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DOI: 10.1055/s-0034-1378654
Synthesis of 1-Aminoisoquinolines via the Coinage Metal Cocatalyzed Reaction of 2-Alkynylbenzaldoximes with Isocyanoacetates
Publication History
Received: 25 May 2014
Accepted after revision: 27 July 2014
Publication Date:
27 August 2014 (online)
Abstract
An efficient reaction of 2-alkynylbenzaldoximes with 2-isocyanoacetates cocatalyzed by silver triflate and gold(I) chloride is described, providing 1-aminoisoquinolines in good to excellent yields under mild conditions. Mechanistic experiments suggest that the gold(I) cation might play a crucial role in the activation of the isocyanide substrate. The observed reactivity and the unique pathway of substrate activation in the cocatalyzed processes are quite informative for further study.
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Key words
1-aminoisoquinolines - coinage metals - deformylation - 2-alkynylbenzaldoximes - isocyanoacetatesIsoquinoline nuclei are key components of pharmacophores, natural products, and versatile synthetic building blocks.[1] In particular, 1-aminoisoquinoline derivatives have been found to act as efficacious inhibitors of mutant B-Raf enzyme,[2] PDE4,[3] adenosine A3 receptor,[4] and dopamine D2 and D3 receptors.[5] In addition, they also exhibit strong cytotoxic activity against different human cancer cell lines.[6] Consequently, continuous effort has been given to the development of methods for the rapid synthesis of these nitrogen-containing heterocycles in both academic and industrial laboratories. Typical 1-aminoisoquinolines are usually prepared starting from haloisoquinolines or metalated isoquinolines.[7] However, this ‘prefunctionalization’ strategy is obviously hindered by the extra preparation efforts to obtain the precursors and the formation of stoichiometric byproducts. Transition-metal-catalyzed C–N bond-formation reactions, which are represented by Buchwald–Hartwig[8] or Ullmann-type[9] amination reactions, are highly versatile, but several instances continue to pose challenges since the transformations need relatively expensive metal catalysts and ligands, or crucial inert conditions. Although much effort has been invested in the synthesis of functionalized isoquinoline derivatives, the preparation of specific 1-aminoisoquinolines remains highly desirable in synthetic organic chemistry. Thus, there is still an urgent need to develop new strategies for the rapid generation of diversified aminoisoquinoline derivatives under gentle conditions.
Transition-metal-catalyzed domino reactions have been well recognized as an efficient synthetic tool because they can provide straightforward access to structurally diverse molecules in a one-pot reaction process.[10] [11] For example, Wu and co-workers have described a novel silver triflate catalyzed/phosphonium salt promoted reaction of 2-alkynylbenzaldoximes with amines for the preparation of 1-aminoisoquinoline derivatives.[12] The reaction relies on silver triflate as an effective catalyst for the formation of the isoquinoline framework, and phosphonium salt as an efficient activator of the in situ formed isoquinoline N-oxide intermediate A (Scheme [1]).[13] Lu and co-workers have disclosed a silver triflate catalyzed tandem reaction of 2-alkynylbenzaldoximes with isothiocyanates to produce 1-aminoisoquinolines in moderate to good yields.[14] Despite these more advanced strategies, the generation of a stoichiometric amount of phosphorus oxide byproducts and the availability of the isothiocyanates as starting materials remain problematic.
Recently, we have been involved in the library construction project of natural-product-like heterocyclic small molecules for the study of chemical genetics.[15] Enlightened by the results noted above and the recent advancement of isocyanide chemistry,[16] we envisioned that a more straightforward method for 1-aminoisoquinoline formation would be feasible when isocyanide derivatives were employed in the catalytic reaction of isoquinoline N-oxide A (Scheme [1]). We reasoned that a metal–carbene intermediate B would be formed from the isocyanide 2 when activated by a suitable catalyst cation [M]+.[17] Then, a [3+2]-cycloaddition reaction of B with isoquinoline N-oxide A would occur to form an active metal–carbenoid intermediate C, which would be easily trapped by a trace amount of water through the known O–H carbenoid insertion reaction to give a key species like D.[18] This intermediate can undergo proton–metal ion exchange transformation followed by a base-promoted aromatization reaction to give the final product 3, along with concomitant regeneration of the catalyst (Scheme [1]). Described herein is our new discovery for the assemblage of 1-aminoisoquinolines via the silver- and gold-cocatalyzed tandem reaction of 2-alkynylbenzaldoximes 1 with isocyanides 2, which should shed light on transition-metal-catalyzed isocyanide activation chemistry, and offers a useful addition to the rapidly expanding, expedient synthetic routes to complex polycyclic skeletons.
The initial investigations were carried out on the reaction of 2-alkynylbenzaldoxime 1a with phenyl isocyanide or an alkyl isocyanide (t-BuNC). Since it was known that silver triflate is an efficient catalyst for the formation of isoquinoline N-oxide A via 6-endo-dig cyclization of 2-alkynylbenzaldoxime 1a, the preliminary reaction was undertaken with 10 mol% of silver triflate as catalyst in the presence of cesium carbonate in tetrahydrofuran at 70 °C. However, to our surprise, no desired product 3 was obtained, as detected by TLC and crude NMR analysis; the starting materials were fully consumed and the reaction quickly turned black (Table [1], entries 1 and 2). Pleasingly, the desired product 3aa was isolated in 5% yield when ethyl isocyanoacetate (2a), which contains an electron-withdrawing ester group in the molecule, was employed as a test substrate (Table [1], entry 3). The structure of compound 3aa was confirmed by X-ray diffraction analysis (Figure [1]).[19] This result demonstrated that the designed reaction was theoretically feasible, although the detailed reaction mechanism with such a particular electron-deficient isonitrile 2a workable in this process remains a puzzle at present.
a Unless otherwise indicated, all reactions were run under the following conditions: 1a (0.20 mmol), isocyanide 2 (1.2 equiv), base (1.2 equiv), solvent (1 mL), 70 °C, under N2.
b Isolated yield based on 1a.
c Using AuOTf as the sole catalyst.
