Subscribe to RSS
DOI: 10.1055/s-0031-1290976
N-Heterocyclic Carbene Catalyzed Intramolecular Hydroacylation of Alkynylphosphonates
Publication History
Received: 13 January 2012
Accepted after revision: 24 March 2012
Publication Date:
02 May 2012 (online)
Abstract
Two exocyclic and endocyclic olefin tautomers of chromone phosphonates were obtained in good to excellent yields at different temperatures by utilizing an N-heterocyclic carbene catalyst in the intramolecular reactions between the formyl group and alkynylphosphonates. The exocyclic olefins can isomerize to the endocyclic derivatives completely when treated with a thiazolium salt precatalyst and potassium carbonate at 30 °C for three to five hours. In addition, the chromone phosphonate derivatives were also applied in the one-pot synthesis of benzopyranopyridine phosphonates in moderated yields.
#
Key words
Stetter reaction - N-heterocyclic carbenes - hydroacylation - one-pot synthesis - chromone - phosphonateOrganic phosphorus compounds are attractive to chemists because of their wide range of biological activities[ 1 ] and catalytic properties in organic synthesis.[ 2 ] Moreover, phosphonyl heterocycles and related compounds have been widely used in the field of pharmaceuticals and agrochemicals as bactericides, insecticides, fungicides, and plant growth regulators.[ 3 ] On the other hand, over the past few decades, the broad application of N-heterocyclic carbenes (NHCs) in organic synthesis has been impressively demonstrated.[ 4 ] Such compounds play a vital role not only as ubiquitous ligands in organometallic chemistry, but also as efficient nucleophilic organocatalysts in a variety of organic reactions,[ 5 ] including benzoin condensation, the Stetter reaction, and a3 to d3 umpolung reactions. The use of NHCs in catalysis in umpolung strategies has been notably adopted in both intra- and intermolecular transformations in the Stetter reaction,[ 6 ] and the electrophilic acceptors of these transformations contain both activated olefins and unactivated derivatives. Recently, Enders et al. and Rovis et al. pioneered the development of a powerful NHC-catalyzed approach to the formation of highly functionalized chromones by an intramolecular Stetter reaction. The NHC-catalyzed hydroacylation of unactivated alkynes led to the formation of α,β-unsaturated chromone, which was first reported by Frank Glorius et al. in 2009.[ 6m ]
According to examples that exploit nucleophilic acyl anion equivalents, acceptors of the Stetter reaction were mainly limited to α,β-unsaturated ketones, α,β-unsaturated esters or phosphonates, and alkynes.[ 7 ] We envisaged that alkynylphosphonates would act as excellent acceptors for the intramolecular Stetter reaction because of their highly electrophilic nature at the β-position.[ 8 ] This prompted us to investigate the possibility of developing a new carbon–carbon bond forming reaction to construct the potentially biologically relevant α,β-unsaturated chromone phosphonates at room temperature, which are useful in many fields including agrochemical and medicinal chemistry[ 9 ] (Scheme [1], equation 1). During the preparation of this manuscript, Liu et al. reported the NHC-catalyzed intramolecular hydroacylation of activated alkynes (Scheme [1], equation 2).[ 6p ]
a Reaction conditions: 1a (0.5 mmol), NHC-HX (5 mol%), base (10 mol%), solvent (2.0 mL), r.t. (17 °C), 3 h.
b Isolated yield.
We decided to employ a series of alkynylphosphonates as electrophilic acceptors in the intramolecular Stetter reaction. Alkynylphosphonates 1 were prepared by using a modified procedure described by Zhao and colleagues (Scheme [2]).[ 10 ] Aerial oxidative coupling of terminal alkynes with H-phosphonates was efficiently catalyzed by copper acetate to generate alkynylphosphonates in high yields. Deprotection of the 1,2-dithiane using ferric nitrate provided 1 in excellent yields.
Our present study commenced with simple phenyl derivative 1a as a model substrate with which to optimize the reaction conditions. Treatment of 1a with the N-heterocyclic carbene generated from the deprotonation of thiazolium salt A by potassium carbonate resulted in the formation of chromone phosphonate derivative 2a at room temperature (17 °C) in three hours, which is a synthetically valuable exocyclic olefin, as a single isomer in 90% yield (Table1, entry 1).
A survey of carbene precursors showed that the use of thiazolium salts A, B, and C gave a single isomer of exocyclic olefin in excellent yields (Table [1], entries 1, 2, and 3). To our surprise, the phenyl-substituted carbene precursor D was completely ineffective (Table [1], entry 4). Interestingly, imidazolium salt E and triazolium salt F provided another isomer; the endocyclic olefin (Table [1], entries 5 and 6). Because of the higher yield, the convenient purification operation, and the higher catalytic activity of A, we chose this carbene precursor as the catalyst in subsequent reactions. At this stage, the effects of various solvents in the reaction were examined with catalyst A as a control (Table [1], entries 7–13). With increasing solvent polarity, the yields of the products were found to be reduced. Surprisingly, no product was detected when polar nonprotonic solvents such as acetonitrile or N,N-dimethylformamide (DMF) were used, however, use of a moderately polar solvent such as dichloromethane was more effective. Using catalyst A and dichloromethane as solvent, we explored the use of a range of bases (Table [1], entries 14–19) and found that potassium carbonate afforded the products in highest yield.
a Reaction conditions: 1 (0.5 mmol), NHC-HX A (5 mol%), base (10 mol%), solvent (2.0 mL).
b Isolated yield.
c The exocyclic olefin products were obtained at 17 °C for 3 h; and endocyclic olefin products at 30 °C for 3 h.
With these optimized conditions in hand, we then turn our attention to the influence of the substituents of the salicylaldehyde-derived alkynylphosphonates on the formation of tautomers (Table [2], entries 4–11). Remarkably, substrates with either electron-donating or electron-withdrawing substituents on the aromatic rings were effective. Competition experiments with different phenyl moieties revealed that the electron-withdrawing substituents could accelerate the reaction rates; in particular, the reaction reached completion within 30 minutes with the nitro-containing reactant (Table [2], entry 4). Finally, we examined the effects of steric hindrance of the phosphonates (R = Et, n-Bu, or i-Pr) on this Stetter type intramolecular hydroacylation reaction (Table [2], entries 1–3). The results showed that the yields decreased slightly with increasing steric hindrance. To establish whether the temperature had an effect on the formation of the tautomers, catalyst A, dichloromethane, and potassium carbonate were used at a range of temperatures; isomer 2a was found to be the major product at lower temperature (17 °C), and isomer 2a′ was formed as the major product at 30 °C.
In view of these interesting results, we wondered whether we could use the exocyclic olefin as a Michael receptor and the α-pyridylmethyl ketone salt as a nucleophile to provide benzopyranopyridine derivatives by the application of Kröhnke method[ 11 ] through a one-pot synthesis. To test our hypothesis, we employed the α-pyridylmethyl ketone salt[ 12 ] as the Michael partner for 1 to yield polycyclic phosphonate derivatives 3a–f. A series of substrates with various substituents on the aromatic ring of the salt were examined (Table [3]).
 |
||||
|
Entry |
R |
R2 |
Product |
Yield (%)b |
|
1 |
H |
Et |
3a |
52 |
|
2 |
H |
n-Bu |
3b |
50 |
|
3 |
H |
i-Pr |
3c |
48 |
|
4 |
OMe |
Et |
3d |
53 |
|
5 |
Me |
Et |
3e |
51 |
|
6 |
F |
Et |
3f |
55 |
|
7 |
NO2 |
Et |
3g |
0 |
a Reaction conditions: (1) 1 (0.5 mmol), NHC-HX A (5 mol%), base (10 mol%), solvent (2.0 mL), r.t. (17 °C), 3 h; (2) α-pyridylmethyl ketone salt (0.5 mmol), NH4Ac (5 equiv), MeOH (3 mL), reflux, 6 h; no prospective product was detected when nitro-substituted substrate was used as reactant (Table [3], entry 7).
b Isolated yield.
The first intramolecular hydroacylation of an electron-neutral triple bond was reported by Frank Glorius, which was followed by the intramolecular hydroacylation of activated alkynes in which the electron-withdrawing groups have mainly been the carbonyl group. Although the ability of the phosphonyl group to withdraw electrons is inferior to that of the carbonyl group, and it might also introduce a certain degree of steric hindrance, the hydroacylation products can be obtained in excellent yield at room temperature, which can be due to a suitable selection of NHCs. The defined electronic effects and steric hindrance of NHCs[ 11 ] will be very useful in catalysts for this type of reaction. In contrast to our reaction system, the formation of exocyclic products or its endocyclic tautomers can depend on the reaction temperature.
