College of Science, University of Calcutta; 92, Acharya Prafulla Chandra Road, Kolkata , India

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1 Indian Journal of hemistry Vol. 50B, June 2011, pp ,3-Dipolar cycloadditions. Part XXI: atalytic effects of Lewis acids on 1,3- dipolar cycloaddition of -(4-chlorophenyl)-N-phenyl nitrone to benzylidene acetophenone Nivedita Acharjee a, Avijit Banerji* a & Thierry Prangé b a entre of Advanced Studies on Natural Products including rganic Synthesis, Department of hemistry, University ollege of Science, University of alcutta; 92, Acharya Prafulla handra Road, Kolkata , India b Laboratoire de ristallographie et RMN biologiques (UMR 8015 NRS). Université Paris Descartes, 4, av. de l'bservatoire, Paris, France ablabcu@yahoo.co.uk Received 9 December 2009; accepted (revised) 11 March 2011 The normal electron demand reaction of -chlorophenyl-n-phenyl nitrone with benzylidene acetophenone and the effects of mild Lewis acid catalysts like metal triflates and magnesium bromide on the reaction rate are reported. Frontier molecular orbital energies are calculated to rationalise the regioselectivity of the cycloaddition. Keywords: 1,3-Dipolar cycloadditions, nitrone, benzylidene acetophenone, Lewis acid catalyst The isoxazolidine skeleton constitutes a fundamental part of numerous natural products and masked forms of various 1,3-difunctionalised compounds. The isoxazolidine skeleton is conveniently generated by 1,3-dipolar cycloaddition of nitrones 1-8. Some isoxazolidines are also known to possess antibacterial activity 4. A number of investigations have been carried out by various research groups to catalytically enhance reaction rates and alter the regio- and stereoselectivities of nitrone cycloadditions to olefins leading to isoxazolidines 5-8. The strategy is to preferentially coordinate one of the substrates and enhance the rate of the reaction. Gothelf et al. 9 had proposed that 1,3-dipolar cycloaddition reactions are accelerated or slowed down in the presence of Lewis acid catalysts due to change in the relative frontier molecular orbital energy of one of the substrates interacting with the catalyst. α,β-unsaturated ketones are suitable dipolarophiles for catalytic studies, as the carbonyl group will coordinate with added Lewis acids. A study of the 1,3- dipolar cycloaddition reactions of -2-methoxyaryl- N-phenyl nitrones bearing varying 5-aryl substituents with chalcones (benzylidene acetophenones) had been investigated earlier by Muthusubramanian et al. 10 The regiochemistry and stereochemistry of the resultant cycloadducts were determined with the help of NMR spectroscopy and X-ray analysis. The reactions were reported to yield a single cycloadduct, viz. the 3,4- trans-4,5-trans-2,3,5-triaryl-4-oxophenyl isoxazolidine. In the present communication we report our studies on the cycloaddition between -(4-chlorophenyl)-Nphenyl nitrone 1 and benzylidene acetophenone (chalcone) 2 and the catalytic effects of metal triflates and magnesium bromide on the outcome of the cycloaddition reaction (Table I). This normal electron demand cycloaddition yielded two diastereoisomeric cycloadducts 3 and 4. The major product was the 3,4- trans-4,5-trans-2,3,5-triaryl-4-oxophenyl isoxazolidine 3, while the minor product was the diastereoisomeric 3,4-cis-4,5-trans compound 4 in the uncatalysed reaction. The regiochemical course of the cycloaddition has been rationalised on the basis of FM analysis using DFT calculated frontier molecular orbital energies of the reactants 1 and 2. Both rate accelerations and rate decelerations were observed in the presence of mild Lewis acid catalysts, depending on the catalyst used (Table I). Remarkable changes in diastereselectivity were also observed in presence of these Lewis acid catalysts. Triflates were selected for the present investigation due to their easy recovery, low toxicity, requirement of mild reaction conditions and high stability. Moreover, these are among the most promising Green hemistry catalysts.