Prompted by this interesting result, we determined to optimize the reaction conditions further. A dramatically enhanced yield of 54% was observed when a weak base, triethylamine, was added instead of cesium carbonate (Table [1], entry 4). Since the efficiency of multicatalytic processes has been well recognized in cascade cyclization reactions,[20] we conceived that the combination of multiple metal catalysts in one reaction could be powerful for the reaction activation of distinct substrates. Other Lewis acid catalysts [Fe(OTf)2, CuI, Bi(OTf)3, Pd(OAc)2] were shown to be less efficient, and no reaction occurred when boron trifluoride–diethyl ether complex was used (Table [1], entries 5–9). A promising result was obtained when gold(I) catalyst was added to the reaction mixture; the yield increased to 77% when gold(I) chloride was employed (Table [1], entries 10 and 11). However, considering that the gold(I) cation is well known as a stronger π-acid than silver(I) for the activation of alkyne, and also that gold(I) chloride would be transferred to gold(I) triflate in situ in the presence of silver triflate, we also tried using gold(I) triflate as the sole catalyst in the whole process, and found that 3aa was only isolated in 59% yield in this reaction (Table [1], entry 12).[13] [21] Increasing the amount of triethylamine to 3.0 equivalents did not facilitate the reaction (Table [1], entry 13).
Next, different bases were examined; however, only inferior results were obtained when other organic or inorganic bases were used (Table [1], entries 14–16). We further explored the reaction carried out in various solvents; tetrahydrofuran was demonstrated as the best choice (Table [1], entries 17–20 vs entry 11).
The scope of this silver triflate and gold(I) chloride cocatalyzed reaction was then investigated under the optimized conditions (10 mol% AgOTf, 5 mol% AuCl, 1.2 equiv Et3N, THF, 70 °C); the results are summarized in Table [2]. In the meantime, methyl isocyanoacetate (2b) was also examined in the reaction with 1a, and the corresponding product 3ab was isolated in good yield without difficulty (Table [2], entry 2). In most cases, the 2-alkynylbenzaldoximes 1 reacted with the 2-isocyanoacetates 2 smoothly to give the corresponding products 3 in good to excellent yields. For example, when R1 = H, reactions of 1 with the R2 group attached to the triple bond with electron-donating or electron-withdrawing functionalities, such as methyl, methoxy, chloro, or fluoro, all worked well to afford the desired products 3b–f in yields ranging from 72–90% (Table [2], entries 3–12). It was found that the intrinsically strained cyclopropyl group of 1g could also be tolerated; the desired products 3ga and 3gb were isolated in 56% and 70% yield, respectively (Table [2], entries 13 and 14). However, the reactions failed to proceed with substrates 1 bearing a tert-butyl group, a terminal hydrogen, or a trimethylsilyl group attached at the R2 position (data not shown in Table [2]).
a Isolated yield based on 2-alkynylbenzaldoximes 1.
To further assess the feasibility of using 2-isocyanoacetates as an efficient agent to introduce amines onto the isoquinoline nucleus, we next attempted the process with different R1 groups attached to the aromatic ring of 2-(phenylethynyl)benzaldoximes 1 (R2 = Ph). As can be seen from Table [2], all reactions worked well to produce the expected 1-aminoisoquinolines 3h–m in good yields (entries 15–26); the phenyl group attached to the triple bond did not affect the efficiency of the transformation, and R1 substitutions including electron-donating or electron-withdrawing groups afforded the desired outcomes.
To gain an insight into the reaction mechanism, we synthesized the isoquinoline N-oxide compound A_1a from readily available starting material 1a according to the literature procedure.[13] Compound A_1a could be recrystallized as a white floccular solid from a solvent mixture of dichloromethane–petroleum ether (1:3, v/v). We then subjected this compound as a starting material in the reaction with ethyl isocyanoacetate (2a) (Scheme [2]). Compound 3aa could be isolated in 81% yield with gold(I) chloride (5 mol%) catalysis and in the presence of triethylamine, whereas only a trace amount of product 3aa was observed when no gold(I) chloride was added. These results indicate that the gold(I) cation is an important activator of the isocyanoacetate in the reaction, thus giving some insight into the research design of isocyanide activation in the synthesis of N-containing heterocycles and the related mechanistic studies. Interestingly, no desired 1-aminoisoquinoline product was obtained in the reaction of isoquinoline N-oxide A_1a with phenyl isocyanide, n-butyl isocyanide, or tert-butyl isocyanide, which suggests the crucial importance of the ester group in the starting isocyanide substrates.
In conclusion, we have described an interesting silver triflate and gold(I) chloride cocatalyzed reaction of 2-alkynylbenzaldoximes with electron-deficient isocyanoacetates, to give 1-aminoisoquinolines in good to excellent yields. The reaction performed well when a weak organic base such as triethylamine was used, and displayed good functional group compatibility under mild conditions. Mechanistic experiments have suggested that the gold(I) cation might play a crucial role in the activation process of the isonitrile substrate into a metal–carbenoid reactive species. The observed reactivity and the unique pathway of substrate activation in the cocatalyzed processes are quite informative for further understanding. Further studies, including mechanistic studies, to extend the scope of this chemistry are being carried out in our laboratory.
Unless otherwise stated, all commercial reagents were used as received. All solvents were dried and distilled according to standard procedures. Flash column chromatography was performed using silica gel (60-Å pore size, 32–63 μm, standard grade). Melting points were determined on an x-4 digital display microscope apparatus. IR spectra were recorded on a Nicolet 6700 spectrophotometer. 1H and 13C NMR spectra were recorded in CDCl3 on a Bruker DRX-400 instrument at 400 MHz and 100 MHz, respectively, with TMS as an internal standard. 1H NMR signals are described as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet). The number of protons (n) for a given resonance is indicated as n H. Coupling constants are reported as J values in Hz. 13C NMR signals are reported as δ (ppm) downfield from TMS and relative to the signal of CDCl3 (δ 77.00, triplet). EI-MS data were measured on a Shimadzu GC/MS-QP2010Ultra (single quadrupole MS filter) mass spectrometer. High-resolution mass spectrometry (HRMS) spectra were obtained on a Bruker micrOTOF II instrument.
