Scientific paper
A Novel Oxidative Rearrangement of .^-Furanyl Carbamates Uncovered During a Planned Synthesis of a Daphniphyllum Alkaloid
Albert Padwa,* Carolyn A. Leverett and Xuechuan Hong
Department of Chemistry, Emory University, Atlanta, Georgia USA * Corresponding author: E-mail: chemap@emory.edu
Received: 30-07-2008 Dedicated to Professor Blanko Stanovnik on the occasion of his 7&h birthday
Abstract
E-Dimethyl 2-(2-oxycyclopentylidene)succinate was prepared by the TiCl4 catalyzed [2+2]-cycloaddition of (trimethyl-silyloxy)cyclopentene with DMAD followed by a base induced ring opening of the initially formed cycloadduct. It was necessary to protect the keto group as the 1,3-dithiane in order to prepare the corresponding W-furanyl carbamate 16. Loss of the Boc group occurs on heating at 130 °C or upon treatment of 16 with Mg(ClO4)2. In an attempt to convert the 1,3-dithiane of the resulting NH-carbamate 17 to the corresponding carbonyl group, the compound was treated with iodine in a basic aqueous solution. Under these conditions, a rather unusual oxidative rearrangement occurred to produce a substituted 5-hydroxy-1ff-pyrrol-2(5fl)-one. Analogous oxidative rearrangements were found to occur with structurally related 2-amidofurans. The mechanism of the oxidative rearrangement is comparable to the aza-Achmatowicz reaction.
Keywords: Furanyl carbamate, oxidative rearrangement, aza-Achmatowicz, daphniphyllum, alkaloid
1. Introduction
Plants of the genus Daphniphyllum contain structurally diversified alkaloids possessing a highly complex polycyclic skeleton.12 They were demonstrated to be derived from squalene-like intermediates by isotope tracer ex-periments3 and biomimetic total synthesis.4 Some of these alkaloids exhibit cytotoxin activities against several tumor cell lines.5'6 Some years ago, Heathcock proposed a bio-genetic pathway and developed biomimetic total syntheses of several members.4 Recently many new alkaloids were isolated from the daphniphyllum species,7 which have attracted interest as challenging targets for total synthe-sis8 as well as biogenetic studies.9-12 Members of this class of alkaloids generally possess an unprecedented he-xacyclic ring framework containing a bridged ABC tricyc-lic 4-azatricyclo[5.2.2.04•8]undecane (Figure 1). Among these, we have focused our attention on longeracinphyllin A (1) which was isolated in 2006 from the leaves of D. longeracemosum. This particular alkaloid contains a daphnilongeranin B type skeleton with a rearranged a,ß-
unsaturated ketone group, and its structure was supported by X-ray crystal data.13
Our synthetic approach toward the hexacyclic core found in the Daphniphyllum alkaloids was guided by a long-standing interest in developing new applications of the intramolecular [4+2]-cycloaddition/rearrangement cascade of 2-amidofurans toward the synthesis of complex natural products.14 Our recently completed syntheses of (±)-erysotramidine,15 (±)-lycoricidine16 and (±)-strychnine17 nicely demonstrate the utility of this process for the construction of various alkaloids. On the basis of our earlier work, we felt that we could also use this methodology for the synthesis of longeracinphyllin A (1) and this is outlined in Scheme 1. As illustrated in this scheme, the final step of the planned synthesis would involve closure of the A-ring by a Bonjoch/Solé palladium-catalyzed intramolecular coupling of the amido-tethered vinyl iodide 2 with a keto-enolate generated anion.1819 Our re-trosynthetic analysis envisions the pentacyclic amide 2 to be derived from an intramolecular Pauson-Khand reaction of alkyne 3, which in turn, should be available in se-
Figure 1. Structures of some Daphniphyllum Alkaloids
Scheme 1
veral straightforward steps from keto-amide 4. A critical step of our synthetic plan relies upon the efficient construction of the oxa-bicyclic intermediate 5 by an intramolecular [4+2]-cycloaddition (IMDAF) of furanyl carbamate 6. Reductive ring opening of cycloadduct 5 was expected to furnish 4.
2. Results and Discussion
Following this approach, we first prepared E-di-methyl 2-(2-oxycyclopentylidene) succinate (10) by making use of a [2+2]-cycloaddition of (trimethylsily-
loxy)cyclopentene (7) with DMAD under titanium tetrachloride catalysis.20 The resulting cyclobutene derivative 8 was then subjected to reaction with sodium hydride in t-butanol to furnish the ring cleavage product 9 as a transient intermediate. This material was readily isomeri-zed under the basic conditions to give the thermodynami-cally more stable isomer 10 (Scheme 2).