2 836 INDIAN J. EM., SE B, JUNE 2011 Table I atalytic studies of 1,3-dipolar cycloadditions a of -(4-chlorophenyl)-N-phenyl nitrone, 1 to benzylidene acetophenone, 2 b Entry Additive c Time (hr) verall conversions to the cycloadducts (%) ycloadduct ratio 3:4 Diastereo-meric excess (de) None Li(Tf) MgBr 2.Et 2 Zn(Tf) 2 u(tf) 2 Yb(Tf) Not detected Not detected 87:13 86:14 65:35 67: a The cycloadditions were performed in refluxing toluene under nitrogen atmosphere and were monitored after 3, 7, 16, 20 and 23 hr, by 1 NMR spectroscopy. b 1: 1.5 molar ratio of dipole: dipolarophile was taken for each cycloaddition. c The additives (Lewis acid catalysts) were taken in 0.2 molar proportion of the nitrone in each cycloaddition. d The yields and diastereoisomeric excess were evaluated from the integration pattern of isoxazolidine ring protons in the 300 Mz 1 NMR spectrum of the crude reaction mixtures. l 1 N Ph Ph 2 Ph Toluene, 110, LA, N 2 l l B B A N D A N D 3 4 Scheme I 1,3-Dipolar cycloaddition of -(4-chlorophenyl)-N-phenyl nitrone, 1 and benzylidene acetophenone, 2 in presence of Lewis acid catalysts (LA) omputational methods The geometries of molecular structures were optimised using the hybrid density functional B3LYP method, i.e., Becke s three parameter nonlocalexchange functional 11 with the nonlocal correlation functional of Lee, Yang, and Parr 12 with the 6-31+G** basis set. The calculations were carried out on a personal computer using Gaussian 2003 set of programs 13 along with the graphical interface Gauss View Results and Discussion The cycloaddition of 1 and 2 in refluxing toluene under nitrogen atmosphere afforded two cycloadducts 3 and 4 (Scheme I). Structures of these cycloadducts were ascertained on the basis of spectroscopical (particularly NMR) and X-Ray diffraction studies for 3. 3 and 5 of 3 appeared as 1 doublets at δ 5.25 (J 3,4 = 7.2 z) and δ 5.31 (J 4,5 = 9.0 z) respectively which suggested 3,4-trans-4,5-trans stereochemistry of the isoxazolidine ring in 3. 4 appeared as a

3 AARJEE et al.: 1,3-DIPLAR YLADDITINS 837 double doublet at δ 4.45 (J 3,4 = 7.2 z, J 4,5 = 9.0 z). X-Ray crystallographic study was carried out to confirm its structure and stereochemistry. The RTEP diagram of 3 is presented in Figure 1 (Tables II-VI give the relevant data). It was decisively established from X-Ray analysis that 3 has an all trans (3,4-trans-4,5-trans) configuration. Also, the nitrogen lone pair was trans- to 3. The isoxazolidine ring has an intermediate envelope/twist conformation with the 1 atom out of the mean plane defined by the four other atoms. LR-SY couplings between 3 and 5 with the corresponding ortho-protons of the aromatic rings of both 3 and 4, indicated their benzylic nature. Thus, 3 and 4 were diastereomeric. 3, 4 and 5 of 4 appeared at δ 5.05 (1 d, J 3,4 = 10.1 z), δ 4.55 (1 dd, J 3,4 = 10.1 z, J 4,5 = 9.5 z) and δ 5.96 (1 d, J 4,5 = 9.5 z) respectively. The coupling constant values of the protons in the isoxazolidine moiety in 4 indicated 3,4-cis-4,5-trans stereochemistry, the Figure 1 RTEP view of 3 (ellipsoids at 40% probability level) Table II Positional parameters ( 10 4 ) and mean recalculated isotropic factors ( 10 3 ) for non-hydrogen atoms of cycloadduct, 3 Atom X Y Z <U> (14) 3183 (8) 2735 (14) 46 (4) N (17) 3803 (9) 2593 (17) 43 (5) (2) 4260 (12) 3501 (2) 43 (5) (3) 4852 (12) 3600 (2) 54 (6) (3) 5317 (14) 4417 (3) 67 (8) (3) 5200 (16) 5148 (3) 71 (8) (3) 4619 (16) 5040 (3) 68 (8) (2) 4143 (14) 4218 (2) 57 (7) (2) 3687 (11) 2561 (2) 42 (5) (2) 3934 (11) 1376 (2) 44 (6) (2) 3967 (14) 1289 (3) 62 (7) (3) 4218 (16) 243 (3) 71 (8) (3) 4447 (14) -715 (2) 63 (8) l (10) 4821 (5) (7) 97 (4) (3) 4409 (19) -666 (3) 81 (1) (3) 4149 (16) 379 (2) 69 (8) (2) 2949 (11) 2805 (19) 41 (5) 4A 8436 (2) 2811 (12) 3611 (2) 46 (6) 4A 8684 (19) 3011 (11) 4680 (16) 74 (6) (2) 2474 (12) 3079 (2) 49 (6) (3) 2052 (18) 2100 (3) 88 (1) (4) 1745 (2) 1638 (4) 120 (1) (4) 1883 (3) 2115 (4) 114 (1) (4) 2279 (3) 3095 (5) 123 (1) (3) 2570 (2) 3598 (4) 103 (1) (2) 2796 (11) 3454 (2) 42 (5) (2) 2106 (12) 3453 (2) 45 (6) (3) 1761 (13) 2348 (2) 55 (6) (3) 1127 (14) 2361 (3) 70 (8) (3) 836 (15) 3470 (4) 80 (9) (3) 1176 (16) 4570 (3) 78 (9) (3) 1809 (14) 4561 (3) 60 (7)