Based on our system and on literature reports,[ 6p ] a possible mechanism is shown in Scheme [3]. The reaction might proceed through different routes at different temperatures. All of the pathways involve tetrahedral intermediates, which are generated by carbene nucleophilic attack on the carbonyl carbon of the aldehyde. The reaction is terminated in the exocyclic Stetter type product at a lower temperature (17 °C). Alternatively, the substrate alkynyl group can isomerize to the allene, followed by proton transfer and carbene release to generate the endo isomers at higher temperature (30 °C). Moreover, the exocyclic olefins 2 are not more stable than the aromatized tautomers 2′, in fact, 2 can isomerize to 2′ completely when the former is treated with catalyst A and potassium carbonate at 30 °C for three to five hours; however, without catalyst A and potassium carbonate, the isomerization of 2 cannot occur.
In conclusion, we have developed an effective organocatalytic intramolecular hydroacylation reaction between phosphonylation alkynyl and compounds containing a formyl group, by utilizing N-heterocyclic carbene catalysis. In addition, the chromone derivatives can also be applied in the one-pot synthesis of benzopyranopyridine phosphonates 3 in moderate yields.
All reagents and solvents were used as received with the following exceptions: THF, toluene, and dioxane were distilled from sodium/ benzophenone. CH2Cl2, MeCN, and DMF were distilled from CaH. EtOH and n-BuOH were distilled from Mg turnings. K2CO3 was dried by heating at 110 °C for 12 h and left to cool under argon. N-Heterocyclic carbene (NHC) precursors A–F were prepared according to the literature.[ 13 ] Substituted salicylaldehyde were synthesized according to the reported method.[ 14 ] All other commercially available solvents and reagents were used without further purification. All reactions were performed in oven-dried apparatus under an N2 or argon atmosphere. Reactions were monitored by thin layer chromatography (TLC) and visualized by short-wave UV light or KMnO4 staining solution followed by heating. 1H, 13C, and 31P NMR spectra were obtained with either a Varian Mercury PLUS 400 or a Varian Mercury PLUS 600 spectrometer. Chemical shifts are reported in parts per million (δ, ppm) from an internal standard [tetramethylsilane (TMS) or chloroform (CHCl3)], multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, and m = multiplet), integration, and coupling constant (Hz). 13C NMR chemical shifts are reported in ppm relative to the signal of CDCl3 (taken as δ = 77.0 ppm). 31P NMR spectra were recorded on the same instrument with 85% H3PO4 as external standard. Mass spectra (ESI) were obtained with an Applied Biosystems API 2000 LC/MS/MS (ESI-MS) spectrometer. Elemental analyses were performed with an Elementar Vario ELШ CHNSO elemental analyzer.
#
Dialkyl 3-(2-Formylphenoxy)prop-1-ynylphosphonate (1); General Procedure
H-Phosphonates (10 mmol), 2-[2-(prop-2-ynyloxy)phenyl]-1,3-dithiolane (12 mmol, 2.95 g), Cu(OAc)2 (10 mol%, 0.19 g), and Et3N (20 mol%, 0.2 g) were dissolved in commercial DMSO (20 mL) and stirred at 50 °C for 24 h under a dry air atmosphere. The resulting mixture was poured into 50 mL H2O and extracted with EtOAc (3 × 50 mL). The organic layer was washed with brine (3 × 50 mL), dried over MgSO4 and concentrated under vacuum and the crude product was purified by silica gel chromatography (petroleum ether–EtOAc, 1:1) to give a yellow oil. The 1,2-dithiane was deprotected by stirring the mixture of the yellow oil (1.0 mmol), ferric nitrate nonahydrate (1.0 mmol), hexane (10 mL), and silica gel (1 g) at ambient temperature under an N2 atmosphere (reaction monitored by TLC). The crude reaction mixture was purified by column chromatography on silica gel (petroleum ether–EtOAc 1:1). Evaporation of solvent afforded the pure product.
#
Diethyl 3-(2-Formylphenoxy)prop-1-ynylphosphonate (1a)
Yield: 153.9 mg (87%); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 10.46 (s, 1 H), 7.88 (d, J = 9.0 Hz, 1 H), 7.59 (t, J = 8.4 Hz, 1 H), 7.14 (t, J = 10.8 Hz, 1 H), 7.08 (d, J = 12.6 Hz, 1 H), 4.95 (d, J = 3.6 Hz, 2 H), 4.16–4.09 (m, 4 H), 1.33 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 189.2 (d, J = 167.4 Hz), 159.1, 135.7, 128.8 (d, J = 17.5 Hz), 125.5, 122.2, 112.9, 93.2 (d, J = 48.6 Hz), 78.0 (d, J = 288 Hz), 63.4 (d, J = 3.9 Hz), 56.1, 15.9.
MS (ESI): m/z = 297 [M + H]+, 319 [M + Na]+.
#
Dibutyl 3-(2-Formylphenoxy)prop-1-ynylphosphonate (1b)
Yield: 214.7 mg (91%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.46 (s, 1 H), 7.88 (d, J = 7.2 Hz, 1 H), 7.58 (t, J = 7.8 Hz, 1 H), 7.13 (t, J = 7.2 Hz, 1 H), 7.08 (d, J = 8.4 Hz, 1 H), 4.96 (d, J = 3.0 Hz, 2 H), 4.70–4.03 (m, 4 H), 1.67–1.62 (m, 4 H), 1.37 (q, J = 7.2 Hz, 4 H), 0.90 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 189.0 (t, J = 89.7 Hz), 159.0, 135.6, 128.7 (d, J = 16.2 Hz), 125.3, 122.1, 112.7, 93.2 (d, J = 51 Hz), 79.1, 67.0, 56.0, 31.9, 18.5, 13.4.
31P NMR (CDCl3, 243 MHz): δ = –8.48.
MS (ESI): m/z = 353 [M + H]+, 375 [M + Na]+.
#
Diisopropyl 3-(2-Formylphenoxy)prop-1-ynylphosphonate (1c)
Yield: 236.5 mg (89%); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 10.46 (s, 1 H), 7.87 (d, J = 7.6 Hz, 1 H), 7.58 (t, J = 8.0 Hz, 1 H), 7.14–7.07 (m, 2 H), 4.95 (d, J = 1.6 Hz, 2 H), 4.76–4.66 (m, 2 H), 1.37 (t, J = 6.4 Hz, 6 H), 1.32 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 188.9 (m), 159.1, 135.6 (d, J =20.7 Hz), 128.5 (d, J =11.5 Hz), 125.2, 121.9, 112.7 (d, J = 6.9 Hz), 92.4 (d, J = 50.5 Hz), 78.9 (d, J =287.4 Hz), 72.6 (d, J = 18.4 Hz), 55.9 (dd, J =13.8, 18.4 Hz), 23.4 (t, J = 41.4 Hz).
MS (ESI): m/z = 325 [M + H]+, 347 [M + Na]+.
#
Diethyl 3-(2-Formyl-4-nitrophenoxy)prop-1-ynylphosphonate (1d)
Yield: 276.2 mg (79%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.45 (s, 1 H), 8.74 (d, J = 3.0 Hz, 1 H), 8.47 (dd, J =9.0, 3.0 Hz, 1 H), 7.23 (d, J = 9.0 Hz, 1 H), 5.08 (d, J = 3.6 Hz, 2 H), 4.17–4.14 (m, 4 H), 1.35 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 187.3, 162.7, 142.5, 130.3 (d, J = 11.7 Hz), 125.2, 124.6 (d, J = 6.0 Hz), 113.2 (d, J = 5.8 Hz), 91.2 (d, J = 48.6 Hz), 78.9 (d, J = 289.9 Hz), 63.5 (d, J = 5.85 Hz), 56.7, 15.9.
MS (ESI): m/z = 342 [M + H]+, 364 [M + Na]+.
#
Diethyl 3-(4-Fluoro-2-formylphenoxy)prop-1-ynylphosphonate (1e)
Yield: 181.5 mg (83%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.40 (s, 1 H), 7.54 (dd, J =8.4, 3.6 Hz, 1 H), 7.31–7.28 (m, 1 H), 7.08 (dd, J = 9.0, 3.6 Hz, 1 H), 4.93 (d, J = 3.6 Hz, 2 H), 4.16–4.09 (m, 4 H), 1.33 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 189.0 (t, J =97.0 Hz), 158.4, 156.8, 155.3, 126.4, 122.3 (d, J = 23.8 Hz), 114.5 (t, J = 50.5 Hz), 92.9 (d, J = 46.3 Hz), 79.1, 63.5 (d, J = 5.5 Hz), 56.8, 15.9 (d, J = 5.7 Hz).
MS (ESI): m/z = 314 [M + H]+, 336 [M + Na]+.
