Stereocontrolled Synthesis of Functionalized cis- Reactions of Azomethine Imines

Transcription

1 Stereocontrolled Synthesis of Functionalized cis- Cyclopentapyrazolidines by 1,3-Dipolar Cycloaddition Reactions of Azomethine Imines Joshua Gergely, Jeremy B. Morgan, and Larry E. verman* Department of Chemistry, 516 Rowland Hall, University of California, Irvine, CA Supporting Information (123 pages) Part A: Experimental procedures and tabulated characterization data for new compounds not reported in the experimental section: pp S2 S22. Part B: 1 H and 13 C NMR Spectra for all reported compounds. 1 H 1 H CSY and NESY data for compound 41: pp S22 S122. Part C: X-Ray models of compounds 34, 35a, and 60: p S123.

2 Part A: Experimental procedures and tabulated characterization data for new compounds not reported in the experimental section. 6-Hydroxy-2-methoxy hex-2-enoic acid methyl ester (7). Freshly distilled DBU (4.0 ml, 26.6 mmol) was added dropwise to a vigorously stirred suspension of lithium chloride (1.1 g, 26.6 mmol) and phosphonate 6 3 (7.1 g, 26.6 mmol) in MeCN (450 ml), and the resulting suspension was maintained at 0 C for 1 h. The mixture was allowed to warm to room temperature and was maintained for 1 h before being recooled to 0 C. Tetrahydrofuran-2-ol 4 (2.8 g, 31.9 mmol) was added dropwise. The mixture was maintained at 0 C for 15 min and then was allowed to warm to room temperature and was maintained for 2 h. Saturated aqueous sodium bicarbonate (20 ml) was added to quench the reaction, and then approximately 350 ml of MeCN was removed in vacuo. Water (100 ml) was added and the biphasic mixture was extracted with Et 2 (3 75 ml). The combined organic phases were washed with brine (50 ml), dried (MgS 4 ), and concentrated in vacuo. The residue, which contained a ca. 1:1 mixture of E and Z olefin isomers, was purified by silica gel chromatography (80% Et 2 /pentane). Mixed fractions containing both E and Z isomers were combined and resubjected to chromatography. The desired Z alkene isomer 7 was isolated as a colorless oil (1.96 g, 43%) along with the E alkene isomer (1.66 g, 36%): 1 H NMR (400 MHz, CDCl 3 ) 6.26 (t, J = 7.8 Hz, 1 H), 3.78 (s, 3 H), 3.67 (s, 3 H), (m, 2 H), 2.34 (q, J = 7.47 Hz 2 H), 1.69 (quint, J = 6.90 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) 201.2, 164.1, 147.0, 126.2, 60.2, 52.1, 42.8, 18.4; IR (film) 3430, 1723, 1650, 1437 cm -1 ; Anal. Calcd for C 8 H 12 2 : C, 55.16; H, Found: C, 55.15; H, Methoxy-6-oxohex-2-enoic acid methyl ester (8). Alcohol 7 (1.9 g, 10.7 mmol) was added dropwise to a vigorously stirred suspension of Dess Martin periodinane (4.5 g, 10.7 mmol) in CH 2 Cl 2 (80 ml) at 0 ºC. The mixture was allowed to warm to room temperature and was maintained for 1 h. Solids were removed by filtration through Celite, and CH 2 Cl 2 was removed in vacuo. The residue was purified by silica gel chromatography (40% Et 2 /pentane) to give 1.7 g (91%) of 8 as a pale yellow oil: 1 H NMR (400 MHz, CDCl 3 ) 9.78 (t, J = 1.1 Hz, 1 H), 6.20 (t, J = 7.4 Hz, 1 H), 3.77 (s, 3 H), 3.67 (s, 3 H), (m, 4 H); 13 C NMR (100 MHz, CDCl 3 ) 201.2, 164.1, 147.0, 126.2, 60.2, 52.1, 42.8, 18.4; IR S2

3 (film) 2845, 2729, 1720, 1651, 1436 cm -1. Anal. Calcd for C 8 H 12 4 : C, 55.81; H, Found: C, 55.91; H, (tert-butyldimethylsilanyloxy)dimethoxyphosphorylacetic acid isopropyl ester (10): A solution of freshly distilled dimethylphosphite (20.2 ml, 220 mmol) in PhH (400 ml) was added in one portion to dihydroxyacetic acid isopropyl ester (23.6 g, 176 mmol), prepared according to the method of Zhong and Shing. 1 The reaction flask was fitted with a Dean Stark trap, and the solution was maintained at 115 ºC for 18 h. Excess dimethylphosphite was removed in vacuo to give a viscous yellow oil (39.7 g). A portion of the crude residue (12 g) was dissolved in DMF (90 ml). Imidazole (9.0 g, 132 mmol) was added in one portion followed by tert-butyldimethylsilyl chloride (10.0 g, 66 mmol), and the solution was maintained at room temperature for 16 h. Saturated aqueous sodium bicarbonate (50 ml) was added to quench the reaction which was then diluted with water (700 ml) and extracted with ethyl acetate (3 75 ml). The combined organic phases were washed with water (2 500 ml) and brine (2 100 ml), dried (MgS 4 ), and concentrated in vacuo to give a yellow oil. The residue was purified by silica gel chromatography (50% ethyl acetate/hexanes) to give 13.9 g (76% over two steps) of 10 as a pale yellow oil: 1 H NMR (400 MHz, CDCl 3 ) 5.12 (sept, J = 6.3 Hz, 1 H), 4.56 (d, J = 17.9 Hz, 1 H), 3.83 (d, J = 7.7 Hz, 3 H), 3.80 (d, J = 7.7 Hz, 3 H) 1.28 (d, J = 6.3 Hz, 3 H), 1.26 (d, J = 6.3 Hz, 3 H), 0.91 (s, 9 H), 0.10 (s, 3 H), 0.09 (s, 3 H); 13 C NMR (100 MHz, CDCl 3 ) 167.5, 70.9 (d, J = 161 Hz), 69.8, 54.3 (d, J = 6.7 Hz), 54.1 (d, J = 6.7 Hz), 25.7, 21.9, 21.7, 18.5, 5.2, 5.4; IR (film) 1750, 1464, 1473, 1260 cm -1 ; HRMS (ESI) m/z Calcd for C 13 H 30 6 PSi (M+H) , Found Anal. Calcd for C 13 H 29 6 PSi: C, 45.87; H, Found: C, 45.96; H, [Benzylcarbamoyl (tert-butyldimethylsilanyloxy) methyl] phosphonic acid dimethyl ester (11): Following the procedure to prepare phosphonate 10, N-Benzyl-2-oxo-acetamide 2 (1.2 g, 6.6 mmol) gave 2.9 g of 11 (89% over two steps) as a thick pale oil: 1 H NMR (500 MHz, CDCl 3 ) (m, 5 H), 6.90 (br s, 1 H), 4.56 (dd, J = 14.8, 6.5 Hz, 1 H), 4.50 (d, J = 15.9 Hz, 1 H), 4.43 (dd, J = 14.8, 6.5 Hz, 1 H), 3.80 (dd, J = 10.7, 1.6 Hz, 6 H), 0.84 (s, 9 H), 0.13 (s, 3 H), 0.07 (s, 3H); 13 C NMR (125 MHz, S3

4 CDCl 3 ) (d, J = 2.5 Hz), 137.7, 128.8, 127.9, 127.7, 71.6 (d, J = 160 Hz), 54.4 (d, J = 7.5 Hz), 53.7 (d, J = 7.5 Hz), 43.4, 25.7, 18.3, 5.1, 5.5; IR (film) 3427, 3300, 2857, 1677, 1521 cm -1 ; HRMS (ESI) m/z Calcd for C 17 H 30 NaN 5 PSi (M+Na) , Found (tert-butyldimethylsilanyloxy) (dimethoxy phosphoryl) thioacetic acid S-ethyl ester (12): Ethane thiol (300 ml, 4.2 mmol) was added to a solution of trimethyl aluminum (228 mg, 4.0 mmol) in benzene (30 ml) at 0 ºC and the solution was maintained for 30 min. The solution was allowed to warm to room temperature, a solution of phosphonate 9 3 (624 mg, 2.0 mmol) in benzene (10 ml) was added dropwise, and the resulting solution was maintained at room temperature overnight. The solution was then quenched with 1 N aqueous HCl (40 ml) and the aqueous phase was extracted with ethyl acetate (2 20 ml). The combined organics were dried over MgS 4, concentrated in vacuo, and purified via flash chromatography (Si 2 gel, 50% EtAc/hexanes) to give 240 mg (35%) of thioester 12 as a thick pale oil: 1 H NMR (500 MHz, CDCl 3 ) 4.53 (dd, J = 17.1, 1.6 Hz, 1 H), 3.77 (dd, J = 10.7, 1.6 Hz, 3 H), 3.74 (dd, J = 10.7, 1.6 Hz, 3 H), 2.82 (qd, J = 7.4, 1.6 Hz, 2 H), 1.19 (td, J = 7.4, 1.6 Hz, 3 H), 0.91 (d, J = 1.6 Hz, 9 H), 0.11 (d, J = 1.4 Hz, 3 H), 0.09 (d, J = 1.4 Hz, 3 H); 13 C NMR (125 MHz, CDCl 3 ) 198.9, 76.8 (d, J = 158 Hz), 54.2 (d, J = 65 Hz), 54.1 (d, J = 65 Hz), 25.6 (d, J = 16.4 Hz), 22.9, 18.4, 14.4, 5.2, 5.4; IR (film) 1728, 1671, 1608, 1519, 1473 cm (tert-Butyldimethylsilanyloxy)-7-methoxy octa-2,6-dienedioic acid dimethyl ester (13): Freshly distilled DBU (0.27 ml, 1.8 mmol) was added dropwise to a vigorously stirred suspension of lithium chloride (81 mg, 1.9 mmol), phosphonate ester 9 (593 mg, 1.9 mmol), and MeCN (13 ml), and the mixture was maintained at 0 C for 1 h. A solution of aldehyde 8 (218 mg, 1.3 mmol) in MeCN (4 ml) was added dropwise. The mixture was maintained at 0 C for 15 min and then was allowed to warm to room temperature and maintained for 5 h. Saturated aqueous sodium bicarbonate (5 ml) was added to quench the reaction. Water (50 ml) was added and the biphasic mixture was extracted with ethyl acetate (3 25 ml). The combined organic phases were washed with brine (25 ml), dried (MgS 4 ), and 1 Zhong, Y. -L.; Shing, T. K. M. J. rg. Chem. 1997, 62, Svetkin, Y. V.; Akmanova, N. A.; Murza, M. M. Zhurnal bshchei Khimii 1971, 41, S4

