Unusual Azetidine or Oxazine Formation upon Reaction of O-Ethyl Dithiocarbonate with 1,2,3-Triphenyl-3-Phthalimidopropyl Iodides; Erythro Selectivity in the Reaction of Iodotrimethylsilane with Phthalimidopropanols$ M. E. Ivanova, V. B. Kurteva, M. J. Lyapova* and I. G. Pojarlieff Institute of Organic Chemistry, Bulgarian Academy of Sciences, ul. Acad. G. Bonchev block 9, So�¡a 1113, Bulgaria Reaction of isomeric 1,2,3-triphenyl-3-phthalimidopropanols with hexamethyldisilane and iodine gave highly selectively iodides 3 with 1,2-erythro configuration which treated with O-ethyl dithiocarbonate yielded from ET-3 the xanthate ester 4, the trans,trans-dihydrooxazine 5 and the olefin 6 as major products while from EE-3 the cis,trans-azetidine 7 was obtained in 75% yield.Our long standing interest in diastereomers with three adjacent chiral centers has been focused on amino- propanols.1 In an extention to aminothiols we attempted to prepare 1,2,3-triphenyl-3-phthalimidopropyl dithiocarbo- nates from the respective alcohols 1 via the chlorides 2.The latter proved too unreactive to O-ethyl dithiocarbonate and for this reason the iodides, 3, were prepared from 1 with iodotrimethylsilane. High yields were obtained and, contrary to the usually observed inversion of con¢çguration,2 this reaction showed high erythro selectivity with the sterically hindered alcohols studied by us: EE-1 gave a single 3-phthalimido iodide of retained con¢çguration while both TT- and ET-1 gave ET-3.This stereochemical result can be rationalized by the involvement of a carbenium ion. As is the case with methine protons next to sp2 carbons,3 the preferred conformation for the cation should be the one with eclipsed hydrogen and a partial double bond. With such a model (A) the preferred attack should be from the side of the smaller substituent Ph, compared to C-3. Reaction of the iodides 3 with ethyl dithiocarbonate in dry ethanol gave the desired phthalimidopropyl dithio- carbonate 4 as a major product only in the case of ET-3 accompanied by considerable amounts of the unexpected oxazine 5 and the elimination product 6.With the EE iso- mer of 3, however, a high yield of the cis,trans-azetidine 7 was obtained. The structure of the cyclic products was deduced from their spectral properties indicating opening of the phthal- imide ring and formation of an ester function. Acid hydro- lysis of oxazine 5 to TT-3-amino-1,2,3-triphenylpropanol con¢çrmed reliably its structure.The 13C NMR signals for C-2 and C-4 of the azetidine 7 coinciding at d 61.88 are incompatible with an oxazine structure where one carbon is bonded to O and the other one to N and thence a large di€erence in the chemical shifts is expected. For oxazine 5 the resonances of the two carbons are separated by 18 ppm. Heating the iodides in ethanol in the absence of dithio- carbonate brought about degradation but none of the cyclic products, implying that dithiocarbonate is involved by adding to a carbonyl.The intermediate forms the oxazine ring by rear attack followed by ethanolysis. For azetidine formation the intermediate breaks down to produce an amide anion. The conformations of the iodides on Scheme 1 are the preferred ones6 and correlate with cyclization reac- tivities: in the ET isomer O¢§ can be trapped by direct attack, in the EE isomer changing to an unfavourable J. Chem. Research (S), 1998, 658¡¾659$ Scheme 1 conformation presumably allows time for break down to amide anion.Cyclization of addition intermediates has been observed in the reaction of aldimine anions with N-(2- $This is a Short Paper as de¢çned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 658 J. CHEM. RESEARCH (S), 1998bromoethyl)phthalimides.4 The involvement of the amideanion in the formation of the azetidine is supported bythe presence of stilbene observed in the fragmentation of asimilar system.1The relative congurations at C-2, C-3 are not aectedin these reactions and so are known from the startingphthalimido propanols 1.5 Azetidine 7 shows vicinal protoncouplings of 5.4 and 9.9 Hz thus revealing a cis,trans con-guration because with equal substituents in positions 2 and4 the other alternative, the cis,cis isomer, would show equalconstants. Slow rotation on the NMR timescale can beexcluded as it would have doubled the signals of cis,trans-7.The oxazine 5 shows the characteristic large couplingsof the trans,trans isomer.The most likely intramolecularcyclization by inversion at C-1 assigns the relative con-gurations of the idodides as given in Scheme 1.The congurations of the dithiocarbonates 4 were onlytentatively assigned. In the case EE-3 the conguration ofthe ether 8 was unequivocally assigned by synthesis fromthe alcohol EE-1 and ethyl iodide and its conguration canbe explained by the model given for the iodides.The samepathway will provide EE-dithiocarbonate from EE-3 andthe ET isomer for ET-3.ExperimentalThe melting points were measured in capillaries, the IR spectraon a Specord IR 75 or Bruker IFS 113v instrument in chloro-form unless stated otherwise, UV spectra on a Specord UV Visspectrometer in ethanol, NMR spectra on a Bruker DRX 250 indeuteriochloroform (chemical shifts are quoted in ppm as d values)and mass spectra on a JEOL JMS-D 300 spectrometer.EE-1,2,3-Triphenyl-3-phthalimidopropanol 1.A solution of EE-3-amino-1,2,3-triphenylpropanol7 (303 mg, 1 mmol) and phthalicanhydride (148 mg, 1 mmol) in dry pyridine (1 ml) was reuxed for2 h.After cooling the mixture was poured onto ice and allowedto stand overnight. The separated material was triturated with10% HCl (50 ml), the solid formed was collected and recrystallizedfrom ethanol to give compound EE-1 (516 mg, yield 95%), mp217¡Ó218 8C; ~max 1710, 1760, 3400 cm£¾1; MS (Cl) [M 1] m/z 434,416, 374, 270, 254, 210 (Found: C, 80.12; H, 5.35; N, 3.18.C29H23NO3, requires C, 80.35; H, 5.35; N, 3.23%).Diastereomeric 1,2,3-Triphenylpropyl-3-phthalimido Iodides (3):General Procedure.Iodine (254 mg, 1 mmol) and hexamethyl-disilane (0.2 ml, 1 mmol) were added to a stirred solution of theappropriate phthalimidopropanol (434 mg, 1 mmol) in dry chloro-form (5 ml) under argon.After 4 h of stirring at room temperaturethe reaction mixture was rapidly extracted with 10% Na2S2O3 (aq),the organic layer was washed with brine, dried (Na2SO4) andevaporated to dryness under reduced pressure.EE-3. From EE-1, as a single diastereoisomer (NMR), yield 95%,mp 145¡Ó147 8C (decomp.); ~max 1710, 1760 cm£¾1; MS (Cl) [M 1]m/z 544, 416, 269, 254, 236, 180, 150, 128.ET-3. (a) From ET-1,5 crude yield 420 mg, mp 177¡Ó179 8C(chloroform¡Óhexane, 59%); ~max 1710, 1760 cm£¾1; MS (EI) [M£¾ I]415, 269, 268, 254, 236, 180, 150, 128, 127.(b) From TT-1, as a mixture of ET-3/ET-1/TT-1 in a ratio of4.4:1:1.2 (NMR) 480 mg.Reaction of Phthalimido Iodide ET-3 with Potassium O-ethylDithiocarbonate.ET-3 (4.9 g, 9 mmol) and KS2C(OEt) (4.3 g,27 mmol) in dry ethanol (400 ml) was reuxed for 6 h.Afterremoval of the solvent in vacuo the residue was extracted withCH2Cl2¡Ówater, the organic layer washed with brine, dried (Na2SO4)and evaporated.The crude reaction product which showed onTLC more than eight closely moving spots was separated byash chromatography on Silica gel (ether¡Óhexane 1:4 as eluent)giving four major products: trans,trans-5,6-dihydro-4H-2 (2-ethoxy-carbonylphenyl)-4,5,6-triphenyl-1,3-oxazine 5 (800 mg, 22%), mp128¡Ó130 8C (diisopropyl ether); ~max 1673, 1715 cm£¾1; 13C NMR(DEPT) C-2 157.21, C-4 64.29, C-5, 53.33, C-6 81.83, COO167.63, CH2 61.10, CH3 14.17; MS (CI) [M 1] m/z 462, 416, 284,236, 180, 149 (Found: C, 80.82; H, 5.74; N, 3.18.C31H27NO3,requires C, 80.67; H, 5.90; N, 3.03%); ET S-O-ethyl-1,2,3-triphenyl-propyl-3-phthalimido dithiocarbonate 4 (1.4 g, 38%), mp 162¡Ó163 8C(ether¡Ópentane); ~max 1050, 1710,760 cm£¾1; max 385 nm(SCSOC2H5); MS(EI) [M£¾ SCSOC2H5] m/z 416, 268, 236, 180,122(SCSOCH2H5) (Found: C, 71.54; H, 5.20; N, 2.50; S, 11.81.C32H27NO3S requires C, 71.48; H, 5.06; N, 2.60; S, 11.92%);z-1,2,3-triphenyl-3-phthalimidoprop-1-ene 6 (864 mmg, 24%), mp197¡Ó199 8C (chloroform¡Óhexane); ~max 1710, 1760 cm£¾1; MS(CI)416, 268, 236, 180 (Found: C, 83.89; H, 5.00; N, 3.59.C29H21NO2requires C, 83.83; H 5.09; N, 3.37).Reaction of Phthalimido Iodide EE-3 with Potassium O-ethylDithiocarbonate.A solution of EE-3 (2.71 g, 5 mmol) andKS2C(OEt) (2.7 g, 15 mmol) in absolute ethanol (150 ml) wastreated in a manner to that described for ET-3 to leave a residue,which was recrystallized from diisopropyl ether to give 1.04 gof cis,trans-N-(2-ethoxycarbonylbenzoyl )-2,3,4-triphenylazetidine 7.A further 0.69 g could be isolated from the evaporated mother-liquor after separation on Silica gel (ether¡Óhexane 1:4 as eluent),total yield 75%, mp 145¡Ó147 8C; ~max 1660, 1715 cm£¾1, 13C NMRC-2 and C-4 61.88 (common signal), C-3, 48.52, CO 156.93, COO168.30, CH2 61.23, CH3 14.17; MS (CI) [M 1] m/z 462, 282, 177(Found: C, 80.54; H, 5.92; N, 3.24.C31H27NO3, requires C, 80.67;H, 5.90; N, 3.03%).Four other products were isolated from thecolumn: EE-O-ethyl S-1,2,3-triphenyl-3-phthalimidopropyl dithio-carbonate 4 (90 mg, 3.4%), mp 182¡Ó184 8C (diisopropyl ether);~max 1050, 1710, 1760 cm£¾1; max 385 nm (SCSOC2H5); MS(EI)[M-CS2] m/z 460, [M-SCSOC2H5] 415, 324, 268, 236, 178,151, 77(CS2); EE-ethyl 1,2,3-triphenyl-3-phthalimidopropyl ether 8(120 mg, 5.2%), mp 222¡Ó224 8C (diisopropyl ether); ~max 1100,1710, 1760 cm£¾1; ESI-FTICR MS m/z 462.2049 (M 1, theoreti-cally 462.2064, C31H28NO3) identical with the product obtainedfrom EE-1 (1 mmol), NaH (4 mmol) and ethyl iodide (4 mmol) inTHF (5 ml) for 6 h at room temperature in 83% yield; 6 (30 mg,1.4%), identical with the product obtained from ET-3 in the samereaction; trans-stillbene (60 mg, 6.7%), identical with an authenticsample.Received, 8th April 1998; Accepted, 30th June 1998Paper E/8/02677GReferences1 V.B. Kurteva, M. J. Lyapova and I. G. Pojarlie, J. Chem. Res.(S), 1993, 270 and references cited therein.2 G.A. Olah and S. C. Narang, Tetrahedron, 1982, 38, 2225.3 U. Berg, T. Liljefors, M. Roussel and J. Sandstrom, Acc. Chem.Res., 1985, 18, 80.4 N. De Kimpe, Z. Yao, L. De Buyck, R. Verhe and N. Schamp,Bull. Soc. Chim. Belg., 1986, 95, 197.5 M. J. Lyapova and M. E. Ivanova, Compt. Rend. Acad. Bulg.Sci., 1982, 35, 1669.6 V. S. Dimitrov, V. B. Kurteva, M. J. Lyapova, B. P. Mikhovaand I. G. Pojarlie, Magn. Reson. Chem., 1988, 26, 564.7 M. J. Lyapova and B. J. Kurtev, Chem. Ber., 1969, 102, 3739;1971, 104, 131.Table 1 1H NMR chemical shifts (d) and coupling constants(in Hz, in parentheses)Compound H-1(J12) H-2a H-3(J23)EE-1b 4.82(2.8) 4.69 6.21 (13.2)ET-1c 5.08(4.20) 4.77 6.11(12.2)TT-1d 5.083(4.5) 4.956 6.076(11.9)EE-3 5.084(3.1) 4.021 5.931(11.9)ET-3 5.525(6.9) 4.665 5.810(11.6)EE-4e 5.136(3.6) 5.250 5.490(12.6)ET-4f 5.421(3.6) 5.319 5.666(12.3)trans,trans-5g 5.030(10.4)h 3.136i 5.491(10.7)jZ-6 6.415(1.9)k,l 6.484(1.9)k,lcis,trans-7m 5.033(5.4)n 3.812o 5.590(9.9)pEE-8q 4.280(2.9) 4.432 6.213(12.3)aCouplings not shown. bOH 1.78(6.0). cOH 1.98(4.6). dOH2.096(4.5). eCH2 4.504, CH3 1.232. fCH2 4.470, CH3 1.225.gCH2 4.237, CH3 1.282. hH-4(J45). iH-5. jH-6(J56). kJ13.lNo NOE enhancement was observed. mCH2, 4.202, CH3 1.230.nH-2(J23). oH-3. pH-4(J45). qCH2 3.203, CH3 1.960.J. CHEM. RESEARCH (S), 1998 659