H, J = 7.1, H-2”), 1.93 (m, 1 H, H-
2’), 3.18 (dd, 1 H, J = 2.7, 2.7, H-3),
3.68 (s, 3 H, OCH3), 3.84 (ddd, 1 H,
J = 10.3, 7.4, 3.0, H-1’), 4.14 (d, 1 H, J
= 2.4, H-4), 4.25 (q, 1 H, J = 7.2, H-1”),
4.94 (d, 1 H, J = 10.2, NH)
18.9, 19.7, 19.9
[3 q, CH(CH3)2, C-
2”], 31.9 (d, C-2’),
53.9, 55.0, 55.2,
57.3 (q, 3 d, C-4,
C-1’, C-1”,
OCH3), 61.6 (C-3),
167.5 (s, C-2)
Synthesis 1999, No. 4, 650–654 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
A Chiral, Oxidatively Cleavable Auxiliary in b-Lactam Synthesis
653
Table (continued)
c
Start-
ing
Diazo
Ket-
one
Start-
ing
Imine
Prod-
ucta
Yield
(ra-
[a]20
mp
IR
1 H NMRd
(500 MHz, CDCl3)
d (ppm), J (Hz)
13C NMRd
(126 MHz, CDCl3)
d (ppm)
D
(ºC)
(Et2O/
PE)
(KBr/film)
tiob)
n (cm–1)
8e
7f
8f
–25
79–80
3340,
2940,
1736,
1712
0.80 [d, 3 H, J = 6.9, CH(CH3)2], 0.86
[d, 3 H, J = 6.8, CH(CH3)2], 1.31 (d,
3 H, J = 7.1, H-2”), 2.13 (m, 1 H,
H-2’), 3.04 (dd, 1 H, J = 9.5, 2.3, H-3),
3.76 (s, 3 H, OCH3), 4.02 (ddd, 1 H,
J = 9.8, 9.8, 4.0, H-1’), 4.19 (d, 1 H,
J = 1.9, H-4), 4.49 (d, 1 H, J = 10.1,
NH), 4.87 (q, 1 H, J = 7.1, H-1”)
16.3, 19.2, 19.8
(3 q, 3 CHCH3),
30.0 (d, C-2’),
51.9, 55.2, 55.5,
58.4 (q, 3 d, C-4,
C-1’, C-1”,
OCH3), 62.4
(d, C-3), 167.4
(s, C-2)
3
4 (R)
41%
7 : 1
+49
oil
3322,
2963,
1740
0.90 [s, 9 H, C(CH3)3], 1.24 (d, 3 H,
J = 7.2, H-2”), 3.26 (dd, 1 H, J = 2.3,
2.3, H-3), 3.72 (s, 3 H, OCH3), 3.83
(dd, 1 H, J = 10.7, 2.1, H-1’), 4.08
(d, 1 H, J = 2.5, H-4), 4.86 (q, 1 H,
J = 7.2, H-1”), 4.98 (d, 1 H, J = 10.8,
NH)
18.8 (q, C-2”),
26.7 [q, C(CH3)3],
34.6
(s, C-2’), 51.7,
55.1, 57.9, 58.2
(q, 3 d, C-4, C-1’,
C-1”, OCH3), 60.4
(d, C-3), 167.3
(s, C-2)
–84
142–
145
3250,
2942,
1744,
1722
0.85 [s, 9 H, C(CH3)3], 1.71 (d, 3 H,
J = 7.1, H-2”), 3.27 (dd, 1 H, J = 4.6,
1.8, H-3), 3.68 (s, 3 H, OCH3), 3.95
(d, 1 H, J = 1.6, H-4), 4.10 (q, 1 H,
J = 7.1, H-1”), 4.13 (dd, 1 H, J = 10.7,
5.2, H-1’), 4.65 (d, 1 H, J = 10.6, NH)
20.4 (q, C-2”),
26.8
[q, C(CH3)3], 34.7
(s, C-2’), 54.2,
55.2, 56.7, 57.7
(q, 3 d, C-4, C-1’,
C-1”, OCH3), 60.7
(d, C-3), 167.6
(s, C-2)
3
6
7ge
72%
11 : 1
+37
oil
3317,
2960,
1746
0.93 [s, 9 H, C(CH3)3], 3.27 (dd, 1 H,
J = 1.9, 1.9, H-3), 3.65 (d, 1 H,
J = 15.3, NCHaHb), 3.69 (s, 3 H,
OCH3), 3.90 (dd, 1 H, J = 10.7, 2.3,
H-1’), 4.17 (d, 1 H, J = 2.3, H-4), 4.75
(d, 1 H, J = 14.9, NCHaHb), 5.07
(d, 1 H, J = 10.7, NH)g
26.7 [q, C(CH3)3],
34.6 (s, C-2’), 43.8
(t, NCH2), 55.1
(d, C-1’), 58.0,
58.1 (q, d, C-4,
OCH3), 61.2 (d,
C-3), 167.0
(s, C-2)g
3
5 (S)
7he
69%
13 : 1
+35
oil
2326,
2963,
1740
0.92 [s, 9 H, C(CH3)3], 1.67 (d, 3 H,
J = 7.1, H-2”), 3.25 (dd, 1 H, J = 2.0,
2.0, H-3), 3.68 (s, 3 H, OCH3), 3.88
(dd, 1 H, J = 10.7, 1.9, H-1’), 4.12
(d, 1 H, J = 2.3, H-4), 4.23 (q, 1 H,
J = 7.1, H-1”), 5.10 (d, 1 H, J = 10.7,
NH)
19.9 (q, C-2”),
26.7 [q, C(CH3)3],
34.6 (s, C-2’),
53.8, 55.1, 57.9,
58.1 (q, 3 d, C-4,
C-1’, C-1”,
OCH3), 60.4
(d, C-3), 167.2
(s, C-2)
a Satisfactory elemental analyses obtained (C ±0.33, H ±0.13, N ±0.14), except for 7f (C –0.44) and 7h (C –0.68). Mass spectra are in accordance
with the proposed structures.
