Thermal Arndt-Eistert reactions of N-tosyl cyclic α-amino acids

Article abstract of DOI:10.1080/00397910500213021

Thermal Arndt-Eistert reactions of N-tosyl cyclic α-amino acids were studied to explore the preparation of α,β-unsaturated esters bearing a terminal tosylamino group. For L-N-tosyl-aziridine 2-carboxylic acid and L-N-tosyl-azetidine 2-carboxylic acid, the corresponding (E)-α,β- unsaturated esters were obtained stereospecifically. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1080/00397910500213021

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Thermal Arndt–Eistert
Reactions of N‐Tosyl Cyclic
α‐Amino Acids
Jing Yi Jin a , Xue Wu a & Guan Rong Tian a
a Department of Chemistry, Yan Bian University, Yan
Ji City, Ji Lin, China
Version of record first published: 18 Aug 2006.
To cite this article: Jing Yi Jin , Xue Wu & Guan Rong Tian (2005): Thermal
Arndt–Eistert Reactions of N‐Tosyl Cyclic α‐Amino Acids, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
35:19, 2535-2541
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Synthetic Communicationsw, 35: 2535–2541, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500213021
Thermal Arndt–Eistert Reactions of
N-Tosyl Cyclic a-Amino Acids
Jing Yi Jin, Xue Wu, and Guan Rong Tian
Department of Chemistry, Yan Bian University, Yan Ji City, Ji Lin, China
Abstract: Thermal Arndt–Eistert reactions of N-tosyl cyclic a-amino acids were
studied to explore the preparation of a,b-unsaturated esters bearing a terminal
tosylamino group. For L-N-tosyl-aziridine 2-carboxylic acid and L-N-tosyl-azetidine
2-carboxylic acid, the corresponding (E)-a,b-unsaturated esters were obtained stereo-
specifically.
Keywords: a-Amino acids, Arndt–Eistert reaction, rearrangement, ring-open,
a,b-unsaturated esters
The Arndt–Eistert reaction has been widely used in the homologation of
carboxylic acids because of its good yield, easy operation, and retention of
the original chirality.[1] The reaction could be catalyzed by silver ions under
thermal conditions or irritated by photolysis. The ketene intermediates
encountered in the rearrangement provided unprecedented chances to
construct some specific molecular skeletons such as fused carbocycles[2]
and pyrrolidinones.[3] For the intensively pursued stereospecific construc-
tion[4] of the a,b-unsaturated systems, rearrangement of a,b-epoxy acids
under Arndt-Eistert conditions not only provided a general methodology of
g-hydroxyl-(E)-a,b-unsaturated esters[5] but also had been applied to syn-
thesize patuloide C and its homo analogs.[6] However, preparation of the
a,b-unsaturated esters with a terminal amino group was still tedious work
because of the rigorous experimental conditions and expensive starting
Received in Japan March 18, 2005
Address correspondence to Guan Rong Tian, Department of Chemistry, Yan Bian
University, Yan Ji City, Ji Lin 133002, China. E-mail: grtn@ybu.edu.cn
2535

2536
J. Y. Jin, X. Wu, and G. R. Tian
materials.[7] Here, we report thermal Arndt–Eistert reactions of N-tosyl cyclic
a-amino acids, which could provide a stereospecific construction of the (E)-
a,b-unsaturated esters with the terminal g- or d-N-tosylamino group in high
yields.
At first, L-N-tosyl-aziridine 2-carboxylic acid (1a) was prepared using
Baldwin’s method starting from L-serine.[8] The corresponding diazo ketone
(2a) was prepared by the mixed-anhydride method using iso-butyl chloro-
formate and triethylamine (TEA). Thermal decomposition of 2a catalyzed
by silver oxide in methanol gave the ring-opening product, methyl N-tosyl-
(2E)-butenoate (3a),[9] and no trace of the Z isomer was detected after purifi-
cation by silica-gel chromatography (Scheme 1).
Such result was different from the photo-rearrangement of the a,b-epoxy
diazo ketones, where the small amounts of Z isomer were obtained (about
10%).[5] The formation of two isomeric products was explained by
proposing generation of two different transition states with unequal energy
levels, namely, transition states with the s-trans and s-cis configurations.
The former is sterically less congested and thus more favorable to the nucleo-
philic addition of the alcohol, which resulted in the majority of the
E-product.[10] As nitrogen analogs of oxiranes,[11] N-tosylated aziridines
have similar nucleophilic ring-opening reactivities, which have been
reported in the aza-Payne rearrangement.[12] Therefore, the similar ketene
intermediate 4a should be encountered during the thermal decomposition of
the a-diazo ketone 2a, but existence of the corresponding s-cis transition
state should be thermodynamically unfavorable because of both the steric
hindrance of the bulky tosyl group and the reaction temperature (refluxing
methanol). Subsequent nucleophilic attack of the methanol to the suggested
s-trans transition state resulted in an anti–ring opening to 3a exclusively
(Scheme 2).
The Arndt–Eistert reaction of L-N-tosyl-azetidine 2-carboxylic acid 1b
was further investigated as follows. L-N-Tosyl-a-amino-g-butyrolactone 5 was
obtained through an intramolecular ring closure starting from L-methionine.[13]
Scheme 1.