5 concentrated in vacuo. The residue was purified by silica gel chromatography (20% ethyl acetate/hexanes) to give 361 mg (79%) of 13 as a pale yellow oil which contained an inconsequential ca. 7:1 mixture of olefin isomers according to 1 H NMR analysis: 1 H NMR (500 MHz, CDCl 3, major diastereomer) 6.25 (t, J = 7.6 Hz, 1 H), 5.49 (t, J = 7.9 Hz, 1 H), 3.78 (s, 3 H), 3.76 (s, 3 H), 3.67 (s, 3 H) 2.59 (q, J = 7.5 Hz, 2 H), 2.36 (q, J = 7.5 Hz, 2 H), 0.94 (s, 9 H), 0.12 (s, 6 H); 13 C NMR (125 MHz, CDCl 3, major diastereomer) 165.3, 164.4, 146.7, 141.1, 128.2, 127.3, 60.3, 52.1, 51.7, 26.2, 25.9, 25.8, 18.4, 4.7; IR (film) 1726, 1636, 1443, 1255, 1204 cm -1 ; HRMS (ESI) m/z Calcd for C 17 H 30 Na 6 Si (M+Na) , Found Anal. Calcd for C 17 H 30 6 Si: C, 56.95; H, Found: C, 56.98; H, (tert-Butyldimethylsilanyloxy)-7-methoxyocta-2,6-dienedioic acid-1-isopropyl ester-8-methyl ester (14): Following general method A to prepare enoxysilane 13, aldehyde 8 (2.0 g, 11.6 mmol) and phosphonate 10 (5.7 g, 16.9 mmol) gave 3.7 g (82%) of 14 as a pale yellow oil which contained a ca. 6:1 mixture of olefin isomers according to 1 H NMR analysis: 1 H NMR (500 MHz, CDCl 3, major diastereomer) 6.25 (t, J = 7.5 Hz, 1 H), 5.45 (t, J = 7.9 Hz, 1 H), 5.08 (sept, J = 6.3 Hz, 1 H), 3.77 (s, 3 H), 3.76 (s, 3 H), 3.66 (s, 3 H) 2.58 (q, J = 7.5 Hz, 2 H), 2.35 (q, J = 7.4 Hz, 2 H), 1.29 (d, J = 6.3 Hz, 6 H), 0.94 (s, 9 H), 0.09 (s, 6 H); 13 C NMR (125 MHz, CDCl 3, major diastereomer) , , 146.6, 141.5, 128.1, 123.6, 68.4, 60.1, 51.9, 26.1, 25.9, 25.7, 22.0, 18.3, 4.7; IR (film, mixture of diastereomers) 1726, 1636, 1443, 1255, 1204 cm -1 ; HRMS (ESI, mixture of diastereomers) m/z Calcd for C 19 H 34 Na 6 Si (M+Na) , Found Benzylcarbamoyl-7-(tert-butyldimethylsilanyloxy)-2-methoxy hepta-2,6-dienoic acid methyl ester (15): Following general method A to prepare enoxysilane 13, aldehyde 8 (160 mg, 0.92 mmol) and phosphonate 11 (720 mg, 1.86 mmol) gave 270 mg (68%) of 15 as a pale yellow oil which contained a ca. 17:1 mixture of olefin isomers according to 1 H NMR analysis: 1 H NMR (500 MHz, CDCl 3, major diastereomer) (m, 5 H), 6.80 (br s, 1 H), 6.28 (t, J = 7.6 Hz, 1 H), 5.24 (t, J = 7.7 Hz, 1 H), 3.75 (s, 3 H), 3.65 (s, 3 H), 2.79 (q, J = 7.4 Hz, 2 H), 2.37 (q, J = 7.5 Hz, 2 H), 0.86 (s, 9 H), 0.13 (s, 6 H); 3 (a) Nakamura, E. Tetrahedron Lett. 1981, 22, 663. (b) Horne, D.; Gaudino, J.; Thompson, W. J. Tetrahedron Lett. 1984, 25, S5

6 13 C NMR (125 MHz, CDCl 3, major diastereomer) 164.5, 164.4, 146.4, 142.1, 138.2, 128.8, 128.7, 127.9, 127.6, 120.1, 60.2, 52.0, 43.2, 26.1, 25.8, 18.1, 4.1, 4.6; IR (film) 3441, 1753, 1725, 1677, 1508, 1473 cm -1 ; HRMS (ESI) m/z Calcd for C 23 H 36 N 5 Si (M+H) , Found (tert-Butyldimethylsilanyloxy)-7-ethylsulfanylcarbonyl-2-methoxy hepta-2,6-dienoic acid methyl ester (16): Following general method A to prepare enoxysilane 13, aldehyde 8 (230 mg, 1.3 mmol) and phosphonate 12 (455 mg, 1.3 mmol) gave 390 mg (75%) of 16 as a pale yellow oil which contained a ca. 18:1 mixture of olefin isomers according to 1 H NMR analysis: 1 H NMR (500 MHz, CDCl 3, major diastereomer) 6.29 (t, J = 7.6 Hz, 1 H), 5.16 (t, J = 7.7 Hz, 1 H), 3.75 (s, 3 H), 3.65 (s, 3 H), 2.82 (q, J = 7.4 Hz, 2 H), 2.63 (q, J = 7.4 Hz, 2 H), 2.33 (q, J = 7.5 Hz, 2 H), 1.24 (t, J = 7.5 Hz, 3 H), 0.98 (s, 9 H), 0.17 (s, 6 H); 13 C NMR (125 MHz, CDCl 3, major diastereomer) 192.3, 164.3, 146.6, 145.5, 128.2, 118.4, 60.3, 52.0, 25.9, 25.9, 25.5, 22.8, 18.4, 14.7, 4.5; IR (film) 2859, 1728, 1669, 1621 cm -1 ; HRMS (ESI) m/z Calcd for C 18 H 32 Na 5 SSi (M+Na) , Found Methoxy-7-oxooct-2-enedioic acid dimethyl ester (17): Solid cesium fluoride (136 mg, 0.89 mmol) was added in one portion to a solution of enoxysilane 13 (100 mg, 0.28 mmol) and acetic acid (0.1 ml, 1.7 mmol) in MeCN (4 ml). The resulting mixture was stirred vigorously at room temperature for 3 h. Saturated aqueous sodium bicarbonate (10 ml) was added, and the biphasic mixture was extracted with ethyl acetate (2 10 ml). The combined organic phases were washed with brine (5 ml), dried (MgS 4 ), and concentrated in vacuo to give 68 mg (99%) of 17 as an unstable pale yellow oil which was used immediately without further purification: 1 H NMR (500 MHz, CDCl 3 ) 6.20 (t, J = 7.7 Hz, 1 H), 3.87, (s, 3 H), 3.78 (s, 3 H), 3.65 (s, 3 H), 2.88 (t, J = 7.2 Hz, 2 H), 2.29 (q, J = 7.5 Hz, 2 H), 1.78 (quint, J = 7.3 Hz, 2 H); 13 C NMR (125 MHz, CDCl 3 ) 193.8, 164.3, 161.6, 147.1, 127.4, 60.3, 53.2, 52.2, 38.7, 24.6, 22.1; IR (film) 1750, 1723, 1650, 1437, 1260, 1201 cm Methoxy-7-oxooct-2-enedioic acid-8-isopropyl ester-1-methyl ester (18): Following general the method to prepare -keto ester 17, silyl enol ether 14 (0.47 g, 1.2 mmol) gave 0.32 g (99%) of 18 as an unstable pale yellow oil which was used immediately without further purification: 1 H NMR (500 MHz, CDCl 3 ) 6.17 (t, J = 7.7 Hz, 1 H), 5.09 (sept, J = 6.3 Hz, 1 H), 3.74 (s, 3 H), 3.61 (s, 3 H), 2.81 (t, J = 7.3, S6

7 2 H), 2.25 (q, J = 7.5 Hz, 2H), 1.73 (quint, J = 7.3 Hz, 2 H), 1.31 (d, J = 6.3 Hz, 6H); 13 C NMR (125 MHz, CDCl 3 ) 194.5, 164.2, 160.8, 146.9, 127.4, 70.8, 60.1, 52.0, 38.6, 24.6, 22.1, 21.7; IR (film) 1721, 1650, 1449, 1436, 1377 cm (Benzoylhydrazono)-2-methoxy oct-2-enedioic acid-8-isopropyl ester-1-methyl ester (19): Concentrated aqueous hydrochloric acid (1.0 μl) was added to a solution of -keto ester 18 (202 mg, 0.74 mmol) and benzoic hydrazide (101 mg, 0.74 mmol) in EtH (3 ml), and the solution was maintained at room temperature overnight. Sodium bicarbonate (10 mg) was added in one portion. Solids were removed by vacuum filtration, and the solution was concentrated in vacuo. The residue was purified by flash chromatography (30 40% ethyl acetate/hexanes) to give 255 mg (88%) of 19 as a colorless oil: 1 H NMR (500 MHz, CDCl 3 ) (br s, 1 H), 7.89 (d, J = 7.4 Hz, 1 H), 7.54 (t, J = 7.4 Hz, 1 H), 7.46 (t, J = 7.5 Hz, 2 H), 6.24 (t, J = 7.6 Hz, 1 H) 5.17 (sept, J = 6.3 Hz, 1 H), 3.75 (s, 3 H), 3.64 (s, 3 H), 2.64 (t, J = 7.3, 2 H), 2.30 (q, J = 7.4 Hz, 2H), (m, 2 H), 1.33 (d, J = 6.3 Hz, 6H); 13 C NMR (125 MHz, CDCl 3 ) 164.3, 163.9, 162.5, 146.6, 141.1, 132.8, 132.6, 128.9, 128.2, 127.7, 70.5, 60.2, 52.0, 33.5, 26.8, 25.2, 21.8; IR (film) 3272, 1723, 1705, 1685, 1581, 1507 cm -1 ; HRMS (ESI) m/z Calcd for C 20 H 26 NaN 2 6 (M+Na) , Found [(Biphenyl-4-carbonyl)hydrazono]-2-methoxy oct-2-enedioic acid 8-isopropyl ester 1-methyl ester (20): Following general method A to prepare hydrazone 19, -ketoester 18 (83 mg, 0.30 mmol) and 4-phenyl benzoic hydrazide (65 mg, 0.30 mmol) gave 130 mg (91%) of 20 as a colorless oil: 1 H NMR (500 MHz, CDCl 3 ) (br s, 1 H), 7.99 (d, J = 8.4 Hz, 2 H), 7.70 (d, J = 8.4 Hz, 2 H), 7.61 (app d, J = 8.1 Hz, 2 H), 7.46 (app t, J = J = 7.3 Hz, 2 H), 7.39 (tt, J = 7.3, 1.3 Hz, 1 H), 6.27 (t, J = 7.6 Hz, 1 H), 5.21 (sept, J = 6.3 Hz, 1 H), 3.77 (s, 3 H) 3.66 (s, 3 H), 2.67 (app t, J = 7.2 Hz, 2 H), 2.33 (q, J = 7.4 Hz, 2 H), 1.78 (quint, J = 7.4 Hz, 2 H), 1.37 (d, J = 6.3 Hz, 2 H); 13 C NMR (125 MHz, CDCl 3 ) 164.3, 163.7, 162.6, 146.6, 145.4, 141.1, 140.0, 131.4, 129.1, 128.3, 128.3, 127.6, 127.4, 127.3, 70.5, 60.2, 52.0, 33.6, 26.9, 25.3, 21.8; IR (film) 3268, 1724, 1698, 1683, 1609, 1582, 1481 cm -1 ; HRMS (ESI) m/z Calcd for C 26 H 30 NaN 2 6 (M+Na) , Found S7

8 7-(Acetyl-hydrazono)-2-methoxy oct-2-enedioic acid 8-isopropyl ester 1-methyl ester (21): Following general method A to prepare hydrazone 19, -ketoester 18 (130 mg, 0.47 mmol) and acetic hydrazide (42 mg, 0.57 mmol) gave 94 mg of 21 (61%) as a colorless oil: 1 H NMR (500 MHz, CDCl 3 ) (br s, 1 H), 6.26 (t, J = 7.6 Hz, 1 H), 5.14 (sept, J = 6.3 Hz, 1 H), 3.78 (s, 3 H) 3.66 (s, 3 H), 2.52 (t, J = 7.3 Hz, 2 H), 2.30 (q, J = 7.5 Hz, 2 H), 2.29 (s, 3 H), 1.71 (quint, J = 7.5 Hz, 2 H), 1.32 (d, J = 6.3 Hz, 2 H); 13 C NMR (125 MHz, CDCl 3 ) 174.0, 164.4, 161.5, 146.7, 136.1, 128.3, 70.0, 60.3, 52.1, 33.0, 25.9, 25.1, 21.9, 20.1; IR (film) 3268, 1724, 1684, 1653, 1577, 1436 cm -1 ; HRMS (ESI) m/z Calcd for C 15 H 24 NaN 2 6 (M+Na) , Found Methoxy-7-(pent-4-enoyl-hydrazono) oct-2-enedioic acid 8-isopropyl ester 1-methyl ester (22): Following general method A to prepare hydrazone 19, -ketoester 18 (110 mg, 0.40 mmol) and 4- pentenoic hydrazide (46 mg, 0.04 mmol) gave 128 mg (86%) of 22 as a colorless oil: 1 H NMR (500 MHz, CDCl 3 ) 6.24 (t, J = H), 5.86 (ddt, J = 16.9, 10.2, 6.5 Hz, 1 H), (m, 2 H), 4.98 (d, J = 10.2 Hz, 1 H) 3.77 (s, 3 H), 3.63 (s, 3H), 2.76 (t, J = 7.3 Hz, 2 H), 2.49 (t, J = 7.41 Hz, 2 H), 2.41 (q, J = 7.3 Hz, 2 H), 2.28 (q, J = 7.5 Hz, 2 H), 1.69 (quint, J = 7.5 Hz, 2 H), 1.30 (d, J = 6.3 Hz, 2 H); 13 C NMR (125 MHz, CDCl 3 ) 175.6, 164.4, 161.5, 146.6, 137.5, 136.0, 127.3, 115.4, 70.0, 60.2, 52.1, 33.0, 31.5, 28.6, 25.9, 25.0, 21.9, 21.8; IR (film) 3261, 1725, 1684, 1651, 1437 cm -1 ; HRMS (ESI) m/z Calcd for C 18 H 28 NaN 2 6 (M+Na) , Found Methyl 2-(tert-butyldimethylsilyloxy)-6-hydroxyhex-2-enoate (23). Freshly distilled DBU (4.5 ml, 30.0 mmol) was added dropwise to a vigorously stirred suspension of lithium chloride (1.27 g, 30.0 mmol) and phosphonate 9 6 (9.37 g, 30.0 mmol) in MeCN (295 ml), and the resulting suspension was maintained at 0 C for 1 h. After this time, tetrahydrofuran-2-ol 4 (2.64 g, 30.0 mmol) in 5 ml MeCN was added dropwise. The mixture was stirred at 0 C for 15 min and then was allowed to warm to room temperature. After 2 h of stirring, saturated aqueous sodium bicarbonate (75 ml) and water (200 ml) was added to quench the reaction. The biphasic mixture was extracted with EtAc (3 200 ml). The combined organic phases were washed with brine (3 75 ml), dried (MgS 4 ), and concentrated in vacuo. The residue was purified by silica gel chromatography (5:1 hexanes/ethyl acetate) to give 4.55 g (55%) of S8

9 23 as a clear oil, which contained a ca. 9:1 mixture of olefin isomers according to 1 H NMR analysis: 1 H NMR (500 MHz, CDCl 3, major diastereomer) 5.47 (t, J = 8.5 Hz, 1 H), 3.75 (s, 3 H), 3.61 (t, J = 6.0 Hz, 2 H), 2.52 (dt, J = 8.5, 7.0 Hz, 2 H), 2.50 (br s, 1 H), 1.67 (quint., J = 6.5 Hz, 2 H), 0.93 (s, 9 H), 0.11 (s, 6 H); 13 C NMR (125 MHz, CDCl 3, major diastereomer) 165.6, 140.9, 124.5, 61.1, 51.6, 32.0, 25.5, 22.7, 18.1, 5.0; IR (film) 3404, 2932, 2859, 1724, 1637, 1351 cm -1 ; HRMS (ESI) m/z Calcd for C 13 H 26 Na 4 Si (M+Na) , Found (6E)-8-Ethyl-1-methyl-2-(tert-butyldimethylsilyloxy)octa-2,6-dienedioate (29). Dess Martin periodinane (2.2 g, 5.2 mmol) was added in two portions to a stirred solution of alcohol 23 (1.1 g, 4.0 mmol) in CH 2 Cl 2 (20 ml) at room temperature. The reaction was stirred for 1 h and monitored by TLC. The reaction was quenched by the addition of saturated aqueous sodium bicarbonate (70 ml) and aqueous 10% sodium thiosulfate (70 ml). The suspension was stirred until all solids were dissolved, the layers were separated and the aqueous layer was extracted with CH 2 Cl 2 (2 40 ml). The combined organic phases were washed with brine (3 75 ml), dried (MgS 4 ), and concentrated in vacuo. Crude aldehyde 24 was then dissolved in 20 ml of CH 2 Cl 2. Solid phosphorylidene 25 (1.47 g, 4.2 mmol) was added to the mixture in one portion. The resulting solution was stirred for 16 h under an N 2 atmosphere. Volatiles were removed in vacuo, and the residue was purified by silica gel chromatography (10:1 hexanes/ethyl acetate) to give 1.12 g (81%) of 29 as a clear oil, which contained a ca. 10:1 mixture of olefin isomers according to 1 H NMR analysis: 1 H NMR (500 MHz, CDCl 3, major diastereomer) 6.95 (dt, J = 15.5, 7.0 Hz, 1 H), 5.84 (dt, J = 15.5, 1.8 Hz, 1 H), 5.46 (t, J = 8.0 Hz, 1 H), 4.18 (q, J = 7.0 Hz, 2 H), 3.76 (s, 3 H), 2.63 (q, J = 7.5 Hz, 2 H), 2.32 (dq, J = 7.0, 1.5 Hz, 2 H), 1.28 (t, J = 7.0 Hz, 3 H), 0.94 (s, 9 H), 0.12 (s, 6 H); 13 C NMR (125 MHz, CDCl 3, major diastereomer) 166.7, 165.2, 148.2, 141.1, 123.9, 122.2, 60.5, 51.7, 32.5, 25.8, 25.5, 14.5, 4.7; IR (film) 2954, 2932, 2859, 1721, 1639, 1437 cm -1 ; HRMS (ESI) m/z Calc d for C 17 H 30 Na 5 Si (M+Na) , Found (6E)-Methyl-2-(tert-butyldimethylsilyloxy)-8-(ethylthio)-8-oxoocta-2,6-dienoate (30): Following general method B to prepare enoxysilane 29, crude aldehyde 24 (1.5 mmol) and phosphorylidene 26 (0.58 g, 1.6 mmol) gave 0.44 g (82%) of 30 as a clear oil, following purification by S9

