Tagged Hypervalent Iodine Reagents: A New Purification Concept based on Ion Exchange through S N 2 Substitution

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1 1 Tagged Hypervalent Iodine Reagents: A New Purification Concept based on Ion Exchange through S N 2 Substitution Eike Kunst, Florian Gallier., Gilles Dujardin, Mekhman S. Yusubov, Andreas Kirschning*, Institut für rganische Chemie der Leibniz Universität Hannover, Schneiderberg 1B, Hannover, Germany, and UC2M, UMR CNRS 6011, Université du Maine, F Le Mans Cedex 9, France and The Siberian State Medical University, 2 Moskovsky trakt, Tomsk, Russia and The Tomsk Polytechnic University, 30 Lenin st., Tomsk, Russia. Supporting information and spectra General Methods. 1 H NMR, 13 C NMR and 1 H, 13 C-CSY as well as NESY spectra were measured on Avance 200/DPX (Bruker) with 200 MHz (50 MHz), Avance 400/DPX (Bruker) 400 MHz (100 MHz) and Avance 500/DRX (Bruker) respectively, using tetramethylsilane as the internal standard. If not otherwise noted, CDCl 3 is the solvent for all NMR experiments. Multiplicities are described using the following abbreviations: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad. Chemical shift values of 13 C NMR spectra are reported as values in ppm relative to residual CHCl 3 (77 ppm) or CD 3 D (49 ppm) as internal standards. The multiplicities refer to the resonances in the off-resonance spectra and were elucidated using the distortionless enhancement by polarisation transfer (DEPT) spectral editing technique, with secondary pulses at 90 and 135. Multiplicities are reported using the following abbreviations: s = singlet (due to quaternary carbon), d = doublet (methine), q= quartet (methyl), t = triplet (methylene). Mass spectra were recorded on a type LCT-spectrometer (Micromass) and on a type VG autospec (Micromass). Ion mass (m/z) signals are reported as values in atomic mass units followed, in parentheses, by the peak intensities relative to the base peak (100%). ptical rotations [α] were collected on a Polarimeter 341 (Perkin Elmer) at a wavelength of 589 nm and are given in 10-1 deg cm 2 g -1. Combustion analyses were performed at the Institut für rganische Chemie, Leibniz Universität Hannover. All solvents used were of reagent grade and were further dried. Reactions were monitored by thin layer chromatography (tlc) on silica gel 60 F 254 (E. Merck, Darmstadt) and spots were detected either by UV-absorption or by charring with H 2 S 4 /4- methoxybenzaldehyde in ethanol. Preparative column chromatography was performed on silica gel 60 (E. Merck, Darmstadt). Preparations of methyl glycoside 15 1, thioglycoside 22 2 and glucopyranose 25 3 have been described before. Methyl-p-iodo-phenylsulfonate (4a) p-iodophenylsulfonyl chloride 3 (1.0 g, 3.3 mmol) was suspended in 5 ml MeH. Then, NaMe (179 mg, 3.3 mmol; 1 eq.) was added and the reaction mixture was stirred for 12 h. After dilution with water and dichloromethane, the aqueous phase was extracted with dichloromethane, the combined organic phases were dried (Na 2 S 4 ) and concentrated under reduced pressure to yield the title compound 4a (450 mg, 1.5 mmol; 46 %). 1 H NMR (400 MHz, CDCl 3 ) δ 3.77 (s, 3H), 7.61 (d, J = 8.6, 2H), 7.92 (d, J = 8.6, 2H) ppm; 13 C NMR (100 MHz, CDCl 3 ) δ 56.5 (q), (d), (d), (d), (d) ppm; HRMS (ESI): calculated for C 7 H 7 I 3 S [M-H] , found (1 -methyl)-ethyl-p-iodo-phenylsulfonate (4b) p-iodophenylsulfonyl chloride 3 (2.0 g, 6.6 mmol) was dissolved in 20 ml abs. pyridine. After addition of 3 ml of 2-propanol the solution was stirred for 1.5 h at rt. The reaction mixture was hydrolyzed with a sat. NaHC 3 solution. After extraction of the aqueous phase with dichloromethane, the combined organic extracts were dried (Na 2 S 4 ) and concentrated under reduced pressure. The crude product was co-distilled with toluene to remove traces of pyridine to yield the title compound 4b (1.19 g, 5.7 mmol, 86 %) as a colorless, amorphous solid. 1 H NMR (400 MHz, CDCl 3 ) δ 1.28 (d, J = 6.2, 6H), 4.76 (sept, J = 6.2, 2H), 7.61 (d, J = 8.6, 2H), 7.89 (d, J = 8.6, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 22.8 (q), 77.9 (d), (d), (d), (d), (d); HRMS (ESI): calculated for C 9 H 11 I 3 S (M + ) , found (2'-methyl)-propyl-4-iodo-phenylsulfonate (4c) To a solution of pispyl chloride 3 (5.52 g, 18.2 mmol) in 20 ml abs. pyridine at rt was added i-butanol (1.68 ml, 1 equiv). After 90 min, the reaction was hydrolyzed by addition of 20 ml of a saturated NaHC 3 solution. The aqueous phase was extracted with CH 2 Cl 2 (3 times), and the combined organic layers were dried (Na 2 S 4 ). After concentration under reduced pressure, the crude product was co-distilled with toluene to remove traces of pyridine. The title product 4c was obtained as a colorless, amorphous solid (5.40 g, 15.9 mmol; 87 % yield). 1 H NMR (400 MHz, CDCl 3 ) δ 0.90 (d, 6H, J = 6.7), 1.95 (m, 2H), 3.82 (d, J = 6.5, 1H), 7.61 (d, J = 8.2, 2H), 7.92 (d, J = 8.2, 2H) ppm; 13 C NMR (100 MHz, CDCl 3 ) δ 18.9 (q), 28.5 (q), 77.2 (d), (d), (d), (d), (d) ppm; HRMS (ESI): calculated for C 10 H 13 I 3 S (M + ): , observed

