Research Journal of Recent Sciences _______________________________________________ Res. J. Recent Sci.  Vol. 1(1), 85-88, Jan. (2012)  International Science Congress Association        
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Short Communication Regioselective Synthesis of  -Butenoildes Mediated by  Silvertrifluroacetate with -Halo Acetals Bello Y. MakamaDepartment of Chemistry, Faculty of Science & Science Education, Kano University of Science & Technology, Wudil, Kano State, NIGERIA 
Available online at: 
www.isca.in
(Received  13th December 2011, accepted 23rd December 2011)Abstract -Butenoildes were prepared by 1,4 addition of -halo acetals with 2-(tert-butyldimethylsiloxy)-3-methylfuranone mediated by silvertrifluroacetate in one step with high regioselectivity The structures of these products were determined using H NMR, 13C NMR, Mass spect. and IR analysis Keywords: -Butenoildes, 1,4 addition, -halo acetals, 2-(tert-butyldimethylsiloxy)-3-methylfuranone Introduction -Butenoildes have remained key precursors towards the synthesis of complex many biologically active natural products. More recently -Butenoildes could emerge to be important synthons for the synthesis of complex iridolactones; Brassoside and littaralissone are typical example.1,2  In our previous report, we have shown an efficient synthesis of 5-(But-3-enyl)-3-methylfuran-2(5H)-one via 1,4 addition with 4-iodobutene with high regioselectivity.  This successful preparation led us to investigate other well functionalized systems as such plans to try to implement the second strategy began.  The key ingredient of this strategy, a -haloacetal (241) could offer the opportunity to furnish the much sought-after butenolides side chain with high regioselectivity (Scheme 1). Material and Methods Commercial reagents were obtained from Aldrich and Lancaster chemical suppliers and were used directly as supplied or purified prior to use following the guidelines of Perrin and Amarego. Dichloromethane and acetonitrile were refluxed over and distilled from CaH prior to use. Diethyl ether and ethanol were obtained dry from Aldrich. THF was dried by distillation from the sodium benzophenone ketyl radical under nitrogen. Light petroleum is the fraction of petroleum ether boiling in the range 30-40 C, and it was fractionally distilled through a 36 cm Vigreux column before use. Non-aqueous reagents were transferred under argon viasyringe. Organic solutions were concentrated under reduced pressure on a Büchi rotary evaporator using a water bath. Thin-layer chromatography (TLC) was performed on Merck aluminium-backed plates coated with 0.2 mm silica gel 60-F plates. Visualization of the developed chromatogram was performed by UV fluorescence quenching at 254nm, or by staining with a KMnO4  solution. H and 13C NMR spectra were recorded on a Bruker DPX250 (250 MHz for protons) and a Brüker AMX400 (400 MHz for protons). Data for H NMR are reported as follows: chemical shift (-ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), integration, coupling constant in (Hz). Data for 13C NMR spectra are reported in terms of chemical shift (ppm) down field from TMS. IR spectra were recorded on a Perkin Elmer Paragon 1000 or a Perkin Elmer 881 spectrometer as a thin film between sodium chloride plates or as a KBr disk. All absorptions are reported in terms of frequency of absorption (cm-1).Mass spectrometric data were recorded on VG Autospec, under conditions of chemical ionisation (C.I) using ammonia as the ionising source. Peaks are quoted in the form /z) (relative intensity).  