#
Diethyl 3-(6-Bromo-2-formylphenoxy)prop-1-ynylphosphonate (1f)
Yield: 201.9 mg (86%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.41 (s, 1 H), 7.86 (d, J = 1.8 Hz, 1 H), 7.84 (d, J = 2.4 Hz, 1 H), 7.22 (t, J = 7.8 Hz, 1 H), 5.02 (d, J = 3.6 Hz, 2 H), 4.13–4.08 (m, 4 H), 1.34 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 188.8 (d, J = 167.4 Hz), 156.5, 139.4 (d, J = 16.8 Hz), 131.8, 127.7 (d, J = 15.6 Hz), 126.7, 117.8, 92.8 (d, J = 49.2 Hz), 79.5 (d, J = 289.1 Hz), 63.4 (d, J = 5.7 Hz), 61.5, 15.9.
MS (ESI): m/z = 375 [M + H]+, 397 [M + Na]+.
#
Diethyl 3-(2-Formyl-4-methoxyphenoxy)prop-1-ynylphosphonate (1g)
Yield: 166.3 mg (95%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.42 (s, 1 H), 7.35 (d, J = 3.6 Hz, 1 H), 7.15 (dd, J =9.0, 3.0 Hz, 1 H), 7.04 (d, J = 9.6 Hz, 1 H), 4.90 (d, J = 3.6 Hz, 2 H), 4.14–4.11 (m, 4 H), 3.82 (s, 3 H), 1.35 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 188.8 (d, J = 27.6 Hz), 154.7, 153.8, 126.1, 123.0, 115.3, 110.6, 93.5 (d, J = 48.3 Hz), 78.9 (d, J = 282.9 Hz), 63.4 (d, J = 4.65 Hz), 57.0 (d, J = 4.65 Hz), 55.7, 15.9 (d, J = 6.9 Hz).
MS (ESI): m/z = 327 [M + H]+, 349 [M + Na]+.
#
Diethyl 3-(4-tert-Butyl-2-formylphenoxy)prop-1-ynylphosphonate (1h)
Yield: 225.3 mg (92%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.45 (s, 1 H), 7.88 (s, 1 H), 7.61 (d, J = 8.4 Hz, 1 H), 7.02 (d, J = 9.0 Hz, 1 H), 4.93 (d, J = 3.0 Hz, 2 H), 4.14–4.11 (m, 4 H), 1.38–1.29 (m, 15 H).
13C NMR (150 MHz, CDCl3): δ = 188.8 (q, J = 55.2 Hz), 157.1, 145.1, 132.8, 125.3, 124.7, 112.7, 93.5 (d, J = 50.5 Hz), 78.9 (d, J = 264.5 Hz), 63.4 (d, J = 4.65 Hz), 56.1 (d, J = 4.5 Hz), 34.3, 31.2 (d, J = 25.4 Hz), 15.8 (d, J = 6.9 Hz).
MS (ESI): m/z = 353 [M + H]+, 375 [M + Na]+.
#
Diethyl 3-(2-Formyl-6-methylphenoxy)prop-1-ynylphosphonate (1i)
Yield: 164.3 mg (93%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.36 (s, 1 H), 7.71 (d, J = 7.8 Hz, 1 H), 7.48 (d, J = 7.2 Hz, 1 H), 7.22 (t, J = 7.8 Hz, 1 H), 4.83 (d, J = 3.0 Hz, 2 H), 4.11–4.09 (m, 4 H), 2.39 (d, J = 3.0 Hz, 3 H), 1.33 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 189.6, 157.9, 137.6, 132.4, 129.6, 127.5, 125.2 (d, J = 52.1 Hz), 93.8 (d, J = 50.5 Hz), 77.5 (d, J = 289.5 Hz), 63.3 (d, J = 5.7 Hz), 60.9 (d, J = 108.3 Hz), 42.5, 15.9 (t, J = 82.8 Hz).
MS (ESI): m/z = 311 [M + H]+, 333 [M + Na]+.
#
Diethyl 3-(4,6-Di-tert-butyl-2-formylphenoxy)prop-1-ynylphosphonate (1j)
Yield: 224.4 mg (90%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.26 (s, 1 H), 7.69 (s, 1 H), 7.65 (s, 1 H), 4.79 (d, J = 3.6 Hz, 2 H), 4.18–4.15 (m, 4 H), 1.45 (s, 9 H), 1.38 (t, J = 7.2 Hz, 6 H), 1.33 (s, 9 H).
13C NMR (150 MHz, CDCl3): δ = 190.3, 157.2, 147.4, 143.2, 131.1, 129.0, 126.1, 94.2, 93.9, 79.1, 77.0, 63.5 (t, J = 35.7 Hz), 35.3, 34.7, 31.2 (d, J = 41.4 Hz), 16.0 (d, J C–P = 6.6 Hz).
MS (ESI): m/z = 409 [M + H]+, 431 [M + Na]+.
#
Diethyl 3-(2-Formylnaphthalen-1-yloxy)prop-1-ynylphosphonate (1k)
Yield: 207.6 mg (82%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.61 (s, 1 H), 8.22 (d, J = 8.4 Hz, 1 H), 7.91 (d, J = 7.8 Hz, 1 H), 7.89 (d, J = 8.4 Hz, 1 H), 7.74 (d, J = 8.4 Hz, 1 H), 7.68 (t, J = 7.2 Hz, 1 H), 7.65 (t, J = 7.2 Hz, 1 H), 5.08 (d, J = 3.6 Hz, 2 H), 4.07–4.03 (m, 4 H), 1.32 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 189.4 (t, J = 111.2 Hz), 158.6, 137.9, 129.5, 128.5, 127.3, 127.2, 125.7 (d, J = 11.3 Hz), 122.8 (d, J = 19.7 Hz), 93.2 (d, J =49.2 Hz), 79.0 (d, J = 288.2 Hz), 63.5 (t, J = 33.7 Hz), 42.6, 15.9.
MS (ESI): m/z = 347 [M + H]+, 369 [M + Na]+.
#
Synthesis of Dialkyl (4-Oxo-2H-chromen-3(4H)-ylidene)methylphosphonates 2; General Procedure
To an oven-dried, round-bottom flask equipped with a magnetic bar was added dialkyl 3-(2-formylphenoxy)prop-1-ynylphosphonate 1 (0.5 mmol, 1.0 equiv), pre-catalyst A (9 mg, 0.025 mmol, 0.05 equiv) and anhydrous K2CO3 (6.9 mg, 0.05 mmol, 0.10 equiv) at r.t. under a nitrogen atmosphere. The mixture was dissolved in anhydrous CH2Cl2 (2.0 mL) under a nitrogen atmosphere and the resulting mixture was stirred for 3 h at the stated temperature (17 or 30 °C). The progress of the reaction was monitored by TLC. Upon completion, the reaction mixture was pre-absorbed on silica gel and purified by flash column chromatography on silica gel (hexane–EtOAc, 1:1) to afford 2 (the appearance of exocyclic olefins is a yellow oil, and the appearance of endocyclic olefins is a white solid).
#
Isomerization of Exocyclic Olefins 2 to Endocyclic Derivatives 2′; General Procedure
To an oven-dried, round-bottom flask equipped with a magnetic bar was added 2 (0.5 mmol, 1.0 equiv), pre-catalyst A (9 mg, 0.025 mmol, 0.05 equiv) and anhydrous K2CO3 (6.9 mg, 0.05 mmol, 0.10 equiv) at r.t. under a nitrogen atmosphere. The mixture was dissolved in anhydrous CH2Cl2 (2.0 mL) under a nitrogen atmosphere and the resulting mixture was stirred at 30 °C for 3–5 h until the reaction was complete. The reaction mixture was pre-absorbed on silica gel and purified by flash column chromatography on silica gel (hexane–EtOAc, 1:1) to afford 2′ as a white solid in nearly quantitative yields.
#
(E)-Diethyl (4-Oxo-2H-chromen-3(4H)-ylidene)methylphosphonate (2a)
The title compound was prepared according to the general procedure.
Yield: 133.2 mg (90%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 7.98 (d, J = 7.8 Hz, 1 H), 7.54 (t, J = 7.2 Hz, 1 H), 7.08 (t, J = 7.8 Hz, 1 H), 7.01 (d, J = 8.4 Hz, 1 H), 6.83 (d, J H–P = 15.0 Hz, 1 H), 5.55 (d, J = 1.2 Hz, 2 H), 4.18–4.14 (m, 4 H), 1.37 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 179.9 (d, J = 21.3 Hz), 161.9, 146.9 (d, J = 7.6 Hz), 136.6, 128.0, 122.9, 122.1, 121.1 (d, J = 24.4 Hz), 118.2, 67.7 (d, J = 6.1 Hz), 62.2 (d, J = 5.7 Hz), 16.1 (d, J = 6.5 Hz).