2 2 Azide ion exchange resin (5) Freshly washed resin IRA-900 (10 g, Cl - form; 2.9 mmol/g theoretical loading according to the information of the commercial provider) was suspended in 20 ml of an aqueous sodium azide solution (2 mol/l) and gently shaken for 1 h at rt. After filtration, the polymer was extensively washed with acetonitrile (or methanol) followed by dichloromethane (or diethyl ether), and dried for at least 4 hours in high vacuo. IR (Golden Gate)= 2010 cm -1. (2'-methyl)-propyl-4-[bis(acetoxy)iodo]-phenylsulfonate (7) A mixture of 60 ml Ac 2 and 14 ml 30 % H 2 2 was kept for 4 h at 40 C (keeping the exact temperature is essential) in the dark. It was then poured onto finely ground i-butyl 4- iodobenzenesulfonate 4c (6.06 g, 17.8 mmol) and cooled to room temperature. After 2 days, this reaction mixture was poured onto 150 ml of ice-water, and the crystals were allowed to grow for 5-10 minutes, before being recovered by filtration on a Büchner funnel. The crystalline material was then washed with another 150 ml of ice-water, dried in high vacuo and the title compound 7 was collected as colorless crystals (5.89 g, 12.8 mmol; 72 % yield). mp C (dec.); 1 H NMR (400 MHz, CDCl 3 ) δ 0.94 (d, J = 6.6, 6H), 2.04 (sept, J = 6.5, 1H), 3.92 (d, J = 6.5, 2H), 7.97 (d, J = 8.7, 2H), 8.26 (d, J = 8.0, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 18.5 (q), 20.3 (q), 28.1 (q), 77.2 (d), (d), (d), (q), (s), (s); HRMS (ESI): calculated for C 14 H 19 I 7 S (M + ) , found Figure 1. X-ray structural analysis of 7. X-ray crystallographic study of 7: A single crystal ( mm) of 7 was investigated on a Stoe IPDS area detector diffractometer using graphite-monochromated Mo- Kα radiation ( pm). The lattice constants were determined by the automatic Search and Indexing routines of the diffractometer. Indexing and refinement of reflections led to a monoclinic unit cell with the dimensions: a = (2) pm, α = 90, b = (2) pm, β = (2), c = (3) pm, γ = 90 (V= (4).106 pm 3 ; Z = 2; g/cm 3 ). The space group P2 4 1 was determined by the reflection conditions. The intensity data of 3615 unique reflections were measured at room temperature (293(2)K) in the range of 2.35 to For Lp correction and data processing the programs of the Stoe IPDS software package were used. The structure was solved by direct methods using the programs SHELXS-97 and SHELXL The atomic parameters of the molecule were then completed by Fourier differences syntheses and refined (anisotropic displacement parameters for non H- atoms) by full-matrix least squares (F2) to the attainable R values R1 = [for reflections I > 2σ(I)], wr 2 = The hydrogen atoms were included as riding atoms. Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Center. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax (international) +44(0) ; (2'-methyl)-propyl-4-iodosyl-phenylsulfonate (8) Finely ground i-butyl 4-[bis(acetoxy)iodo]- benzenesulfonate (846 mg, 1.85 mmol) was placed in a 100 ml beaker and 30 ml of NaH (3N) was added over 5 minutes with vigorous stirring. The mixture was triturated with a spatula for 15 minutes in order to become homogeneous. After standing for 45 minutes, water was added (20 ml) with vigorous stirring, and the solid was collected on a Büchner funnel. It was returned to the beaker, triturated with water (40 ml) and collected again. Washing with water (3 times, 40 ml) and drying in high vacuo yields a yellowish solid 8 (523.4 mg; 1.47 mmol; 80 % yield), which is insoluble in common solvents. mp C (dec.); IR (film) 708, 729, 745, 768, 811, 843, 944, 976, 1091, 1176, 1182, 1357, 1469, 1568, 2962 cm -1. µ-xo-bis-[triflyloxy(4-iso-butyl)benzenesulfonato]- iodane (9) In an oven dried round-bottom flask, under argon atmosphere, freshly distilled CH 2 Cl 2 (3 ml) was added to 8 (1 g, 2.80 mmol). After cooling to 0 C, triflic anhydride (235 µl, 0.5 equiv) was added to the suspension, which immediately turned into a yellow solution. A yellow solid precipitated after minutes which was recovered by filtration under argon atmosphere (using the Schlenk filtration technique) and dried in high vacuo for 2 h. The title compound 9 was isolated (553 mg, 0.56 mmol; 40 %) and stored at 0 C under inert atmosphere (preferentially glove-box). This solid is very temperature sensitive and storage at room temperature (under argon atmosphere) commonly affords 4-iodophenylsulfonic acid overnight. Although the title compound 9 was prepared freshly before each reaction, it can be stored as a suspension (in dichloromethane under argon at 0 C) for several days, without a significant loss of activity. 1 H NMR (400 MHz, CD 3 CN, CHD 2 CN = 1.94 ppm) δ 0.74 (d, J = 6.6, 6H), (m, 1H), 3.73 (d, J = 6.6, 2H), 7.90 (m, 2H), 8.21 (m, 2H) ppm; 13 C NMR (100 MHz, CD 3 CN, CD 3 CN = 1.32 ppm) δ 18.4 (q), 28.2 (q), (d), (d), (d), (d), (s) ppm.