10 silica gel chromatography (10:1 hexanes/ethyl acetate). The product contained a ca. 8:1 mixture of olefin isomers according to 1 H NMR analysis: 1 H NMR (500 MHz, CDCl 3, major diastereomer) 6.88 (dt, J = 15.5, 7.0 Hz, 1 H), 6.13 (d, J = 15.5 Hz, 1 H), 5.45 (t, J = 8.0 Hz, 1 H), 3.77 (s, 3 H), 2.94 (q, J = 7.5 Hz, 2 H), 2.64 (q, J = 7.5 Hz, 2 H), 2.32 (q, J = 7.0 Hz, 2 H), 1.28 (t, J = 7.0 Hz, 3 H), 0.94 (s, 9 H), 0.12 (s, 6 H); 13 C NMR (125 MHz, CDCl 3, major diastereomer) 190.2, 165.2, 144.1, 141.2, 129.5, 123.6, 51.7, 32.5, 25.8, 25.5, 23.3, 18.4, 15.0, 4.7; IR (film) 2953, 2931, 2858, 1725, 1674, 1634, 1436 cm -1 ; HRMS (ESI) m/z Calcd for C 17 H 30 Na 4 SSi (M+Na) , Found (6E)-Methyl-2-(tert-butyldimethylsilyloxy)-8-(methoxy(methyl)amino)-8-oxoocta-2,6-dienoate (31): Following general method B to prepare enoxysilane 29, crude aldehyde 24 (2.0 mmol) and phosphorylidene 27 (0.80 g, 2.2 mmol) gave 0.45 g (63%) of 31 as a clear oil, following purification by silica gel chromatography (3:1 hexanes/ethyl acetate). The product contained a ca. 13:1 mixture of olefin isomers according to 1 H NMR analysis: 1 H NMR (500 MHz, CDCl 3, major diastereomer) 6.97 (dt, J = 15.5, 7.0 Hz, 1 H), 6.43 (d, J = 15.5 Hz, 1 H), 5.48 (t, J = 8.0 Hz, 1 H), 3.76 (s, 3 H), 3.69 (s, 3 H), 3.24 (s, 3 H), 2.64 (q, J = 7.5 Hz, 2 H), 2.35 (dq, J = 7.0, 1.0 Hz, 2 H), 0.93 (s, 9 H), 0.11 (s, 6 H); 13 C NMR (125 MHz, CDCl 3, major diastereomer) 166.9, 165.1, 146.5, 140.8, 124.0, 119.4, 77.3, 61.7, 51.6, 32.7, 25.6, 18.2, 4.9; IR (film) 2931, 1743, 1614, 1636, 1353, 1251 cm -1 ; HRMS (ESI) m/z Calcd for C 17 H 31 NaN 5 Si (M+Na) , Found Methyl 2-(tert-butyldimethylsilyloxy)-7-methoxyhepta-2,6-dienoate (32): Following general method B to prepare enoxysilane 29, a solution of crude aldehyde 24 (1.5 mmol) in toluene (1.75 ml) was added to in situ generated phosphorylidene 28 (1.65 mmol) in 1:1 toluene/thf (3.5 ml) at 0 ºC under an N 2 atmosphere. The mixture was held at 0 ºC for 15 min before warming to room temperature. After 2 hours of stirring, volatiles were removed by rotary evaporation. The residue was purified by silica gel chromatography (10:1 hexanes/ethyl acetate) to give 0.24 g (54%) of 32 as a clear oil, which contained a ca. complex mixture of olefin isomers according to 1 H NMR analysis: 1 H NMR (500 MHz, CDCl 3, major diastereomer) 6.33 (d, J = 12.5 Hz, 1 H), 6.02 (t, J = 7.5 Hz, 1 H), 4.73 (dt, J = 13.0, 7.0 Hz, 1 H), 3.75 (s, 3 H), 3.51 (s, 3 H), 2.25 (q, J = 7.5 Hz, 2 H), 2.04 (q, J = 7.3 Hz, 2 H), 0.97 (s, 9 H), 0.16 (s, 6 H); IR S10

11 (film) 2932, 1725, 1653, 1437, 1363, 1131 cm -1 ; HRMS (ESI) m/z Calcd for C 15 H 28 Na 4 Si (M+Na) , Found (E)-1-Ethyl-8-methyl 7-oxooct-2-enedioate (33): Solid cesium fluoride (1.46 g, 9.6 mmol) was added in one portion to a solution of enoxysilane 29 (1.03 g, 3.0 mmol) and acetic acid (1.0 ml, 18.0 mmol) in MeCN (43 ml). The resulting mixture was stirred vigorously at room temperature for 3 h. Saturated aqueous sodium bicarbonate (75 ml) was added, and the biphasic mixture was extracted with ethyl acetate (2 75 ml). The combined organic phases were washed with brine (50 ml), dried (MgS 4 ), and concentrated in vacuo to give 0.67 g (98%) of 33 as an unstable pale yellow oil which was used directly without further purification: 1 H NMR (500 MHz, CDCl 3 ) 6.90 (dt, J = 15.5, 7.0 Hz, 1 H), 5.83 (d, J = 15.5 Hz, 1 H), 4.17 (q, J = 7.0 Hz, 2 H), 3.86 (s, 3 H), 2.87 (t, J = 7.3 Hz, 2 H), 2.25 (q, J = 7.3 Hz, 2 H), 1.82 (quint, J = 7.8 Hz, 2 H), 1.28 (t, J = 7.0 Hz, 3 H); 13 C NMR (125 MHz, CDCl 3 ) 193.4, 166.3, 161.2, 147.3, 122.3, 60.2, 52.9, 38.3, 31.0, 21.2, 14.2; IR (film) 2956, 1716, 1654, 1438, 1369, 1268, 1188 cm -1 ; HRMS (ESI) m/z Calcd for C 11 H 16 Na 5 (M+Na) , Found (2E,7Z)-1-Ethyl-8-methyl 7-(2-benzoylhydrazono)oct-2-enedioate (34): Concentrated aqueous hydrochloric acid (1.0 μl) was added to a solution of -keto ester 33 (69 mg, 0.3 mmol) and benzoic hydrazide (45 mg, 0.33 mmol) in Et 2 (3.0 ml), and the solution was maintained at room temperature overnight. The resulting suspension was diluted with CH 2 Cl 2 and sodium acetate (30 mg) was added in one portion. The mixture was dried over Na 2 S 4, filtered, and the solution was concentrated in vacuo. The residue was purified by silica gel chromatography (2:1 hexanes/ethyl acetate) to give 83 mg (80%) of 34 as a white solid: 1 H NMR (500 MHz, CDCl 323 K) (br s, 1 H), (d, J = 7.0 Hz, 2 H), 7.56 (t, J = 7.5 Hz, 1 H), 7.49 (t, J = 7.0 Hz, 2 H), 6.95 (dt, J = 16.0, 7.0 Hz, 1 H) 5.85 (d, J = 15.5 Hz, 1 H), 4.19 (q, J = 7.0 Hz, 2 H), 3.91 (s, 3 H), 2.67 (t, J = 7.8, 2 H), 2.30 (q, J = 7.0 Hz, 2H), 1.84 (pent, J = 7.5 Hz, 2 H), 1.29 (t, J = 7.3 Hz, 3H); 13 C NMR (125 MHz, CDCl 3 ) 166.5, 163.2, 148.1, 139.9, 132.5, 128.8, 127.6, 121.9, 60.2, 52.6, 33.0, 31.6, 25.8, 14.2; IR (film) 3266, 2931, 1701, 1508, 1482, 1257, 1135 cm -1 ; HRMS (ESI) m/z Calc d for C 18 H 22 NaN 2 5 (M+Na) , Found S11