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1-Aminoisoquinolines 3 via the Gold-Catalyzed 1,3-Dipolar Cycloaddition Reaction; General Procedure
A THF solution (1.0 mL) containing a 2-alkynylbenzaldoxime 1 (0.20 mmol, 1.0 equiv) and AgOTf (0.02 mmol, 10 mol%) was heated to 70 °C for about 3 h under N2; then, AuCl (0.01 mmol, 5 mol%) and Et3N (0.24 mmol, 1.2 equiv) were added to the solution, followed by the addition of a 2-isocyanoacetate 2 (0.24 mmol, 1.2 equiv) in THF (0.5 mL) solution. The resulting mixture was stirred at 70 °C for a further 18–26 h. After completion of the reaction, as indicated by TLC, the reaction mixture was cooled to r.t., concentrated on a rotary evaporator, and purified by flash column chromatography (EtOAc–n-hexane, 1:6 to 1:10) to give the desired product 3 as a white or light yellow solid.
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Ethyl (3-Phenylisoquinolin-1-ylamino)acetate (3aa)
Yield: 47 mg (77%); mp 123–125 °C.
IR (KBr): 3430, 2988, 1729, 1622, 1530, 1212, 1179, 766 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.32 (t, J = 7.2 Hz, 3 H), 4.27 (q, J = 7.2 Hz, 2 H), 4.47 (d, J = 5.2 Hz, 2 H), 5.89 (br s, 1 H), 7.36 (t, J = 7.2 Hz, 1 H), 7.41–7.48 (m, 4 H), 7.58 (t, J = 7.2 Hz, 1 H), 7.73 (d, J = 8.4 Hz, 1 H), 7.85 (d, J = 8.4 Hz, 1 H), 8.15 (d, J = 7.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 14.2, 44.0, 61.2, 107.6, 117.5, 121.6, 125.8, 126.6, 127.6, 128.1, 128.4, 129.9, 138.0, 139.8, 148.4, 153.8, 171.8.
MS (EI): m/z (%) = 306 (34) [M+], 233 (100), 204 (45).
HRMS (ESI): m/z [M + H]+ calcd for C19H18N2O2: 307.1447; found: 307.1478.
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Methyl (3-Phenylisoquinolin-1-ylamino)acetate (3ab)
Yield: 50 mg (86%); mp 157–159 °C (Lit.[14] 158–159 °C).
1H NMR (400 MHz, CDCl3): δ = 3.83 (s, 3 H), 4.48 (d, J = 5.2 Hz, 2 H), 5.94 (br s, 1 H), 7.40 (t, J = 7.2 Hz, 2 H), 7.47 (d, J = 7.2 Hz, 3 H), 7.56 (t, J = 7.2 Hz, 1 H), 7.72 (d, J = 8.0 Hz, 1 H), 7.82 (d, J = 8.4 Hz, 1 H), 8.16 (d, J = 7.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 43.9, 52.2, 107.7, 117.4, 121.6, 125.9, 126.6, 127.6, 128.2, 128.5, 129.9, 137.9, 139.8, 148.4, 153.8, 172.3.
MS (EI): m/z (%) = 292 (37) [M+], 233 (100), 204 (43).
HRMS (ESI): m/z [M + Na]+ calcd for C18H16N2O2: 315.1109; found: 315.1121.
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Ethyl (3-p-Tolylisoquinolin-1-ylamino)acetate (3ba)
Yield: 56 mg (88%); mp 158–160 °C.
IR (KBr): 3426, 2985, 1727, 1603, 1508, 1276, 1154, 768 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.34 (t, J = 7.2 Hz, 3 H), 2.43 (s, 3 H), 4.30 (q, J = 7.2 Hz, 2 H), 4.47 (d, J = 4.8 Hz, 2 H), 5.95 (br s, 1 H), 7.28 (d, J = 8 Hz, 2 H), 7.39 (t, J = 7.2 Hz, 1 H), 7.45 (s, 1 H), 7.55 (t, J = 7.2 Hz, 1 H), 7.71 (d, J = 8 Hz, 1 H), 7.82 (d, J = 8.4 Hz, 1 H), 8.07 (d, J = 7.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 14.3, 21.3, 44.0, 61.2, 107.1, 117.3, 121.6, 125.6, 126.3, 126.5, 127.5, 129.2, 129.8, 137.1, 138.0, 148.5, 153.8, 171.9.
MS (EI): m/z (%) = 320 (38) [M+], 247 (100), 218 (47).
HRMS (ESI): m/z [M + H]+ calcd for C20H20N2O2: 321.1603; found: 321.1603.
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Methyl (3-p-Tolylisoquinolin-1-ylamino)acetate (3bb)
Yield: 54 mg (88%); mp 140–142 °C.
IR (KBr): 3427, 2984, 1727, 1614, 1524, 1277, 1105, 768 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.43 (s, 3 H), 3.83 (s, 3 H), 4.48 (d, J = 4.8 Hz, 2 H), 5.92 (br s, 1 H), 7.29 (d, J = 8.0 Hz, 2 H), 7.38 (t, J = 8.0 Hz, 1 H), 7.46 (s, 1 H), 7.55 (t, J = 7.2 Hz, 1 H), 7.71 (d, J = 8.0 Hz, 1 H), 7.81 (d, J = 8.0 Hz, 1 H), 8.06 (d, J = 7.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 21.3, 43.9, 52.1, 107.2, 117.3, 121.6, 125.6, 126.5, 127.5, 129.0, 129.2, 129.8, 137.1, 138.0, 148.5, 153.7, 172.3.
MS (EI): m/z (%) = 306 (38) [M+], 247 (100), 218 (42).