Thermal Arndt–Eistert Reactions
2537
Scheme 2.
After being refluxed with thionyl chloride in methanol, the optical lactone was
converted to the methyl ester quantitatively. Formation of the azetidine ring
was achieved using NaOMe as base in methanol. Subsequent hydrolysis
resulted in the acid 1b, which was transformed to the diazo ketone 2b. Sub-
sequent decomposition also provided methyl 5-tosylamino-(2E)-pentenoate
3b as the single product under the thermal Arndt–Eistert conditions (Scheme 3).
We also found that the thermal Arndt–Eistert reaction of L-N-tosyl
proline 1c[14] gave both the ring-opening product 3c (29%) and the normal
rearrangement product 8 (27%) in almost equal yield.[15] (Scheme 4). Such
results indicated that the nucleophilic addition of the methanol molecule to
the ketene intermediate 4c could occur competitively through the normal
homologation or the ring-opening pathway.
Scheme 3.

2538
J. Y. Jin, X. Wu, and G. R. Tian
Scheme 4.
Further studies on the corresponding racemic substrates also gave
the same results, which indicated that such ring opening is highly stereo-
specific regardless of the configuration of the original chiral center. In brief,
our research indicated new stereospecific synthetic possibilities for the
a,b-unsaturated esters with an E configuration bearing a terminal tosylamino
group from a-amino acids. We hope our reports could be some helpful to the
synthetic methodologies.
EXPERIMENTAL
General Procedures for Preparation of a-Diazomethyl Ketones 2a–c
All diazomethyl ketones were prepared by a mixed-anyhydride method using
iso-butyl chloroformate. Typically, the N-tosyl cyclic a-amino acid 1
(1.0 mmol) was dissolved in ethyl ether (5 mL). At 258C, triethylamine
(153mL) and iso-butyl chloroformate (143mL) were slowly added simul-
taneously. After stirring for another 30 min at the same temperature, the
reaction mixture was filtered. The filtrate was added slowly to the diazo-
methane ethereal solution (containing diazomethane 3–4 eq.) in an ice bath.
The solvents were removed under reduced pressure after 2 h. The obtained
oil was purified on a silica-gel column.
Compound 2a, L-N-tosyl-2-diazoacetylaziridine: Yield: 72%. Mp: 74–
768C. [a]2D0 24.28 (c, 0.5, CHCl3). IR (KBr, cm21): 2117, 1648, 1167. H
1