2-(iodopropan 2-yl)-1, 3-dioxalane (217)4 : To a solution of methacrolein (241) (1.70 g, 24.3 mmol, 1.00 equiv), of sodium iodide (4.40 g, 29.5 mmol, 1.20 equiv) in acetonitrrile (60 mL) was rapidly added with vigorous stirring chlorotrimethylsilane (3.80 g, 34.9 mmol, 1.20 equiv). The resulting suspension was stirred for 5 minutes after which the reaction mixture was poured into (80 mL) of (5%) NaHCO overlaid with (100 mL) of pentane. This produced after thorough mixing three distinct layers. The lower aqueous layer was removed and the remaining layers were washed with (5%) Na (8 x 60 mL) and saturated NaCl (60 mL) until only a single organic layer was evident. The pentane layer was dried over KCO and the solvent removed in vacou. Column chromatography on neutral alumina with hexane afforded the title compound as a colourless oil (4.92 g, 84%); max (thin film/cm-1), 2967, 2935, 2882, 1461, 1426, 726; H (250 MHz, CDCl) 4.68 (1H, d, J 4.6 Hz, CHO ), 3.92-3.78  (4 H, m, OCHCHO), 
Research Journal of Chemical Sciences _________________________________________________________ Res. J. Recent Sci. Vol. 1(1), 85-88, Jan. (2012)  International Science Congress Association 
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3.26 (1H, dd, J 4.5 Hz, CHI), 3.05 (1H, dd,  4.5 Hz, CHI), 1.81-1.73 (1H, m, CHCHI ), 1.02 (3H, d,  3.5 Hz CHCH); C (62.5 MHz, CDCl) 105.0, 64.2, 64.3, 38.3, 14.5, 8.3;  m(C.I) 242 ( MH, 15 %), 115 (100%), 114 (2.3%), 113 (4.1%), 101 (1.7%),  C 13IO, requires 242.9882, found 242.9878 
OO
I
5-(2-(1, 3-dioxalan-2yl) propyl)-3-methylfuran-2-(5)-one(156): To a stirred suspension of silver trifluoroacetate (140 mg, 0.63 mmol, 1.30 equiv) in dry DCM (4 mL) under argon at -78 C was added 2-(tert-butyldimethyl siloxy)-3-methylfuran (125) (100 mg, 0.5 mmol, 1.00 equiv), followed by dropwise addition of 2-(iodopropan 2-yl)-1, 3-dioxalane (217) (0.12 g, 0.63 mmol, 1.30 equiv) over a period of 10 minutes. The temperature was increased to 10 C over 4 hours. The mixture was filtered through Celite washing with ether (4 x 10 mL). The solvent was removed carefully removed under reduced pressure and the residue was purified by flash chromatography on silica, eluting with hexane : ether  (2:1) to afford a colourless oil (58 mg, 55%); max (thin film/cm-1), 2979, 2875, 2254, 1734, 1657, 734;  (250 MHz, CDCl) 6.97 (1H, bd,  1.6 Hz,  CH=C), 6.97 (1H,  bd,   1.6 Hz, CH=C) 4.97-4.93 (1H, m, CHO), 4.97-4.93 (1H, m, CHO), 4.63 (1H, d,  4.4 Hz, CHO), 4.61 (1H, d, J 4.1 Hz, CHO), 3.87-3.76 (4H, m, OCHCHO), 3.87-3.76 (4H, m, OCHCHO), 1.95-1.90 (1H, m, CHCH), 1.95-1.90 (1H, m CHCH), 1.83 (3H, bs, CHC=C), 1.83 (3H, bs, CHC=C), 1.78-1.38 (2H, dm, CH), 1.78-1.38 (2H, dm, CH), 0.94 (3H,  bd,  J 5.2 Hz,  1.7 Hz, CHCH), 0.94 (3H,  bd, J 5.2 Hz,   1.7 Hz, CHCH); C (62.5 MHz, CDCl) 173.3, 148.2, 147.9, 128.8, 128.7, 128.7, 106.0, 79.3, 78.0, 63.9, 63.9, 34.6, 34.2, 33.2, 32.6, 24.6, 14.5, 13.3, 9.60; m (C.I) 213 (MH, 100%), 169 (40%),102 (30%),101 (11.4%), C1118, requires 213.1128, found 213.1127.  