b Determined by HPLC and 1H NMR spectrsocopy.
c c = 0.5 – 1.6 (CHCl3).
d NMR data of the Cbz group and the aromatic rings are omitted.
e The minor isomer was not isolated. The diastereoselectivity was determined by evaluation of the proton signals at C-3 which are not covered
by other signals: 8a: d 3.34; 8d: d 3.17; 8g: d 3.24; 8h: d 3.18.
f The diastereoisomers could not be separated by MPLC. Pure 7a was obtained by recrystallization (Et2O / PE).
g 1H NMR: 250 MHz, 13C NMR: 63 MHz.
Synthesis 1999, No. 4, 650–654 ISSN 0039-7881 © Thieme Stuttgart · New York

654
J. Podlech, S. Steurer
PAPER
b-Lactams 7 and 8; General Procedure
(3) (a) Podlech, J. Synlett 1996, 582.
In a quartz photo reactor diazo ketone (2 mmol) and imine (4 mmol)
were dissolved in Et2O (300 mL), the mixture was cooled to –15 oC
and irradiated for 90 min. The mixture was stirred for further 30 min
at this temperature and then warmed to r.t. The solvent was removed
and the isomer ratio was determined by HPLC and 1H NMR
spectroscopy. The diastereoisomers were separated by flash chro-
matography or MPLC.
(b) Podlech, J.; Linder, M. R. J. Org. Chem. 1997, 62, 5873.
(4) Masamune, S.; Choy, W.; Petersen, J. S.; Sita, L. R. Angew.
Chem. 1985, 97, 1; Angew. Chem. Int. Ed. Engl. 1985, 24, 1.
Juaristi, E.; Escalante, J.; León-Romo, J. L.; Reyes, A.
Tetrahedron: Asymmetry 1998, 9, 715.
see as well: Krämer, B.; Franz, T.; Picasso, S.; Pruschek, P.;
Jäger, V. Synlett 1997, 295.
(5) Wild, H. in The Organic Chemistry of b-Lactams; Georg, G.
(3R,4S,1’S)-3-[1-(Benzyloxycarbonylamino)ethyl]-4-phenylaze-
tidin-2-one (9)
I., Ed.; VCH: New York, 1993, p 1.
Ojima, I. in The Organic Chemistry of b-Lactams; Georg, G.
I., Ed.; VCH: New York, 1993, p 197.
Thomas, R. C. Tetrahedron Lett. 1989, 30, 5239.
(6) Yamaura, M.; Suzuki, T.; Hashimoto, H.; Yoshimura, J.;
Okamoto, T.; Shin, C.-g. Bull. Chem. Soc. Jpn. 1985, 58,
1413.
(7) Fukuyama, T.; Jow, C.-K.; Cheung, M. Tetrahedron Lett.
1995, 36, 6373.
(8) KocieÒski, P. J., Protecting Groups; Thieme: Stuttgart, 1994,
p. 224.
CAN (540 mg, 985 mmol) was added at 0 ºC to a solution of b-lac-
tam 7b (150 mg, 327 mmol) in a mixture of H2O (4.6 mL) and
MeCN (3.5 mL) and the mixture was allowed to warm to r.t. After
4 h, the solution was extracted with EtOAc (3 × 20 mL) and re-ex-
tracted with sat. NaHCO3 (20 mL) and brine (20 mL). The resulting
NaHCO3 and brine solutions were additionally extracted with
EtOAc (20 mL) and the combined organic phases were dried
(MgSO4) and the solvents were removed. Chromatography (PE/
EtOAc 9: 1 → 2: 1) yielded b-lactam 9 (80 mg, 75%) and 4-meth-
oxyacetophenone (29 mg, 59%).
(9) Shiozaki, M.; Ishida, N.; Hiraoka, T.; Marayuma, H.
Tetrahedron 1984, 40, 1795.
Compound 9
Fetter, J.; Lempert, K.; Kajtár-Peredy, M.; Simig, G. J. Chem.
Soc., Perkin Trans. 1 1988, 1135.