3 3 General procedure for the oxidation of alcohols Method A: To a mixture of alcohol ( mmol) and bis(acetoxy)iodoarene 7 ( mmol) in 0.5 ml of aqueous acetonitrile (MeCN H 2 = 5:1) an aqueous solution of RuCl 3 (0.25 M, μl; mmol) was added with stirring at room temperature. An instantaneous formation of a cotton-like, off-white, precipitate was observed. The reaction mixture was stirred for a period of time indicated in Table 2 (the reactions were monitored by tlc). Then, 1.0 ml of acetonitrile and mg of IRA 900 (5, azide form) was added and heated under microwave irradiation (100 C, 150 W) for 1 h. The polymer was removed by filtration and the solution was concentrated in vacuo to afford NMR-pure carbonyl compound. The ketones 17 and 20 were additionally characterized as 2,4-dinitrophenylhydrazones prepared by treatment of the reaction mixtures with a standard solution of 2,4-dinitrophenylhydrazine. 17: m.p C; 2,4-dinitrophenyl-hydrazone: m.p C (m.p. 236 C 6 ). 18: 1 H NMR (200 MHz, CDCl 3 ): δ = 1.26 (m, 10H), 1.75 (m, 10H), 2.45 (m, 2H). 19: (200 MHz, CDCl 3 ): δ = 1.17 (s, 3H), 1.22 (s, 3H), 1.93 (s, 1H), 3.95 (s, 1H). The data are in accordance with those reported in ref : 2,4-dinitrophenyl-hydrazone: C (m.p o C 8 ) 21: (400 MHz, CDCl 3 ): δ = 2.68 (dd, J = 14.6, 1.0 Hz, 1H), 2.84 (dd, J = 14.6, 4.6 Hz, 1H), 3.38 (s, 3H), 3.92 (t, J = 10.0 Hz, 1H), 4.16 (ddd, J = 10.0, 10.0, 4.6 Hz, 1H), 4.30 (dd, J = 10.0, 1.0 Hz, 1H), 4.38 (dd, J = 10.0, 4.6 Hz, 1H), 5.15 (d, J = 4.6 Hz, 1H), 5.59 (s, 1H), (m, 5H). The data are in accordance with those reported in ref. 9. For product 18 the ruthenium determination was determined to be at around 10 ppm using an inductively coupled plasma mass spectrometer (ICP-MS) Thermo X7 ICP-MS (Thermo Electron GmbH, Dreieich, Germany). This quadrupol instrument had a power of 1200 W throughout the measurement. The gas flow rates were 1.0 ml/min (Nebuliser), 1.2 ml/min (Auxiliary) and 13 ml/min (Cool) argon 4.8, respectively. Under the conditions used the limit of detection for ruthenium was 1 ng/l. Method B: Bis(acetoxy)iodoarene 7 (46 mg, 0.10 mmol) was added to an aqueous solution of NaHC 3 (84 mg in 0.5 ml of aqueous acetonitrile (MeCN H 2 ; 5:1)) and the mixture was stirred until the solution has cleared up. Then, the methyl glycoside 15 (8.4 mg, mmol) and an aqueous solution of RuCl 3 (0.5 μl of M solution; μmol) was added at room temperature with stirring. The reaction mixture was stirred for 28 h (the reactions were monitored by TLC). Then 1.0 ml of acetonitrile and 300 mg of IRA 900 (5, azide form) were added and heated under microwave irradiation (100 C, 150 W) for 1 h. The polymer was removed by filtration and the solution was extracted with Et 2. The combined organic extracts were removed in vacuo to afford the NMR-pure ulose 21. General procedure for the