12 (2E)-1-Ethyl-8-methyl-7-(2-(benzyloxycarbonyl)hydrazono)oct-2-enedioate (35): Following general method B to prepare hydrazone 34, -keto ester 33 (228 mg, 1.0 mmol) and benzyl carbazate (166 mg, 1.0 mmol) gave 198 mg (53%) of 35a and 90 mg (24%) of 35b as white solids, following purification by silica gel chromatography (1:1 hexanes/ethyl acetate): 1 H NMR (500 MHz, CDCl 3, major diastereomer, 35a) (br s, 1 H), (m, 5 H), 6.94 (dt, J = 16.0, 7.0 Hz, 1 H), 5.83 (dt, J = 15.5, 1.5 Hz, 1 H), 5.27 (s, 2 H), 4.19 (q, J = 7.0 Hz, 2 H), 3.84 (s, 3 H), 2.56 (t, J = 7.5, 2 H), 2.26 (dq, J = 7.5, 1.5 Hz, 2H), 1.76 (quint, J = 7.5 Hz, 2 H), 1.29 (t, J = 7.0 Hz, 3H); 1 H NMR (500 MHz, CDCl 3, minor diastereomer, 35b): 8.39 (br s, 1 H), (m, 5 H), 6.89 (dt, J = 15.5, 7.0 Hz, 1 H), 5.83 (dt, J = 15.5, 1.5 Hz, 1 H), 5.28 (s, 2 H), 4.17 (q, J = 7.0 Hz, 2 H), 3.84 (s, 3 H), 2.53 (t, J = 8.0, 2 H), 2.24 (q, J = 7.0 Hz, 2H), 1.66 (quint, J = 7.5 Hz, 2 H), 1.27 (t, J = 7.0 Hz, 3H); 13 C NMR (125 MHz, CDCl 3, major diastereomer, 35a) 166.5, 162.6, 153.3, 148.1, 137.0, 135.6, 128.5, 128.4, 121.9, 67.6, 60.1, 52.3, 32.8, 31.5, 25.6, 14.2; 13 C NMR (125 MHz, CDCl 3, minor diastereomer, 35b) 166.3, 164.6, 146.9, 143.8, 135.2, 128.6, 122.5, 68.3, 60.3, 52.8, 31.7, 24.7, 23.7, 14.2; IR (film, major diastereomer, 35a) 3274, 2958, 1719, 1653, 1482, 1266, 1165 cm -1 ; IR (film, minor diastereomer, 35b) 3246, 2952, 1719, 1653, 1526, 1437, 1162 cm -1 ; HRMS (ESI, major diastereomer, 35a) m/z Calcd for C 19 H 24 NaN 2 6 (M+Na) , Found ; HRMS (ESI, minor diastereomer, 35b) m/z Calcd for C 19 H 24 NaN 2 6 (M+Na) , Found Methoxy-6-(5-oxo-3-thioxo-2,3,4,5-tetrahydro[1,2,4]triazin-6-yl)-hex-2-enoic acid methyl ester (36): A mixture of 17 (110 mg, 4.1 mmol) and thiosemicarbazide (27.4 mg, 0.30 mmol) in d 6 - ethanol (1.0 ml) was maintained at 120 C for 48 h. Solids were removed by vacuum filtration, and the solution was concentrated in vacuo. The residue was purified by silica gel chromatography (40% ethyl acetate/hexanes) to give 10.8 mg (93%) of 36 as a colorless oil: 1 H NMR (500 MHz, CDCl 3 ) (br s, 1 H), 9.68, (br s, 1 H), 6.19 (t, J = 7.7 Hz, 1 H), 3.76 (s, 3 H), 3.63 (s, 3 H) 2.64 (t, J = 7.5 Hz, 2 H), 2.29 (q, J = 7.5 Hz, 2 H), 1.76 (quint, J = 7.6 Hz, 2 H); 13 C NMR (125 MHz, CDCl 3 ) 173.1, 164.3, 152.1, 151.0, 146.9, 127.6, 60.3, 52.3, 29.4, 25.04, 25.01; IR (film) 3239, 1697, 1650, 1601, 1530, 1435 cm -1 ; HRMS (ESI) m/z Calcd for C 11 H 15 NaN 3 4 S (M+Na) , Found Anal. Calcd for C 11 H 15 N 3 4 S: C, 46.31; H, 5.30; N, Found: C, 46.21; H, 5.20; N, S12

13 3-Methoxy-2-thiocarbamoylhexahydrocyclopentapyrazole-3,6a-dicarboxylic acid 6a-isopropyl ester 3-methyl ester (38): A solution of -ketoester 18 (8.0 mg, 0.03 mmol) and thiosemicarbazide (2.7 mg, 0.03 mmol) in d 6 -ethanol was maintained at 75 C for 12 h, at 85 C for 5 h, and then at 100 C for 48 h. The solution was concentrated in vacuo and then purified by silica gel chromatography (35% ethyl acetate/hexanes) to give 6.7 mg (67%) of bicycle 38 as a clear glaze and 1.1 mg (14%) of tricycle 39 as a clear glaze: 1 H NMR (500 MHz, CDCl 3 ) 7.59 (br s, 1 H), 6.05 (br s, 1 H), 5.08 (sept, J = 6.3 Hz, 1 H), 4.16 (br s, 1 H), 3.76 (s, 3 H), 3.75 (s, 3H), 3.61 (dd, J = 9.3, 2.9 Hz, 1H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 2 H), (m, 1 H), 1.28 (d, J = 6.3 Hz, 3 H), 1.26 (d, J = 6.3 Hz, 3 H); 13 C NMR (125 MHz, CDCl 3 ) 181.8, 173.3, 168.0, 95.2, 78.4, 69.5, 66.0, 55.0, 53.1, 35.0, 27.7, 21.9, 21.8; IR (film) 3448, 3334, 3257, 3149, 1741, 1727, 1578 cm -1 ; HRMS (ESI) m/z Calcd for C 14 H 23 NaN 3 5 S (M+Na) , Found Anal. Calcd for C 14 H 23 N 3 5 S: C, 48.68; H, 6.71; N, Found: C, 48.66; H, 6.72; N, a-Methoxy-3-oxo-1-thioxooctahydro-2,7,7a-triazacyclopenta[a]pentalene-6a-carboxylic acid isopropyl ester (39): A solution of -ketoester 18 (2.1 g, 7.7 mmol), thiosemicarbazide (0.74 g, 8.1 mmol), and citric acid (7.4 g, 38.6 mmol) in t-buh (75 ml) was maintained at 110 C for 60 h. t-buh was removed in vacuo and the resulting yellow oil was dissolved in EtAc (100 ml) and washed with saturated aqueous sodium bicarbonate (2 25 ml) and brine (25 ml). The organics were dried over MgS 4, concentrated in vacuo, and the resulting oil was purified via flash chromatography (25% EtAc/hexanes) to yield 2.25 g (93%) of triazatricycle 39 as an off-white solid. An X-ray quality crystal was obtained by recrystallization from hot EtAc and hexanes (1:3) to produce clear cubic crystals (mp C): 1 H NMR (500 MHz, CDCl 3 ) 8.30 (br s, 1 H), 4.94 (sept, J = 6.3 Hz, 1 H), 4.52 (br s, 1 H), 3.40 (dd, J = 8.0, 2.6 Hz, 1 H), 3.32 (s, 3 H), (m, 1 H), (m, 4 H), (m, 1 H), 1.24 (d, J = 6.3 Hz, 3 H), 1.23 (d, J = 6.3 Hz, 3 H); 13 C NMR (125 MHz, CDCl 3 ) 185.4, 172.5, 169.2, 99.9, 83.6, 70.2, 55.0, 52.9, 35.1, 27.2, 27.0, 21.7, 21.6; IR (film) 3250, 3218, 1763, 1735, 1725, 1449, 1428 cm -1 ; HRMS (ESI) m/z Calcd for C 13 H 19 NaN 3 4 S (M+Na) , Found Anal. Calcd for C 13 H 19 N 3 4 S: C, 49.83; H, 6.11; N, Found: C, 49.61; H, 6.09; N, S13

14 2-Benzoyl-3-methoxy hexahydrocyclopentapyrazole-3,6a-dicarboxylic acid-6a-isopropyl ester- 3-methyl ester (41): Method 1: Following general method A to prepare cycloadduct 40, -ketoester 18 (24 mg, 0.09 mmol) and benzoic hydrazide (13 mg, 0.10 mmol) gave 30 mg (88%) of cycloadduct 41 as a clear glaze with spectroscopic data identical to that previously described. Method 2: A solution of hydrazone 19 (18 mg, 0.05 mmol) in sec-buh (2.0 ml) was heated in a 255 W microwave reactor at 200 C for 2 hours. Solvent was removed in vacuo, and the residue was purified with silica gel chromatography (20% EtAc/hexanes) to give 14.7 mg (82%) of cycloadduct 41 as a clear glaze with spectroscopic data identical to that previously described. 2-Acetyl-3-methoxyhexahydrocyclopentapyrazole-3,6a-dicarboxylic acid 6a-isopropyl ester-3- methyl ester (42): Following general method A to prepare cycloadduct 40, -ketoester 18 (59 mg, 0.22 mmol) and acetyl hydrazide (18 mg, 0.24 mmol) gave 40 mg (56%) of cycloadduct 42 as a clear glaze: 1 H NMR (500 MHz, CDCl 3 ) 5.09 (sept, J = 6.3 Hz, 1 H), 4.13 (s, 1H), 3.71 (s, 3H), 3.48 (s, 3 H), 3.43 (dd, J = 9.2, 3.0 Hz, 3H), 2.34 (s, 3H), (m, 1 H), (m, 2 H), (m, 1 H), (m, 2H), (m, 1 H), 1.29 (d, J = 6.3 Hz, 3 H), 1.27 (d, J = 6.3 Hz, 3 H); 13 C NMR (125 MHz, CDCl 3 ) 174.0, 164.4, 161.5, 146.7, 136.1, 128.3, 70.0, 60.3, 52.1, 33.0, 25.9, 25.1, 21.9, 20.1; IR (film) 3263, 1758, 1746, 1670, 1451 cm -1 ; HRMS (ESI) m/z Calcd for C 15 H 24 NaN 2 6 (M+Na) , Found Anal. Calcd for C 15 H 24 N 2 6 : C, 54.87; H, 7.37; N, Found: C, 54.62; H, 7.29; N, Methoxy tetrahydrocyclopentapyrazole-2,3,6a-tricarboxylic acid 2-benzyl ester-6a-isopropyl ester-3-methyl ester (43): Following general method A to prepare cycloadduct 40, -ketoester 18 (40 mg, 0.15 mmol) and benzyl carbazate (27 mg, 0.16 mmol) in EtH (2.9 ml) was maintained at 100 C for 60 h to provide 51 mg (82%) of cycloadduct 43 as a clear glaze: 1 H NMR (500 MHz, CDCl 3 ) 7.37 (d, J = 7.0 Hz, 2 H), (m, 3 H), 5.21 (d, J = 12.3 Hz, 1 H), 5.12 (d, J = 12.3 Hz, 1 H), 5.00 (sept, J = 6.3 Hz, 1 H), 4.26 (s, 3 H), 4.40 (br s, 1 H), 3.55 (s, 3 H), (m, 1 H), 3.41 (s, 3 H), (m, 1 H), (m, 1 H), (m, 3 H), (m, 1 H), 1.19 (d, J = 6.3 Hz, 3 H), 1.15 (d, J = 6.3 Hz, 3 H); 13 C NMR (125 MHz, CDCl 3 ) 173.5, 168.7, 153.9, 136.3, , , 128.4, 93.7, 78.9, S14