4 838 INDIAN J. EM., SE B, JUNE 2011 Table III Positional parameters ( 10 3 ) and mean isotropic factors ( 10 3 ) for hydrogen atoms of cycloadduct, 3 Atom X Y Z <U> stereochemistry at 4,5- being determined by that of the dipolarophile. omparison of the coupling constants of the isoxazolidine ring protons to those of the cycloadducts obtained from the reaction of 1 and similar nitrones to other electron-deficient dipolarophiles was also in agreement with the assigned stereochemistry of 4. ycloadduct 3 is obtained by the endo-carbonyl approach, while 4 is obtained by the exo-carbonyl approach of the dipolarophile 15,16. We observed some interesting facts while comparing the reaction rates and selectivities of the Lewis acid catalysed cycloadditions compared to the uncatalysed one. The results are given in Table I. There was a remarkable rate enhancement using lithium triflate. ycloadducts 3 and 4 were obtained in good yields after 3 hr in the presence of lithium triflate (de 0.72) with almost unaltered diastereomeric excess as the uncatalysed reaction (de 0.74). Magnesium bromide also caused enhancement in reaction rate. Zinc triflate catalyst caused enhancement to a lesser extent, but also aided decomposition of the products, the best yields being observed after 7 hr. Both magnesium bromide and zinc triflate catalysts led to considerable changes in diastereoselectivity. The diastereomeric excess (de) of 3 over 4 was 0.30 and 0.34, respectively in case of magnesium bromide and zinc triflate. This was apparently due to the greater bulk of the complexed unsaturated ketonic species, which would inhibit the endo-approach. Thus, magnesium bromide and zinc triflate led to decrease in the endo-selectivity of the cycloaddition. Shimizu et al. 17 had reported earlier that magnesium bromide leads to remarkable changes in the stereoselectivities of 1,3-dipolar cycloadditions of acyclic nitrones due to stabilisation of the exo-transition state in presence of magnesium ion relative to the uncatalysed reaction. The cycloaddition between 1 and 2 was completely inhibited in the presence of ytterbium triflate and copper triflate, and no products were detected in the 300Mz 1 NMR spectra of the crude reaction-mixtures recorded after several hours for both the reactions. We had earlier reported completely regioselective 1,3-dipolar cycloadditions of,n-diaryl nitrones to ethyl crotonate 18 where 5-methyl-4-carbethoxy cycloadducts were isolated exclusively. In the present study, the cycloaddition between 1 and 2 was also found to be completely regioselective leading to 4- oxophenyl substituted isoxazolidines. 1 NMR (300 Mz) analysis of the crude reaction-mixture showed the formation of only 3 and 4 as products. The regioselectivity of this cycloaddition can be rationalised on the basis of FM theory. We have recently reported experimental and theoretical spectroscopic investigations of -aryl-n-methyl nitrones 2,19 ; the computational results were found to be in good agreement with the experimentally recorded spectral data of the nitrones. So, we attempted to rationalise the observed regioselectivity of the reaction from FM theory using the same level of DFT calculations. The M and LUM energies of the reactants 1 and 2 were calculated at DFT/B3LYP/6-31+G** level of theory. The molecular orbital surfaces are shown in Figure 2. The M and LUM energies of 1 are calculated to be 5.959eV and 2.204eV respectively and that of 2 were 6.666eV and 2.340eV respectively. Thus the M dipole -LUM dipolarophile and M dipolarophile - LUM dipole frontier orbital energy differences are 3.619eV and 4.462eV respectively. It is evident from the calculated energy differences that M dipole - LUM dipolarophile is the predominant interaction (normal electron demand cycloadditions), and will determine the regioselectivity of the process.