glycosidation of thioglycosides To a solution of thioglycoside and glycosyl acceptor (azeotropically dried with toluene followed by 1 h in high vacuum) in a mixture of dry acetonitrile and nitromethane (4:1; 50 ml / mmol) was added freshly activated molecular sieves (4 Å, 1 g/mmol). This suspension was cooled to -80 C. The activating agent was freshly prepared by adding Tf 2 (0.5 equiv) or TMSTf (1 equiv) to a suspension of compound 8 in abs. dichloromethane (5 ml/mmol) at 0 C. Within a few minutes, a yellow precipitate is formed (formation of compound 9) which, after dissolution in a minimum amount of dry acetonitrile, was transfered (1.3 equiv) to the reaction mixture from above. After completion of the reaction (monitored by TLC), dry Amberlyst A-21 (1 g/mmol) was added to terminate the reaction. Filtration through a pad of silica or celite afforded a crude oil which was then submitted to the scavenging protocol. The crude compound was dissolved in acetonitrile (20 ml/mmol) and azide resin 5 was added (~2 g/mmol). The scavenging proceeds within 1 hour at 100 C under microwave irradiating conditions (150 W) or within two days at 60 C under thermal conditions. When phenylthioglycosides were employed, diphenyldisulfide is formed during the reaction. This by-product was scavenged by adding borohydride loaded resin (2.9 g/mmol) in isopropanol for 15 h. The compounds obtained were usually free of by-products. In order to collect analytically pure material, or for separation of anomers a sample was chromatographically purified over silica gel. 1-Benzyl 3,4-di--acetyl-2,6-dideoxy-α/β-L-arabinohexopyranoside (23) The title compound 23 (23.5 mg, mmol; 73 % yield; α/β ratio 1.1:1; colorless oil) was prepared according to the general procedure using phenyl thioglycoside 22 (α/β ratio= 3:1; 32 mg, 0.1 mmol), benzyl alcohol (10 µl, 0.1 mmol) in CH 3 CN/Et 2 (2 + 4 ml), MS 4Å (100 mg), oxidizing agent 9 (prepared from 36 mg, 0.1 mmol 8 and 8.5 µl, 14 mg, 0.5 mmol, 0.5 eq. Tf 2 in 0.5 ml CH 2 Cl 2 ). The glycosidation proceeded within 3 hours at -78 C. Work-up: a) Amberlyst A-21 (1g/mmol), b) IRA (BH 4 form 1g/mmol in i-prh for 12 h), c) IRA (N 3 form, 1 g/mmol in CH 3 CN under microwave irradiating conditions). α -23: 1 H-NMR (400 MHz, CDCl 3 ) δ 1.28 (d, J = 6.2 Hz, 3H), 2.05 (m, 6H), 2.32 (m, 2H), 3.46 (dq, J = 9.5, 6.2 Hz, 1H), 4.60 (d, J = 11.9 Hz, 1H), 4.75 (dd, J = 9.5, 9.5 Hz,1H), 4.89 (d, J = 11.9 Hz, 1H), 4.96 (m, 1H), 5.31 (ddd, J = 11.6, 9.5, 5.4 Hz, 1H), (m, 5H, Ar) ppm. β -23: 1 H-NMR (400 MHz, CDCl 3 ) δ 1.19 (d, J = 6.3 Hz, 3H), 1.81 (m, 2H), 2.05 (m, 6H), 3.90 (dq, J = 9.7, 6.3 Hz, 1H), 4.48 (d, J = 12.1 Hz, 1H), 4.60 (m, 1H), 4.67 (d, J = 12.1 Hz, 1H), 4.75 (m, 1H), 4.95 (m, 1H), (m, 5H, Ar) ppm. The data are in accordance with those published in ref (1':2',3':4'-Di--isopropylidene-galacto-α-D-