HRMS (ESI): m/z [M + Na]+ calcd for C19H18N2O2: 329.1266; found: 329.1263.
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Ethyl [3-(4-Methoxyphenyl)isoquinolin-1-ylamino]acetate (3ca)
Yield: 48 mg (72%); mp 150–152 °C.
IR (KBr): 3427, 2982, 1724, 1614, 1576, 1276, 1105, 755 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.34 (t, J = 7.2 Hz, 3 H), 3.88 (s, 3 H), 4.30 (q, J = 7.2 Hz, 2 H), 4.48 (d, J = 4.8 Hz, 2 H), 5.98 (br s, 1 H), 7.01 (d, J = 8.8 Hz, 2 H), 7.41 (t, J = 5.2 Hz, 2 H), 7.57 (t, J = 7.2 Hz, 1 H), 7.71 (d, J = 8.4 Hz, 1 H), 7.86 (d, J = 8.4 Hz, 1 H), 8.11 (d, J = 8.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 14.3, 44.1, 55.4, 61.3, 106.6, 113.9, 114.1, 117.2, 121.8, 125.6, 127.4, 127.9, 132.5, 138.2, 153.8, 159.9, 171.9.
MS (EI): m/z (%) = 336 (30) [M+], 263 (100), 234 (48).
HRMS (ESI): m/z [M + Na]+ calcd for C20H20N2O3: 359.1372; found: 359.1371.
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Methyl [3-(4-Methoxyphenyl)isoquinolin-1-ylamino]acetate (3cb)
Yield: 50 mg (78%); mp 133–135 °C.
IR (KBr): 3428, 2984, 1726, 1603, 1509, 1276, 1154, 768 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.81 (s, 3 H), 3.87 (s, 3 H), 4.47 (d, J = 4.8 Hz, 2 H), 5.89 (br s, 1 H), 7.01 (d, J = 8.8 Hz, 2 H), 7.39 (d, J = 6.4 Hz, 2 H), 7.55 (t, J = 7.6 Hz, 1 H), 7.70 (d, J = 8.4 Hz, 1 H), 7.81 (d, J = 8.4 Hz, 1 H), 8.10 (d, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 43.9, 52.2, 55.3, 106.5, 113.8, 117.1, 121.6, 125.5, 127.4, 127.8, 129.8, 132.5, 138.1, 148.2, 153.7, 159.9, 172.3.
MS (EI): m/z (%) = 322 (32) [M+], 263 (100), 234 (43).
HRMS (ESI): m/z [M + Na]+ calcd for C19H18N2O3: 345.1215; found: 345.1203.
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Ethyl [3-(3-Fluorophenyl)isoquinolin-1-ylamino]acetate (3da)
Yield: 58 mg (90%); mp 158–160 °C.
IR (KBr): 3428, 2984, 1727, 1603, 1508, 1238, 1154, 768 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.35 (t, J = 7.2 Hz, 3 H), 4.31 (q, J = 7.2 Hz, 2 H), 4.43 (d, J = 4.4 Hz, 2 H), 6.10 (br s, 1 H), 7.06 (t, J = 8 Hz, 1 H), 7.34–7.41 (m, 2 H), 7.43 (s, 1 H), 7.53 (t, J = 7.6 Hz, 1 H), 7.68 (d, J = 8 Hz, 1 H), 7.79 (t, J = 8.4 Hz, 1 H), 7.90 (t, J = 8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 14.2, 44.0, 61.3, 107.9, 113.6 (d, 2 J CF = 22.8 Hz), 114.8 (d, 2 J CF = 21.3 Hz), 117.7, 121.6, 121.8, 126.1, 127.6, 129.7 (d, 3 J CF = 8.2 Hz), 129.9, 137.7, 142.3 (d, 3 J CF = 7.9 Hz), 146.9, 153.9, 163.4 (d, 1 J CF = 242.5 Hz), 171.9.
MS (EI): m/z (%) = 324 (36) [M+], 251 (100), 222 (41).
HRMS (ESI): m/z [M + Na]+ calcd for C19H17FN2O2: 347.1172; found: 347.1192.
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Methyl [3-(3-Fluorophenyl)isoquinolin-1-ylamino]acetate (3db)
Yield: 55 mg (88%); mp 187–189 °C.
IR (KBr): 3427, 2983, 1724, 1614, 1508, 1275, 1178, 766 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.84 (s, 3 H), 4.45 (d, J = 5.2 Hz, 2 H), 5.96 (br s, 1 H), 7.05 (t, J = 8.4 Hz, 1 H), 7.37–7.44 (m, 2 H), 7.45 (s, 1 H), 7.57 (t, J = 7.2 Hz, 1 H), 7.71 (d, J = 8 Hz, 1 H), 7.82 (d, J = 8 Hz, 1 H), 7.88 (d, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 43.8, 52.1, 108.0, 110.9 (d, 2 J CF = 22.7 Hz), 114.8 (d, 2 J CF = 21.4 Hz), 117.7, 121.6, 121.8, 126.2, 127.6, 129.7 (d, 3 J CF = 7.9 Hz), 130.0, 137.8, 142.3 (d, 3 J CF = 7.8 Hz), 147.0, 153.8, 163.3 (d, 1 J CF = 242.4 Hz), 172.2.
MS (EI): m/z (%) = 310 (29) [M+], 251 (100), 222 (37).
HRMS (ESI): m/z [M + Na]+ calcd for C18H15FN2O2: 333.1015; found: 333.1033.
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Ethyl [3-(4-Fluorophenyl)isoquinolin-1-ylamino]acetate (3ea)
Yield: 51 mg (78%); mp 174–176 °C.