5 AARJEE et al.: 1,3-DIPLAR YLADDITINS 839 Table IV Anisotropic thermal parameters ( 10 3 ) for non-hydrogen atoms of cycloadduct, 3 Atom U11 U22 U33 U23 U13 U (8) 48 (10) 56 (9) 0 (7) 14 (7) 0 (7) N2 34 (10) 47 (11) 48 (10) 0 (8) 6 (8) 0 (8) (12) 49 (14) 42 (12) 2 (10) 6 (10) -6 (10) (13) 53 (15) 61 (15) -3 (12) 9 (12) -2 (11) (18) 57 (17) 77 (18) -12 (14) 19 (16) -10 (14) (2) 74 (2) 65 (17) -18 (15) 8 (15) -23 (16) (15) 81 (2) 62 (16) 0 (15) -9 (13) -17 (15) (14) 61 (16) 60 (15) 6 (12) 0 (12) -5 (12) 3 33 (11) 52 (14) 42 (12) -2 (10) 8 (9) -2 (10) (12) 48 (13) 45 (12) -3 (10) 3 (10) 0 (10) (14) 76 (19) 65 (16) 16 (14) 5 (12) -2 (13) (14) 82 (2) 80 (2) 11 (16) -7 (14) -1 (13) (18) 66 (18) 49 (15) 0 (13) -10 (13) 4 (14) l34 98 (7) 107 (7) 64 (5) 10 (4) -24 (4) 17 (5) (19) 127 (3) 47 (15) 16 (16) 10 (14) 14 (19) (15) 108 (2) 51 (15) 9 (15) 11 (13) 10 (15) 4 33 (11) 50 (14) 39 (11) -3 (10) 8 (9) -3 (10) 4A 40 (12) 58 (15) 42 (13) 0 (10) 11 (10) -1 (11) 4A 63 (12) 116 (17) 47 (10) -16 (10) 21 (9) -24 (11) (13) 56 (15) 51 (13) 2 (11) 17 (11) -6 (11) (2) 112 (3) 79 (2) -29 (2) 39 (18) -52 (2) (3) 167 (4) 88 (2) -38 (3) 40 (2) -90 (3) (3) 159 (4) 107 (3) -6 (3) 19 (2) -58 (3) (2) 158 (4) 169 (4) -43 (4) 57 (3) -33 (2) (2) 141 (3) 120 (3) -50 (3) 51 (2) -33 (2) 5 36 (12) 50 (14) 41 (11) -1 (10) 10 (10) -1 (10) (11) 51 (14) 53 (13) 3 (11) 12 (10) -1 (10) (15) 55 (16) 61 (15) -2 (12) 16 (12) 1 (12) (17) 56 (18) 100 (2) -16 (16) 30 (17) -6 (14) (19) 50 (17) 127 (3) 13 (19) 28 (2) 7 (14) (19) 69 (2) 97 (2) 31 (19) 10 (17) 10 (16) (15) 66 (18) 61 (16) 11 (14) 9 (12) 4 (13) Qualitatively, -3 > -1 in the M of the nitrone 1, for the dipolarophile 2, α < β in both M and LUM. Thus, M dipole -LUM dipolarophile interactions will lead to 4-oxophenyl substituted isoxazolidines allowing the large-large and small-small favourable interactions, as per ouk s rule 20. It follows therefore that the 4-oxophenyl-5-phenyl substituted isoxazolidines will be generated preferentially from the cycloaddition of 1 and 2. This prediction based on FM theory is in complete agreement with the experimental observations. Experimental Section Elemental analyses were performed by using a Perkin Elmer 2400 Series II analyser. Melting points were recorded on an electrically heated Köfler Block apparatus and uncorrected. UV spectrum of 3 was recorded in dry methanol using a Shimadzu UV-3101 P spectrophotometer. IR spectra were recorded in KBr pellets using a Perkin Elmer RX-9 FT-IR spectrophotometer with a resolution of 2 cm NMR and 13 NMR spectra were recorded using a Bruker AV-300 NMR spectrometer at 300 and 75.5