15 69.3, 68.0, 64.1, 53.5, 52.6, 35.3, 27.6, 27.2, 21.8, 21.7; IR (film) 3268, 1752, 1701, 1453, 1401, 1345 cm -1 ; HRMS (ESI) m/z Calcd for C 21 H 28 NaN 2 7 (M+Na) , Found Anal. Calcd for C 21 H 28 N 2 7 : C, 59.99; H, 6.71; N, Found: C, 59.83; H, 6.66; N, Methoxy tetrahydrocyclopentapyrazole-2,3,6a-tricarboxylic acid 6a-isopropyl ester 3-methyl ester 2-(2,2,2-trichloroethyl) ester (44): Following general method A to prepare cycloadduct 40, ketoester 18 (39 mg, 0.14 mmol) and 2,2,2-trichloroethylcarbonyl hydrazide (33 mg, 0.16 mmol) gave 43 mg (82%) of cycloadduct 44 as a clear glaze: 1 H NMR (500 MHz, CDCl 3 ) 5.07 (sept, J = 6.3 Hz, 1 H), 4.89 (br s, 1 H), 4.76 (br s, 1 H), 4.70 (br s, 1 H), 3.74 (s, 3 H), 3.51 (s, 3 H), 3.46 (dd, J = 9.4, 3.6 Hz, 1 H), (m, 1 H), (m, 1 H), (m, 3 H), (m, 1 H), 1.28 (d, J = 6.3 Hz, 3 H), 1.26 (d, J = 6.3 Hz, 3 H); 13 C NMR (125 MHz, CDCl 3 ) 173.4, 168.4, 152.0, 95.2, 93.7, 78.6, 75.3, 69.4, 63.9, 53.7, 53.0, 35.4, 27.6, 27.1, 21.9, 21.8; IR (film) 3270, 1756, 1715, 1451, 1400 cm -1 ; HRMS (ESI) m/z Calcd for C 16 H 23 Cl 3 NaN 2 7 (M+Na) , Found Anal. Calcd for C 16 H 23 Cl 3 N 2 7 : C, 41.62; H, 5.02; N, Found: C, 41.60; H, 4.93; N, Benzoyl-6a-benzylcarbamoyl-3-methoxy octahydrocyclopentapyrazole-3-carboxylic acid methyl ester (46): Following general method C to prepare cycloadduct 45, enoxysilane 15 (52.0 mg, 0.12 mmol) gave 47.2 mg (90%) of cycloadduct 46 as a clear glaze: 1 H NMR (500 MHz, CDCl 3 ) (m, 5 H), 7.20 (app t, J = 7.8, Hz, 2 H), 7.02 (app dd, J = 7.7, 2.4 Hz, 2 H), 6.76 (t, J = 6.1 Hz, 1 H), 4.56 (s, 3 H), 4.31 (dd, J = 14.7, 6.7 Hz, 1 H), 3.98 (dd, J = 14.7, 6.7 Hz, 1 H), 3.77 (s, 3 H), 3.63 (dd, J = 9.2, 3.0 Hz, 1 H), 3.59 (s, 3 H), (m, 1 H), (m, 2 H), (m, 3 H); 13 C NMR (125 MHz, CDCl 3 ) 173.3, 168.9, 168.4, 138.2, 134.2, 130.6, 128.6, 128.1, 128.0, 127.9, 127.5, 94.0, 80.3, 61.6, 54.2, 52.9, 43.3, 36.4, 27.7, 27.7; IR (film) 3377, 3241, 1758, 1746, 1651, 1523 cm -1 ; HRMS (ESI) m/z Calcd for C 24 H 27 NaN 3 5 (M+Na) , Found Anal. Calcd for C 24 H 27 N 3 5 : C, 65.89; H, 6.22; N, Found: C, 65.70; H, 6.16; N, Benzoyl-3-methoxy-6a-thiopropionyloctahydrocyclopentapyrazole-3-carboxylic acid methyl ester (47): Following general method C to prepare cycloadduct 45, enoxysilane 16 (48.0 mg, 0.12 mmol) gave 25.3 mg (52%) of cycloadduct 47 as a clear glaze: 1 H NMR (500 MHz, CDCl 3 ) 7.79 (dd, J = 8.5, S15

16 1.5 Hz, 2 H), 7.48 (td, J = 8.5, 1.5 Hz, 1 H), 7.41 (td, J = 8.5, 1.5 Hz, 2 H), 4.52 (br s, 1H), 3.78 (s, 3 H), 3.61 (s, 3 H), 3.56 (dd, J = 9.0, 3.0 Hz, 1 H), 2.72 (q, J = 7.5 Hz, 1 H), 2.67 (q, J = 7.5 Hz, 1 H), (m, 1 H), (m, 5 H), 1.13 (t, J = 7.5 Hz, 3 H); 13 C NMR (125 MHz, CDCl 3 ) 204.9, 169.5, 168.5, 134.5, 130.8, 129.3, 127.7, 93.8, 85.6, 61.6, 54.3, 52.8, 37.7, 27.7, 27.6, 23.4, 14.5; IR (film) 3249, 1759, 1744, 1654, 1448 cm -1 ; HRMS (ESI) m/z Calcd for C 19 H 24 NaN 2 5 S (M+Na) , Found Anal. Calcd for C 19 H 24 N 2 5 S: C, 58.15; H, 6.16; N, Found: C, 58.29; H, 6.21; N, Methoxy-7-oxohept-2-enoic acid methyl ester (48): A solution of methoxymethyl triphenylphosphonium chloride (860 mg, 2.5 mmol) in dry THF (12.5 ml) was cooled to 78 C and KHMDS (2.4 ml, 1 M in THF) was added dropwise. The resulting red suspension was allowed to warm to 0 C and was added via cannula to a solution of aldehyde 8 (215 mg, 1.3 mmol) in THF (10 ml) at 0 C. The reaction was allowed to warm to room temperature and was maintained for 1 h. The reaction was then quenched with saturated aqueous ammonium chloride (10 ml) and extracted with EtAc (3 20 ml). The combined organics were washed with brine (10 ml), dried over MgS 4, and concentrated in vacuo. The resulting oil was purified via silica gel flash chromatography (10% EtAc/hexanes) to provide 213 mg (85%) of an inconsequential 2:1 mixture of methyl enol ether olefin isomers: 1 H NMR (500 MHz, CDCl 3, major diastereomer) 6.31 (d, J = 12.6 Hz, 1 H), 6.23 (t, J = 7.6 Hz, 1 H), 4.69 (dt, J = 12.6, 7.4 Hz, 1 H), 3.75 (s, 3 H), 3.63 (s, 3 H), 3.48 (s, 3 H), 2.67 (q, J = 7.4 Hz, 2 H), 2.03 (q, J = 7.4 Hz, 2 H); 1 H NMR (500 MHz, CDCl 3, minor diastereomer) 5.88 (d, J = 6.2 Hz, 1 H), 6.25 (t, J = 7.5 Hz, 1 H), 4.32 (q, J = 6.6 Hz, 1 H), 3.75 (s, 3 H), 3.63 (s, 3 H), 3.56 (s, 3 H), 2.67 (q, J = 7.4 Hz, 2 H), 2.16 (q, J = 7.4 Hz, 2 H); 13 C NMR (125 MHz, CDCl 3, mixture of diastereomers) 164.6, 164.5, 148.0, 147.1, 146.4, 146.3, 129.2, 128.5, 105.5, 101.9, 60.3, 60.2, 59.7, 56.1, 52.0, 52.0, 27.2, 27.0, 25.9, 23.2; IR (film, mixture of diastereomers) 1724, 1653, 1449, 1436 cm -1 ; HRMS (ESI) m/z Calcd for C 10 H 16 Na 4 (M+Na) , Found A solution of the methyl enol ether mixture prepared above (51 mg, 0.25 mmol) in THF (0.5 ml) and 1 N aqueous HCl (0.5 ml) was stirred vigorously at room temperature for 3 h. The reaction was quenched with saturated aqueous sodium bicarbonate (5 ml) and was extracted with EtAc (3 5 ml). The S16