IR (KBr): 3428, 2985, 1727, 1603, 1508, 1276, 1154, 768 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.33 (t, J = 7.2 Hz, 3 H), 4.29 (q, J = 7.2 Hz, 2 H), 4.45 (d, J = 5.2 Hz, 2 H), 5.94 (br s, 1 H), 7.14 (t, J = 8.4 Hz, 2 H), 7.41 (d, J = 10.8 Hz, 2 H), 7.56 (t, J = 7.2 Hz, 1 H), 7.70 (t, J = 8.4 Hz, 1 H), 7.82 (t, J = 8.4 Hz, 1 H), 8.12 (t, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 14.2, 44.0, 61.2, 107.2, 115.2 (d, 2 J CF = 21 Hz), 117.3, 121.6, 125.8, 127.5, 128.2 (d, 3 J CF = 8.2 Hz), 129.9, 135.9, 137.9, 147.5, 153.8, 163.1 (d, 1 J CF = 245.5 Hz), 171.7.
MS (EI): m/z (%) = 324 (33) [M+], 251 (100), 222 (38).
HRMS (ESI): m/z [M + Na]+ calcd for C19H17FN2O2: 347.1172; found: 347.1179.
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Methyl [3-(4-Fluorophenyl)isoquinolin-1-ylamino]acetate (3eb)
Yield: 46 mg (74%); mp 179–181 °C.
IR (KBr): 3427, 2983, 1724, 1613, 1525, 1276, 1178, 755 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.82 (s, 3 H), 4.46 (d, J = 4.8 Hz, 2 H), 5.92 (br s, 1 H), 7.14 (t, J = 8.8 Hz, 2 H), 7.41 (d, J = 11.2 Hz, 2 H), 7.56 (t, J = 7.2 Hz, 1 H), 7.80 (d, J = 8 Hz, 1 H), 7.81 (t, J = 8.4 Hz, 1 H), 8.16 (t, J = 6.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 43.8, 52.1, 107.3, 115.2 (d, 2 J CF = 21.2 Hz), 117.3, 121.6, 125.9, 127.5, 128.2 (d, 3 J CF = 8 Hz), 130.0, 135.9, 137.9, 147.5, 153.8, 163.1 (d, 1 J CF = 245.5 Hz), 172.2.
MS (EI): m/z (%) = 310 (33) [M+], 251 (100), 222 (41).
HRMS (ESI): m/z [M + H]+ calcd for C18H15FN2O2: 311.1196; found: 311.1227.
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Ethyl [3-(4-Chlorophenyl)isoquinolin-1-ylamino]acetate (3fa)
Yield: 50 mg (73%); mp 202–204 °C.
IR (KBr): 3428, 2962, 1729, 1622, 1529, 1260, 1128, 766 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.34 (t, J = 7.2 Hz, 3 H), 4.30 (q, J = 7.2 Hz, 2 H), 4.45 (d, J = 5.2 Hz, 2 H), 5.98 (br s, 1 H), 7.42–7.44 (d, J = 9.2 Hz, 4 H), 7.58 (t, J = 7.2 Hz, 1 H), 7.72 (t, J = 8 Hz, 1 H), 7.84 (d, J = 8.4 Hz, 1 H), 8.10 (d, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 14.3, 44.1, 61.3, 107.6, 117.6, 121.7, 126.1, 127.6, 127.9, 128.6, 130.1, 134.1, 137.9, 138.3, 147.3, 153.9, 171.8.
MS (EI): m/z (%) = 340 (28) [M+], 305 (14), 267 (100), 238 (39).
HRMS (ESI): m/z [M + Na]+ calcd for C19H17ClN2O2: 363.0876; found: 363.0884.
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Methyl [3-(4-Chlorophenyl)isoquinolin-1-ylamino]acetate (3fb)
Yield: 50 mg (76%); mp 173–175 °C.
IR (KBr): 3428, 2981, 1725, 1613, 1529, 1275, 1178, 755 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.83 (s, 3 H), 4.46 (d, J = 4.8 Hz, 2 H), 5.85 (br s, 1 H), 7.38 (t, J = 7.2 Hz, 1 H), 7.42–7.49 (m, 4 H), 7.63 (t, J = 8.8 Hz, 1 H), 7.80 (s, 1 H), 8.11 (t, J = 7.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 43.8, 52.2, 107.1, 117.9, 121.2, 126.5, 128.4, 128.5, 129.0, 130.6, 131.2, 136.3, 139.4, 148.9, 152.9, 172.1.
MS (EI): m/z (%) = 326 (26) [M+], 291 (12), 267 (100), 238 (37).
HRMS (ESI): m/z [M + Na]+ calcd for C18H15ClN2O2: 349.0720; found: 349.0756.
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Ethyl (3-Cyclopropylisoquinolin-1-ylamino)acetate (3ga)
Yield: 30 mg (56%); mp 112–114 °C.
IR (KBr): 3428, 2983, 1727, 1613, 1509, 1275, 1178, 767 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.86–0.90 (m, 2 H), 1.06–1.10 (m, 2 H), 1.34 (t, J = 7.2 Hz, 3 H), 2.00 (s, 1 H), 4.25–4.30 (m, 4 H), 5.78 (br s, 1 H), 6.90 (s, 1 H), 7.34 (t, J = 7.6 Hz, 1 H), 7.52 (t, J = 7.2 Hz, 1 H), 7.58 (d, J = 8.4 Hz, 1 H), 7.77 (d, J = 8.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 8.3, 14.3, 16.8, 43.9, 61.2, 108.0, 116.6, 121.6, 124.6, 126.3, 129.8, 137.8, 153.7, 154.0, 171.9.
MS (EI): m/z (%) = 270 (46) [M+], 197 (100), 168 (43).
HRMS (ESI): m/z [M + H]+ calcd for C16H18N2O2: 271.1447; found: 271.1466.
Methyl (3-Cyclopropylisoquinolin-1-ylamino)acetate (3gb)
Yield: 36 mg (70%); mp 185–187 °C (Lit.[14] 187–188 °C).