6 840 INDIAN J. EM., SE B, JUNE 2011 Table V Distances (Å) for non-hydrogen atoms with e.s.d.'s in parentheses of cycloadduct, 3 M of 1 LUM of 1 M of 2 LUM of 2 Figure 2 M and LUM surfaces of 1 and 2 (DFT/B3LYP level using 6-31+G** basis set) Mz respectively. hemical shifts for 1 NMR and 13 NMR are reported in ppm, downfield from tetramethylsilane (TMS). Dry thiophene-free distilled toluene (from Merck hemical o.) was used as solvent. Benzylidene acetophenone was synthesised according to literature 21. -(4-chlorophenyl)-N-phenyl nitrone was prepared according to the existing procedure of refluxing p-chlorobenzaldehyde and phenyl hydroxylamine in alcohol 15,16. Neutral alumina (Activity I-II, Merck) was used for column chromatography. Analytical TL was performed using Merck silica gel G support. rganic extracts were dried over anhydrous sodium sulphate. ycloaddition of -(4-chlorophenyl)-N-phenyl nitrone, 1 with benzylidene acetophenone, 2 -(4-hlorophenyl)-N-phenyl nitrone ( mol, 1.02 g) and benzylidene acetophenone ( mol, 1- N (2) 4-4A (3) (3) (3) N (3) 4A- 4A (3) N (3) 4A (3) (3) (4) (3) (4) (4) (5) (4) (6) (4) (6) (4) (5) (3) (3) (3) (3) (4) (3) (3) (4) (4) (4) (4) (5) (4) (4) 34- l (3) (4) 1.37 g) were refluxed in dry thiophene-free toluene (5 ml) under nitrogen atmosphere for upto 23 hr. In the catalytic studies, Lewis acid catalysts (20 mol percent of the nitrone in each case) were added and the catalysed reactions were also continued upto 23 hr in each case. The reactions were monitored after 3, 7, 16, 20 and 23 hr by 300 Mz 1 NMR spectroscopy. onversions (corresponding to total yields) and product ratios of the diastereomeric mixtures were determined from the integration of isoxazolidine ring protons in the 300Mz 1 NMR spectra of the crude reaction mixtures. onversions are given in Table I along with the respective diastereomeric excess. Toluene was removed under reduced pressure in a Büchi rotary evaporator and the crude post reaction mixture was chromatographed over neutral alumina to isolate the cycloadducts 3 and 4. 3,4-trans-4,5-trans-3-(4-hlorophenyl)-4-oxophenyl-2,5-diphenyl-isoxazolidine 3: White needle shaped crystals (37%, 0.72 g) isolated from 10% benzene in pet. ether (60-80 ) eluates, m.p. 120, UV (acetonitrile): λ 245 nm [log ε max = 4.00]; IR (KBr): 3045, 1677, 1594, 1487, 825, 755, 695 cm -1 ; 1 NMR (Dl 3, TMS): δ 5.25 (1, d, J = 7.2 z, 3), δ 4.45 (1, dd, J = 7.2, 9.0 z, 4), 5.31 (1, d, J = 9.0 z, 5), 6.96 (2, d, J = 7.7z, 2,6 (A)), 6.90 (1, tt, J = 7.3, 1.0 z, 4 (A)), (11, m), (5, m); 13 NMR (Dl 3 ): δ 69.4

7 AARJEE et al.: 1,3-DIPLAR YLADDITINS 841 Table VI Bond angles ( ) for non-hydrogen atoms with e.s.d.'s in parentheses of cycloadduct, 3 N (15) 21- N (16) 21- N (18) 1- N (16) (2) N (2) N (2) (2) (3) (3) (3) (3) N (18) N (17) (18) (2) (2) (2) (3) (3) (2) l (2) l (2) (3) (3) 4A (18) 4A (19) (17) 4A- 4A (2) 4A- 4A (2) 41-4A (19) (3) A (2) A (2) (3) (4) (3) (4) (3) (18) (16) (19) (2) (2) (2) (3) (3) (3) (3) (3) (4), 74.5 (3), 84.8 (5), (1(A)), (2,6(A)), (4(A)), (4(B)), (4()), (1(B),1(D)), (1()), (4(D)), 126.8, 127.9, 128.8, 128.7, 128.5, 129.1, (aromatic carbons), (=). Anal. alcd. for ln 2 :, 76.44;, 5.04; N, Found:, 76.22;, 5.08; N, 3.06%. 