4 4 hexopyranosyl)-1-6 2,6-dideoxy-3,4-di--acetoxy-α/β-Larabino-hexopyranoside (24) The title compound 24 (36 mg, mmol; 76 % yield; α/β ratio 1:1.4; colorless oil) was prepared according to the general procedure using phenyl thioglycoside 22 (α/β ratio = 3:1; 32 mg, 0.1 mmol), 1':2',3':4'-di--isopropylidene galactose (26 mg, 0.1 mmol) in CH 2 Cl 2 /CH 3 CN (4 + 2 ml), MS 4Å (100 mg), oxidizing agent 9 (prepared from 36 mg, 0.1 mmol 8 and 8.5 µl, 14 mg, 0.5 mmol, 0.5 equiv Tf 2 in 0.5 ml CH 2 Cl 2 ). The glycosidation proceeded within 2 hours at -78 C. Work-up: a) Amberlyst A-21 (1g/mmol), b) IRA-900 (BH 4 - form 1g/mmol in i-prh for 12 h), c) IRA (N 3 - form, 1 g/mmol in CH 3 CN under microwave irradiating conditions). α -24: 1 H-NMR (400 MHz, CDCl 3 ) δ 1.15 (d, J = 6.2 Hz, 3H), (4s, 12H), 1.77 (ddd, J = 12.8, 11.7, 3.8 Hz, 1H), (2s, 6H), 2.24 (ddd, J = 12.8, 5.4, 1.0 Hz, 1H), 3.56 (dd, J = 9.9, 6.4 Hz, 1H), 3.82 (dd, J = 9.9, 6.7 Hz, 1H), 3.95 (dq, J = 6.2, 9.6 Hz, 1H), 4.00 (m, 1H), 4.28 (m, 1H), 4.30 (m, 1H), 4.60 (m, 1H), 4.72 (dd, J = 9.6, 9.6 Hz, 1H), 4.93 (d, J = 3.8 Hz, 1H), 5.24 (ddd, J = 5.4, 9.6, 11.7 Hz, 1H), 5.50 (d, J = 4.8 Hz, 1H) ppm. β -24: 1 H-NMR (400 MHz, CDCl 3 ) δ 1.21 (s, J = 6.2 Hz, 3H), (4s, 12H), 1.72 (ddd, J = 12.3, 12.1, 9.8, 1H), 2.02 (s, 3H), 2.04 (s, 3H), 2.33 (ddd, J = 12.3, 5.3, 2.0 Hz, 1H), 3.46 (dq, J = 6.2, 9.5 Hz, 1H), 3.75 (dd, J = 10.0, 8.0 Hz, 1H), 3.90 (dd, J = 10.0, 5.9 Hz, 1H), 4.00 (ddd, J = 5.9, 8.0, 1.8 Hz, 1H), 4.29 (dd, J = 8.0, 1.8 Hz, 1H), 4.31 (dd, J = 2.5, 5.0 Hz, 1H), 4.58 (dd, J = 9.8, 2.0 Hz, 1H), 4.61 (dd, J = 2.5, 8.0 Hz, 1H), 4.72 (dd, J = 9.5, 9.5 Hz, 1H), 4.96 (ddd, J = 12.1, 9.5, 5.3 Hz, 1H), 5.51 (d, J = 5.0 Hz, 1H) ppm. 13 C-NMR (100 MHz, CDCl 3 ) δ: 170.4, 170.3, 170.2, (4 s, C 3 α, C 3 β, C 4 α, C 4 β) ; ; ; ; (4 s, C 9 α, C 9 β, C 10 α, C 10 β) ; 99.8 (d, C 1 β) ; 96.6 (d, C 1 α) ; 96.3 ; 96.2 (2 d, C 1' α, C 1' β) ; 74.8 (d, C 4 α) ; 74.1 (d, C 4 β) ; 70.9 (d, C 3 β) ; 70.7 ; 70.6 ; 70.6 ; 70.6 ; 70.5 (6 d, C 2' α, C 2' β, C 3' α, C 3' β, C 4' α, C 4' β) ; 70.0 (d, C 5 β) ; 69.1 (d, C 3 α) ; 67.9 (t, C 6' β) ; 66.7 (d, C 5' α) ; 65.9 (d, C 5' β) ; 65.5 (d, C 5 α) ; 65.2 (t, C 6' α) ; 36.4 (t, C 2 β) ; 35.2 (t, C 2 α) ; 26.1 ; 26.1 ; 26.0 ; 24.9 ; 24.9 ; 24.5 ; 24.4 (8 q, C 5 α, C 5 β, C 6 α, C 6 β, C 7 α, C 7 β, C 8 α, C 8 β) ; 21.0 ; 20.9 ; 20.8 ;20.8 (4 q, C 1 α, C 1 β, C 2 α, C 2 β) ; 17.6 (q, C 6 β) ; 17.4 (q, C 6 α); HRMS (ESI) calculated for C 22 H Na [M+Na] , observed The data are in accordance with those published in ref ,4-Bis--[tert-butyl(dimethyl)silyl]-2,6-dideoxy-α/β-Larabino-hexopyranose (27) To a solution of di(tert-butyldimethylsilyloxy)-l-rhamnal (108 mg; 0.3 mmol) in a mixture CH 3 CN/H 2 (100:1; ml) was added at room temperature PPh 3 HBr (5 mg; 5 mol %). After 6 hours, the mixture is neutralized by addition of freshly washed Amberlyst A-21 (25 mg). After filtration and washing with CH 2 Cl 2, the solvent is concentrated in vacuo, and the residue is purified by column chromatography (petroleum ether/etac 9:1) to afford the pure pyranose 27 (56 mg; 0.15 mmol; 49 % yield) as a mixture of anomers (α/β 1.5:1). HRMS (ESI): calculated for C 20 H 43 N 4 Si 2 Na [M + CH 3 CN + Na] , found α-27 : 1 H-NMR (400 MHz, CDCl 3 ) δ 0.08 (s, 3H), 0.10 (s, 3H), 0.90 (s, 9H), 1.23 (d, J = 6.5 Hz, 3H), 1.65 (ddd, J = 13.0, 10.4, 2.3 Hz, 1H), 2.05 (ddd, J = 13.0, 4.3, 2.6 Hz, 1H), 3.01 (bs, 1H, H), 3.16 (dd, J = 7.6, 7.6 Hz, 1H), 3.87 (dd, J = 7.6, 6.5 Hz, 1H), 3.98 (ddd, J = 10.4, 7.6, 4.3 Hz, 1H), 5.25 (bd, J = 2.6 Hz, 1H) ppm; 13 C-NMR (100 MHz, CDCl 3 ) δ 4.4, 4.1, 3.3, 3.0, 18.1, 18.2, 18.6, 26.1, 26.2, 39.1, 69.8, 70.3, 77.7, 91,3 ppm. β-27 : 1 H-NMR (400 MHz, CDCl 3 ) δ 0.08 (s, 3H), 0.10 (s, 3H), 0.89 (s, 9H), 1.30 (d, J = 6.2 Hz, 3H), 1.57 (ddd, J = 12.7, 11.0, 9.1 Hz, 1H), 2.23 (ddd, J = 12.7, 4.5, 2.1 Hz, 1H), 3.19 (dd, J = 7.9, 7.9 Hz, 1H), 3.33 (dd, J = 7.9, 6.2, 1H), 3.68 (ddd, J = 11.0, 7.9, 4.5 Hz, 1H), 3.73 (d, J = 6,7 Hz, 1H), 4.84 (ddd, J = 9.1, 6.7, 2.1 Hz, 1H) ppm; 13 C- NMR (100 MHz, CDCl 3 ) δ 4.3, 4.0, 3.1, 2.8, 18.0, 18.3, 18.9, 26.1, 26.3, 41.7, 72.7, 72.9, 77.3, 93.5 ppm. General procedure for fragmentation To a solution of pyranose in dry cyclohexane (25 ml/mmol) was successively added 9 (1.2 equiv) and I 2 (1 equiv). After completion of the reaction (monitored by TLC), excess of iodine was reductively removed by addition of IRA-900 (loaded with S , 1 g/mmol). The crude mixture (after washing, filtration of the polymer and evaporation of the solvents) was submitted to the scavenging procedure for the tagged aryl iodo compounds (addition of IRA-900, azide form 5 in acetontrile) under microwave irradiation (100 C, 1 h, 150 W). Purification, if necessary, was achieved by column chromatography (silica gel). (2R, 3R, 4S)-5-Acetoxy-1,3,4,5-tetrabenzyloxy-pentan-2- yl formate (26) The general procedure (reaction time 7h) using per-benzylated glucose 25 (108 mg, 0.2 mmol), 7 (110 mg, 0.24 mmol; 1.2 eq.) and I 2 (51 mg, 0.2 mmol) in toluene (5 ml) gave an unseparable diastereomeric mixture (1.35:1) of the title compound 26 (90 mg, 0.15 mmol; 75 % yield) after scavenging and column chromatography (petroleum ether/etac = 5:1) as a colorless oil. major isomer: 1 H-NMR (400 MHz, CDCl 3 ) δ 2.03 (s, 3H), (m, 2H), 3.81 (dd, J = 2.9, 2.9 Hz, 1H), 3.98 (dd, J = 5.5, 4.1 Hz, 1H), (m, 8H), 5.35 (ddd, J = 5.5, 5.5, 2.9 Hz, 1H), 6.20 (d, J = 5.5 Hz, 1H), (m, 20H), 7.96 (s, 1H) ppm; 13 C-NMR (100 MHz, CDCl 3 ) δ 21.1, (6C), 77.3, 78.6, 92.7, (24C, aromatic), 160.3, ppm. minor isomer: 1 H-NMR (400 MHz, CDCl 3 ) δ 1.96 (s, 3H), (m, 2H), 3.84 (dd, J = 2.9, 2.9 Hz, 1H), 4.08 (dd, J = 6.1, 3.4 Hz, 1H), (m, 8H), 5.32 (ddd, J = 5.5, 5.5, 3.1 Hz, 1H), 6.26 (d, J = 6.5 Hz, 1H), (m, 20H), 7.99 (s, 1H) ppm; 13 C-NMR (100 MHz, CDCl 3 ) δ 21.0, (6C), 77.4, 79.5, 96.1, (24C, aromatic), 160.3, ppm. HRMS (ESI) calculated for C 36 H 38 8 Na [M + Na] , found (2S, 3S, 4R)-5-iodo-3,4-di--(tert-butyldimethylsilyl)- pentan-2-yl formate (28) The general procedure (reaction time 12 h) using protected