O
O
OO
5-(2-(1, 3-dioxalan-2yl) propyl) furan-2-(5)-one(242): To a stirred suspension of silvertrifluoroacetate (290 mg, 1.3 mmol, 1.30 equiv) in dry DCM (10 mL) under argon at -78 C was added 2-(tert-butyldimethyl siloxy)-3-methylfuran (235) (200 mg, 1.0 mmol, 1.00 equiv), followed by drop wise addition of 2-(iodopropan 2-yl)-1, 3-dioxalane (217) (334 mg, 1.3 mmol, 1.3 equiv) over a period of 10 minutes. The temperature was increased to 10 C over 4 hours. The mixture was filtered through Celite washing with ether (4 x 15 mL).The solvent was removed carefully removed under reduced pressure and the residue was purified by flash chromatography on silica, eluting with hexane : ether (2:1) to afford a colourless oil (142 mg, 71%); max (thin film/cm-1), 2989, 2975, 2244, 1733, 1618, 734;  (250 MHz, CDCl) 7.53 (1H, bt,  5.0 Hz,   2.5 Hz,  CH=CH), 7.53 (1H, bt, 5.0 Hz,   2.5 Hz,  CH=CH), 6.11 (1H, bd,  2.5 Hz, CH=CH) 6.11 (1H, bd,  2.5 Hz, CH=CH), 5.27-5.17 (1H, m, CHO), 5.27-5.17 (1H, m, CHO), 4.73 (1H, bt,   5.0 Hz, CHO), 4.73 (1H, bt J 5.0 Hz, CHO), 3.99-3.83 (4H, m, OCHCHO), 3.99-3.83 (4H, m, OCHCHO), 2.11-2.00 (1H, m, CHCH), 211-2.00 (1H, m CHCH), 1.97-1.80 (1H, dm, CH), 1.97-1.80 (1H, dm, CH), 1.65-1.42 (1H, dm, CH), 1.65-1.42 (1H, dm, CH), 1.05 (3H, bd,  2.5 Hz, CHCH), 1.05 (3H,  bd,  2.5 CHCH); C (62.5 MHz, CDCl) 157.1, 156.8, 121.2, 121.1, 106.6,  106.9, 82.7, 81.5, 64.9, 64.7, 34.1, 33.9, 33.5, 14.3, 14.1;  m (C.I) 199 (MH, 100%), 198 (36%), 180 (35%), 156 (19%), C1015, requires 199.0971, found 199.0974.  
O
OO
  O
O
HO
O
O
OO
O
O
OO
(236)R=Me
OTBDMS
(235)R=H(238)(237)(239)Scheme-1 
Research Journal of Chemical Sciences _________________________________________________________ Res. J. Recent Sci. Vol. 1(1), 85-88, Jan. (2012)  International Science Congress Association 
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2-methyl-3-(4-methyl-5-oxo-2,5-dihydrofuran-2-yl) propanal(157): A solution of 5-[2-(1, 3-dioxalan-2yl)propyl]-3-methylfuran -2-(5H)-one (156) (100 mg, 0.47 mmol, 1.00 equiv) in (12 mL) acetone/water (5:1, 12 mL) was treated with pTSOH (116 mg, 0.47 mmol, 0.99 equiv) and the resulting solution was heated at reflux for 3 h. The reaction was cooled and quenched with saturated NaHCOsolution, extracted with ether (5 x 4 mL), dried with NaSOand concentrated in vacuo. Purification of the residue by column chromatography on silica eluting with hexane : ethyl acetate (1:1) afforded the title compound as a pale yellow oil (34 mg, 43%); max (thin film/cm-1), 2978, 2929, 2874, 1752, 1718;   (250 MHz, CDCl) 9.67 (1H, bd, J 9.8 Hz, CHO), (1H, bd,  9.8 Hz, CHO), 7.07 (1H, bd,  3.1 Hz, CH=C), 7.07 (1H, bd,  3.1 Hz, CH=C), 5.03-4.94 (1H, m,  CHO), 5.03-4.94 (1H, m, CHO), 2.74-2.63 (1H, m, CHCH), 2.74-2.63 (1H, m, CHCH), 2.29-2.18 (1H, m, CH), 2.24-2.22 (1H, m, CH), 2.04-1.97 (1H, m, CH), 2.05-1.97 (1H, m, CH), 1.93-1.92 (1H, m, CH), 1.93-1.92 (1H, m, CH), 1.92 (3H, bs CHC=C), 1.92 (3 H, bs  CHC=C), 1.81-1.76 (1H, m, CH), 1.42-1.26 (1H, m, CH), 1.25 (3H, bd,  5.2 Hz, CHCH), 1.22 (3H, bd,  5.3 Hz, CHCH); C (62.5 MHz, CDCl) 203.7, 203.6, 169.8, 169.4, 148.8, 148.8, 79.6, 78.9, 43.5, 42.9, 34.7, 33.9, 30.1, 14.9, 13.9, 11.1;  m (C.I) 169 (MH, 100 %), 130 (80%), 111 (45%), C 13IO, requires 169.0865, found ,169.0865 
O
O
H