Colourless solid, mp 177 – 178 ºC (Et2O/PE); Rf = 0.29 (TLC, PE /
EA 1: 1); [a]20D +22 (c = 0.5, CHCl3).
(10) (a) Podlech, J.; Seebach, D. Liebigs Ann. 1995, 1217.
(b) Matthews, J. L.; Braun, C.; Guibourdenche, C.; Overhand,
M.; Seebach, D. in Enantioselective Synthesis of b-Amino
Acids; Juaristi, E., Ed.; Wiley-VCH: New York, 1997, p 105.
(11) Texier-Boullet, F. Synthesis 1985, 679.
(12) Reetz, M. T.; Dreisbach, C. Chimia 1994, 48, 570.
Larsson, A. L. E.; Persson, B. A.; Bäckvall, J.-E. Angew.
Chem. 1997, 109, 1256; Angew. Chem., Int. Ed. Engl. 1997,
36, 1211.
IR (film): n = 3250 (NH), 3050 (CH), 1740, 1690 (C=O) cm–1.
1H NMR (500 MHz, CDCl3): d = 1.36 (d, 3 H, J = 7.0 Hz, H-2’),
3.14 (mc, 1 H, H-3), 4.28 (br s, 1 H, H-1’), 4.54 (br s, 1 H, H-4), 5.03
(d, 1 H, J = 9.0 Hz, OCHaHb), 5.11–5.17 (m, 2 H, carbamate-NH,
OCHaHb), 6.11 (br s, 1 H, lactam-NH), 7.32 – 7.37 (m, 10 H, 2 Ph).
13C NMR (126 MHz, CDCl3): d = 19.6 (q, C-2'), 45.1 (d, C-1'), 54.1
(d, C-4), 67.0 (d, C-3), 66.4 (t, OCH2), 125.6, 128.1, 128.3, 128.3,
128.6, 128.9 (6 d, 2 Ph), 136.3, 139.4 (2 s, 2 Ph), 156.3 (s, OC=O),
168.4 (s, C-2).
Balkenhohl, F.; Ditrich, K.; Hauer, B.; Ladner, W. J. Prakt.
Chem. 1997, 339, 381.
Balkenhohl, F.; Hauer, B.; Landner, W.; Pressler, U. (BASF
AG, Germany), DE 4332738 A1, Germany 1995; Chem.
Abstr. 1995, 112, 289035k.
+
MS (EI): m/z = 324 (M+, 6), 296 (26), 146 (59), 91 (C7H7 , 100).
Anal. calcd for C19H20N2O3 (324.4): C, 70.35%; H, 6.21%; N,
8.64%. Found: C, 70.14%; H, 6.16%; N, 8.53%.
(13) Ojima, I.; Chen, H.- J. C. J. Chem. Soc., Chem. Commun.
1987, 625.
Acknowledgement
Ojima, I.; Chen, H.-J. C.; Qiu, X. Tetrahedron Lett. 1988, 44,
5307.
The help of all members of the Institut für Organische Chemie, es-
pecially of Prof. Dr. V. Jäger and Prof. Dr. Dr. h. c. F. Effenberger
is gratefully acknowledged. We also thank Dr. A. Klein for his help
with the electrolytical experiments and M. Schütz for his work as
part of the advanced practical course. This work was further suppor-
ted by the Fonds der Chemischen Industrie, the Deutsche For-
schungsgemeinschaft, the Stiftungsfonds Mitsubishi Electric
Europe, the Landesgraduiertenförderung Baden-Württemberg, the
BASF AG (donation of enantiopure amines), and the Degussa AG
(amino acids).
(14) Classon, B.; Garegg, P. J.; Samuelsson, B. Acta Chem. Scand.,
Ser. B 1984, 38, 419.
(15) Takaku, H.; Kamaike, K. Chem. Lett. 1982, 189.
(16) Rao, A. S.; Mohan, H. R. in Encyclopedia of Reagents for
Organic Synthesis, Vol. 2; Paquette, L. A., Ed.; Wiley:
Chichester, 1995, p 1192.
(17) Murray, R. W.; Jeyaraman, R. J. Org. Chem. 1985, 50, 2847.
(18) Corley, E. G.; Karady, S.; Abramson, N. L.; Ellison, D.;
Weinstock, L. M. Tetrahedron Lett. 1988, 29, 1497.
(19) Bhattarai, K.; Cainelli, G.; Panunzio, M. Synlett 1990, 229.
(20) Yoshimura, J.; Yamaura, M.; Suzuki, T.; Hashimoto, H.
Chem. Lett. 1983, 1001.
References
Johansson, R.; Samuelsson, B. J. Chem. Soc., Perkin Trans. 1
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(21) Podlech, J.; Seebach, D. Helv. Chim. Acta 1995, 78, 1238.
(1) Gräfe, U. Biochemie der Antibiotika; Spektrum Akademischer
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(2) Georg, G. I.; Ravikumar, V. T. in The Organic Chemistry of
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Synthesis 1999, No. 4, 650–654 ISSN 0039-7881 © Thieme Stuttgart · New York