The base induced saponification of diester 10 proceeded smoothly with NaOH at 0 °C to give the expected mono-carboxylic acid 11 in excellent yield. However, all of our attempts to convert carboxylic acid 11 into furanyl carbamate 6 using either its acid chloride or mixed anhydride with the lithiated Boc-protected aminofuran 12 fai-
Scheme 2
led. Instead, the only product obtained corresponded to a-pyrone 13 (Scheme 3). Apparently, intramolecular cycli-zation of the activated carboxylic acid to a-pyrone 13 occurs at a much faster rate than bimolecular reaction with the lithiated amidofuran.
As a consequence of this ready cyclization, we decided to protect the keto group present in 10 so as to avoid a-pyrone formation in the coupling step. Thus, treatment of diester 10 with ethane-1,2-dithiol in the presence of 1 equiv of titanium tetrachloride furnished dithiane 14 in 85% yield. A subsequent base promoted saponification produced the expected carboxylic acid 15 which was smoothly converted to the corresponding furanyl carba-mate 16 according to the reactions outlined in Scheme 4. Unfortunately, all of our attempts to induce the IMDAF reaction by heating 16 at 130 °C in toluene failed to give
any cycloaddition product. Instead, the only product obtained corresponded to amide 17 derived by thermal loss of the Boc group. This same product could also be prepared by stirring a sample of 16 in CH3CN at 50 °C in the presence of Mg(ClO4)2.
Our previous studies dealing with the bimolecular [4+2]-cycloaddition of 2-amino substituted furans have shown that the reaction rates and product of these ther-molyses are markedly dependent upon the electronic properties of the alkenyl group.21 Because electron-withdrawing substituents on the n-bond exhibit a powerful influence on the rate of HOMO-dienyl [4+2]-cycloaddi-tions,22 we reasoned that it might be possible to induce the desired thermal IMDAF reaction by converting the 1,3-

Scheme 4
dithiane functionality of 17 back to the corresponding car-bonyl group. This would result in a lowering of the LU-MO energy of the olefinic n-bond and should facilitate the HOMO/LUMO cycloaddition reaction of the resulting furanyl carbamate.
As a carbonyl protecting group, the S,S-ketal function has found wide use in organic synthesis due to its easy access and high stability towards both acidic and basic conditions.23 1,3-Dithianes are particularly important as intermediates for carbon-carbon bond formation reactions by way of temporary inversion of reactivity of elec-trophilic carbonyl carbon (umpolung) through metalla-tion.24 A large number of methods are available for depro-tection of dithioketals to carbonyls.25 However, the regeneration of the parent carbonyl compounds is not always a facile and straightforward process and therefore develop-
ment of dethioketalization protocols has engaged the attention of organic chemists over the years.26 Many of the reported methods suffer from serious drawbacks such as the use of expensive catalysts,27 toxic reagents28 and in a few cases, more than stoichiometric amounts required of the reagents.29
With this background in mind, we opted to adopt a simple and generally convenient method for the deprotec-tion of dithianes30 and this involved stirring a sample of 17 with iodine in a basic aqueous medium at 0 °C for 3 h. Rather than converting the 1,3-dithiane functionality in 17 into the corresponding keto group, a rather unusual oxida-tive rearrangement occurred. The major and unexpected product obtained from this reaction (81%) was identified as 5-hydroxy-1^-pyrrol-2(5H)-one 18 on the basis of its spectral data (Scheme 5). Related iodine induced oxidati-ve rearrangements were also found to occur with amido-furan 19 as well as with furanyl carbamates 20 and 21.