Results and DiscussionLarson,4 reported a much improved method for the preparation of -halo acetals, which employs chlorotrimethylsilane and sodium iodide in acetonitrile in lieu of the more difficult to handle iodotrimethylsilane Scheme 2. 0. Thus, addition of chlorotrimethylsilane to a rapidly stirred solution of methacrolein and sodium iodide produced an immediate precipitate and a yellow solution, which became dark orange with time. The addition of ethylene glycol and workup gave (241) in 84% yield. The  H NMR spectrum showed the appearance of a four proton multiplet at  3.89-3.80 ppm   characteristic of the dioxalane protons and  two  multiplets integrating to two protons, a multiplet at  3.25-3.23 ppm and at  3.08-3.01 ppm due to the diastereotopic methylene (CHI) group. Mass spectrometric analysis confirmed the mass ion to be m/z 242 Scheme 2.13.   
O
H
OO
(240)
(241)(a) (CHOH), NaI, MeSiCl, acetonitrile, 84% Scheme-2 Synthesis of 5-(2-(1, 3-dioxolan-2yl) propyl)-3-methylfuran-2-(5H)-one: The simple transformation necessary to convert (236) to (238) was anticipated to proceed through condensation with (241). Subsequently the condensation went according to plan through the agency of 2-(iodopropan-2-yl)-1,3-dioxolane (241) and 2-(tertbutyldimethylsiloxy)-3-methylfuranone (236) in DCM and silver trifluoroacetate to furnish 5-(2-(1,3-dioxalan-2yl)propyl)-3-methylfuran-2-(5H)-one (156) as a pair of diastreoisomers with an overall yield of 55%. The diastereoisomers were not separated at this stage in order to establish the validity of the cyclization protocol. The H NMR spectrum showed overlap of the resonances corresponding to the two diastreoisomers, with a broad doublet at  6.97 ppm corresponding to the olefinic proton of the lactone and a multiplet at  4.97-4.93 ppm for the lactone methine proton. Mass spectrometric analysis confirmed the mass ion to be m/z 212. The IR spectrum amongst other things exhibited a characteristic carbonyl band at 1734 cm-1 in accord with that expected for  unsaturated ester in a five-membered ring Scheme 3.0. 
OTBDMS
O
O
OO
(236)
OO
(241)
(a)  silver trifluoroacetate, DCM, 55% Scheme-3 The successful preparation of 5-(2-(1, 3-dioxalan-2yl) propyl)-3-methylfuran-2-(5H)-one (156) opened the pathway towards the preparation of other model analogues to test the validity of the cyclization methods. As outlined earlier, such a reaction was to proceed through condensation with 2-(tertbutyldimethylsiloxy)furan (235)Consequently protected furan (235) was converted in 71% yield to 5-(2-(1, 3-
Research Journal of Chemical Sciences _________________________________________________________ Res. J. Recent Sci. Vol. 1(1), 85-88, Jan. (2012)  International Science Congress Association 
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dioxalan-2yl) propyl) furan-2-(5H)-one (242)The IR spectrum of (242) showed the ester at 1741 cm-1 and an absorption corresponding to a (C=C) double bond appeared at 1640 cm-1The H NMR spectrum not only revealed the disappearance of the two sharp singlet resonances due to the tert-butyl and dimethyl groups, but also revealed a signal at 4.73 ppm ( 5.0 Hz) corresponding to the methine in the lactone. The diastereotopic methylene protons appeared as two double multiplets, at  1.97-1.80 ppm and at  1.97-1.80 ppm Scheme 2.15. 