5 5 L-rhamnose 27 (53 mg, 0.14 mmol), 7 (77 mg, mmol; 1.2 equiv) and I 2 (36 mg, 0.14 mmol) in cyclohexane (5 ml) gave the title compound 27 (46 mg, mmol; 69 % yield) after scavenging and column chromatography (petroleum ether/etac = 5:1) as a colorless oil. 1 H-NMR (400 MHz, CDCl 3 ) δ 0.08 (s, 3H), 0.11 (s, 3H), 0.11 (s, 3H), 0.18 (s, 3H), 0.90 (s, 9H), 0.92 (s, 9H), 1.26 (d, J = 6.4 Hz, 3H), 3.03 (dd, J = 10.0, 8.6 Hz, 1H), 3.53 (dd, J = 10.0, 3.4 Hz, 1H), 3.82 (dd, J = 4.4, 3.0 Hz, 1H), 3.95 (ddd, J = 7.9, 4.4, 3.4 Hz), 5.26 (ddq, J = 6.4, 3.0, 0.9 Hz), 8.00 (s, 1H) ppm. 13 C-NMR (100 MHz, CDCl 3 ) δ -4.7, -4.5, -4.3, -4.2, 7.7, 16.4, 18.0, 18.1, 25.7, 25.8, 70.3, 75.7, 76.8, ppm; HRMS (ESI) calculated for C 10 H 21 3 Si fragment [M C 8 H 18 ISi] , found (fragmentation occurred during analysis). References: (1) a) sborn, H. M. I.; Meo, P.; N., Rajdeep, K., Tetrahedron: Asymmetry 2005, 16, b) Chambers, D. J.; Evans, G. R.; Fairbanks, A. J., Tetrahedron: Asymmetry 2003, 14, (2) a) berthuer, M.; Leimkuhler, Catherine; K., Ryan G.; Lu, W.; Walsh, C. T.; Kahne, D., J. Am. Chem. Soc. 2005, 127, b) Priebe, W.; Grynkiewicz, G.; Neamati, N., Tetrahedron Lett. 1991, 32, (3) a) Tiwari, P.; Misra, A. K., Tetrahedron Lett. 2006, 47, b) de Figueiredo, R. M.; Bailliez, V.; Dubreuil, D.; lesker, A.; Cleophax, J., Synthesis 2003, (4) International Tables for Crystallography; Vol. A; (Ed.: Hahn, T.), 2nd ed., Dordrecht, (5) Sheldrick, G. M., SHELXS-86, Acta Crytallogr. 1990, A46, (6) Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R., Vogel s Textbook of Practical rganic Chemistry, 5th ed., Longman, London, 1989, 1514 pp. (7) a) Dehmlow, E. V; Kinnius, J.; Buchholz, M.; Hannemann, D., J. prakt. Chem. 2000, 342, b) Toeroek, B.; Felfoeldi, K.; Molnar, A., Bartok, M., J. rganomet. Chem. 1993, 460, (8) Yusubov, M. S.; Chi, K.-W.; Park, J. Y.; Karimov, R.; Zhdankin, V. V. Tetrahedron Lett. 2006, 47, (9) a) Chapleur, Y.; Longchambon, F.; Gillier, H., Chem. Commun. 1988, b) Chapleur, Y.; Euvrard, M. N., Chem. Commun. 1987, (10) a) Kolar, C.; Dehmel, K.; Moldenhauer, H Carbohydr. Res. 1990, 208, b) Ramiliarison, C.; Monneret, C. J. Carbohydr. Chem., 1989, 8, (11) a) Tetrahedron Lett. 2003, 44, ; b) Tetrahedron Lett. 1989, 30,

6 The following section contains 1 H- and 13 C-NMR spectroscopic data of iodo arenes.

7 S I 4b ppm S I 4b ppm

8 8

9 S Ac I Ac ppm

10 S Ac I Ac ppm

11 Tf Tf S I I S ppm Tf Tf S I I S ppm

12 12

13 13

14 14

15 15

16 Forwarded message from Date: Wed, 11 Jul :23: (BST) From: CCDC Data Depository Reply-To: CCDC Data Depository Subject: X-Ray/Journal: rganic Letters/Kirschning et al. - CCDC To: ekunst@uoguelph.ca Dear Depositor The following crystal structure has been deposited at the Cambridge Crystallographic Data Centre and allocated the deposition number CCDC If we have any queries relating to these data then we will contact you later. Summary of Data CCDC Authors: E.Kunst,F.Gallier,G.Dujardin,M.S.Yusubov,A.Kirschning Journal: rganic Letters (1336) Compound: (2'-methyl)-propyl-4-(bis(acetoxy)iodo)-phenylsulfonate Formula: C14 H19 I1 7 S1

17 17 Unit cell parameters: a 8.818(2) b 9.020(2) c (3) beta (3) space group P21 Any publication carrying this CCDC number will refer to the most recent set of deposited data; previous depositions carrying this number will not be retained. Please note, if data have not appeared in a journal publication 3 years after the date of deposition, and the CCDC cannot contact you to discuss the matter, then the CCDC will automatically include the data in the CSD as a Private Communication. Many thanks for your help. Best wishes Data Acquisition Team -- Data Acquisition - the Cambridge Crystallographic Data Centre deposit@ccdc.cam.ac.uk Telephone: (44) Facsimile: (44) Postal Address: CCDC, 12 Union Road, CAMBRIDGE CB2 1EZ, UK LEGAL NTICE Unless expressly stated otherwise, information contained in this message is confidential. If this message is not intended for you, please inform postmaster@ccdc.cam.ac.uk and delete the message. The Cambridge Crystallographic Data Centre is a company Limited by Guarantee and a Registered Charity. Registered in England No Registered Charity No Registered office 12 Union Road, Cambridge CB2 1EZ End forwarded message -----