17 combined organics were washed with brine (5 ml), dried over MgS 4, and concentrated in vacuo. The resulting oil was purified via silica gel flash chromatography (15% EtAc/hexanes) to provide 47.4 mg (99%) of aldehyde 48 as a clear oil: 1 H NMR (500 MHz, CDCl 3 ) 9.76 (t, J = 1.5 Hz, 1 H), 6.19 (t, J = 7.7 Hz, 1 H), 3.76 (s, 3 H), 3.63 (s, 3 H), 2.46 (td, J = 7.3, 1.5 Hz, 2 H), 2.26 (q, J = 7.4 Hz, 2 H), 1.74 (quint, J = 7.5 Hz, 2 H); 13 C NMR (125 MHz, CDCl 3 ) 202.1, 164.2, 146.9, 127.5, 60.2, 52.1, 43.3, 24.8, 21.2; IR (film) 2726, 1720, 1650, 1436, 1449 cm -1 ; HRMS (ESI) m/z Calcd for C 9 H 14 Na 4 (M+Na) , Found Benzoyl-3-methoxy octahydrocyclopentapyrazole-3-carboxylic acid methyl ester (49): Following general method A to prepare cycloadduct 40, aldehyde 48 (48 mg, 0.26 mmol) and benzoic hydrazide (39 mg, 0.28 mmol) gave 74.5 mg (95%) of cycloadduct 49 as a clear glaze: 1 H NMR (500 MHz, CDCl 3 ) 7.73 (app d, J = 7.4 Hz, 2H), (m, 3 H), 4.10 (t, J = 6.4 Hz, 1 H), 3.80 (s, 3 H), 3.59 (s, 3 H), 3.22 (td, J = 9.0, 3.9 Hz, 1 H), (m, 1 H), (m, 3 H), (m, 2 H); 13 C NMR (125 MHz, CDCl 3 ) 169.3, 168.7, 134.7, 130.9, 128.9, 127.9, 93.6, 67.3, 58.2, 54.0, 52.9, 29.7, 26.4, 26.2; IR (film) 3247, 1750, 1638, 1461, 1447 cm -1 ; HRMS (ESI) m/z Calcd for C 16 H 20 NaN 2 4 (M+Na) , Found Anal. Calcd for C 16 H 20 N 2 4 : C, 63.14; H, 6.62; N, Found: C, 63.01; H, 6.60; N, Ethyl-6a-methyl-2-benzoyloctahydrocyclopenta[c]pyrazole-3,6a-dicarboxylate (50): Following general method A to prepare cycloadduct 40, a solution of -keto ester 33 (34 mg, 0.15 mmol) and benzoic hydrazide (25 mg, 0.18 mmol) in sec-butanol (1.5 ml) was heated at 100 ºC for 24 h under an inert atmosphere. The solvent was removed in vacuo, and the residue was purified by flash chromatography (1:1 hexanes/ethyl acetate) to give 49 mg (95%) of 50 as a clear oil with spectroscopic data identical to that previously report. 2-Benzyl-3-ethyl-6a-methylhexahydrocyclopenta[c]pyrazole-2,3,6a(1H)-tricarboxylate (51): Method 1: Following general method A to prepare cycloadduct 40, a solution of -keto ester 33 (34 mg, 0.15 mmol) and benzyl carbazate (30 mg, 0.18 mmol) in sec-butanol (1.5 ml) was heated at 100 ºC for 24 h under an inert atmosphere. The solvent was removed in vacuo, and the residue was purified by flash S17

18 chromatography (2:1 hexanes/ethyl acetate) to give 30 mg (54%) of 51 as a clear oil with spectroscopic data identical to that previously report. Method 2: Following general method D to prepare cycloadduct 50, a solution of hydrazone 35b (15 mg, 0.04 mmol) in sec-butanol (0.4 ml) was heated at 100 ºC for 24 h under an inert atmosphere. The solvent was then removed in vacuo. 1 H NMR of the residue indicated complete conversion to cyclopentapyrazolidine Ethyl-2,6a-dimethylhexahydrocyclopenta[c]pyrazole-2,3,6a(1H)-tricarboxylate (52): Following general method E to prepare 51, -keto ester 33 (0.17 mmol) and methyl carbazate (18 mg, 0.20 mmol) gave 43 mg (85%) of 52 as a clear viscous oil, following purification by silica gel chromatography (1:1 hexanes/ethyl acetate): 1 H NMR (500 MHz, CDCl 323 K) 5.41 (br s, 1 H), 4.56 (s, 1 H), 4.19 (dq, J = 7.1, 3.7 Hz, 2 H), 3.78 (s, 3 H), 3.75 (s, 3 H), 3.07 (ddd, J = 7.8, 5.6, 1.8 Hz, 1 H), (m, 1 H), (m, 1 H), (m, 3 H), (m, 1 H), 1.27 (t, J = 7.3 Hz, 3 H); 13 C NMR (125 MHz, CDCl 323 K) 173.6, 170.6, (br), 67.0, 61.6, 57.0, 53.2, 52.7, 38.1, 33.4, 29.6, 26.5, 14.0; IR (film) 2960, 1734, 1697, 1458, 1369, 1243, 1193 cm -1 ; HRMS (ESI) m/z Calcd for C 13 H 20 NaN 2 6 (M+Na) , Found Ethyl-6a-methyl-2-(2,2,2-trichloroethyl)hexahydrocyclo penta[c]pyrazole-2,3,6a(1h)- tricarboxylate (53): Following general method E to prepare cycloadduct 51, -keto ester 33 (0.17 mmol) and 2,2,2-trichloroethyl carbazate (42 mg, 0.20 mmol) gave 46 mg (65%) of 53 as a clear viscous oil, following purification by silica gel chromatography (3:1 hexanes/ethyl acetate): 1 H NMR (500 MHz, CDCl 323 K) 5.50 (br s, 1 H), 4.77 (br s, 2 H), 4.60 (br s, 1 H), (m, 2 H), 3.77 (s, 3 H), 3.11 (t, J = 6.0 Hz, 1 H), 2.34 (dt, J = 13.5, 6.5 Hz, 1 H), (m, 1 H), (m, 1 H), (m, 2 H), (m, 1 H), 1.27 (t, J = 7.0 Hz, 3 H); 13 C NMR (125 MHz, CDCl 3, carbamate rotomers observed) 173.7, 170.2, 154.7, 152.5, 95.3, 76.2, 75.0, 67.1, 61.9, 57.1, 53.0, 38.3, 38.0, 33.5, 29.7, 26.6, 14.1; IR (film) 2960, 1724, 1437, 1395, 1200, 1123 cm -1 ; HRMS (ESI) m/z Calcd for C 14 H 19 Cl 3 NaN 2 6 (M+Na) , Found Ethyl-6a-methyl-2-(2-(trimethylsilyl)ethyl)hexahydrocyclopenta[c]pyrazole-2,3,6a(1H)- tricarboxylate (54): Following general method E to prepare cycloadduct 51, -keto ester 33 (0.17 mmol) S18

19 and 2-trimethylsilylethyl carbazate (36 mg, 0.20 mmol) gave 47 mg (72%) of 54 as a clear viscous oil, following purification by silica gel chromatography (3:1 hexanes/ethyl acetate): 1 H NMR (500 MHz, CDCl 323 K) 5.36 (br s, 1 H), 4.56 (br s, 1 H), (m, 2 H), (m, 2 H), 3.74 (s, 3 H), 3.05 (ddd, J = 7.8, 4.5, 2,0 Hz, 1 H), 2.31 (dt, J = 13.0, 6.5 Hz 1 H), (m, 1 H), (m, 3 H), (m, 1 H), 1.26 (t, J = 7.0 Hz, 3 H), 1.05 (t, J = 8.5 Hz, 2 H), 0.03 (s, 9 H); 13 C NMR (125 MHz, CDCl 3 ) 173.8, 170.8, (br), 66.8, 64.7, 61.6, 57.1, 52.8, 38.1, 33.5, 29.7, 26.6, 18.0, 14.0, 1.5; IR (film) 2957, 1744, 1701, 1449, 1396, 1261, 1198 cm -1 ; HRMS (ESI) m/z Calcd for C 17 H 30 NaN 2 6 Si (M+Na) , Found Ethyl-6a-methyl-2-(benzylcarbamothioyl)octahydrocyclo penta[c]pyrazole-3,6adicarboxylate (55): Following general method E to prepare cycloadduct 51, -keto ester 33 (0.17 mmol) and 4-benzyl-3-thiosemicarbazide (37 mg, 0.20 mmol) gave 46 mg (65%) of 55 as a clear viscous oil, following purification by silica gel chromatography (3:1 hexanes/ethyl acetate): 1 H NMR (500 MHz, CDCl 323 K) 7.73 (s, 1 H), (m, 5 H), 5.70 (s, 1 H), 5.40 (s, 1 H), (m, 2 H), (m, 1 H), 3.77 (s, 3 H), 3.09 (ddd, J = 8.0, 5.0, 2.0 Hz, 1 H), 2.26 (dt, J = 8.0, 3.5 Hz, 1 H), (m, 1 H), (m, 1 H), (m, 3 H), 1.29 (t, J = 7.0 Hz, 3 H); 13 C NMR (125 MHz, CDCl 323 K) 181.3, 173.5, 170.8, 138.0, 128.7, 127.8, 127.5, 76.9, 68.9, 61.6, 56.9, 52.8, 49.0, 38.5, 33.2, 26.4, 14.1; IR (film) 3334, 2958, 1734, 1522, 1454, 1296, 1196 cm -1 ; HRMS (ESI) m/z Calcd for C 19 H 25 NaN 3 4 S (M+Na) , Found Ethyl-6a-methyl-2-(biphenylcarbonyl)octahydrocyclopenta[c]pyrazole-3,6a-dicarboxylate (56): Following general method E to prepare cycloadduct 51, -keto ester 33 (0.17 mmol) and 4- phenylbenzoic hydrazide (43 mg, 0.20 mmol) gave 66 mg (92%) of 56 as a clear viscous oil, following purification by silica gel chromatography (2:1 hexanes/ethyl acetate): 1 H NMR (500 MHz, CDCl 323 K) (m, 2 H), (m, 4 H), 7.44 (t, J = 7.8 Hz, 2 H), 7.36 (t, J = 7.3 Hz, 1 H), 5.68 (s, 1 H), 5.13 (br s, 1 H), (m, 2 H), 3.77 (s, 3 H), 3.11 (br s, 1 H), (m, 1 H), (m, 1 H), (m, 4 H), 1.31 (t, J = 7.8 Hz, 3 H); 13 C NMR (125 MHz, CDCl 323 K) 173.7, 170.6, 169.7, 143.6, 140.4, 133.1, 129.9, 128.8, 127.8, 127.2, 126.4, 65.4, 61.6, 56.5, 52.8, 37.4, 33.4, 29.7, 26.5, S19

20 14.1; IR (film) 2957, 1734, 1636, 1609, 1473, 1370, 1300, 1198 cm -1 ; HRMS (ESI) m/z Calcd for C 24 H 26 NaN 2 5 (M+Na) , Found Benzyl-6a-methyl-4,5,6,6a-tetrahydrocyclopenta[c]pyrazole-2,6a(1H)-dicarboxylate (59): Following general method F to prepare cycloadduct 57, enoxysilane 32 (0.2 mmol) gave 36 mg (59%) of 59 as a white solid, following purification by silica gel chromatography (2:1 hexanes/ethyl acetate): 1 H NMR (500 MHz, CDCl 323 K) 8.61 (s, 1 H), 8.27 (br s, 1 H), (m, 5 H), 5.25 (s, 2 H), 3.76 (s, 3 H), 2.90 (t, J = 7.3 Hz, 2 H), 2.75 (tt, J = 7.5, 2.3 Hz, 2 H), 1.91 (quint, J = 7.8 Hz, 2 H); 13 C NMR (125 MHz, CDCl 323 K) 165.6, 153.2, 149.9, 141.8, 135.9, 134.9, 128.5, 128.3, 128.2, 67.6, 51.4, 34.5, 33.5, 21.5; IR (film) 3246, 2953, 1705, 1618, 1541, 1437, 1214 cm -1 ; HRMS (ESI) m/z Calcd for C 16 H 18 NaN 2 4 (M+Na) , Found Benzyl-6a-methyl-3-(methoxy(methyl)carbamoyl)hexahydrocyclo penta[c]pyrazole- 2,6a(1H)-dicarboxylate (58): Following general method F to prepare cycloadduct 57, enoxysilane 31 (0.2 mmol) gave 56 mg (72%) of 58 as a clear viscous oil, following purification by silica gel chromatography (1:1 hexanes/ethyl acetate): 1 H NMR (500 MHz, CDCl 323 K) (m, 5 H), 5.57 (s, 1 H), 5.22 (d, J = 27.5 Hz, 1 H), 5.19 (d, J = 28.0 Hz, 1 H), 4.91 (br s, 1 H), 3.76 (s, 3 H), 3.70 (br s, 3 H), 3.17 (s, 3 H), 2.96 (br s, 1 H), (m, 1 H), (m, 1 H), (m, 4 H); 13 C NMR (125 MHz, CDCl 323 K) 173.8, 171.6, 136.6, 128.4, 128.1, 128.0, 67.7, 64.8, 61.3, 56.8, 52.5, 38.4, 33.4, 32.2, 26.3; IR (film) 2957, 1734, 1670, 1465, 1388, 1282, 1118 cm -1 ; HRMS (ESI) m/z Calcd for C 19 H 25 NaN 3 6 (M+Na) , Found Benzyl-3-ethyl-6a-methyl-1-(benzoylcarbamothioyl)hexahydrocyclopenta[c]pyrazole- 2,3,6a(1H)-tricarboxylate (60): A solution of cyclopentapyrazolidine 51 (23 mg, 0.06 mmol) and benzoyl isothiocyanate (16 μl, 0.12 mmol) in toluene (1.2 ml) was heated to 50 ºC for 20 h under an inert atmosphere. Solvent was then removed in vacuo, and the residue was purified by silica gel chromatography (1:1 hexanes/ethyl acetate) to give 24 mg (73%) of 60 as a pale yellow solid: 1 H NMR (500 MHz, CDCl 3 ) (br s, 1 H), 7.85 (d, J = 7.6 Hz, 2 H), 7.55 (t, J = 7.3 Hz, 1 H), 7.43 (d, J = 7.6 Hz, 2 H), (m, 2 H), (m, 3 H), 5.25 (d, J = 34.7 Hz, 1 H), 5.22 (d, J = 34.7 Hz, 1 H), 5.00 (s, 1 H), S20

21 (m, 2 H), 3.62 (s, 3 H), 3.33 (t, J = 8.8, 1 H), 2.98 (dt, J = 13.9, 5.6 Hz, 1 H), (m, 1 H), (m, 1 H), (m, 2 H), (m, 1 H), 1.26 (t, J = 7.3 Hz, 3 H); 13 C NMR (125 MHz, CDCl 3 ) 174.9, 169.6, 169.4, 134.4, 133.9, 132.8, 129.1, 129.0, 128.9, 128.1, 127.9, 78.9, 70.2, 65.7, 62.9, 57.4, 53.0, 36.4, 32.6, 27.1, 14.3; IR (film) 3315, 2957, 1724, 1521, 1490, 1271, 1252, 1158 cm - 1 ; HRMS (ESI) m/z Calc d for C 27 H 29 NaN 3 7 S (M+Na) , Found (Biphenyl-4-carbonyl)-3-methoxy hexahydrocyclopentapyrazole-3,6a-dicarboxylic acid 6aisopropyl ester 3-methyl ester (61): Following general method B used to prepare cycloadduct 41, hydrazone 20 (100 mg, 0.21 mmol) gave 86 mg (86%) of cycloadduct 61 as a clear glaze: 1 H NMR (500 MHz, CDCl 3 ) 8.24 (app d, J = 8.3 Hz, 2 H), 7.63 (app dd, J = 8.3, 6.6 Hz, 4 H), 7.46 (t, J = 8.0 Hz, 2 H), 7.38 (t, J = 7.5 Hz, 1 H), 5.09 (sept, J = 6.3 Hz, 1 H), 4.34 (s, 1 H) 3.78 (s, 3 H), 3.60 (s, 3 H), 3.55 (dd, J = 9.2, 2.9 Hz, 1 H), (m, 1 H), (m, 1 H), (m, 3 H), (m, 1 H), 1.22 (d, J = 6.3 Hz, 3 H), 1.19 (d, J = 6.3 Hz, 3 H); 13 C NMR (125 MHz, CDCl 3 ) 173.5, 168.5, 167.5, 143.8, 140.5, 132.7, 130.6, 129.0, 128.0, 127.4, 126.4, 93.6, 79.7, 69.2, 62.7, 54.2, 52.8, 35.5, 27.7, 27.4, 21.8, 21.7; IR (film) 3252, 1757, 1746, 1722, 1636, 1609 cm -1 ; HRMS (ESI) m/z Calcd for C 26 H 30 NaN 2 6 (M+Na) , Found Anal. Calcd for C 26 H 30 N 2 6 : C, 66.94; H, 6.48; N, Found: C, 66.81; H, 6.40; N, Methoxy-2-pent-4-enoylhexahydrocyclopentapyrazole-3,6a-dicarboxylic acid-6a-isopropyl ester-3-methyl ester (62): Following general method B used to prepare cycloadduct 41 (the only difference being a reaction time of 6 h instead of 45 min), hydrazone 22 (44 mg, 0.12 mmol) gave 26 mg (59%) of cycloadduct 61 as a clear glaze: 1 H NMR (500 MHz, CDCl 3 ) 5.86 (ddt, J = 16.9, 10.5, 6.5 Hz, 1 H), (m, 2 H), 4.98 (dq, J = 10.5, 1.5 Hz, 1 H), 4.05 (s, 1 H), 3.70 (s, 3 H), 3.45 (s, 1 H), 3.42 (dd, J = 9.5, 3.5 Hz, 1 H), 2.87 (td, J = 7.0, 2.5 Hz, 1 H), (m, 1 H), (m, 1 H), (m, 5 H), 1.27 (d, J = 8.0 Hz, 3 H), 1.23 (d, J = 8.0 Hz, 3 H); 13 C NMR (125 MHz, CDCl 3 ) 173.5, 172.9, 168.8, 137.7, 115.3, 92.6, 79.5, 69.2, 63.9, 53.9, 52.7, 35.1, 32.9, 29.1, 27.7, 27.2, 21.9, 21.9; IR (film) 3259, 1721, 1665, 1449 cm -1 ; HRMS (ESI) m/z Calcd for C 18 H 28 NaN 2 6 (M+Na) , S21