3,4-cis-4,5-trans-3-(4-hlorophenyl)-4-oxophenyl- 2,5-diphenyl-isoxazolidine, 4: White crystals (4%, 0.08g) isolated from 20% benzene in pet. ether (60-80 ) eluates from the mother liquor left after removing the crystals of 3, m.p. 110, IR (KBr): 3043, 1668, 1591, 1486, 827, 756, 695 cm -1 ; 1 NMR (Dl 3, TMS): δ 5.05 (1, d, J = 10.1 z, 3), 4.55 (1, dd, J = 10.1, 9.5 z, 4), 5.96 (1, d, J = 9.5 z, 5), 6.92 (3, m), (11, m), (5, m). Anal. alcd. for ln 2 :, 76.44;, 5.04; N, Found:, 76.30;, 5.10; N, 3.04%. X-Ray crystallographic study of 3 rystals of the cycloadduct 3, Nl 2 (M.W ) were dispersed in oil (nujol) and a suitable crystal was fished with a nylon loop under microscope and directly mounted on a D KAPPA NNIUS diffractometer operating the Mo Kα radiation (λ = Å). Refinement was done with the SELXL program, using isotropic, then anisotropic thermal parameters. The hydrogen atoms were localised on Fourier difference maps and introduced with an isotropic thermal factor equal to that of the bonded atom. The statistics of the data are summarised below. System, space group - Monoclinic, P21/c; Z = 4; ell parameters: a = (2) Å, b = (2) Å, c = (2) Å, α = γ = 90, β = (1) ; Volume (Å 3 ) (6). No of measured reflections: 13014; Resolution limits (θ min-max) ; Resolution range (Å) ; No of independent reflections: 4313; ompleteness (%): 99.1; R merge on equivalent reflections: ; No. of observed reflections*: 2871 (criterion for observation: I 2σ(I); Average I/σ(I): No of reflections used: 4176; No of observed reflections: 2871; No. of refined parameters: 290; R-factor (observed Fs): 0.058; R-factor (all data): 0.087; Rw on F 2 (observed): 0.153; Rw on F 2 (all data): 0.173; Goodness of fit: 1.031; Min.-max. in last F density map (e-): / The X-ray crystallographic data are collected in Tables II to VI. The D number for 3 is D ; this contains the supplementary crystallographic data for this paper. These data can be obtained free of charge on application to The ambridge rystallographic Data entre via onclusion 1,3-dipolar cycloaddition of -(4-chlorophenyl)-Nphenyl nitrone and benzylidene acetophenone have been reported in the presence and absence of Lewis acid catalysts. The cycloaddition was completely regioselective in each case leading to 4-oxophenyl substituted isoxazolidines. The endo-cycloadduct was obtained as the major cycloadduct in all the reactions. The cycloaddition was accelerated in the presence of lithium triflate, magnesium bromide and zinc triflate. It was observed that the endo-selectivity of the reaction was considerably decreased in presence of magnesium bromide and zinc triflate. This was apparently due to the greater bulk of the complexed unsaturated ketonic species, which would inhibit the endo-approach. These investigations are suggestive for proper selection of Lewis acid catalysts in order to

8 842 INDIAN J. EM., SE B, JUNE 2011 improve the selectivities and yields of this and related 1,3-Ds. The regiochemistry of the investigated cycloaddition could be rationalised in terms of DFT/B3LYP/6-31+G** calculated frontier molecular orbital energy differences. Acknowledgements ne of the authors Nivedita Acharjee (S.R.F., SIR File no: 09/028(0679)/2006-EMR-I) is thankful to ouncil of Scientific and Industrial Research (SIR), New Delhi for financial support and University