OTBDMS
O
O
OO
(235)
OO
(241)
(a)  silver trifluoroacetate, DCM, 71% Scheme - 4The preparation of these key intermediates (237) and (238) set the stage for the synthesis of the desired aldehyde under mild acid conditions.5, 6 We chose initially to attempt the reaction with PTSA in acetone/water (5:1), this being the most conventional and straightforward method for the removal of the dioxolane. Purification of the residue by column chromatography on silica eluting with hexane-ethyl acetate (1:1) afforded compound (238) from (239), as a pair of diastereoisomers in 43% yield. The H NMR spectrum showed a pair of overlapping doublets (J 1.0 Hz) centred at 9.67 ppm corresponding to the terminal aldehyde and the resonances due to dioxolane were absent. The IR spectrum showed two characteristic absorptions at 1752 cm-1 due to the lactone,  and 1718 cm-1, clear evidence for C=O stretching of an aldehyde. Mass spectrometric analysis confirmed the molecular ion to be m/z 168 Scheme 5.0.
O
HO
(rac)-(239)
O
OO
(238)
(a) TsOH, acetone/water, reflux, 43%Scheme-5 Conclusion The synthesis on a suitable scale of the key -Butenoildes mediated by Silvertrifluroacetate with -halo acetals was efficiently pursued. Our initial inspection of the intermediate (235) and (236) suggests that it could be conveniently assembled by coupling the C-5 cabanion -halo acetals went smooth with high regioselectivity. AcknowledgementsI would like to extend my sincere gratitude to Professor Laurence Harwood, The University of Reading, United Kingdom for providing both mentorship and Laboratory space. CHEERS BOSS YOU MADE THIS HAPPENED & I AM EVER SO GRATFUL!!! References1.  Ishibashi, M.; Kimihoro, M.; Li, Y. S., Ohizumi, Y. Littoralisone, A Novel Neuritogenic Iridolactone Having an Unprecedented Heptacyclic Skeleton Including Four- and Nine-Membered Rings Consisting of Glucose from Verbena littoralis, Journal of Organic Chemistry, 66, 2165 (2001)  2.  Macmillan, D. W. C. & Mangion, I. K. Total Synthesis of Brasoside and Littoralisone, Journal of  the   American Chemical Society, 127, 3697 (2005)3.  Makama, B. Y. (2010) Synthesis of an enantioenriched tricyclci iridolactone core in Brasoside, Science World Journal, , 15 (2010) 4.   Larson, G. L. ; Klesse, R. An Improved Synthesis of the Ethylene Acetal of 3-Iodopropanal and The Ethylene Ketal of 4-Iodo-2-butanone, J. Org. Chem., 50, 3627 (1985)                                                 5.  Oku, A.,  Kinugasa, M.,  Kamada, T. Deprotection of Acetals and Silyl Ethers by DDQ. Is DDQ a Neutral Catalyst, Chem. Lett.,22,165 (1993)
6.
Tanemura, K., Suzuki, T.,  Horaguchi, T. 2,3-Dichloro-5,6-dicyano--benzoquinone as a mild and efficient catalyst for the deprotection of acetals  J. Chem. Soc., Chem, Commun., 979 (1992)7. Perrin, D. D.; Amarego, W. L. F. Purification of Laboratory Chemicals, Pergamon Press Oxford 1998)
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