A Facile Regioselective Synthesis of Novel Spiroacenaphthene Pyrroloisoquinolines Through 1,3-Dipolar Cycloaddition Reactions

2’-Benzoyl-1’-phenyl-2’,5’,6’,10b’-tetrahydro-1’H,2Hspiro[acenaphthylene-1,3’-pyrrolo[2,1-a]isoquinolin]-2-one (4a) Yellow solid (0.366 g, 82%); m.p. 183-185 °C; IR (KBr) νmax/cm 1713, 1681; H NMR (400 MHz, CDCl3) d 7.93-6.72 (m, 20H, Ar-H), 5.37 (d, 1H, J 9.6 Hz, Hc), 4.62 (d, 1H, J 9.2 Hz, Ha), 4.48 (t, 1H, J 9.6 Hz, Hb), 2.98-2.89 (m, 2H), 2.66-2.49 (m, 2H); C NMR (100 MHz, CDCl3) d 209.3, 197.3, 142.5, 140.3, 138.2, 137.2, 136.9, 134.7, 132.0, 131.9, 131.7, 129.8, 129.1, 129.1, 128.8, 128.7, 127.8, 127.4, 127.2, 126.9, 126.3, 125.5, 125.1, 124.7, 123.5, 120.7, 74.7 (C-Spiro), 64.3, 63.8, 50.9, 42.5, 30.4; anal. calcd. for C36H27NO2: C, 85.52; H, 5.38; N, 2.77; found: C, 85.1; H, 5.05; N, 2.35; MS (m/z): 505.


Equipments
All chalcones and nitrostyrenes were prepared according to literature procedures. 36,37All other reagents and solvents were purchased from commercial suppliers and used without further purification.Reactions were monitored by thin-layer chromatography (TLC) on silica gel.Melting points were measured on an Electrothermal 9100 apparatus.Infrared spectra were recorded on a Shimadzu IR-8300 series FT-IR spectrophotometer. 1 H NMR and 13 C NMR spectra were recorded on a Bruker 400-MHz instrument in CDCl 3 solvent with TMS as a standard.Mass spectra were recorded on a JEOL DX303 HF mass spectrometer.Elemental analyses were carried out using a Perkin-Elmer CHN 2400 instrument.

X-ray crystallographic analysis
Suitable single crystals of the compounds 4i and 7f were selected and the diffraction data were collected using a STOE IPDS II diffractometer with graphite monochromated Mo-K a radiation (λ = 0.71073 Å), in the rotation method, at room temperature.The structures were solved by using SHELXS. 38The structure refinement and data reduction were carried out with SHELXL of the X-Step32 suite of programs. 39The nonhydrogen atoms were refined anisotropically by full matrix least-squares on F 2 values.Hydrogen atoms were located from expected geometry and were not refined.The crystal data are deposited at the Cambridge Crystallographic Data Centre, CCDC 949978 and 949977, for compounds 4i and 7f, respectively.

Results and discussion
In our initial studies, acenaphthenequinone 1, 1,2,3,4-tetrahydroisoquinoline 2 and chalcone 3a were treated at reflux in ethanol to afford the corresponding spiroacenaphthene pyrroloisoquinoline 4a as sole product in good yield (Scheme 1).After completion of the reaction, as indicated by TLC, the pure cycloadduct was obtained by recrystallization from ethanol.
Scheme 1. Regioselective synthesis of spiropyrroloisoquinolines 4a-i.Vol. 24, No. 12, 2013   We applied this protocol to a series of chalcone derivatives 3a-i in order to obtain the corresponding spiropyrroloisoquinoline adducts 4a-i in moderate to good yields.As shown in Table 1, the [3 + 2] cycloaddition of several chalcones having electron-donating substituent and electron-withdrawing groups with non-stabilized azomethine ylide, which were generated through [1,5]-H shift, afforded the corresponding cycloadducts with regioand stereoselective manner.
The structure and regiochemistry of the cycloadducts were confirmed by spectroscopic data and X-ray crystal structure analysis (Figure 1).
Information concerning to the crystallographic data collection and refinement of the structures are given in Table 2.
The 1 H NMR spectrum of 4b exhibited two doublets at d 5.43 (J 9.6 Hz) and 4.62 (J 9.6 Hz) for the H c and H a    for the spiro carbon.The IR spectrum of 4b showed two sharp peaks at 1708 cm -1 and 1681 cm -1 for the carbonyl groups and in addition, the appearance of a molecular ion peak at m/z 523 (M+) confirmed the formation of the cycloadduct.The stereochemistry of compound 4i was established by X-ray single crystal analysis (Figure 1).I n o r d e r t o f u r t h e r ex p a n d t h e s c o p e o f this protocol for spiro-heterocyclic synthesis, we investigated reactions involving acenaphthenequinone 1, 1,2,3,4-tetrahydroisoquinoline 2 and nitrostyrene derivatives 6a-l and a new series of spiropyrroloisoquinoline adducts 7a-l were obtained in good yields (Scheme 2, Table 3).
From Table 3, it is evident that the rate of the reaction and the yields of the cycloadducts are similar when nitrostyrene derivatives were employed as dipolarophiles instead of acenaphthenequinones.The structure of the final products was elucidated through X-ray crystal structure analysis in addition to standard IR, 1 H and 13 C NMR techniques.The IR spectrum of 7a showed a sharp peak at 1708 cm -1 for the carbonyl group and two peaks corresponding to NO 2 at 1553 and 1366 cm -1 .The 1 H NMR spectrum of 7a exhibited two doublets at d 5.99 (J 7.0 Hz) and 4.78 (J 4.8 Hz) for the H b and H a protons, respectively, and a doublet of doublet at 6.27 ppm (J 7.0, 4.8 Hz) for H (R 3 ).The 13 C NMR spectrum of 7a showed a peak at d 79 ppm reflecting the presence of the spiro carbon and the acenaphthenequinone carbonyl carbon exhibited a peak at d 206.3.The mass spectrum of the compound confirmed the formation of cycloadduct.Finally, the regio-and stereochemical outcome of the cycloaddition reaction was obviously confirmed through the X-ray diffraction analysis of 7f (Figure 2).
The proposed mechanism of the cycloaddition reactions is shown in Scheme 3.For this 1,3-dipolar cycloaddition reaction, four reactive channels are possible.They are related to two regioisomeric and two stereoisomeric approaches.The stereochemistry of the observed products is consistent with expected preference of an S-shaped ylide and subsequent cycloaddition through an endo transition state.
The endo-control is presumably determined by stabilizing secondary orbital interactions.
There is no evidence in spectroscopic data for the formation of the other regioisomer arising from the reactions.

Conclusions
In summary, we have demonstrated a multicomponent 1,3-dipolar cycloaddition which gives an array of containing spiroacenaphthene pyrroloisoquinolines using chalcone and nitrostyrene derivatives as dipolarophiles.The products were isolated by recrystallization without involving further purification process like column chromatography.Vol. 24, No. 12, 2013

Full
and -0.348 0.186 and -0.188 protons, respectively, and a triplet at 4.55 ppm (J 10.8 Hz) for H b .The 13 C NMR of 4b showed two signals at d 209.3 and 196.7 ppm for carbonyl groups and a signal at 74.7 ppm

Table 2 .
Crystal data and structure refinement of compounds 4i and 7f
a Isolated yield.number