1H NMR (400 MHz, CDCl3): δ = 0.83–0.88 (m, 2 H), 1.03–1.06 (m, 2 H), 1.97 (s, 1 H), 3.79 (s, 3 H), 4.27 (d, J = 5.4 Hz, 2 H), 5.74 (br s, 1 H), 6.89 (s, 1 H), 7.32 (t, J = 7.6 Hz, 1 H), 7.50 (t, J = 7.2 Hz, 1 H), 7.56 (d, J = 8.0 Hz, 1 H), 7.73 (d, J = 8.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 8.2, 16.8, 43.7, 52.1, 108.1, 116.5, 121.5, 124.6, 126.2, 129.7, 137.8, 153.7, 153.9, 172.3.
MS (EI): m/z (%) = 256 (45) [M+], 197 (100), 168 (41).
HRMS (ESI): m/z [M + Na]+ calcd for C15H16N2O2: 279.1109; found: 279.1096.
#
Ethyl (7-Methyl-3-phenylisoquinolin-1-ylamino)acetate (3ha)
Yield: 49 mg (77%); mp 144–146 °C.
IR (KBr): 3426, 2984, 1725, 1603, 1508, 1276, 1154, 769 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.36 (t, J = 7.2 Hz, 3 H), 2.46 (s, 3 H), 4.32 (q, J = 7.2 Hz, 2 H), 4.48 (d, J = 4.8 Hz, 2 H), 6.01 (br s, 1 H), 7.39 (t, J = 8.0 Hz, 2 H), 7.46–7.50 (t, J = 8.0 Hz, 3 H), 7.61 (d, J = 7.6 Hz, 2 H), 8.17 (d, J = 7.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 14.3, 21.9, 44.1, 61.3, 107.6, 117.6, 121.0, 126.5, 127.4, 128.0, 128.5, 131.9, 135.8, 136.0, 140.0, 147.5, 153.5, 172.1.
MS (EI): m/z (%) = 320 (38) [M+], 247 (100), 218 (49).
HRMS (ESI): m/z [M + Na]+ calcd for C20H20N2O2: 343.1422; found: 343.1396.
#
Methyl (7-Methyl-3-phenylisoquinolin-1-ylamino)acetate (3hb)
Yield: 49 mg (80%); mp 167–169 °C.
IR (KBr): 3427, 2984, 1724, 1603, 1508, 1276, 1154, 768 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.41 (s, 3 H), 3.85 (s, 3 H), 4.48 (d, J = 5.2 Hz, 2 H), 6.04 (br s, 1 H), 7.33–7.41 (m, 2 H), 7.44 (s, 1 H), 7.49 (t, J = 7.2 Hz, 2 H), 7.57 (d, J = 8.8 Hz, 2 H), 8.17 (d, J = 8.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 21.8, 43.9, 52.2, 107.6, 117.5, 121.0, 126.4, 127.3, 128.0, 128.4, 131.8, 135.8, 135.9, 140.0, 147.4, 153.4, 172.7.
MS (EI): m/z (%) = 306 (31) [M+], 247 (100), 218 (46).
HRMS (ESI): m/z [M + H]+ calcd for C19H18N2O2: 307.1447; found: 307.1467.
#
Ethyl (6-Methoxy-3-phenylisoquinolin-1-ylamino)acetate (3ia)
Yield: 50 mg (75%); mp 161–163 °C.
IR (KBr): 3427, 2930, 1729, 1621, 1517, 1251, 1145, 766 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.35 (t, J = 7.2 Hz, 3 H), 3.90 (s, 3 H), 4.30 (q, J = 7.2 Hz, 2 H), 4.45 (d, J = 5.6 Hz, 2 H), 5.94 (br s, 1 H), 7.00 (d, J = 2.0 Hz, 2 H), 7.40 (d, J = 4.8 Hz, 2 H), 7.48 (t, J = 7.2 Hz, 2 H), 7.72 (d, J = 9.2 Hz, 1 H), 8.16 (d, J = 7.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 14.3, 44.1, 55.4, 61.3, 106.2, 107.5, 117.5, 123.5, 126.7, 127.4, 128.2, 128.5, 140.0, 149.0, 153.8, 153.8, 160.6, 172.1.
MS (EI): m/z (%) = 336 (30) [M+], 263 (100), 234 (44).
HRMS (ESI): m/z [M + H]+ calcd for C20H20N2O3: 337.1552; found: 337.1563.
#
Methyl (6-Methoxy-3-phenylisoquinolin-1-ylamino)acetate (3ib)
Yield: 41 mg (63%); mp 138–140 °C.
IR (KBr): 3427, 2984, 1726, 1603, 1508, 1277, 1154, 768 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.82 (s, 3 H), 3.90 (s, 3 H), 4.45 (d, J = 5.2 Hz, 2 H), 5.83 (br s, 1 H), 7.00 (d, J = 8.4 Hz, 2 H), 7.35–7.40 (m, 2 H), 7.46 (t, J = 7.6 Hz, 2 H), 7.71 (d, J = 8.4 Hz, 1 H), 8.13 (d, J = 8.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 43.8, 52.1, 55.3, 106.1, 107.5, 112.4, 117.5, 123.4, 126.7, 128.1, 128.4, 139.9, 139.9, 149.1, 153.7, 160.6, 172.4.
MS (EI): m/z (%) = 322 (29) [M+], 263 (100), 234 (43).
HRMS (ESI): m/z [M + Na]+ calcd for C19H18N2O3: 345.1215; found: 345.1231.
#
Ethyl (6,7-Dimethoxy-3-phenylisoquinolin-1-ylamino)acetate (3ja)
Yield: 41 mg (57%); mp 135–137 °C.
IR (KBr): 3424, 2982, 1725, 1612, 1508, 1276, 1154, 755 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.38 (t, J = 6.8 Hz, 3 H), 3.47 (s, 3 H), 3.95 (s, 3 H), 4.30 (q, J = 7.2 Hz, 2 H), 4.38 (d, J = 5.2 Hz, 2 H), 6.71 (br s, 1 H), 6.83 (d, J = 5.2 Hz, 2 H), 7.35 (d, J = 8.8 Hz, 2 H), 7.43–7.47 (t, J = 7.8 Hz, 2 H), 8.15 (d, J = 7.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 14.4, 44.4, 55.5, 55.8, 61.3, 101.1, 105.8, 107.1, 112.3, 126.3, 127.7, 128.4, 133.7, 140.1, 146.5, 148.7, 151.7, 152.9, 174.0.