of alcutta for the laboratory and computational facilities. References 1 Acharjee N & Banerji A, Indian J hem, 49A, 2010, (a) Acharjee N, Das T K, Banerji A, Banerjee M & Prangé T, J Phys rg hem, 23, 2010, 1187; (b) Acharjee N, Banerji A, Banerjee M & Das T K, Indian J hem, 48A, 2009, (a) Merino P, in Science of Synthesis, Vol. 27, hapter 13, edited by A Padwa (Georg Thieme Verlag, Stuttgart, Germany), p.511, 2004; (b) Torsell K B G, Nitrile oxide, Nitrones and Nitronates in rganic Synthesis (V, New York, Weinheim), 1988; (c) Padwa A & Pearson W, Synthetic applications of 1,3-Dipolar ycloaddition hemistry towards eterocycles and Natural products (John Wiley & Sons, New York), 2002; (d) Feuer, Nitrile oxide, Nitrones and Nitronates in rganic Synthesis: Novel Strategies in Synthesis, edited by K B G Torsell, 2nd Edn (Wiley, oboken, New Jersey), Iannazzo D, Piperno A, Pistarà V, Rescifina A & Romeo R, Tetrahedron, 58, 2002, Kobayashi S & Kawamura M, J Am hem Soc, 120, 1998, ashimoto T, mote M, Kano T & Maruoka K, rganic Lett, 9, 2007, uang Z Z, Kang Y B, Zhou J, Ye M & Tang Y, rganic Lett, 6, 2004, how S S, Nevalainen M, Evans A & Johannes W, Tetrahedron Lett, 48, 2007, (a) Gothelf K V & Jørgensen K A, hem Rev, 98, 1998, 863; (b) Gothelf K V & Jørgensen K A, hem ommun, 2000, 2000, Sridharan V, Muthusubramanian S, Sivasubramanian S & Polborn K, Tetrahedron, 60, 2004, Becke A D, J hem Phys, 98, 1993, Lee, Yang W & Parr R G, Phys Rev B, 37, 1988, Gaussian 03W Program, (Gaussian Inc, Pittsburgh PA) Frisch M J, Trucks G W, Schlegel B, Scuseria G E, Robb M A, heeseman J R, Zakrzewski V G, Montgomery J A Jr, Stratmann R E, Burant J, Dapprich S, Millam J M, Daniels A D, Kudin K N, Strain M, Farkas, Tomasi J, Barone V, ossi M, ammi R, Mennucci B, Pomelli, Adamo, lifford S, chterski J, Petersson G A, Ayala P Y, ui Q, Morokuma K, Malick D K, Rabuck A D, Raghavachari K, Foresman J B, ioslowski J, rtiz J V, Baboul A G, Stefanov B B, Liu G, Liashenko A, Piskorz P, Komaromi I, Gomperts R, Martin R L, Fox D J, Keith T, Al-Laham M A, Peng Y, Nanayakkara A, Gonzalez, hallacombe M, Gill P M W, Johnson B, hen W, Wong M W, Andres J L, Gonzalez, ead-gordon M, Replogle E S & Pople J A, Gaussian 03, Revision D.01, Gaussian, Inc., Wallingford, T, Banerji A, Gupta M, Biswas P K, Prangé T & Neumann A, J eterocycl hem, 44, 2007, Banerji A, Maiti K K, aldar S, Mukhopadhyay, Banerji J, Prangé T & Neumann A, Monatshefte für hemie, 131, 2000, Banerji A & Sengupta P, J Indian Inst Sci, 81, 2001, Shimizu T, Ishizaki M & Nitada N, hem Pharm Bull, 50, 2002, Banerji A, Dasgupta S, Sengupta P, Prange T & Neuman A, Indian J hem, 43B, 2004, Banerji A & Acharjee N, J Indian hem Soc, 86, 2009, (a) ouk K N, Acc hem Res, 8, 1975, 361; (b) ouk K N, Sims J, Duke R E Jr, Strozier R W & George J K, J Am hem Soc, 95, 1973, 7287; (c) ouk K N, Sims J, Watts R & Luskus L J, J Am hem Soc, 95, 1973, rganic Synthesis, oll Vol 1, edited by Gilman (John Wiley, New York), p.78, 1941; rganic Synthesis, Vol 2, edited by E J Grabowski (John Wiley, New York), p.1, 1922.