.Scheme 5
It is well known that 2-furyl carbinols can be oxida-tively rearranged to pyranones by a variety of reagents, such as bromine in methanol.31 This transformation has become recognized as the Achmatowicz rearrangement in recognition of the pioneering work of O. Achmatowicz and his school in this area.32 The aza-Achmatowicz oxidation corresponds to a related process which involves the conversion of furylamides into 1,6-dihydro-2^-pyridin-3-ones.33 This novel oxidative rearrangement is often used for the synthesis of azasaccharides,34 izidine structures, ß-lactam intermediates, and unusual amino acids and has been shown to possess significant potential for the preparation of a variety of piperidine-based alkaloids.35
The oxidative process that we have uncovered and which is outlined in Scheme 5 is closely related to the aza-Achmatowicz reaction. The major difference is that the ni-
trogen atom is now attached directly to the furan ring rather than being separated from the heterocycle by a single carbon atom. More than likely the oxidative rearrangement proceeds by a mechanism related the aza-Achmato-wicz reaction. This would involve electrophilic attack of iodine on the activated furan to sequentially provide intermediate 25 and then 26 which ultimately culminates in cyclization to furnish the 5-hydroxy-1^-pyrrol-2(5H)-one skeleton (Scheme 6). In the case of the dithianyl substituted carbamate 17, the furan ring oxidation simply occurs at a faster rate than reaction at the S,S-ketal functionality.
Scheme 6
3. Conclusion
In conclusion, several 2-amidofurans were found to undergo a novel oxidative rearrangement when exposed to iodine to afford 5-hydroxy-1^-pyrrol-2(5H)-ones. The reaction proceeds by a mechanism similar to the aza-Ach-matowicz oxidation. Electrophilic addition of iodine at the furan ring occurs at a faster rate than reaction at the 1,3-dithiane center with compound 17, thereby preventing formation of the furanyl carbamate required for a synthesis of longeracinphyllin A. Application of other methods to generate the parent carbonyl compound from the 1,3-dithianyl substituted carbamate 17 is currently underway, the results of which will be disclosed in due course.
4. Experimental
(£)-Dimethyl 2-(2-oxocyclopentylidene)succinate (10).
To a -78 °C solution containing 0.5 g (3.5 mmol) of dimethyl acetylenedicarboxylate and 0.96 g (5 mmol) of titanium tetrachloride in 10 mL of CH2Cl2 was added a solution of 0.55 g (3.5 mmol) of (trimethylsilyloxy)cyclo-pentene in 10 mL of CH2Cl2 dropwise over a period of 5 min. After stirring for an additional 20 min at -78 °C, ether was added and the organic layer was separated and
washed with water, brine, dried over MgSO4, and evaporated under reduced pressure. The residue was subjected to silica gel chromatography to give dimethyl 1-hydroxy-bicyclo[3.2.0]hept-6-ene-6,7-dicarboxylate (8)20 as a colorless oil in 20% yield: IR (film) 3400, 1710, 1640, 1280, and 1150 cm-1; 1H-NMR (400 MHz, CDCl3) 5 1.67 (m, 6H), 3.08 (m, 1H), and 3.82 (s, 6H); Anal. Calcd for C11H14O5: C, 58.40; H. 6.24. Found: C, 58.27; H, 6.21.
A mixture containing 0.3 g (1.3 mmol) of the above alcohol 8 in 25 mL of tert-butyl alcohol was treated with sodium hydride (2 mmol) at 15 °C. After stirring for 10 min, several drops of acetic acid were added and the mixture was taken up in ether, washed with water, brine, dried over MgSO4, and evaporated under reduced pressure. The residue was subjected to silica gel chromatography to give 0.18 g (60%) of 10 as a pale yellow oil; IR (film) 1735, 1700, 1620, 1200, and 990 cm-1; 1H-NMR (400 MHz, CDCl3) 5 41.95 (p, 2H, J = 7.6 Hz), 2.42 (t, 2H, J = 7.6 Hz), 3.12 (t, 2H, J = 7.6 Hz), 3.68 (s, 3H), 3.80 (s, 3H), and 4.06 (s, 2H); Anal. Calcd for C11H14O5: C, 58.40; H,
6.24. Found: C, 58.32; H, 6.21. 11 14 5
(£)-Dimethyl 2-(1,4-dithiaspiro[4.4]nonan-6-ylide-ne)succinate (14). To a stirred solution containing 0.37 g (1.6 mmol) of the above diester 10 and 176 pL (2.1 mmol) of 1,2-ethanedithiol in 10 mL of CH2Cl2 at -78 °C was added 212 pL (1.9 mmol) of TiCl4 dropwise. The reaction mixture was slowly stirred while warming to 0 °C over 2 h and then diluted with H2O and extracted with EtjO. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography to give 0.42 g (85%) of 14 as a colorless oil; IR (thin film) 2951, 2870, 1732, 1434, 1333, 1278, 1197, 1166, and 1015 cm-1; 1H-NMR (400 MHz, CDCl3) 5 1.68 (p, 2H, J = 7.2 Hz), 2.17 (t, 2H, J = 7.2 Hz), 2.81 (t, 2H, J = 7.2 Hz), 3.24-3.31 (m, 2H), 3.35-3.41 (m, 2H), 3.59 (s, 3H), 3.66 (s, 3H), and 3.81 (s, 2H); 13C-NMR (100 MHz, CDCl3) 5 24.5, 34.3, 35.1, 40.1, 50.2, 51.5, 51.6, 71.3, 123.5, 158.4, 167.7, and 171.7; HRMS Calcd. for [C13H18S2O4 + H+]: 303.0725. Found: 303.0723.