MS (ESI): m/z = 297 [M + H]+, 319 [M + Na]+, 335 [M + K].
Anal. Calcd for C14H17O5P: C, 56.76; H, 5.78. Found: C, 56.57; H, 5.84.
#
Diethyl (4-Oxo-4H-chromen-3-yl)methylphosphonate (2a′)
The title compound was prepared according to the general procedure.
Yield: 134.7 mg (91%); white solid; mp 56 °C.
1H NMR (600 MHz, CDCl3): δ = 8.23 (d, J = 7.8 Hz, 1 H), 8.13 (d, J = 3.6 Hz, 1 H), 7.68 (t, J = 7.2 Hz, 1 H), 7.45 (d, J = 8.4 Hz, 1 H), 7.41 (t, J = 7.8 Hz, 1 H), 4.15–4.10 (m, 4 H), 3.12 (d, J H–P = 20.4 Hz, 2 H), 1.30 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 176.3, 156.2, 154.3 (d, J = 7.8 Hz), 133.6, 125.9, 125.2, 123.4, 118.1, 115.9, 62.2 (d, J = 7.8 Hz), 20.9 (d, J = 142.1 Hz), 16.2 (d, J = 5.9 Hz).
MS (ESI): m/z = 297 [M + H]+, 319 [M + Na]+, 335 [M + K].
Anal. Calcd for C14H17O5P: C, 56.76; H, 5.78. Found: C, 56.90; H, 5.56.
#
(E)-Dibutyl (4-Oxo-2H-chromen-3(4H)-ylidene)methylphosphonate (2b)
The title compound was prepared according to the general procedure.
Yield: 142.6 mg (81%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 7.98 (d, J = 7.8 Hz, 1 H), 7.53 (t, J = 7.2 Hz, 1 H), 7.08 (t, J = 7.8 Hz, 1 H), 7.01 (d, J = 8.4 Hz, 1 H), 6.84 (d, J H–P = 15.0 Hz, 1 H), 5.54 (d, J = 1.2 Hz, 2 H), 4.10–4.07 (m, 4 H), 1.70–1.66 (m, 4 H), 1.44–1.40 (m, 4 H), 0.93 (t, J = 7.8 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 180.1, 162.1, 147.1, 136.7, 128.1 (d, J = 23.1 Hz), 122.7, 122.2, 121.0 (d, J = 78.2 Hz), 118.3, 67.9, 66.1, 32.3, 18.6, 13.5.
31P NMR (CDCl3, 243 MHz): δ = 13.39.
MS (ESI): m/z = 353 [M + H]+, 375 [M + Na]+, 391 [M + K].
Anal. Calcd for C18H25O5P: C, 61.36; H, 7.15. Found: C, 61.23; H, 7.29.
#
(E)-Diisopropyl (4-Oxo-2H-chromen-3(4H)-ylidene)methylphosphonate (2c)
The title compound was prepared according to the general procedure.
Yield: 127.9 mg (79%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 7.98 (d, J = 7.8 Hz, 1 H), 7.53 (t, J = 7.2 Hz, 1 H), 7.08 (t, J = 7.8 Hz, 1 H), 7.01 (d, J = 8.4 Hz, 1 H), 6.84 (d, J H–P = 15.0 Hz, 1 H), 5.54 (d, J = 1.8 Hz, 2 H), 4.73 (q, J = 6.6 Hz, 2 H), 1.37 (d, J = 6.0 Hz, 6 H), 1.33 (d, J = 6.6 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 180.2 (d, J = 21.45 Hz), 162.1, 146.0 (d, J = 7.8 Hz), 136.6 (d, J = 7.6 Hz), 128.1 (d, J = 23.3 Hz), 124.6 (d, J = 180.9 Hz), 123.3, 122.1, 121.1, 118.3, 71.4 (d, J = 11.7 Hz), 68.0, 24.0 (d, J = 5.7 Hz).
MS (ESI): m/z = 325 [M + H]+, 347 [M + Na]+, 363 [M + K].
Anal. Calcd for C16H21O5P: C, 59.26; H, 6.53. Found: C, 59.15; H, 6.31.
#
Diethyl (6-Nitro-4-oxo-4H-chromen-3-yl)methylphosphonate (2d′)
The title compound was prepared according to the general procedure.
Yield: 155.2 mg (91%); white solid; mp 75 °C.
1H NMR (600 MHz, CDCl3): δ = 9.10 (d, J = 2.4 Hz, 1 H), 8.51 (dd, J = 3.0, 9.0 Hz, 1 H), 8.19 (d, J = 3.6 Hz, 1 H), 7.62 (d, J = 9.6 Hz, 1 H), 4.16–4.13 (m, 4 H), 3.11 (d, J H–P = 20.4 Hz, 2 H), 1.31 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 175.6, 160.3, 158.6, 154.5, 152.5, 124.4 (d, J = 7.8 Hz), 122.0 (d, J = 25.65 Hz), 120.3, 115.3 (d, J = 7.8 Hz), 110.6 (t, J = 16.65 Hz), 62.3 (d, J = 6.75 Hz), 21.1 (d, J = 140.7 Hz), 16.3.
MS (ESI): m/z = 342 [M + H]+, 364 [M + Na]+, 380 [M + K].
Anal. Calcd for C14H16NO7P: C, 49.27; H, 4.73. Found: C, 49.34; H, 4.65.
#
(E)-Diethyl (6-Fluoro-4-oxo-2H-chromen-3(4H)-ylidene)methylphosphonate (2e)
The title compound was prepared according to the general procedure.
Yield: 139.7 mg (89%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 7.61 (d, J = 8.4 Hz, 1 H), 7.24 (d, J = 7.8 Hz, 1 H), 7.01 (d, J = 9.0 Hz, 1 H), 6.84 (d, J H–P = 15 Hz, 1 H), 5.52 (d, J = 3.6 Hz, 2 H), 4.17–4.14 (m, 4 H), 1.36 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 179.85, 158.93, 146.28, 124.46, 123.50 (d, J =25.95 Hz), 122.2 (d, J = 25.2 Hz), 112.82 (d, J = 13.8 Hz), 68.09, 62.5 (d, J = 19.25 Hz), 16.3 (d, J = 8.20 Hz).
MS (ESI): m/z = 315 [M + H]+, 337 [M + Na]+, 353 [M + K].
Anal. Calcd for C14H16FO5P: C, 53.51; H, 5.13. Found: C, 53.37; H, 5.24.
#
Diethyl (6-Fluoro-4-oxo-4H-chromen-3-yl)methylphosphonate (2e′)
The title compound was prepared according to the general procedure.
Yield: 146.1 mg (93%); yellow solid; mp 78 °C.
1H NMR (600 MHz, CDCl3): δ = 8.20 (d, J = 3.6 Hz, 1 H), 8.17 (d, J = 7.8 Hz, 1 H), 7.91 (d, J = 7.8 Hz, 1 H), 7.30 (d, J = 7.8 Hz, 1 H), 4.15–4.13 (m, 4 H), 3.11 (d, J H–P = 20.4 Hz, 2 H), 1.31 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 175.7, 154.2, 152.8, 137.1, 125.7, 125.3, 124.6, 116.3 (d, J = 9.0 Hz), 111.6, 62.3 (d, J = 6.75 Hz), 20.9 (d, J = 141.75 Hz), 16.2 (d, J = 6.75 Hz).
MS (ESI): m/z = 315 [M + H]+, 337 [M + Na]+, 353 [M + K].
Anal. Calcd for C14H16FO5P: C, 53.51; H, 5.13. Found: C, 53.67; H, 5.20.
#
Diethyl (8-Bromo-4-oxo-4H-chromen-3-yl)methylphosphonate (2f′)
The title compound was prepared according to the general procedure.
Yield: 163.1 mg (87%); white solid; mp 90 °C.
1H NMR (600 MHz, CDCl3): δ = 8.14 (d, J = 3.6 Hz, 1 H), 7.85 (dd, J = 3.0, 8.4 Hz, 1 H), 7.49–7.47 (m, 1 H), 7.41–7.39 (m, 1 H), 4.16–4.11 (m, 4 H), 3.11 (d, J H–P = 20.4 Hz, 2 H), 1.29 (q, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 176.3, 156.2, 154.3 (d, J = 7.8 Hz), 133.6, 125.9, 125.2, 123.4, 118.1, 115.9, 62.2 (d, J = 7.8 Hz), 20.9 (d, J = 142.1 Hz), 16.3 (d, J = 5.85 Hz).
MS (ESI): m/z = 376 [M + H]+, 398 [M + Na]+, 414 [M + K].
Anal. Calcd for C14H16BrO5P: C, 44.82; H, 4.30. Found: C, 44.96; H, 4.23.