MS (EI): m/z (%) = 366 (28) [M+], 293 (100), 264 (42).
HRMS (ESI): m/z [M + Na]+ calcd for C21H22N2O4: 389.1477; found: 389.1485.
#
Methyl (6,7-Dimethoxy-3-phenylisoquinolin-1-ylamino)acetate (3jb)
Yield: 46 mg (66%); mp 177–179 °C (Lit.[14] 176–177 °C).
1H NMR (400 MHz, CDCl3): δ = 3.53 (s, 3 H), 3.85 (s, 3 H), 3.96 (s, 3 H), 4.40 (q, J = 5.2 Hz, 2 H), 6.54 (br s, 1 H), 6.85 (d, J = 6.0 Hz, 2 H), 7.36 (d, J = 5.6 Hz, 2 H), 7.46 (t, J = 7.2 Hz, 2 H), 8.13 (d, J = 7.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 44.2, 52.2, 55.6, 55.8, 101.1, 105.9, 107.2, 112.2, 126.2, 127.8, 128.4, 133.8, 140.0, 146.6, 148.8, 151.9, 152.8, 174.1.
MS (EI): m/z (%) = 352 (31) [M+], 293 (100), 264 (45).
HRMS (ESI): m/z [M + Na]+ calcd for C20H20N2O4: 375.1321; found: 375.1334.
#
Ethyl (6-Fluoro-3-phenylisoquinolin-1-ylamino)acetate (3ka)
Yield: 47 mg (72%); mp 176–178 °C.
IR (KBr): 3427, 2981, 1721, 1613, 1526, 1276, 1178, 768 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.37 (t, J = 7.2 Hz, 3 H), 4.32 (q, J = 7.2 Hz, 2 H), 4.44 (d, J = 5.2 Hz, 2 H), 6.23 (br s, 1 H), 7.00 (dt, J = 8.8, 2.4 Hz, 1 H), 7.24 (m, 1 H), 7.40 (t, J = 7.2 Hz, 2 H), 7.49 (t, J = 7.2 Hz, 2 H), 7.76 (dd, J = 5.2, 8.8 Hz, 1 H), 8.15 (d, J = 7.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 14.3, 44.0, 61.4, 107.2 (d, 4 J CF = 3.9 Hz), 110.9 (d, 2 J CF = 20.4 Hz), 114.4, 115.2, 115.4, 124.5 (d, 3 J CF = 9.6 Hz), 126.7, 128.5, 139.5, 139.8 (d, 3 J CF = 9 Hz), 149.6, 153.8, 163.2 (d, 1 J CF = 248.5 Hz), 172.2.
MS (EI): m/z (%) = 324 (26) [M+], 251 (100), 222 (40).
HRMS (ESI): m/z [M + Na]+ calcd for C19H17FN2O2: 347.1172; found: 347.1177.
#
Methyl (6-Fluoro-3-phenylisoquinolin-1-ylamino)acetate (3kb)
Yield: 35 mg (57%); mp 172–174 °C (Lit.[14] 178–179 °C).
1H NMR (400 MHz, CDCl3): δ = 3.84 (s, 3 H), 4.45 (d, J = 5.2 Hz, 2 H), 6.10 (br s, 1 H), 7.02 (t, J = 8.8 Hz, 1 H), 7.26 (d, J = 9.2 Hz, 1 H), 7.39 (t, J = 7.2 Hz, 2 H), 7.47 (d, J = 7.2 Hz, 2 H), 7.75 (dd, J = 5.6, 8.4 Hz, 1 H), 8.12 (t, J = 8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 43.8, 52.2, 107.2 (d, 4 J CF = 3.9 Hz), 108.2, 110.9 (d, 2 J CF = 20.5 Hz), 114.3, 115.3 (d, 2 J CF = 24.6 Hz), 124.4 (d, 3 J CF = 9.5 Hz), 126.6, 128.5, 139.5, 139.7 (d, 3 J CF = 10 Hz), 149.6, 153.7, 163.2 (d, 1 J CF = 248.3 Hz), 172.5.
MS (EI): m/z (%) = 310 (25) [M+], 251 (100), 222 (38).
HRMS (ESI): m/z [M + Na]+ calcd for C18H15FN2O2: 333.1015; found: 333.1037.
#
Ethyl (7-Fluoro-3-phenylisoquinolin-1-ylamino)acetate (3la)
Yield: 45 mg (69%); mp 180–182 °C.
IR (KBr): 3428, 2984, 1725, 1604, 1508, 1276, 1107, 767 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.35 (t, J = 7.2 Hz, 3 H), 4.11 (q, J = 7.2 Hz, 2 H), 4.50 (d, J = 5.2 Hz, 2 H), 5.84 (br s, 1 H), 7.32–7.40 (m, 2 H), 7.46–7.50 (m, 4 H), 7.70–7.73 (m, 1 H), 8.13 (s, 1 H), 8.15 (d, J = 1.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 14.2, 44.0, 61.3, 106.2 (d, 2 J CF = 21.6 Hz), 107.2, 117.9, 119.8 (d, 2 J CF = 24.2 Hz), 126.5, 128.2, 128.4, 129.8 (d, 3 J CF = 8 Hz), 134.8, 139.5, 148.0, 153.4 (d, 4 J CF = 4.3 Hz), 160.4 (d, 1 J CF = 245.8 Hz), 171.8.
MS (EI): m/z (%) = 324 (30) [M+], 251 (100), 222 (43).
HRMS (ESI): m/z [M + Na]+ calcd for C19H17FN2O2: 347.1172; found: 347.1208.
#
Methyl (7-Fluoro-3-phenylisoquinolin-1-ylamino)acetate (3lb)
Yield: 55 mg (88%); mp 164–166 °C.