1-Methyl 2-(1,4-dithiaspiro[4.4]non-6-ylidene)succina-te (15). To a stirred solution containing 0.9 g (4.0 mmol) of diester 14 in 35 mL of a 10:1-mixture of THF/H2O at 0 °C was added 26 mL of a 0.25 M NaOH solution (6.4 mmol) and the solution was stirred at rt for 4 h. The aqueous layer was acidified with 1 N HCl, extracted with Et-OAc, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 0.38 g (45%) of 15 as a white solid,36 mp 144-145 °C; IR (thin film) 3184, 2953, 2922, 2730, 2636, 1704, 1636, 1434, 1289, 1192, 1165, 1093, 1063, 949, and 808 cm-1; 1H-NMR (400 MHz, CDCl3) 5 1.72-1.79 (m, 2H), 2.25 (t, 2H, J = 7.4 Hz), 2.88 (t, 2H, J = 7.4 Hz), 3.32-3.38 (m, 2H), 3.43-3.49 (m,
2H), 3.74 (s, 3H), and 3.93 (s, 2H); 13C-NMR (100 MHz, CDCl3) 5 25.0, 35.0, 35.6, 40.6, 50.6, 52.0, 71.7, 123.4, 159.7, 168.1, and 177.4.
Methyl 4-(^er^-Butoxycarbonyl-furan-2-yl-amino)-2-(1,4-dithiaspiro[4.4]non-6-ylidene)-4-oxo-butyra-te(16). To a solution containing 0.4 g (2.2 mmol) of furan-2-yl carbamic acid tert-butyl ester (12) in 5 mL of THF at 0 °C was added dropwise 1.6 mL (2.2 mmol) of n-BuLi (2.5 M in hexane). The reaction mixture was stirred at 0 °C for 20 min. In a separate flask, 0.37 g (1.4 mmol) of 1-methyl 2-(1,4-dithiaspiro[4.4]non-6-ylidene)succinate (15) was dissolved in 5 mL of CH2Cl2 at -78 °C and 0.36 mL (4.0 mmol) of oxalyl chloride was added dropwise. After stirring for 25 min., the reaction mixture was warmed to 0 °C for 3 h and the solvent was removed under reduced pressure. The residue was taken up in 5 mL of THF and cooled to -78 °C and the above preformed lithiate was added dropwise via syringe. After stirring at -78 °C for 20 min and 0 °C for an additional 1 h, the reaction mixture was quenched with H2O and extracted with EtOAc. The organic layer was washed with a saturated aqueous Na-HCO3 solution, dried over MgSO4, and concentrated under reduced pressure. The residue was subjected to flash silica gel chromatography to afford 0.28 g (36%) of the titled compound 16 as a pale yellow oil; IR (neat) 2956, 2928, 1714, 1435, 1394, 1202, 1154, and 1095 cm-1; 1H-NMR (400 MHz, CDCl3) 5 1.42 (s, 9H), 1.70-1.74 (m, 2H), 2.21 (t, 2H, J = 5.8 Hz), 2.85 (t, 2H, J = 5.8 Hz), 3.31-3.35 (m, 2H), 3.43-3.46 (m, 2H), 3.69 (s, 3H), 4.37 (s, 2H), 6.11 (dd, 1H, J = 2.4 and 0.8 Hz), 6.37 (dd, 1H, J = 1.6 and 1.2 Hz), and 7.28-7.29 (m, 1H); 13C-NMR (100 MHz, CDCl3) 5 24.6, 27.7, 35.1, 38.0, 40.1, 50.2, 51.5, 71.5, 83.6, 105.7, 111.0, 124.2, 140.3, 143.6, 151.6, 157.4, 167.8 and 172.9; HRMS Calcd. for [C21H27NOgS2 + H+]: 453.1280. Found: 453.1277.
Methyl 2-(1,4-Dithia-spiro[4.4]non-6-ylidene)-^-furan-2-yl-succinamate (17). To a solution containing 0.22 g (0.49 mmol) of methyl 4-(tert-butoxycarbonyl-furan-2-yl-amino)-2-(1,4-dithiaspiro[4.4]non-6-ylidene)-4-oxo-but-yrate (16) in 5 mL of CH3CN was added 0.14 g (0.6 mmol) of magnesium perchlorate. The solution was heated at 45 °C for 1.5 h, then cooled to room temperature and the solvent was removed under reduced pressure. The residue was subjected to flash silica gel chromatography to give 0.14 g (85% yield) of the titled compound 17 as a colorless oil; IR (neat) 3281, 2956, 2925, 1694, 1608, 1548, 1432, 1297, 1238, 1198, and 1145 cm-1; 1H-NMR (400 MHz, CDCl3) 5 1.74-1.83 (m, 2H), 2.25 (t, 2H, J = 6.4 Hz), 2.85 (t, 2H, J = 6.4 Hz), 3.32-3.37 (m, 2H), 3.46-3.51 (m, 2H), 3.73 (s, 3H), 3.91 (s, 2H), 6.25 (d, 1H, J = 3.2 Hz), 6.99 (s, 1H), and 8.16 (s, 1H); 13C-NMR (100 MHz, CDCl3) 5 24.9, 35.7, 37.8, 40.8, 50.7, 52.3, 71.4, 95.1, 111.7, 124.2, 135.2, 145.8, 159.9, 167.1 and 168.4; HRMS Calcd. for [C1gH19NO4S2 + H+]: 354.0834. Found: 354.0833.
Methyl 2-(1,4-Dithiaspiro[4.4]non-6-ylidene)-4-(2-hy-droxy-5-oxo-2,5-dihydropyrr-ol-1-yl)-4-oxo-butyrate (18). A mixture containing 0.036 g (0.43 mmol) of sodium bicarbonate and 0.054 mg (0.21 mmol) of iodine were successively added to 0.025 g (0.07 mmol) of methyl 2-(1,4-dithia-spiro[4.4]non-6-ylidene)-N-furan-2-yl-suc-cinamate (17) in 5 mL of a 2:1-mixture of acetone/water at 0 °C. The reaction mixture was stirred for 3 h at 0 °C and then 15 mL of a saturated sodium thiosulfate solution was added. The solution was extracted with EtOAc and washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude oil was purified by flash chromatography on silica gel to afford 0.021 g (81%) of the titled compound 18 as a pale yellow oil: IR (neat) 3441, 2926, 1731, 1434, 1361, 1232, and 1201 cm-1; 1H-NMR (400 MHz, CDCl3) 5 1.73-1.80 (m, 2H), 2.24 (t, 2H, J = 6.4 Hz), 2.92 (t, 2H, J = 6.8 Hz), 3.26-3.34 (m, 2H), 3.40-3.47 (m, 2H), 3.72 (s, 3H), 4.31 (brs, 1H), 4.49 (m, 1H), 6.14 (s, 1H), 6.20 (d, 1H, J = 6.4 Hz), and 7.16 (dd, 1H, J = 6.4 and 2.0 Hz); 13C-NMR (100 MHz, CDCl23) 5 24.7, 35.2, 37.2, 40.3, 50.4, 51.7, 71.5, 82.1, 123.2, 128.4, 147.5, 158.7, 167.8, 168.1 and 172.4.
1-Acetyl-5-hydroxy-1H-pyrrol-2(5H)-one (22). To a
stirred solution containing 0.08 g (0.65 mmol) of N-(fu-ran-2-yl)acetamide 37 in 50 mL of a 20:1-acetone/H2O mixture at 0 °C was added 0.33 g (3.9 mmol) of NaHCO3 and the reaction mixture was stirred for 10 min. A 0.49 g (1.9 mmol) sample of iodine was added in 3 portions and the mixture was stirred at 0 °C for 3 h, then quenched with a saturated aqueous sodium thiosulfate solution and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography to give 0.05 g (77%) of 22 as a white solid, mp 86-87 °C (lit38 mp 90-91 °C); 1H-NMR (400 MHz, CDCl3) 5 2.54 (s, 3H), 4.48 (d, 1H, J = 4.0 Hz), 6.14-6.15 (m, 1H), 6.21 (dd, 1H, J = 6.0 and 1.2 Hz), and 7.16 (dd, 1H, J = 6.0 and 1.6 Hz); 13C-NMR (100 MHz, CDCl3) 5 24.3, 81.6, 128.2, 147.5, 167.8, and 171.3; Anal. Calcd. for CgH7NO3: C, 51.06; H, 5.00; N, 9.92. Found: C, 50.87; H, 4.91; NN, 9.89.
Ethyl 2-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-1-car-boxylate (23). To a stirred solution of 6.1 g of furan-2-ylcarbamic acid ethyl ester (39 mmol) in 650 mL of a 10:1-acetone/H2O mixture at 0 °C was added 19.8 g (236 mmol) of NaHCO3 and the reaction mixture was stirred for 5 min. A 30 g sample (118.1 mmol) of iodine was added in 3 portions and the mixture was stirred at 0 °C for 3 h, then quenched with a saturated aqueous sodium thio-sulfate solution and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to provide 4.2 g
(63%) of 23 as a pale yellow oil; IR (thin film) 3424, 3103, 2985, 1775, 1726, 1532, 1427, 1374, 1305, 1207, 1172, 1098, and 1052 cm-1; 1H-NMR (400 MHz, CDCl3) 5 1.40 (t, 3H, J = 7.2 Hz), 4.11 (brs, 1H), 4.40 (q, 2H, J = 7.2 Hz), 6.05 (s, 1H), 6.19-6.21 (m, 1H), and 7.10 (dd, 1H, J = 6.0 and 2.0 Hz); 13C-NMR (100 MHz, CDCl3) 5 14.6, 63.5, 82.4, 128.9, 146.7, 151.9, and 166.0; HRMS Calcd. for [C7H9NO4 + H+]: 172.0610. Found: 172.0609.
tert-Butyl 2-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate (24). To a stirred solution of 0.37 g of furan-2-ylcarbamic acid tert-butyl ester (12) (2.0 mmol) in 35 mL of a 10:1-acetone/H2O mixture at 0 °C was added 1.0 g (12.0 mmol) of NaHCO3 and the reaction mixture was stirred for 10 min. A 1.5 g (6.0 mmol) sample of iodine was added in 3 portions and the mixture was stirred at 0 °C for 3 h, then quenched with a saturated aqueous sodium thiosulfate solution and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to provide 0.35 g (87%) of 24 as a pale yellow solid, mp 80-81 °C; IR (thin film) 3428, 3102, 2981, 2935, 1766, 1368, 1314, 1258, 1160, 1106, and 1047 cm-1; 1H-NMR (400 MHz, CDCl3) 5 1.51 (s, 9H), 4.267-4.274 (m, 1H), 5.93 (d, 1H, J = 2.4 Hz), 6.09 (d, 1H, J = 4.4 Hz), and 7.00 (dd, 1H, J = 4.4 and 1.2 Hz); 13C-NMR (100 MHz, CDCl3) 5 28.0, 82.1, 83.9, 128.4, 146.3, 149.9 and 166.4; HRM3S Calcd. for [C9H13NO4 + H+]: 200.0923 Found 200.0921.
5. Acknowledgement
The financial support provided by the National Science Foundation (CHE-0450779) is greatly appreciated.
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Povzetek
£-Dimetil 2-(2-oksiciklopentilidenesuccinate je bil pripravljen s TiCl4 katalizirano [2+2]-cikloadicijo (trimetilsililok-si)ciklopentena z DMAD ter sledečim bazno induciranim odprtjem [2+2]-cikloadukta. Za nadaljnjo pretvorbo do N-fu-ranil karbamata 16 je bilo potrebno keto skupino zaščititi kot 1,3-ditiane. Odstranitev Boc skupine z intermediata 16 in pretvorba v NH-karbamat je potekla v prisotnosti Mg(ClO4)2 pri 130 °C. Pri poskusu odstranitve Boc skupine z jodom pod bazičnimi pogoji pa je potekla precej nenavadna premestitev spojine 16 v substituiran 5-hidroksi-1ff-pirol-2(5fl)-on. Analogne oksidativne premestitev so potekle tudi s strukturno sorodnimi 2-amidofurani. Mehanizem omenjene ok-sidativne premestitve je primerljiv z aza-Achmatowiczevo reakcijo.