#
(E)-Diethyl (6-Methoxy-4-oxo-2H-chromen-3(4H)-ylidene)methylphosphonate (2g)
The title compound was prepared according to the general procedure.
Yield: 150.0 mg (92%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 7.35 (d, J = 3.6 Hz, 1 H), 7.14 (dd, J =9.0, 3.0 Hz, 1 H), 6.94 (d, J = 9.0 Hz, 1 H), 6.78 (d, J H–P = 15.6 Hz, 1 H), 5.48 (d, J = 3.6 Hz, 2 H), 4.17–3.82 (m, 4 H), 3.82 (s, 3 H), 1.37 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 175.7, 154.2, 152.8, 137.1, 125.7, 125.3, 124.6, 116.3 (d, J = 9.0 Hz), 111.6, 67.9 (d, J = 6.75 Hz), 62.4 (d, J = 21.9 Hz), 55.7 (d, J = 26.5 Hz), 16.2 (d, J = 6.75 Hz).
MS (ESI): m/z = 327 [M + H]+, 349 [M + Na]+, 365 [M + K].
Anal. Calcd for C15H19O6P: C, 55.22; H, 5.87. Found: C, 55.11; H, 5.97.
#
Diethyl (6-Methoxy-4-oxo-4H-chromen-3-yl)methylphosphonate (2g′)
The title compound was prepared according to the general procedure.
Yield: 146.7 mg (90%); white solid; mp 83 °C.
1H NMR (600 MHz, CDCl3): δ = 8.12 (d, J = 4.2 Hz, 1 H), 7.57 (d, J = 3.0 Hz, 1 H), 7.41 (d, J = 9.0 Hz, 1 H), 7.27 (d, J = 9.0 Hz, 1 H), 4.16–4.11 (m, 4 H), 3.98 (s, 3 H), 3.13 (d, J H–P = 20.4 Hz, 2 H), 1.32 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 176.0 (d, J = 18.6 Hz), 156.8, 154.1, 151.1, 123.8 (d, J = 82.8 Hz), 119.5, 114.9 (d, J = 7.5 Hz), 104.7, 62.2 (d, J = 7.5 Hz), 55.7, 20.9 (d, J = 140.3 Hz), 16.3 (d, J = 6.9 Hz).
MS (ESI): m/z = 327 [M + H]+, 349 [M + Na]+, 365 [M + K].
Anal. Calcd for C15H19O6P: C, 55.22; H, 5.87. Found: C, 55.13; H, 5.94.
#
Diethyl (6-tert-Butyl-4-oxo-4H-chromen-3-yl)methylphosphonate (2h′)
The title compound was prepared according to the general procedure.
Yield: 149.6 mg (85%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 8.20 (d, J = 1.8 Hz, 1 H), 8.12 (d, J = 3.0 Hz, 1 H), 7.73 (d, J = 9.0 Hz, 1 H), 7.40 (d, J = 9.0 Hz, 1 H), 4.15–4.12 (m, 4 H), 3.13 (d, J H–P = 20.4 Hz, 2 H), 1.38 (s, 9 H), 1.30 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 175.6, 154.5, 148.5, 131.6, 122.7, 121.6, 117.7, 115.5, 62.3 (d, J = 6.75 Hz), 34.8, 31.2, 21.1 (d, J = 140.7 Hz), 16.3.
MS (ESI): m/z = 353 [M + H]+, 375 [M + Na]+, 391 [M + K].
Anal. Calcd for C18H25O5P: C, 61.36; H, 7.15. Found: C, 61.27; H, 7.31.
#
Diethyl (8-Methyl-4-oxo-4H-chromen-3-yl)methylphosphonate (2i′)
The title compound was prepared according to the general procedure.
Yield: 137.9 mg (89%); white solid; mp 97 °C.
1H NMR (600 MHz, CDCl3): δ = 8.11 (s, 1 H), 7.99 (d, J = 7.8 Hz, 1 H), 7.43 (d, J = 6.0 Hz, 1 H), 7.22 (t, J = 6.6 Hz, 1 H), 4.08–4.03 (m, 4 H), 3.04 (t, J H–P = 20.4 Hz, 2 H), 2.39 (s, 3 H), 1.24 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 176.6, 154.8, 154.1, 134.5, 127.6, 124.7, 123.2 (d, J = 19.95 Hz), 115.5 (d, J = 7.8 Hz), 62.3 (d, J = 6.75 Hz), 20.9 (d, J = 140.7 Hz), 16.2, 15.5.
MS (ESI): m/z = 311 [M + H]+, 333 [M + Na]+, 349 [M + K].
Anal. Calcd for C15H19O5P: C, 58.06; H, 6.17. Found: C, 58.15; H, 6.09.
#
Diethyl (6,8-Di-tert-butyl-4-oxo-4H-chromen-3-yl)methylphosphonate (2j′)
The title compound was prepared according to the general procedure.
Yield: 163.2 mg (80%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 8.13 (d, J = 3.0 Hz, 1 H), 8.03 (d, J = 1.8 Hz, 1 H), 7.63 (d, J = 1.8 Hz, 1 H), 4.08–4.06 (m, 4 H), 3.06 (d, J H–P = 20.4 Hz, 2 H), 1.42 (s, 9 H), 1.30 (s, 9 H), 1.24 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 175.9, 153.2 (d, J = 12.3 Hz), 147.5, 138.5, 128.7, 123.5, 119.7, 114.9 (d, J = 7.8 Hz), 62.3 (d, J = 6.75 Hz), 34.9 (d, J = 35.7 Hz), 31.3, 30.5 (t, J = 78 Hz), 20.9 (d, J = 140.5 Hz), 16.3 (d, J = 5.85 Hz).
MS (ESI): m/z = 409 [M + H]+, 431 [M + Na]+, 447 [M + K].
Anal. Calcd for C22H33O5P: C, 64.69; H, 8.14. Found: C, 64.55; H, 8.31.
#
Diethyl (4-Oxo-4H-benzo[h]chromen-3-yl)methylphosphonate (2k′)
The title compound was prepared according to the general procedure.
Yield: 155.7 mg (90%); white solid; mp 86 °C.
1H NMR (600 MHz, CDCl3): δ = 8.44 (d, J = 8.4 Hz, 1 H), 8.32 (d, J = 3.6 Hz, 1 H), 8.13 (d, J = 8.4 Hz, 1 H), 7.90 (d, J = 8.4 Hz, 1 H), 7.74 (d, J = 9.0 Hz, 1 H), 7.69 (t, J = 7.2 Hz, 1 H), 7.67 (t, J = 7.8 Hz, 1 H), 4.18–4.13 (m, 4 H), 3.19 (d, J H–P = 21.0 Hz, 2 H), 1.31 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 175.9, 153.6, 153.4, 135.6, 129.2, 127.9, 127.1, 125.3, 123.8, 122.1, 120.7, 119.5, 117.2 (d, J = 7.8 Hz), 62.3 (d, J = 7.8 Hz), 20.9 (d, J = 140.7 Hz), 16.2 (d, J = 5.85 Hz).
MS (ESI): m/z = 347 [M + H]+, 369 [M + Na]+, 385 [M + K].
Anal. Calcd for C18H19O5P: C, 62.43; H, 5.53. Found: C, 62.58; H, 5.60.
#
Synthesis of Dialkyl 2-Aryl-5H-chromeno[4,3-b]pyridin-4-yl Phosphonate 3; General Procedure
To an oven-dried, round-bottom flask equipped with a magnetic bar was added the diethyl 3-(2-formylphenoxy)prop-1-ynylphosphonate derivative 1 (0.5 mmol, 1.0 equiv), pre-catalyst A (9 mg, 0.025 mmol, 0.05 equiv) and anhydrous K2CO3 (6.9 mg, 0.05 mmol, 0.10 equiv) at r.t. (17 °C) under a nitrogen atmosphere. The mixture was dissolved in anhydrous CH2Cl2 (2.0 mL) under nitrogen and the resulting mixture was then stirred at r.t. (17 °C) for 3 h. The α-pyridylmethyl ketone salt (0.5 mmol) and excess NH4OAc (5 equiv) in MeOH (4 mL) was added and the mixture was heated at reflux for 6 h. Upon cooling to r.t., the mixture was filtered and washed with EtOAc (3 × 10 mL). The filtrate was collected and purified by flash column chromatography on silica gel (hexane–EtOAc, 1:1) to give 3.
#
Diethyl 2-Phenyl-5H-chromeno[4,3-b]pyridin-4-ylphosphonate (3a)
The title compound was prepared according to the general procedure.