Thermal Arndt–Eistert Reactions
2539
NMR (300 MHz, CDCl3): d 7.81 (d, J ¼ 8.2 Hz, 2H), 7.37 (d, J ¼ 8.2 Hz, 2H),
5.50 (s, 1H), 3.26 (dd, J ¼ 4.0, 7.5 Hz, 1H), 2.81 (d, J ¼ 7.5 Hz, 1H), 2.47
(s, 3H), 2.43 (d, J ¼ 4.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): d 187.6,
145.8, 134.1, 130.4, 128.6, 126.3, 54.2, 41.2, 33.2, 22.1. Anal. calcd. for
C11H11N3O3S: C, 49.80; H, 4.18; N, 15.84. Found: C, 49.79; H, 4.32; N, 15.57.
Compound 2b: Yield: 82%. Mp: 162–1638C (Dec.); [a]2D0 ¼ þ1.3 (c, 0.08,
CHCl3); IR (KBr, cm21): 2121, 1611, 1358, 1157. 1H NMR (300 MHz,
CDCl3): d 7.73 (d, J ¼ 8.1 Hz, 2H), 7.42 (d, J ¼ 8.1 Hz, 2H), 6.27 (s, 1H),
4.28–4.22 (m, 1H), 3.81–3.73 (m, 1H), 3.61 (q, J ¼ 8.5 Hz, 1H), 2.49
(s, 3H), 2.30–2.17 (m, 2H). 13C NMR (75 MHz, CDCl3): d 193.5, 145.3,
130.9, 130.5, 129.0, 128.7, 66.1, 54.6, 48.6, 22.0, 21.1. Anal. calcd. for
C12H13N3O3S: C, 51.60; H, 4.69; N, 15.04. Found: C, 51.56; H, 4.70;
N, 14.76. All data of compound 2c is in a good agreement with reference 14.
General Procedures for Thermal Decomposition of a-Diazomethyl
Ketones 2a–c
a-Diazomethyl ketone 2 (1.0 mmol) was dissolved in methanol (10 mL), and
then triethylamine (14 mL) and silver oxide (57 mg) were added. Under
nitrogen atmosphere, the reaction mixture was refluxed for 40–60 min in
darkness. After cooling, decolorization with activated charcoal, and evapo-
ration under reduced pressure, the obtained pale yellow oil was purified on
a silica-gel column (EtOAc–n-hexane, 1 : 1) to afford the products.
Compound 3a, methyl 4-tosylamino-(2E)-butenoate: Yield: 77%. All data
is in a good agreement with reference 9.
Compound 3b, methyl 5-tosylamino-(2E)-pentenoate: Yield: 84%. IR
1
(film, cm21): 3278, 1717, 1651, 1436, 1160. H NMR (300 MHz, CDCl3):
d 7.74 (d, J ¼ 8.1 Hz, 2H), 7.32 (d, J ¼ 8.1 Hz, 2H), 6.79 (dt, J ¼ 7.0,
15.6 Hz, 1H), 5.81 (d, J ¼ 15.6 Hz, 1H), 4.88 (br, 1H), 3.72 (s, 3H),
3.11–3.05 (m, 2H), 2.44 (s, 3H), 2.39–2.35 (m, 2H). 13C NMR (75 MHz,
CDCl3): d 166.8, 144.8, 137.2, 130.2, 127.5, 124.0, 52.0, 41.9, 32.7, 22.0.
HRMS (EI) calcd. for C13H17NO4S: 283.0878. Found: 283.0883.
Compound 3c, methyl 6-tosylamino-(2E)-hexenoate: Yield: 29%. Mp:
70–718C. IR (KBr): 3262 (br), 1719, 1659 cm21 1H NMR (300 MHz,
.
CDCl3): d 7.71 (d, J ¼ 8.4 Hz, 2H), 7.36 (d, J ¼ 8.4 Hz, 2H), 6.85 (dt,
J ¼ 6.8, 16.0 Hz, 1H), 5.77 (d, J ¼ 16.0 Hz, 1H), 4.58 (br, 1H), 3.72 (s, 3H),
2.98–2.92 (m, 2H), 2.45 (s, 3H), 2.25–2.02 (m, 2H), 1.67–1.59 (m, 2H). 13
C
NMR (75 MHz, CDCl3): d 166.8, 147.8, 143.3, 136.9, 129.6, 127.0, 121.6,
51.3, 42.3, 28.9, 27.9, 21.4. Anal. calcd. for C14H19NO4S: C, 56.55; H,
6.44; N, 4.71. Found: C, 56.78; H, 6.41; N, 4.72.

2540
J. Y. Jin, X. Wu, and G. R. Tian
Compound 8, L-N-tosyl homoproline methyl ester: Yield: 27%. Mp: 101–
1
1038C. [a]2D0 23.4 (c, 0.2, CHCl3). IR (KBr, cm21): 1730, 1159. H NMR
(300 MHz, CDCl3): d 7.74 (d, J ¼ 8.2 Hz, 2H); 7.33 (d, J ¼ 8.0 Hz, 2H);
3.96–3.92 (m, 1H); 3.69 (s, 3H); 3.48–3.43 (m, 1H); 3.12–3.06 (m, 2H);
2.51 (dd, J ¼ 10.0, 16.2 Hz); 2.44 (s, 3H); 1.80–1.73 (m, 2H); 1.70–1.64
(m, 1H); 1.57–1.51 (m, 1H). 13C NMR (75 MHz, CDCl3): d 172.10, 144.0,
134.5, 130.1, 128.0, 57.0, 52.0, 49.6, 41.6, 32.1, 24.2, 21.9. Anal. calcd. for
C14H19NO4S: C, 56.55; H, 6.44; N, 4.71. Found: C, 56.47; H, 6.49; N, 4.85.
Yields were calculated after purification by silica-gel column chromato-
graphy.
ACKNOWLEDGMENTS
This work was supported by grants from the National Natural Science Foun-
dation of China and the Science and Technology Committee of Ji Lin
Province, China. We also thank Professor D. H. Kim and his group at the
Pohang University of Science and Technology in Korea for their great help
with this research.
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