IR (KBr): 3426, 2985, 1725, 1605, 1508, 1274, 1154, 768 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.83 (s, 3 H), 4.45 (d, J = 5.2 Hz, 2 H), 5.79 (br s, 1 H), 7.30–7.39 (m, 2 H), 7.41–7.50 (m, 4 H), 7.68–7.71 (t, J = 7.2 Hz, 1 H), 8.11 (d, J = 7.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 43.8, 52.1, 106.1 (d, 2 J CF = 21.4 Hz), 107.2, 117.8 (d, 3 J CF = 6.5 Hz), 119.8 (d, 2 J CF = 24.2 Hz), 126.4, 128.2, 128.4, 129.9 (d, 3 J CF = 8 Hz), 134.8, 139.5, 148.0, 153.3, 160.4 (d, 1 J CF = 245.3 Hz), 172.1.
MS (EI): m/z (%) = 310 (28) [M+], 251 (100), 222 (41).
HRMS (ESI): m/z [M + Na]+ calcd for C18H15FN2O2: 333.1015; found: 333.1035.
#
Ethyl (7-Chloro-3-phenylisoquinolin-1-ylamino)acetate (3ma)
Yield: 50 mg (74%); mp 164–166 °C.
IR (KBr): 3427, 2983, 1722, 1613, 1525, 1274, 1177, 754 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.35 (t, J = 7.2 Hz, 3 H), 4.31 (q, J = 7.2 Hz, 2 H), 4.46 (d, J = 4.8 Hz, 2 H), 5.91 (br s, 1 H), 7.39 (t, J = 7.2 Hz, 1 H), 7.44–7.51 (m, 4 H), 7.65 (d, J = 8.8 Hz, 1 H), 7.83 (s, 1 H), 8.14 (d, J = 7.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 14.3, 44.1, 61.4, 107.1, 118.0, 121.3, 126.6, 128.4, 128.5, 129.1, 130.7, 131.2, 136.3, 139.5, 149.0, 153.0, 171.8.
MS (EI): m/z (%) = 340 (26) [M+], 305 (15), 267 (100), 238 (42).
HRMS (ESI): m/z [M + Na]+ calcd for C19H17ClN2O2: 363.0876; found: 363.0896.
#
Methyl (7-Chloro-3-phenylisoquinolin-1-ylamino)acetate (3mb)
Yield: 56 mg (86%); mp 178–180 °C.
IR (KBr): 3428, 2919, 1728, 1618, 1516, 1252, 1103, 768 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.82 (s, 3 H), 4.46 (d, J = 5.2 Hz, 2 H), 5.94 (br s, 1 H), 7.42 (d, J = 6.8 Hz, 4 H), 7.57 (t, J = 7.6 Hz, 1 H), 7.70 (d, J = 8.0 Hz, 1 H), 7.81 (d, J = 8.8 Hz, 1 H), 8.06 (d, J = 8.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 43.8, 52.2, 107.6, 117.5, 121.6, 126.1, 127.6, 127.8, 128.6, 130.0, 134.0, 137.8, 138.3, 147.2, 153.8, 172.2.
MS (EI): m/z (%) = 326 (24) [M+], 291 (12), 267 (100), 238 (40).
HRMS (ESI): m/z [M + Na]+ calcd for C18H15ClN2O2: 349.0720; found: 349.0741.
#
#
Acknowledgment
We thank Prof. Jie Wu at Fudan University for valuable discussions during the course of this research. Financial support from the National Natural Science Foundation of China (Nos. 21262018, 20862007, 21202065) and the Natural Science Foundation of Jiangxi Province (2010GZH0070) is gratefully acknowledged.
Supporting Information
- for this article is available online at http://www.thieme-connect.com.accesdistant.sorbonne-universite.fr/products/ejournals/journal/
10.1055/s-00000084.
- Supporting Information
Primary Data
- for this article are available online at http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000084 and can be cited using the following DOI: 10.4125/pd0059th.
- Primary Data
-
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- 21 Notably, 1,3-dipolar intermediate A could be formed in almost quantitative yield when silver triflate was used as the catalyst. For examples, see ref. 13 and also Scheme 2 (vide infra).
For reviews, see:
For selected examples, see:
For reviews, see:
For selected examples, see:
For a reference work, see:
For selected reviews, see:
For selected reviews, see:
For selected reviews, see:
-
References
- 1a Chrzanowska M, Rozwadowska MD. Chem. Rev. 2004; 104: 3341
- 1b Scott JD, Williams RM. Chem. Rev. 2002; 102: 1669
- 1c Bailly C. Curr. Med. Chem.: Anti-Cancer Agents 2004; 4: 363
- 1d Marco E, Laine W, Tardy C, Lansiaux A, Iwao M, Ishibashi F, Bailly C, Gago F. J. Med. Chem. 2005; 48: 3796
- 1e Vincent G, Williams RM. Angew. Chem. Int. Ed. 2007; 46: 1517
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- 2b Smith AL, DeMorin FF, Paras NA, Huang Q, Petkus JK, Doherty EM, Nixey T, Kim JL, Whittington DA, Epstein LF, Lee MR, Rose MJ, Babij C, Fernando M, Hess K, Le Q, Beltran P, Carnahan J. J. Med. Chem. 2009; 52: 6189
- 3 Govek SP, Oshiro G, Anzola JV, Beauregard C, Chen J, Coyle AR, Gamache DA, Hellberg MR, Hsien JN, Lerch JM, Liao JC, Malecha JW, Staszewski LM, Thomas DJ, Yanni JM, Noble SA, Shiau AK. Bioorg. Med. Chem. Lett. 2010; 20: 2928
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- 21 Notably, 1,3-dipolar intermediate A could be formed in almost quantitative yield when silver triflate was used as the catalyst. For examples, see ref. 13 and also Scheme 2 (vide infra).
For reviews, see:
For selected examples, see:
For reviews, see:
For selected examples, see:
For a reference work, see:
For selected reviews, see:
For selected reviews, see:
For selected reviews, see:
