Indium Triflate-Assisted Nucleophilic Aromatic Substitution Reactions of. Nitrosobezene-Derived Cycloadducts with Alcohols

Transcription

1 Supporting Information Indium Triflate-Assisted ucleophilic Aromatic Substitution Reactions of itrosobezene-derived Cycloadducts with Alcohols Baiyuan Yang and Marvin J. Miller* Department of Chemistry and Biochemistry, University of otre Dame, otre Dame, Indiana Table of Content General Methods S2 Experimental Details and Spectroscopic Data...S2 Presentation of MR Spectral Data 1 MR spectrum of 1d S8 13 C MR spectrum of 1d S9 1 MR spectrum of 4a S10 13 C MR spectrum of 4a S11 1 MR spectrum of 4b S12 13 C MR spectrum of 4b S13 gcsy spectrum of 4b S14 gsqc spectrum of 4b S15 1 MR spectrum of 5b S16 13 C MR spectrum of 5b S17 gcsy spectrum of 5b S18 gsqc spectrum of 5b S19 1 MR spectrum of 4c S20 13 C MR spectrum of 4c S21 1 MR spectrum of 5c S22 13 C MR spectrum of 5c S23 1 MR spectrum of 5d S24 13 C MR spectrum of 5d S25 1 MR spectrum of 5e S26 13 C MR spectrum of 5e S27 1 MR spectrum of 4f S28 13 C MR spectrum of 4f S29 1 MR spectrum of 5f S30 13 C MR spectrum of 5f S31 1 MR spectrum of 5g S32 13 C MR spectrum of 5g S33 -S1-

2 1 MR spectrum of 5h S34 13 C MR spectrum of 5h S35 1 MR spectrum of 5i S36 13 C MR spectrum of 5i S37 1 MR spectrum of 5j S38 13 C MR spectrum of 5j S39 1 MR spectrum of S40 13 C MR spectrum of S41 1 MR spectrum of S42 13 C MR spectrum of S43 1 MR spectrum of S44 13 C MR spectrum of S45 1 MR spectrum of 12 and S46 13 C MR spectrum of 12 and S47 General Methods: Commercially available reagents were used without further purification except as indicated. Reactions were carried out in oven-dried glassware under an atmosphere of dry argon. All reactions were magnetically stirred and monitored by analytical thin-layer chromatography using aluminum-backed 0.2 mm silica gel 60 F-254 plates. Visualization was accomplished by UV light (254 nm), or by staining with potassium permanganate. Flash chromatography was performed with silica gel 60 ( mesh). 1 MR and 13 C MR spectra were recorded at ambient temperature with the residual solvent peaks as internal standards. The line positions of multiplets are given in ppm (δ) and the coupling constants (J) are given as absolute values in ertz. Infrared spectra were recorded with a FT-IR spectrometer and reported as cm -1. All melting points were recorded uncorrected. igh-resolution mass spectra (RMS) data were obtained as specified. Yields refer to chromatographically and spectrographically pure compounds, unless otherwise noted. 1d 3-Phenyl-2-oxa-3-aza-bicyclo[2.2.2]oct-5-ene (1d). To a solution of nitrosobenzene (150 mg, 1.40 mmol) in DCM (3 ml) at 0 o C was added 1,3-cyclohexadiene (0.267 ml, 2.80 mmol), and the reaction mixture was stirred at 0 o C for 30 min. The solvent was removed under reduced pressure and the crude product was purified using silica gel column chromatography (hexanes:etac, 3:1) to afford 1d as a white solid (247 mg, 87% yield). mp: o C; IR (neat): 3054, 2986, 1595, 1486, 1421, 1265, 738, 705 cm -1 ; 1 MR (600 Mz, CDCl 3 ) δ (m, 2 ), (m, 2 ), (m, 1 ), 6.59 (ddd, J = 8.0, 5.9, 1.8 z, 1 ), 6.15 (ddd, J = 7.8, 5.7, 1.5 z, 1 ), (m, 1 ), (m, 1 ), (m, 1 ), (m, 1 ), (m, 1 ), (m, 1 ); 13 C MR (150 Mz, CDCl 3 ) δ 152.5, 131.7, 130.1, 128.5, 122.1, 117.6, 69.3, 56.6, 24.1, Me 4a -S2-

3 (+)-cis-4-(4-methoxyphenylamino)cyclopent-2-enol (4a). To a solution of nitrosobenzene (100 mg, 0.93 mmol) in DCM (2 ml) at rt was added 1,3-cyclopentadiene (0.15 ml, 1.86 mmol) and stirred for 30 min until nitrosobenzene was consumed (TLC analysis). Then methanol (3 ml) was added, followed by the addition of In(Tf) 3 (262 mg, 0.47 mmol). The mixture was stirred under Ar for 12 h, then solvent was removed under reduced pressure. Water and EtAc (3 + 5 ml) were added and separated. The aqueous layer was extracted with EtAc (3 x 5 ml). The combined organic layers were washed with brine, dried over a 2 S 4, filtered and concentrated by rotary evaporation. The crude product was purified using silica gel column chromatography (hexanes:etac, 1:1) to afford 4a as a yellow oil (51.3 mg, 31% yield in two steps). 1 MR (600 Mz, DMS-d 6 ) δ 6.70 (d, J = 8.8 z, 2 ), 6.57 (d, J = 8.8 z, 2 ), 5.85 (br m, 2 ), 5.14 (d, J = 8.5 z, 1 ), 4.88 (d, J = 5.8 z, 1 ), (m, 1 ), (m, 1 ), 3.63 (s, 3 ), 2.66 (dt, J = 12.9, 7.3 z, 1 ), 1.29 (dt, J = 12.9, 5.9 z, 1 ); 13 C MR (150 Mz, DMS-d 6 ) δ 150.6, 142.4, 136.3, 133.7, 114.5, 113.6, 73.6, 57.2, 55.2, 41.8; RMS (ESI) [M + ] + C calcd for , found General procedure for In(Tf) 3 -assisted nucleophilic aromatic substitution of 1d with alcohols. A solution of cycloadduct 1d (50 mg, 0.27 mmol) in alcohol (2 ml) was treated with anhydrous In(Tf) 3 (75 mg, 0.13 mmol) and quickly heated to 70 o C. The reaction mixture was stirred under Ar until 1d was consumed (TLC analysis). Then the mixture was cooled to rt and concentrated in vacuo to a slurry. Water (3 ml) and EtAc (5 ml) were added and separated. The aqueous layer was extracted with EtAc (3 x 5 ml). The combined organic layers were washed with brine, dried over a 2 S 4 and filtered. The solvent was removed in vacuo and the residue was purified by silica gel column chromatography. Me Me 4b 5b (+)-cis-4-(2-methoxyphenylamino)cyclohex-2-enol (4b) and (+)-cis-4-(4-methoxyphenylamino)cyclohex-2-enol (5b). Prepared following the general procedure with 2 ml of Me. The crude product was purified by column chromatography using solvent gradient from hexanes:etac (1:1) to afford 4b (6.5 mg, 11% yield) as a colorless oil, then hexanes:etac (1:1 to 1:2) to afford 5b (35.3 mg, 60%) as a colorless oil (71% total combined yield). Products ratio was determined by 1 MR spectroscopy of the crude reaction mixture. 4b: IR (neat): 3424, 3019, 1511, 1424, 1215, 1041, 755, 669 cm -1 ; 1 MR (600 Mz, DMS-d 6 ) δ 6.82 (dd, J = 8.0, 1.2 z, 1 ), 6.77 (ddd, J = 8.0, 7.6, 1.2 z, 1 ), 6.62 (dd, J = 8.2, 1.4 z, 1 ), 6.56 (ddd, J = 8.2, 7.6, 1.4 z, 1 ), (m, 1 ), (m, 1 ), 4.76 (d, J = 5.9 z, 1 ), 4.31 (d, J = 9.1 z, 1 ), 3.98 (br m, 1 ), 3.90 (br m, 1 ), 3.77 (s, 3 ), (m, 3 ), (m, 1 ); 13 C MR (150 Mz, DMS-d 6 ) δ 146.4, 136.5, 133.8, 129.2, 121.0, 115.9, 109.8, 63.7, 55.3, 46.4, 28.5, 24.4; RMS (ESI) [M + a] + calcd for C a , found b: IR (neat): 3404, 3019, 2977, 1521, 1476, 1424, 1216, 1046, 772, 669 cm -1 ; 1 MR (600 Mz, DMS-d 6 ) δ 6.69 (d, J = 9.1 z, 2 ), 6.56 (dd, J = 9.1 z, 2 ), 5.73 (m, 1 ), 5.67 (m, 1 ), 5.06 (d, J = 8.5 z, 1 ), 4.74 (d, J = 4.4 z, 1 ), 3.99 (br m, 1 ), 3.72 (br m, 1 ), 3.63 (s, 3 ), (m, 4 ); 13 C MR (150 Mz, DMS-d 6 ) δ 150.5, 142.0, 132.9, 129.8, 114.6, 113.6, 63.6, 55.2, 47.5, 28.6, 24.5; RMS (ESI) [M + a] + calcd for C a , found c 5c (+)-cis-4-(2-isopropoxyphenylamino)cyclohex-2-enol (4c) and -S3-

4 (+)-cis-4-(4-isopropoxyphenylamino)cyclohex-2-enol (5c). Prepared following the general procedure with 2 ml of i Pr. The crude product was purified by column chromatography using solvent gradient from hexanes:etac (1:1) to afford 4c (4.7 mg, 7% yield) as a colorless oil, then hexanes:etac (1:1 to 1:2) to afford 5c (33.5 mg, 51%) as a yellowish oil (58% total combined yield). Products ratio was determined by 1 MR spectroscopy of the crude reaction mixture. 4c: IR (neat): 3405, 3054, 2986, 1599, 1508, 1422, 1265, 896, 705 cm -1 ; 1 MR (600 Mz, CDCl 3 ) δ (m, 1 ), (m, 1 ), (m, 2 ), (m, 2 ), (m, 1 ), 4.30 (br s, 1 ), 4.24 (br s, 1 ), 3.94 (m, 1 ), (m, 2 ), (m, 2 ), 1.35 (d, J = 6.2 z, 6 ); 13 C MR (150 Mz, CDCl 3 ) δ 145.2, 138.0, 132.1, 131.9, 121.3, 116.6, 112.9, 110.7, 70.9, 65.5, 47.9, 29.3, 25.0, 22.5, 22.5; RMS (ESI) [M + ] + calcd for C , found c: IR (neat): 3400, 3054, 2987, 1607, 1508, 1421, 1265, 896, 738 cm -1 ; 1 MR (600 Mz, CDCl 3 ) δ 6.79 (d, J = 8.8 z, 2 ), 6.58 (dd, J = 8.8 z, 2 ), (m, 2 ), (m, 1 ), 4.22 (m, 1 ), 3.87 (m, 1 ), (m, 2 ), (m, 2 ), 1.30 (d, J = 6.2 z, 6 ); 13 C MR (150 Mz, CDCl 3 ) δ 150.3, 141.3, 132.0, 131.8, 118.2, 114.9, 71.3, 65.3, 49.0, 29.1, 25.0, 22.3; RMS (ESI) [M + ] + calcd for C , found d (+)-cis-4-(4-(exyloxy)phenylamino)cyclohex-2-enol (5d). Prepared following the general procedure with 2 ml of 1-hexanol. The crude product was purified by column chromatography using solvent hexanes:etac (1:1 to 1:2) to afford 5d (43.1 mg, 56% yield) as a white glass. IR (neat): 3440, 3054, 2987, 1510, 1421, 1265, 896, 705 cm -1 ; 1 MR (600 Mz, CDCl 3 ) δ 6.79 (d, J = 8.9 z, 2 ), 6.59 (d, J = 8.9 z, 2 ), (m, 2 ), 4.21 (m, 1 ), 3.89 (t, J = 6.6 z, 2 ), 3.87 (m, 1 ), (m, 2 ), (m, 4 ), (m, 2 ), (m, 4 ), 0.91 (m, 3 ); 13 C MR (150 Mz, CDCl 3 ) δ 151.9, 141.0, 132.0, 131.9, 116.0, 115.1, 68.9, 65.4, 49.2, 31.8, 29.6, 29.1, 25.9, 25.0, 22.8, 14.2; RMS (ESI) [M + ] + calcd for C , found e (+)-cis-4-(4-tert-butoxyphenylamino)cyclohex-2-enol (5e). Prepared following the general procedure with 2 ml of t Bu. The crude product was purified by column chromatography using solvent hexanes:etac (1:2) to afford 5e (26.2 mg, 37% yield) as a yellowish oil. IR (neat): 3430, 3054, 2987, 1642, 1512, 1421, 1265, 896 cm -1 ; 1 MR (600 Mz, CDCl 3 ) δ 6.69 (d, J = 8.8 z, 2 ), 6.51 (d, J = 8.8 z, 2 ), 5.83 (m, 1 ), 5.75 (m, 1 ), 4.00 (m, 1 ), 3.81 (m, 1 ), (m, 4 ), 1,23 (s, 9 ); 13 C MR (150 Mz, CDCl 3 ) δ 147.9, 141.2, 133.5, 130.5, 116.4, 115.3, 74.2, 65.3, 48.5, 28.5, 28.3, 25.4; RMS (ESI) [M + a] + calcd for C a , found f 5f (+)-cis-4-(2-(allyloxy)phenylamino)cyclohex-2-enol (4f) and (+)-cis-4-(4-(allyloxy)phenylamino)cyclohex-2-enol (5f). Prepared following the general procedure with 2 ml of allyl alcohol. The crude product was purified by column chromatography using solvent gradient from hexanes:etac (1:1) to afford 4f (9.5 mg, 8 % yield) as a yellowish oil, then hexanes:etac (1:1 to 1:2) to afford 5f (53.0 mg, 60%) as a yellowish glass (68% total combined yield). Products ratio was determined by 1 MR -S4-

5 spectroscopy of the crude reaction mixture. 4f: IR (neat): 3442, 3054, 2986, 1422, 1265, 909, 744, 650 cm -1 ; 1 MR (600 Mz, CDCl 3 ) δ 6.87 (m, 1 ), 6.79 (dd, J = 8.4, 1.5 z, 1 ), 6.65 (m, 2 ), (m, 1 ), 5.92 (m, 2 ), 5.39 (ddd, J = 17.3, 3.1, 1.6 z, 1 ), 5.29 (ddd, J = 10.4, 2.8, 1.4 z, 1 ), 4.57 (dt, J = 5.4, 1.5 z, 2 ), 4.34 (br s, 1 ), 4.23 (br m, 1 ), 3.96 (m, 1 ), (m, 2 ), (m, 2 ); 13 C MR (150 Mz, CDCl 3 ) δ 146.1, 137.2, 133.7, 132.1, 131.9, 121.7, 117.8, 116.6, 111.4, 110.6, 69.4, 65.5, 47.7, 29.2, 25.0; RMS (ESI) [M + ] + calcd for C , found f: IR (neat): 3447, 3054, 2987, 1509, 1422, 1265, 1026, 896, 821, 748 cm -1 ; 1 MR (600 Mz, CDCl 3 ) δ 6.81 (d, J = 8.8 z, 2 ), 6.58 (d, J = 8.8 z, 2 ), (m, 1 ), 5.90 (m, 2 ), 5.40 (ddd, J = 17.3, 3.1, 1.6 z, 1 ), 5.26 (ddd, J = 10.6, 2.6, 1.5 z, 1 ), 4.47 (dt, J = 5.3, 1.5 z, 2 ), 4.23 (br m, 1 ), 3.96 (m, 1 ), 4.22 (m, 1 ), 3.87 (m, 1 ), (m, 2 ), (m, 2 ); 13 C MR (150 Mz, CDCl 3 ) δ 151.4, 141.3, 134.0, 132.0, 132.0, 117.5, 116.3, 116.0, 115.0, 114.9, 69.8, 65.4, 49.1, 29.1, 25.1; RMS (ESI) [M + ] + calcd for C , found g (+)-cis-4-(4-(propynyloxy)phenylamino)cyclohex-2-enol (5g). Prepared following the general procedure with 2 ml of propargyl alcohol. The crude product was purified by column chromatography using hexanes:etac (1:1) to afford 5g (35.1 mg, 58% yield) as a yellowish oil. IR (neat): 3402, 3054, 2987, 1509, 1421, 1265, 1034, 896, 705 cm -1 ; 1 MR (600 Mz, CDCl 3 ) δ 6.87 (d, J = 8.8 z, 2 ), 6.59 (d, J = 8.8 z, 2 ), 5.89 (m, 2 ), 4.62 (d, J = 2.3 z, 2 ), 4.22 (m, 1 ), 3.88 (m, 1 ), 2.50 (t, J = 2.6 z, 1 ), (m, 2 ), (m, 2 ); 13 C MR (150 Mz, CDCl 3 ) δ 150.2, 142.0, 132.1, 131.8, 116.8, 114.7, 79.3, 75.3, 65.4, 57.0, 48.9, 29.1, 25.0; RMS (ESI) [M + a] + calcd for C a , found h (+)-cis-4-(4-(benzyloxy)phenylamino)cyclohex-2-enol (5h). A solution of cycloadduct 1d (50 mg, 0.27 mmol) in TF (2 ml) was treated with benzyl alcohol (0.14 ml, 1.33 ml) and anhydrous In(Tf) 3 (75 mg, 0.13 mmol). The reaction was quickly heated to 70 o C. The reaction mixture was stirred under Ar until 1d was consumed (TLC analysis). Then the mixture was cooled to rt and concentrated in vacuo to a slurry. Water (3 ml) and EtAc (5 ml) were added and separated. The aqueous layer was extracted with EtAc (3 x 5 ml). The combined organic layers were washed with brine, dried over a 2 S 4 and filtered. The solvent was removed in vacuo and the residue was purified by silica gel column chromatography using solvent hexanes:etac (2:3) to afford 5h (43.2 mg, 55% yield) as a white solid. mp: o C; IR (neat): 3413, 3055, 1640, 1509, 1422, 1264, 895, 748 cm -1 ; 1 MR (600 Mz, CDCl 3 ) δ (m, 2 ), (m, 2 ), (m, 1 ), 6.86 (d, J = 8.9 z, 2 ), 6.59 (d, J = 8.9 z, 2 ), (m, 2 ), 5.00 (s, 2 ), 4.22 (m, 1 ), 3.87 (m, 1 ), 3.41 (br s, 1 ), (m, 2 ), (m, 2 ); 13 C MR (150 Mz, CDCl 3 ) δ 151.6, 141.4, 137.7, 132.0, 131.9, 128.6, 127.9, 127.6, 116.4, 114.9, 71.0, 65.3, 49.0, 29.1, 25.0; RMS (ESI) [M + ] + calcd for C , found Me 5i (+)-cis-4-(4-(4-methoxybenzyloxy)phenylamino)cyclohex-2-enol (5i). Prepared following the procedure for synthesis of 5h. Crude material was purified by silica gel column chromatography using solvent hexanes:etac -S5-

6 (1:2) to afford 5i (42.8 mg, 49% yield) as a white glass. IR (neat): 3415, 3054, 2987, 1510, 1422, 1265, 896, 705 cm -1 ; 1 MR (600 Mz, CDCl 3 ) δ 7.35 (d, J = 8.8 z, 2 ), 6.91 (d, J = 8.8 z, 2 ), 6.85 (d, J = 8.9 z, 2 ), 6.59 (d, J = 8.9 z, 2 ), (m, 2 ), 4.92 (s, 2 ), 4.21 (m, 1 ), 3.87 (m, 1 ), 3.82 (s, 3 ), (m, 2 ), (m, 2 ); 13 C MR (150 Mz, CDCl 3 ) δ 159.5, 151.7, 141.3, 132.0, 131.9, 129.7, 129.4, 116.4, 115.0, 114.1, 70.8, 65.3, 55.4, 49.1, 29.1, 25.0; RMS (ESI) [M + ] + calcd for C , found j (+)-cis-4-(4-(4-itrobenzyloxy)phenylamino)cyclohex-2-enol (5j). Prepared following the procedure for synthesis of 5h. Crude material was purified by silica gel column chromatography using solvent hexanes:etac (1:2) to afford 5j (35.5 mg, 39% yield) as a yellow oil. IR (neat): 3435, 3054, 2987, 1604, 1510, 1421, 1348, 1265, 896, 738, 705 cm -1 ; 1 MR (600 Mz, CDCl 3 ) δ 8.24 (d, J = 8.8 z, 2 ), (m, 2 ), 6.84 (d, J = 9.0 z, 2 ), 6.59 (d, J = 9.0 z, 2 ), 5.89 (d, J = 1.3 z, 2 ), 5.10 (s, 2 ), 4.21 (m, 1 ), 3.87 (m, 1 ), 3.43 (br s, 1 ), (m, 2 ), (m, 2 ); 13 C MR (150 Mz, CDCl 3 ) δ 150.8, 147.6, 145.3, 141.9, 132.2, 131.7, 127.7, 123.9, 116.4, 114.8, 69.7, 65.3, 48.9, 29.1, 25.0; RMS (ESI) [M + ] + calcd for C , found (+)-cis-4-(phenylamino)cyclohex-2-enol (6). A solution of cycloadduct 1d (50 mg, 0.26 mmol) in Me (2 ml) was treated with anhydrous CuCl (26.4 mg, 0.26 mmol) and quickly heated to 70 o C. The reaction mixture was stirred under Ar for 3 h. Then the mixture was cooled to rt and concentrated in vacuo to a slurry, then water (3 ml) and EtAc (5 ml) were added and separated. The aqueous layer was extracted with EtAc (3 x 5 ml). The combined organic layers were washed with brine, dried over a 2 S 4 and filtered. The solvent was removed in vacuo and the residue was purified by column chromatography. The crude product was purified by column chromatography using solvent hexanes:etac (1:2) to afford 6 (35.4 mg, 70% yield) as a yellowish solid. mp: o C; IR (neat): 3445, 3054, 2987, 1601, 1503, 1422, 1265, 896, 705 cm -1 ; 1 MR (600 Mz, DMS-d 6 ) δ 7.04 (dd, J = 8.5, 7.3 z, 2 ), 6.60 (d, J = 7.6 z, 2 ), 6.49 (t, J = 7.3 z, 1 ), 5.75 (m, 1 ), 5.68 (m, 1 ), 5.53 (d, J = 8.5 z, 1 ), 4.76 (d, J = 4.4 z, 1 ), 4.00 (m, 1 ), 3.81 (m, 1 ), (m, 4 ); 13 C MR (150 Mz, DMS-d 6 ) δ 146.7, 132.1, 131.4, 129.3, 117.5, 113.2, 65.2, 47.8, 28.9, (2-Pyridyl)-2-oxa-3-aza-bicyclo[2.2.2]oct-5-ene (10). To a solution of 2-nitrosopyridine (100 mg, 0.93 mmol) in DCM (3 ml) at 0 o C was added 1,3-cyclohexadiene (0.178 ml, 1.87 mmol), and the reaction mixture was stirred at 0 o C for 30 min. The solvent was removed under reduced pressure and the crude product was purified using silica gel column chromatography (hexanes:etac, 5:1) to afford 10 as a white solid (165 mg, 95% yield). mp: o C; 1 MR (600 Mz, CDCl 3 ) δ 8.20 (ddd, J = 4.8, 1.9, 0.9 z, 1 ), 7.51 (ddd, J = 9.2, 7.3, 1.9 z, 1 ), 6.91 (dt, J = 8.4, 1.0 z, 1 ), 6.76 (ddd, J = 7.2, 4.8, 1.0 z, 1 ), 6.48 (ddd, J = 8.2, 5.8, 1.9 z, 1 ), 6.32 (ddd, J = 8.2, 5.8, 1.6 z, 1 ), 5.29 (m, 1 ), 4.72 (m, 1 ), (m, 2 ), (m, 1 ), S6-

7 (m, 1 ); 13 C MR (150 Mz, CDCl 3 ) δ 164.3, 147.4, 137.6, 132.1, 131.0, 116.7, 111.5, 69.9, 52.3, 24.4, Me Me anti-1-(-(2-pyridyl)--hydroxyamino)-2-methoxycyclohex-3-ene (12) and anti-1-(-(2-pyridyl)--hydroxyamino)-4-methoxycyclohex-2-ene (13). A solution of cycloadduct 10 (62 mg, 0.33 mmol) in Me (2 ml) was treated with anhydrous In(Tf) 3 (92 mg, 0.16 mmol) and quickly heated to 70 o C. The reaction mixture was stirred under Ar for 3 h until 10 was consumed. The mixture was cooled to rt and concentrated in vacuo to a slurry, then water (3 ml) and EtAc (5 ml) were added and separated. The aqueous layer was extracted with EtAc (3 x 5 ml). The combined organic layers were washed with brine, dried over a 2 S 4 and filtered. The solvent was removed in vacuo and the residue was purified by column chromatography. The crude product was purified by column chromatography using solvent gradient from hexanes:etac (3:1) to afford 12 (24.3 mg, 33% yield) as a white glass, and hexanes:etac (2:1) to afford a mixture of 12 and 13 (40.9 mg, 57% yield) as a white glass (90% total combined yield). Products ratio was determined by 1 MR spectroscopy of the crude reaction mixture. 12: IR (neat): 3416, 3020, 1520, 1421, 1363, 1216, 1090, 766, 669 cm -1 ; 1 MR (600 Mz, DMS-d 6 ) δ 8.99 (s, 1 ), 8.11 (ddd, J = 4.8, 1.9, 0.9 z, 1 ), 7.58 (ddd, J = 9.1, 7.2, 1.9 z, 1 ), 7.05 (dt, J = 8.4, 0.9 z, 1 ), 6.69 (ddd, J = 7.2, 4.8, 0.9 z, 1 ), 5.77 (m, 1 ), 5.71 (m, 1 ), 4.59 (ddd, J = 12.3, 8.9, 3.4 z, 1 ), 4.24 (m, 1 ), 3.21 (s, 3 ), 2.08 (br m, 2 ), (m, 1 ), (m, 1 ); 13 C MR (150 Mz, DMS-d 6 ) δ 163.0, 147.0, 137.4, 128.8, 127.8, 114.1, 108.5, 74.7, 58.9, 54.7, 24.8, 23.2; RMS (ESI) [M + ] + calcd for C , found : IR (neat): 3406, 3020, 1521, 1424, 1216, 1046, 766, 669 cm -1 ; 1 MR (600 Mz, DMS-d 6 ) δ 8.96 (s, 1 ), 8.15 (ddd, J = 4.8, 1.9, 0.9 z, 1 ), 7.61 (ddd, J = 9.1, 7.2, 1.9 z, 1 ), 7.06 (dt, J = 8.4, 0.9 z, 1 ), 6.75 (ddd, J = 7.2, 4.8, 0.9 z, 1 ), 5.84 (m, 1 ), 5.62 (m, 1 ), 5.12 (m, 1 ), 3.84 (m, 1 ), 3.26 (s, 3 ), 2.15 (br m, 1 ), (m, 2 ), (m, 1 ); 13 C MR (150 Mz, DMS-d 6 ) δ 162.5, 147.1, 137.6, 131.3, 130.9, 114.8, 109.2, 74.9, 56.3, 54.8, 27.9, 22.5; RMS (ESI) [M + ] + calcd for C , found S7-

8 1.56 1d ( 1 MR, 600 Mz, CDCl 3 ) S8-

9 1d ( 13 C MR, 150 Mz, CDCl 3 ) S9-

10 5.0 -S Me 4a ( 1 MR, 600 Mz, DMS-d 6 )

11 Me 4a ( 13 C MR, 150 Mz, DMS-d 6 ) S11-

12 Me 4b ( 1 MR, 600 Mz, DMS-d 6 ) S12-

13 Me 4b ( 13 C MR, 150 Mz, DMS-d 6 ) S13-

14 Spectrum Title: Std proton Frequency (Mz): (f2) (f1) riginal Points Count: (f2) 1153 (f1) 256 Actual Points Count: (f2) 2048 (f1) 1024 Acquisition Time (sec): (f2) (f1) Spectral Width (ppm): (f2) (f1) Pulse Program: gcsy umber of Scans: Me b (gcsy, DMS-d 6 ) ppm (f1 8.0 ppm (f2) S14-

15 Spectrum Title: Std proton Frequency (Mz): (f2) (f1) riginal Points Count: (f2) 2048 (f1) 512 Actual Points Count: (f2) 2048 (f1) 2048 Acquisition Time (sec): (f2) (f1) Spectral Width (ppm): (f2) (f1) Pulse Program: gsqc umber of Scans: 16 Me 150 4b (gsqc, DMS-d 6 ) ppm (f1 8.0 ppm (f2) S15-

16 Me 5b ( 1 MR, 600 Mz, DMS-d 6 ) S16-

17 Me 5b ( 13 C MR, 150 Mz, DMS-d 6 ) S17-

18 Spectrum Title: Std proton Frequency (Mz): (f2) (f1) riginal Points Count: (f2) 1153 (f1) 256 Actual Points Count: (f2) 2048 (f1) 1024 Acquisition Time (sec): (f2) (f1) Spectral Width (ppm): (f2) (f1) Pulse Program: gcsy umber of Scans: Me 5b (gcsy, DMS-d 6 ) ppm (t1 8.0 ppm (t2) S18-

19 Spectrum Title: new experiment Frequency (Mz): (f2) (f1) riginal Points Count: (f2) 2048 (f1) 512 Actual Points Count: (f2) 2048 (f1) 2048 Acquisition Time (sec): (f2) (f1) Spectral Width (ppm): (f2) (f1) Pulse Program: gsqc umber of Scans: Me 5b (gsqc, DMS-d 6 ) ppm (f1 ppm (f2) S19-

20 4c ( 1 MR, 600 Mz, CDCl 3 ) ppm (f1) S20-

21 4c ( 13 C MR, 150 Mz, CDCl 3 ) 200 ppm (f1) S21-

22 5c ( 1 MR, 600 Mz, CDCl 3 ) Chemical Shift (ppm) -S22-

23 5c ( 13 C MR, 150 Mz, CDCl 3 ) S23-

24 5d ( 1 MR, 600 Mz, CDCl 3 ) ppm (f1) S24-

25 5d ( 13 C MR, 150 Mz, CDCl 3 ) ppm (f1) S25-

26 5e ( 1 MR, 600 Mz, CDCl 3 ) S26-

27 5e ( 13 C MR, 150 Mz, CDCl 3 ) S27-

28 4f ( 1 MR, 600 Mz, CDCl 3 ) ppm (f1) S28-

29 4f ( 13 C MR, 150 Mz, CDCl 3 ) ppm (f1) S29-

30 5f ( 1 MR, 600 Mz, CDCl 3 ) 10.0 ppm (f1) S30-

31 5f ( 13 C MR, 150 Mz, CDCl 3 ) ppm (f1) S31-

32 5g ( 1 MR, 600 Mz, CDCl 3 ) S32-

33 5g ( 13 C MR, 150 Mz, CDCl 3 ) S33-

34 5h ( 1 MR, 600 Mz, CDCl 3 ) S34-

35 5h ( 13 C MR, 150 Mz, CDCl 3 ) S35-

36 Me 5i ( 1 MR, 600 Mz, CDCl 3 ) S36-

37 Me 5i ( 13 C MR, 150 Mz, CDCl 3 ) S37-

38 2 5j ( 1 MR, 600 Mz, CDCl 3 ) S38-

39 2 5j ( 13 C MR, 150 Mz, CDCl 3 ) S39-

40 6 ( 1 MR, 600 Mz, DMS-d 6 ) S40-

41 6 ( 13 C MR, 150 Mz, DMS-d 6 ) S41-

42 10 ( 1 MR, 600 Mz, CDCl 3 ) S42-

43 10 ( 13 C MR, 150 Mz, CDCl 3 ) S43-

44 Me 12 ( 1 MR, 600 Mz, DMS-d 6 ) S44-

45 Me 12 ( 13 C MR, 150 Mz, DMS-d 6 ) ppm (f1) S45-

46 + Me Me ( 1 MR, 600 Mz, DMS-d 6 ) S46-

47 + Me Me ( 13 C MR, 150 Mz, DMS-d 6 ) S47-