Experimental Procedures and Spectroscopic Data for the Transformations of Allylic Alkylation Products Transformations of Allylic Alkylation Products

1.7.2 EXPERIMENTAL PROCEDURES AND SPECTROSCOPIC DATA

1.7.2.6 Experimental Procedures and Spectroscopic Data for the Transformations of Allylic Alkylation Products Transformations of Allylic Alkylation Products

mg, 23% combined yield). The major diastereomer was isolated as a colorless oil by preparatory HPLC (4% EtOAc/hexanes, two Agilent Zorbax RX-sil silica columns in series; flow rate = 15 mL/min; λ = 254 nm): 65% ee; [α]D25 –43.3 (c 0.2, CHCl3); ¹H NMR (400 MHz, CDCl3) δ 8.05 (dt, J = 8.0, 0.9 Hz, 1H), 7.47 (td, J = 7.5, 1.5 Hz, 1H), 7.33 – 7.27 (m, 1H), 7.19 (dtt, J = 7.7, 1.2, 0.6 Hz, 1H), 5.64 (ddd, J = 17.0, 10.2, 8.8 Hz, 1H), 5.27 – 4.94 (m, 2H), 3.46 – 3.32 (m, 1H), 3.16 (dddt, J = 17.4, 12.6, 4.7, 1.1 Hz, 1H), 2.84 (ddd, J = 17.4, 5.0, 2.7 Hz, 1H), 2.47 (ddd, J = 13.5, 4.7, 2.7 Hz, 1H), 2.12 – 2.06 (m, 1H), 2.09 (s, 3H), 1.06 (d, J = 6.8 Hz, 3H); ¹³C NMR (101 MHz, CDCl3) δ 204.7, 196.8, 144.2, 138.3, 134.1, 132.8, 129.0, 128.0, 126.7, 116.5, 68.4, 42.6, 26.9, 25.9, 24.7, 16.3; IR (Neat Film, NaCl) 3076, 2971, 2937, 1708, 1674, 1599, 1446, 1359, 1295, 1231, 1208, 1120, 995, 912, 781, 754, 737 cm^-1; HRMS (FAB+) m/z calc’d for C16H19O2 [M+H]⁺: 243.1385, found 243.1381; HPLC conditions: 1% EtOH/hexanes, 1 mL/min, Chiralpak AD then AD-H column, λ = 254 nm, tR (min): major = 11.271, minor

= 11.944.

1.7.2.6 Experimental Procedures and Spectroscopic Data for the

4 h, whereupon the reaction was quenched with a saturated NH4Cl aqueous solution (1 mL). The aqueous layer was then extracted with EtOAc (3 x 5 mL) and the combined organic layers were washed with brine (5 mL), dried over Na2SO4, and concentrated under reduced pressure. The crude residue was purified by preparatory TLC (9%

Et2O/hexanes) to give alcohol 61 as a colorless oil (31 mg, 71% yield): [α]D25 +27.3 (c 0.3, CHCl3); ¹H NMR (400 MHz, CDCl3) δ 7.56 – 7.50 (m, 1H), 7.20 – 7.14 (m, 2H), 7.10 – 7.02 (m, 1H), 5.99 (ddd, J = 17.1, 10.2, 8.5 Hz, 1H), 5.65 (ddt, J = 17.2, 10.2, 7.1 Hz, 1H), 4.98 – 4.85 (m, 2H), 4.85 – 4.76 (m, 1H), 4.68 (ddd, J = 17.1, 1.9, 1.0 Hz, 1H), 4.33 – 4.19 (m, 2H), 4.01 (s, 1H), 2.94 – 2.86 (m, 2H), 2.72 (ddt, J = 8.6, 7.0, 0.8 Hz, 1H), 2.52 – 2.30 (m, 3H), 2.21 – 2.12 (m, 1H), 1.35 (t, J = 7.1 Hz, 3H), 0.80 (d, J = 7.0 Hz, 3H); ¹³C NMR (101 MHz, CDCl3) δ 175.9, 142.0, 140.7, 134.1, 133.7, 127.9, 126.7, 126.3, 125.5, 117.5, 114.7, 76.6, 61.1, 56.4, 47.2, 41.2, 25.2, 23.3, 16.7, 14.4; IR (Neat Film, NaCl) 3492, 3075, 2978, 2930, 2853, 1732, 1694, 1640, 1455, 1376, 1267, 1213, 1026, 914, 766, 732, 665 cm^-1; HRMS (FAB+) m/z calc’d for C20H27O3 [M+H]⁺: 315.1960, found 315.1954.

Ethyl (4bR,8S,8aS)-4b-hydroxy-8-methyl-5,8,9,10-tetrahydrophenanthrene-

8a(4bH)-carboxylate (62). A solution of bis-olefin 61 (4.0 mg, 0.013 mmol, 1 equiv), Hoveyda-Grubbs Catalyst-II (1.4 mg, 2.6 µmol, 0.2 equiv), and CH2Cl2 (0.5 mL) was stirred at ambient temperature for 18 h, whereupon the reaction mixture was concentrated under reduced pressure. The crude residue was purified by preparatory TLC (9%

HO

CO2Et

EtOAc/hexanes) to give tricycle 62 as a colorless oil (3.0 mg, 81% yield): [α]D25 +7.9 (c 0.2, CHCl3); ¹H NMR (400 MHz, CDCl3) δ 7.55 – 7.46 (m, 1H), 7.22 – 7.16 (m, 2H), 7.13 – 7.06 (m, 1H), 5.82 (ddt, J = 10.1, 5.1, 2.6 Hz, 1H), 5.56 (ddt, J = 10.1, 2.6, 1.8 Hz, 1H), 3.96 (qd, J = 7.1, 1.0 Hz, 2H), 3.36 (ddt, J = 18.0, 3.8, 2.6 Hz, 1H), 3.09 – 2.96 (m, 1H), 2.96 – 2.78 (m, 2H), 2.70 – 2.57 (m, 1H), 2.49 – 2.38 (m, 1H), 2.28 – 2.11 (m, 1H), 1.12 (d, J = 7.6 Hz, 3H), 1.07 (t, J = 7.1 Hz, 3H); ¹³C NMR (101 MHz, CDCl3) δ 172.2, 140.0, 136.0, 130.6, 129.6, 127.9, 126.3, 125.1, 124.1, 70.5, 60.0, 52.2, 36.8, 36.4, 26.4, 25.5, 16.2, 14.2; IR (Neat Film, NaCl) 3488, 3019, 2972, 2934, 1727, 1715, 1451, 1368, 1293, 1251, 1177, 1027, 887, 761, 694 cm^-1; HRMS (FAB+) m/z calc’d for C18H23O3

[M+H]⁺: 287.1647, found 287.1637. Please note that the exchangeable hydroxy proton was not observed in the ¹H NMR spectrum.

Ethyl (4bR,6R,7S,8R,8aS)-4b,6,7-trihydroxy-8-methyl-5,6,7,8,9,10-

hexahydrophenanthrene-8a(4bH)-carboxylate (63). A solution of olefin 62 (18 mg, 0.058 mmol, 1 equiv), K2OsO4 (1.0 mg, 2.8 µmol, 0.05 equiv), N-methylmorpholine N- oxide (11 mg, 0.093 mmol, 1.6 equiv), and THF/H2O (3:1, 0.2 mL) was stirred at ambient temperature for 18 h, whereupon the reaction was quenched with saturated Na2S2O3

aqueous solution (1 mL). The aqueous layer was then extracted with EtOAc (5 x 5 mL) and the combined organic layers were washed with brine (5 mL), dried over Na2SO4, and concentrated under reduced pressure. The crude residue was purified by preparatory TLC (17% EtOAc/hexanes) to give triol 63 as a colorless oil (11 mg, 59% yield): [α]D25 +3.8 (c

CO2Et HO

OH OH

0.2, CHCl3); ¹H NMR (400 MHz, CDCl3) δ 7.34 (dd, J = 7.8, 1.5 Hz, 1H), 7.19 (td, J = 7.4, 1.5 Hz, 1H), 7.16 – 7.05 (m, 2H), 4.26 (q, J = 3.3 Hz, 1H), 3.82 (q, J = 7.1 Hz, 2H), 3.74 (dd, J = 11.0, 3.5 Hz, 1H), 3.70 – 3.56 (m, 1H), 3.06 – 2.92 (m, 3H), 2.78 (dd, J = 14.6, 3.0 Hz, 1H), 2.61 – 2.44 (m, 1H), 2.24 – 2.05 (m, 2H), 1.10 (d, J = 6.8 Hz, 3H), 0.90 (t, J = 7.1 Hz, 3H); ¹³C NMR (101 MHz, CDCl3) δ 172.9, 139.4, 136.9, 129.6, 128.4, 125.8, 123.8, 73.0, 72.7, 70.5, 60.4, 56.1, 37.3, 35.3, 25.9, 25.1, 13.9, 12.3; IR (Neat Film, NaCl) 3284, 2970, 2928, 1723, 1452, 1382, 1259, 1234, 1189, 1103, 1054, 1020, 867, 834, 763, 722 cm^-1; HRMS (MM: ESI-APCI–) m/z calc’d for C18H24O5Cl [M+Cl]^–: 355.1318, found 355.1326. Please note that two of the exchangeable hydroxy protons were not observed in the ¹H NMR spectrum.

(1R,2R)-2-((S)-But-3-en-2-yl)-2-(hydroxymethyl)-1,2,3,4-tetrahydronaphthalen-1-ol (64). DIBAL (0.071 mL, 0.40 mmol, 4 equiv) was added dropwise to a solution of ethyl ester 58a (27 mg, 1.0 mmol, 1 equiv) in THF (0.6 mL) at –78 °C. The mixture was stirred at –78 °C for 6 h, whereupon the reaction was quenched with a saturated Rochelle’s salt aqueous solution (1 mL) and stirred for 18 h at ambient temperature. The aqueous layer was then extracted with EtOAc (3 x 5 mL) and the combined organic layers were washed with brine (5 mL), dried over Na2SO4, and concentrated under reduced pressure. The crude residue was purified by preparatory TLC (20% EtOAc/hexanes) to give diol 64 as a colorless oil (10 mg, 43% yield):[α]D25 +105.7 (c 0.7, CHCl3); ¹H NMR (400 MHz, CDCl3) δ 7.49 – 7.44 (m, 1H), 7.24 – 7.18 (m, 2H), 7.11 (ddd, J = 5.5, 2.4, 1.2 Hz, 1H),

OH

OH

6.30 (ddd, J = 17.2, 10.1, 9.1 Hz, 1H), 4.99 (ddd, J = 10.1, 2.1, 0.6 Hz, 1H), 4.90 (ddd, J

= 17.3, 2.1, 0.9 Hz, 1H), 4.80 (d, J = 7.3 Hz, 1H), 3.81 (dd, J = 11.3, 5.5 Hz, 1H), 3.59 (dd, J = 11.4, 3.7 Hz, 1H), 2.91 – 2.66 (m, 2H), 2.65 – 2.57 (m, 2H), 2.19 (bs, 1H), 1.75 (ddd, J = 13.8, 7.2, 6.5 Hz, 1H), 1.64 – 1.50 (m, 1H), 1.04 (d, J = 7.0 Hz, 3H); ¹³C NMR (101 MHz, CDCl3) δ 144.5, 138.9, 135.9, 128.4, 127.3, 127.0, 126.5, 115.1, 75.3, 67.3, 43.7, 39.8, 25.8, 25.7, 15.5; IR (Neat Film, NaCl) 3404, 3069, 3020, 2932, 1634, 1602, 1455, 1417, 1374, 1268, 1217, 1191, 1045, 991, 913, 774, 741, 641 cm^-1; HRMS (FAB+) m/z calc’d for C15H19O2 [(M+H)–H2]⁺: 231.1385, found 231.1385. Please note that a minor amount of epimeric product is present in the ¹H NMR spectrum.

(3S,4R)-5-(Hydroxymethyl)-4-methyl-3',4,4',5-tetrahydro-1'H,2H-spiro[furan-3,2'- naphthalene]-1',2-dione (65). A solution of methyl ester 54 (20.0 mg, 0.077 mmol, 1 equiv), K2OsO4 (3.0 mg, 0.0081 mmol, 0.11 equiv), N-methylmorpholine N-oxide (15 mg, 0.12 mmol, 1.6 equiv), and THF/H2O (3:1, 0.4 mL) was stirred at ambient temperature for 12 h, whereupon a second addition of K2OsO4 and N-methylmorpholine N-oxide was added and the reaction was stirred for an additional 24 h. The reaction was quenched with saturated Na2S2O3 aqueous solution (1 mL). The aqueous layer was then extracted with EtOAc (5 x 5 mL) and the combined organic layers were washed with brine (5 mL), dried over Na2SO4, and concentrated under reduced pressure. The crude residue was purified by preparatory TLC (33% EtOAc/hexanes) to give lactone 65 as a colorless oil (13 mg, 65% yield): [α]D25 +7.0 (c 0.2, CHCl3); ¹H NMR (400 MHz, CDCl3)

O O

O

OH

δ 8.07 (dd, J = 7.9, 1.4 Hz, 1H), 7.52 (td, J = 7.5, 1.5 Hz, 1H), 7.38 – 7.31 (m, 1H), 4.26 (ddd, J = 10.5, 5.6, 2.4 Hz, 1H), 4.01 (ddd, J = 12.8, 7.0, 2.5 Hz, 1H), 3.82 (dt, J = 12.4, 6.0 Hz, 1H), 3.59 (dq, J = 10.5, 7.0 Hz, 1H), 3.47 – 3.34 (m, 1H), 2.98 (dt, J = 17.0, 3.8 Hz, 1H), 2.32 – 2.25 (m, 2H), 1.94 (t, J = 6.7 Hz, 1H), 1.03 (d, J = 7.0 Hz, 3H); ¹³C NMR (101 MHz, CDCl3) δ 192.6, 173.5, 144.0, 134.4, 131.8, 129.0, 128.8, 127.2, 84.3, 62.9, 57.7, 36.1, 25.6, 25.3, 10.8; IR (Neat Film, NaCl) 3444, 2928, 2851, 1760, 1682, 1599, 1455, 1308, 1239, 1217, 1166, 1094, 1056, 1021, 914, 759, 733, 656 cm^-1; HRMS (FAB+) m/z calc’d for C15H17O4 [M+H]⁺: 261.1127, found 261.1129.

NOE correlation:

Ethyl (1R,2S)-2-((S)-but-3-en-2-yl)-3,4-dihydro-2H-spiro[naphthalene-1,2'-oxirane]- 2-carboxylate (66). (CH3)3SOI (35 mg, 0.17 mmol, 1.7 equiv) and NaH (5.0 mg, 0.15 mmol, 1.5 equiv, 60 wt %) were dissolved in DMSO (1.5 mL). The mixture was stirred for 20 min at ambient temperature, whereupon a solution of ketone 58a (27 mg, 0.10 mmol, 1 equiv) in DMSO (1.0 mL) was added. The resulting solution was stirred for an additional 18 h. H2O (2.0 mL) was then added to the reaction mixture and the aqueous layer was extractd with EtOAc (3 x 5 mL). The organic layer was washed with H2O (5.0 mL) and brine (5.0 mL), dried over Na2SO4, and concentrated under reduced pressure.

O O

O

OH H H H

NOE

CO₂Et O

The crude residue was purified by preparatory TLC (3% Et2O/hexanes) to give epoxide 66 as a colorless oil (23 mg, 82% yield): [α]D25 +10.4 (c 0.1, CHCl3); ¹H NMR (400 MHz, CDCl3) δ 7.23 – 7.15 (m, 3H), 7.15 – 7.07 (m, 1H), 6.07 (ddd, J = 17.1, 10.3, 8.1 Hz, 1H), 4.93 (ddd, J = 10.2, 1.9, 0.8 Hz, 1H), 4.74 (ddd, J = 17.1, 2.0, 1.1 Hz, 1H), 4.29 – 4.06 (m, 2H), 3.01 – 2.94 (m, 1H), 2.98 (d, J = 5.1 Hz, 1H), 2.93 – 2.82 (m, 1H), 2.82 – 2.71 (m, 1H), 2.62 (d, J = 5.1 Hz, 1H), 2.35 (ddd, J = 14.0, 8.2, 5.7 Hz, 1H), 2.09 (ddd, J

= 14.2, 6.9, 5.5 Hz, 1H), 1.29 (t, J = 7.1 Hz, 3H), 0.99 (d, J = 6.9 Hz, 3H); ¹³C NMR (101 MHz, CDCl3) δ; 173.4, 140.9, 138.2, 136.4, 127.8, 127.4, 126.8, 123.4, 115.1, 61.0, 59.1, 56.5, 51.9, 40.2, 28.0, 26.2, 15.8, 14.4; IR (Neat Film, NaCl) 3073, 2977, 2938, 1723, 1489, 1456, 1368, 1296, 1255, 1233, 1213, 1134, 1096, 1025, 915, 760 cm^-1; HRMS (FAB+) m/z calc’d for C18H21O3 [(M+H)–H2]⁺: 285.1491, found 285.1487. Please note that the relative stereochemistry of 16 has been assigned via analogy to 11 and 14.