Yield: 102.7 mg (52%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 8.42 (d, J = 7.2 Hz, 1 H), 8.18 (d, J = 7.8 Hz, 2 H), 8.13 (d, J = 7.2 Hz, 1 H), 7.50 (t, J = 7.8 Hz, 2 H), 7.46 (d, J = 7.2 Hz, 1 H), 7.35 (t, J = 7.8 Hz, 1 H), 7.15 (t, J = 7.8 Hz, 1 H), 6.98 (d, J = 7.8 Hz, 1 H), 5.25 (s, 2 H), 4.30–4.16 (m, 4 H), 1.38 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 156.4 (d, J = 18.45 Hz), 149.2 (d, J = 11.55 Hz), 138.1, 134.4, 133.2, 131.6, 129.5, 128.7, 126.9, 126.0 (d, J = 9.15 Hz), 125.2 (d, J = 9.15 Hz), 122.8, 122.3, 121.9, 116.7, 66.3, 62.8, 16.3.
MS (ESI): m/z = 396 [M + H]+, 418 [M + Na]+, 434 [M + K].
Anal. Calcd for C22H22NO4P: C, 66.83; H, 5.61; N, 3.54. Found: C, 66.90; H, 5.73; N, 3.52.
#
Dibutyl 2-Phenyl-5H-chromeno[4,3-b]pyridin-4-ylphosphonate (3b)
The title compound was prepared according to the general procedure.
Yield: 112.8 mg (50%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 8.42 (d, J = 7.8 Hz, 1 H), 8.18 (t, J = 7.8 Hz, 2 H), 8.13 (d, J = 14.4 Hz, 1 H), 7.52 (t, J = 7.2 Hz, 2 H), 7.46 (t, J = 7.2 Hz, 1 H), 7.35 (t, J = 7.8 Hz, 1 H), 7.15 (t, J = 7.8 Hz, 1 H), 6.99 (d, J = 7.8 Hz, 1 H), 5.51 (s, 2 H), 4.21–4.16 (m, 2 H), 4.12–4.07 (m, 2 H), 1.72–1.67 (m, 4 H), 1.45–1.39 (m, 4 H), 0.93 (t, J = 7.2 Hz, 6 H).
13C NMR (CDCl3, 150 MHz): δ = 156.4, 149.2, 138.2, 134.4, 133.2, 131.7, 129.5, 128.7, 126.9, 125.9, 125.2, 122.9, 122.3, 122.0, 116.8, 66.4, 62.8, 31.2, 19.2, 16.4.
31P NMR (CDCl3, 243 MHz): δ = 14.59.
MS (ESI): m/z = 452 [M + H]+, 474 [M + Na]+, 490 [M + K].
Anal. Calcd for C26H30NO4P: C, 69.17; H, 6.70; N, 3.10. Found: C, 69.03; H, 6.59; N, 3.05.
#
Diisopropyl 2-Phenyl-5H-chromeno[4,3-b]pyridin-4-ylphosphonate (3c)
The title compound was prepared according to the general procedure.
Yield: 101.5 mg (48%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 8.41 (d, J = 7.8 Hz, 1 H), 8.19–7.16 (m, 3 H), 7.51 (t, J = 7.2 Hz, 2 H), 7.45 (t, J = 7.8 Hz, 1 H), 7.35 (t, J = 7.2 Hz, 1 H), 7.14 (t, J = 7.8 Hz, 1 H), 6.98 (d, J = 8.4 Hz, 1 H), 5.51 (s, 2 H), 4.81–4.77 (m, 2 H), 1.38 (d, J = 7.2 Hz, 6 H), 1.24 (d, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 156.3 (t, J = 16.05 Hz), 149.0, 138.2, 135.8, 134.6, 131.6, 129.5, 128.7, 126.9, 125.8, 125.3, 122.9, 122.3, 122.0, 116.8, 72.0, 66.4, 24.0 (d, J = 16.2 Hz).
MS (ESI): m/z = 424 [M + H]+, 446 [M + Na]+ 462 [M + K]+.
Anal. Calcd for C24H26NO4P: C, 68.07; H, 6.19; N, 3.31. Found: C, 67.95; H, 6.33; N, 3.47.
#
Diethyl 2-(4-Methoxyphenyl)-5H-chromeno[4,3-b]pyridin-4-ylphosphonate (3d)
The title compound was prepared according to the general procedure.
Yield: 112.6 mg (53%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 8.40 (dd, J = 1.8, 7.2 Hz, 1 H), 8.15 (d, J = 8.4 Hz, 2 H), 8.07 (d, J = 15.0 Hz, 1 H), 7.34 (t, J = 7.2 Hz, 1 H), 7.14 (t, J = 7.2 Hz, 1 H), 7.02 (d, J = 9.0 Hz, 2 H), 6.98 (d, J = 8.4 Hz, 1 H), 5.49 (s, 2 H), 4.28–4.11 (m, 4 H), 3.88 (s, 3 H), 1.37 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 160.9, 156.4, 156.1, 148.9, 134.1, 133.0, 131.6, 130.8, 128.3, 125.0, 123.0, 122.3, 119.0, 116.8, 114.1, 66.3, 62.8, 55.3, 16.3.
MS (ESI): m/z = 426 [M + H]+, 448 [M + Na]+, 464 [M + K].
Anal. Calcd for C23H24NO5P: C, 64.94; H, 5.69; N, 3.29. Found: C, 64.79; H, 5.50; N, 3.07.
#
Diethyl 2-p-Tolyl-5H-chromeno[4,3-b]pyridin-4-ylphosphonate (3e)
The title compound was prepared according to the general procedure.
Yield: 104.3 mg (51%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 8.40 (dd, J = 1.2, 7.8 Hz, 1 H), 8.12–8.08 (m, 3 H), 7.35 (t, J = 7.2 Hz, 1 H), 7.31 (d, J = 7.8 Hz, 2 H), 7.14 (t, J = 7.8 Hz, 1 H), 6.98 (d, J = 7.8 Hz, 1 H), 5.51 (d, J = 1.8 Hz, 2 H), 4.27–4.16 (m, 4 H), 2.43 (s, 3 H), 1.37 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 156.4, 149.1 (d, J = 12.3 Hz), 139.7, 135.4, 134.2, 133.0, 131.6, 129.5, 128.5 (d, J = 7.8 Hz), 126.7, 125.5, 125.2, 122.9, 122.3, 116.7, 66.3, 62.8 (d, J = 5.55 Hz), 21.3, 16.3.
MS (ESI): m/z = 410 [M + H]+, 432 [M + Na]+, 447 [M + K].
Anal. Calcd for C23H24NO4P: C, 67.47; H, 5.91; N, 3.42. Found: C, 67.60; H, 5.79; N, 3.53.
#
Diethyl 2-(4-Fluorophenyl)-5H-chromeno[4,3-b]pyridin-4-ylphosphonate (3f)
The title compound was prepared according to the general procedure.
Yield: 103.3 mg (50%); white solid; mp 78 °C.
1H NMR (600 MHz, CDCl3): δ = 8.38 (dd, J = 1.2, 7.2 Hz, 1 H), 8.19–8.16 (m, 2 H), 8.09 (d, J = 15.0 Hz, 1 H), 7.37–7.34 (m, 1 H), 7.18 (t, J = 8.4 Hz, 2 H), 7.13 (q, J = 7.2 Hz, 1 H), 6.98 (d, J = 7.8 Hz, 1 H), 5.51 (s, 2 H), 4.27–4.16 (m, 4 H), 1.37 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 164.5, 162.9, 156.4, 155.3 (d, J = 13.8 Hz), 149.1 (d, J = 13.8 Hz), 134.3 (d, J = 34.5 Hz), 133.3, 131.8, 128.7 (d, J = 6.9 Hz), 125.8 (d, J = 9.15 Hz), 125.2, 122.5 (d, J = 57.45 Hz), 121.6 (d, J = 9.15 Hz), 116.8, 115.6 (d, J = 20.7 Hz), 66.3, 62.9, 16.3.
MS (ESI): m/z = 414 [M + H]+, 436 [M + Na]+, 452 [M + K].
Anal. Calcd for C22H21FNO4P: C, 63.92; H, 5.12; N, 3.39. Found: C, 64.11; H, 5.04; N, 3.27.
#
#
Acknowledgment
This work was supported by the Natural Science Foundation of China (No. 20872046) and the Fundamental Research Funds for the Central Universities (No. CCNU09A02013).
-
References
- 1a Mader MM, Bartlett PA. Chem. Rev. 1997; 97: 1281
- 1b Brassfield HA, Jacobson RA, Verkade JG. J. Am. Chem. Soc. 1975; 97: 4143
- 1c Darrow JW, Drueckhammer DG. J. Org. Chem. 1994; 59: 2976
- 1d Morita I, Kunimoto K, Tsuda M, Tada SI, Kise M, Kimura K. Chem. Pharm. Bull. 1987; 35: 4144
- 1e Stewart JD, Liotta LJ, Benkovic SJ. Acc. Chem. Res. 1993; 26: 396
- 1f Collard JN, Benezra C. Tetrahedron Lett. 1982; 23: 3725
- 2a Brunel JM, Buono G. Top. Curr. Chem. 2002; 220: 79
- 2b Tang W, Zhang X. Chem. Rev. 2003; 103: 3029
- 3a Cupta HC. L. Insecticides: Toxicology and Uses . Agrotech Publishing Academy Press; Udaipur (India): 1999: 51211
- 3b Matsumura F. Toxicology of Insecticides . 2nd ed. New York; Plenum Press: 1985: 62-90
- 4a Enders D, Balensiefer T. Acc. Chem. Res. 2004; 37: 534
- 4b Enders D, Niemeier O, Henseler A. Chem. Rev. 2007; 107: 5606
- 4c Marion N, Diéz-González S, Nolan SP. Angew. Chem. Int. Ed. 2007; 46: 2988
- 4d Biju AT, Kuhl N, Glorius F. Acc. Chem. Res. 2011; 44: 1182
- 4e Shen LT, Shao PL, Ye S. Adv. Synth. Catal. 2011; 353: 1943
- 4f Bugaut X, Liu F, Glorius F. J. Am. Chem. Soc. 2011; 133: 8130
- 4g Enders D, Grossmann A, Huang H, Raabe G. Eur. J. Org. Chem. 2011; 4298
- 4h Park JH, Bhilare SV, Youn SW. Org. Lett. 2011; 13: 2228
- 5a Enders D, Kallfass U. Angew. Chem. Int. Ed. 2002; 41: 1743
- 5b Nair V, Bindu S, Sreekumar V, Rath NP. Org. Lett. 2003; 5: 665
- 5c Hachisu Y, Bode JW, Suzuki K. Adv. Synth. Catal. 2004; 346: 1097
- 5d Mennen SM, Gipson JD, Kim YR, Miller SJ. J. Am. Chem. Soc. 2005; 127: 1654
- 5e Burstein C, Tschan S, Xie XL, Glorius F. Synthesis 2006; 2418
- 5f Wang L, Thai K, Gravel M. Org. Lett. 2009; 11: 891
- 5g Kaeobamrung J, Mahatthananchai J, Zheng PG, Bode JW. J. Am. Chem. Soc. 2010; 132: 8810
- 5h Wu KJ, Li GQ, Li Y, Dai LX, You SL. Chem. Commun. 2011; 47: 493
- 5i Rose M, Notzon A, Heitbaum M, Nickerl G, Paasch S, Brunner E, Glorius F, Kaskel S. Chem. Commun. 2011; 47: 4814
- 5j Boddaert T, Coquerel Y, Rodriguez J. Chem.–Eur. J. 2011; 17: 2266
- 6a Stetter H, Kuhlmann H. Angew. Chem., Int. Ed. Engl. 1974; 13: 539
- 6b Stetter H, Kuhlmann H. Org. React. 1991; 40: 407
- 6c Ciganek E. Synthesis 1995; 1311
- 6d Braun RU, Zeitler K, Müller TJ. J. Org. Lett. 2001; 3: 3297
- 6e Grasa GA, Singh R, Nolan SP. Synthesis 2004; 971
- 6f Read de Alaniz J, Rovis T. J. Am. Chem. Soc. 2005; 127: 6284
- 6g Cullen SC, Rovis T. Org. Lett. 2008; 10: 3141
- 6h Read de Alaniz J, Kerr MS, Moore JL, Rovis T. J. Org. Chem. 2008; 73: 2033
- 6i He J, Tang S, Liu J, Su Y, Pan X, She X. Tetrahedron 2008; 64: 8797
- 6j Enders D, Han J. Synthesis 2008; 3864
- 6k Liu Q, Rovis T. Org. Lett. 2009; 11: 2856
- 6l DiRocco DA, Oberg KM, Dalton DM, Rovis T. J. Am. Chem. Soc. 2009; 131: 10872
- 6m Hirano K, Biju AT, Piel I, Glorius F. J. Am. Chem. Soc. 2009; 131: 14190
- 6n Biju AT, Wurz NE, Glorius F. J. Am. Chem. Soc. 2010; 132: 5970
- 6o Filloux CM, Lathrop SP, Rovis T. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 20666
- 6p Vedachalam S, Wong QL, Maji B, Zeng J, Ma JM, Liu XW. Adv. Synth. Catal. 2011; 353: 219
- 6q Piel I, Steinmetz M, Hirano K, Fröhlich R, Grimme S, Glorius F. Angew. Chem. Int. Ed. 2011; 50: 4983
- 6r Moore JL, Silvestri AP, Read de Alaniz J, DiRocco DA, Rovis T. Org. Lett. 2011; 13: 1742
- 7a Mennen SM, Blank JT, Tran-Dubé MB, Imbriglio JE, Miller SJ. Chem. Commun. 2005; 195
- 7b Ma C, Yang YW. Org. Lett. 2005; 7: 1343
- 7c Ma C, Ding HF, Wu GM, Yang YW. J. Org. Chem. 2005; 70: 8919
- 7d Wang L, Thai K, Gravel M. Org. Lett. 2009; 11: 891
- 7e Sun FG, Huang XL, Ye S. J. Org. Chem. 2010; 75: 273
- 7f O’Brien JM, Hoveyda AH. J. Am. Chem. Soc. 2011; 133: 7712
- 7g Padmanaban M, Biju AT, Glorius F. Org. Lett. 2011; 13: 5624
- 7h Bugaut X, Liu F, Glorius F. J. Am. Chem. Soc. 2011; 133: 8130
- 7i Padmanaban M, Biju AT, Glorius F. Org. Lett. 2011; 13: 98
- 8a Miller SI, Fujii A. J. Am. Chem. Soc. 1971; 93: 3694
- 8b Redmore D. Chem. Rev. 1971; 71: 315
- 8c Al Quntar AA. A, Srivastava HK, Srebnik M, Melman A, Ta-Shma R, Shurki A. J. Org. Chem. 2007; 72: 4932
- 8d Kee JM, Villani B, Carpenter LR, Muir TW. J. Am. Chem. Soc. 2010; 132: 14327
- 9a Duval RA, Lewin G, Peris E, Chahboune N, Garofano A, Dröse S, Cortes D, Brandt U, Hocquemiller R. Biochemistry 2006; 45: 2721
- 9b Nutley BP, Smith NF, Hayes A, Kelland LR, Brunton L, Golding BT, Smith GC. M, Martin NM. B, Workman P, Raynaud FI. Br. J. Cancer 2005; 93: 1011
- 10 Gao YX, Wang G, Chen L, Xu PX, Zhao YF, Zhou YB, Han LB. J. Am. Chem. Soc. 2009; 131: 7956
- 11a Kröhnke F. Synthesis 1976; 24
- 11b Zecher W, Kröhnke F. Chem. Ber. 1961; 94: 690
- 11c Kelly TR, Lee YJ, Mears RJ. J. Org. Chem. 1997; 62: 2774
- 11d Bark T, Von Zelewsky A. Chimia 2000; 54: 589
- 11e Malkov AV, Bella M, Stara IG, Kocovsky P. Tetrahedron Lett. 2001; 42: 3045
- 12 Eryazici I, Moorefield CN, Durmus S, Newkome GR. J. Org. Chem. 2006; 71: 1009
- 13a Pesch J, Harms K, Bach T. Eur. J. Org. Chem. 2004; 2025
- 13b Van Den Berg HJ, Challa G, Pandit UK. J. Mol. Catal. 1989; 51: 1
- 13c Kerr MS, Read de Alaniz J, Rovis T. J. Org. Chem. 2005; 70: 5725
- 13d Arduengo AJ, Krafczyk R, Schmutzler R, Craig HA, Goerlich JR, Marshall WJ, Unverzagt M. Tetrahedron 1999; 55: 14523
- 13e Enders D, Gielen H. J. Organomet. Chem. 2001; 70: 617-618
- 13f Jazzar R, Liang HZ, Donnadieu B, Bertrand G. J. Organomet. Chem. 2006; 691: 3201
- 13g Matsuoka Y, Ishida Y, Saigo K. Tetrahedron Lett. 2008; 49: 2985
- 14 For synthetic routes to substituted salicylaldehyde, see: Bhatt S, Nayak SK. Tetrahedron Lett. 2009; 50: 5823
For reviews, see:
For recent reviews on NHC catalysis, see:
For synthetic routes to the NHC precursors, see:
-
References
- 1a Mader MM, Bartlett PA. Chem. Rev. 1997; 97: 1281
- 1b Brassfield HA, Jacobson RA, Verkade JG. J. Am. Chem. Soc. 1975; 97: 4143
- 1c Darrow JW, Drueckhammer DG. J. Org. Chem. 1994; 59: 2976
- 1d Morita I, Kunimoto K, Tsuda M, Tada SI, Kise M, Kimura K. Chem. Pharm. Bull. 1987; 35: 4144
- 1e Stewart JD, Liotta LJ, Benkovic SJ. Acc. Chem. Res. 1993; 26: 396
- 1f Collard JN, Benezra C. Tetrahedron Lett. 1982; 23: 3725
- 2a Brunel JM, Buono G. Top. Curr. Chem. 2002; 220: 79
- 2b Tang W, Zhang X. Chem. Rev. 2003; 103: 3029
- 3a Cupta HC. L. Insecticides: Toxicology and Uses . Agrotech Publishing Academy Press; Udaipur (India): 1999: 51211
- 3b Matsumura F. Toxicology of Insecticides . 2nd ed. New York; Plenum Press: 1985: 62-90
- 4a Enders D, Balensiefer T. Acc. Chem. Res. 2004; 37: 534
- 4b Enders D, Niemeier O, Henseler A. Chem. Rev. 2007; 107: 5606
- 4c Marion N, Diéz-González S, Nolan SP. Angew. Chem. Int. Ed. 2007; 46: 2988
- 4d Biju AT, Kuhl N, Glorius F. Acc. Chem. Res. 2011; 44: 1182
- 4e Shen LT, Shao PL, Ye S. Adv. Synth. Catal. 2011; 353: 1943
- 4f Bugaut X, Liu F, Glorius F. J. Am. Chem. Soc. 2011; 133: 8130
- 4g Enders D, Grossmann A, Huang H, Raabe G. Eur. J. Org. Chem. 2011; 4298
- 4h Park JH, Bhilare SV, Youn SW. Org. Lett. 2011; 13: 2228
- 5a Enders D, Kallfass U. Angew. Chem. Int. Ed. 2002; 41: 1743
- 5b Nair V, Bindu S, Sreekumar V, Rath NP. Org. Lett. 2003; 5: 665
- 5c Hachisu Y, Bode JW, Suzuki K. Adv. Synth. Catal. 2004; 346: 1097
- 5d Mennen SM, Gipson JD, Kim YR, Miller SJ. J. Am. Chem. Soc. 2005; 127: 1654
- 5e Burstein C, Tschan S, Xie XL, Glorius F. Synthesis 2006; 2418
- 5f Wang L, Thai K, Gravel M. Org. Lett. 2009; 11: 891
- 5g Kaeobamrung J, Mahatthananchai J, Zheng PG, Bode JW. J. Am. Chem. Soc. 2010; 132: 8810
- 5h Wu KJ, Li GQ, Li Y, Dai LX, You SL. Chem. Commun. 2011; 47: 493
- 5i Rose M, Notzon A, Heitbaum M, Nickerl G, Paasch S, Brunner E, Glorius F, Kaskel S. Chem. Commun. 2011; 47: 4814
- 5j Boddaert T, Coquerel Y, Rodriguez J. Chem.–Eur. J. 2011; 17: 2266
- 6a Stetter H, Kuhlmann H. Angew. Chem., Int. Ed. Engl. 1974; 13: 539
- 6b Stetter H, Kuhlmann H. Org. React. 1991; 40: 407
- 6c Ciganek E. Synthesis 1995; 1311
- 6d Braun RU, Zeitler K, Müller TJ. J. Org. Lett. 2001; 3: 3297
- 6e Grasa GA, Singh R, Nolan SP. Synthesis 2004; 971
- 6f Read de Alaniz J, Rovis T. J. Am. Chem. Soc. 2005; 127: 6284
- 6g Cullen SC, Rovis T. Org. Lett. 2008; 10: 3141
- 6h Read de Alaniz J, Kerr MS, Moore JL, Rovis T. J. Org. Chem. 2008; 73: 2033
- 6i He J, Tang S, Liu J, Su Y, Pan X, She X. Tetrahedron 2008; 64: 8797
- 6j Enders D, Han J. Synthesis 2008; 3864
- 6k Liu Q, Rovis T. Org. Lett. 2009; 11: 2856
- 6l DiRocco DA, Oberg KM, Dalton DM, Rovis T. J. Am. Chem. Soc. 2009; 131: 10872
- 6m Hirano K, Biju AT, Piel I, Glorius F. J. Am. Chem. Soc. 2009; 131: 14190
- 6n Biju AT, Wurz NE, Glorius F. J. Am. Chem. Soc. 2010; 132: 5970
- 6o Filloux CM, Lathrop SP, Rovis T. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 20666
- 6p Vedachalam S, Wong QL, Maji B, Zeng J, Ma JM, Liu XW. Adv. Synth. Catal. 2011; 353: 219
- 6q Piel I, Steinmetz M, Hirano K, Fröhlich R, Grimme S, Glorius F. Angew. Chem. Int. Ed. 2011; 50: 4983
- 6r Moore JL, Silvestri AP, Read de Alaniz J, DiRocco DA, Rovis T. Org. Lett. 2011; 13: 1742
- 7a Mennen SM, Blank JT, Tran-Dubé MB, Imbriglio JE, Miller SJ. Chem. Commun. 2005; 195
- 7b Ma C, Yang YW. Org. Lett. 2005; 7: 1343
- 7c Ma C, Ding HF, Wu GM, Yang YW. J. Org. Chem. 2005; 70: 8919
- 7d Wang L, Thai K, Gravel M. Org. Lett. 2009; 11: 891
- 7e Sun FG, Huang XL, Ye S. J. Org. Chem. 2010; 75: 273
- 7f O’Brien JM, Hoveyda AH. J. Am. Chem. Soc. 2011; 133: 7712
- 7g Padmanaban M, Biju AT, Glorius F. Org. Lett. 2011; 13: 5624
- 7h Bugaut X, Liu F, Glorius F. J. Am. Chem. Soc. 2011; 133: 8130
- 7i Padmanaban M, Biju AT, Glorius F. Org. Lett. 2011; 13: 98
- 8a Miller SI, Fujii A. J. Am. Chem. Soc. 1971; 93: 3694
- 8b Redmore D. Chem. Rev. 1971; 71: 315
- 8c Al Quntar AA. A, Srivastava HK, Srebnik M, Melman A, Ta-Shma R, Shurki A. J. Org. Chem. 2007; 72: 4932
- 8d Kee JM, Villani B, Carpenter LR, Muir TW. J. Am. Chem. Soc. 2010; 132: 14327
- 9a Duval RA, Lewin G, Peris E, Chahboune N, Garofano A, Dröse S, Cortes D, Brandt U, Hocquemiller R. Biochemistry 2006; 45: 2721
- 9b Nutley BP, Smith NF, Hayes A, Kelland LR, Brunton L, Golding BT, Smith GC. M, Martin NM. B, Workman P, Raynaud FI. Br. J. Cancer 2005; 93: 1011
- 10 Gao YX, Wang G, Chen L, Xu PX, Zhao YF, Zhou YB, Han LB. J. Am. Chem. Soc. 2009; 131: 7956
- 11a Kröhnke F. Synthesis 1976; 24
- 11b Zecher W, Kröhnke F. Chem. Ber. 1961; 94: 690
- 11c Kelly TR, Lee YJ, Mears RJ. J. Org. Chem. 1997; 62: 2774
- 11d Bark T, Von Zelewsky A. Chimia 2000; 54: 589
- 11e Malkov AV, Bella M, Stara IG, Kocovsky P. Tetrahedron Lett. 2001; 42: 3045
- 12 Eryazici I, Moorefield CN, Durmus S, Newkome GR. J. Org. Chem. 2006; 71: 1009
- 13a Pesch J, Harms K, Bach T. Eur. J. Org. Chem. 2004; 2025
- 13b Van Den Berg HJ, Challa G, Pandit UK. J. Mol. Catal. 1989; 51: 1
- 13c Kerr MS, Read de Alaniz J, Rovis T. J. Org. Chem. 2005; 70: 5725
- 13d Arduengo AJ, Krafczyk R, Schmutzler R, Craig HA, Goerlich JR, Marshall WJ, Unverzagt M. Tetrahedron 1999; 55: 14523
- 13e Enders D, Gielen H. J. Organomet. Chem. 2001; 70: 617-618
- 13f Jazzar R, Liang HZ, Donnadieu B, Bertrand G. J. Organomet. Chem. 2006; 691: 3201
- 13g Matsuoka Y, Ishida Y, Saigo K. Tetrahedron Lett. 2008; 49: 2985
- 14 For synthetic routes to substituted salicylaldehyde, see: Bhatt S, Nayak SK. Tetrahedron Lett. 2009; 50: 5823
For reviews, see:
For recent reviews on NHC catalysis, see:
For synthetic routes to the NHC precursors, see:
