Compound 4¹:

i. To a flame dried flask was added compound 3² (5.85 g, 15.6 mmol, 1 equiv.) and THF³ (150 mL) under Argon. The solution was cooled to –78 °C and LDA⁴ (1.0 M in THF, 20.0 mL, 20.0 mmol, 1.3 equiv.) was added dropwise over 10 minutes. The mixture was stirred for 15 minutes at –78 °C, warmed to 0 °C and stirred for 10 minutes, then cooled back to –78 °C and stirred for 5 minutes. MeI (1.6 mL, 25.6 mmol, 1.6 equiv.) was added dropwise at –78 °C and the solution stirred for 30 minutes at –78 °C. The mixture was then slowly warmed to 0 °C and stirring continued for 2.5 hours at this temperature. The reaction was partitioned between saturated aqueous NH₄Cl (250 mL) and Et₂O (200 mL) and the aqueous layer extracted with Et₂O⁵ (200 mL, 2X). The combined organic layers were washed with brine (500 mL), dried (MgSO₄), and the volatiles removed in vacuo⁶ to yield the crude α-methyl ketone (6.1 g) as a single diastereomer.

ii. The aforementioned crude α-methyl ketone (6.1 g, 15.7 mmol, 1 equiv.) was dissolved in THF (125 mL) and TBAF⁷ (1.0 M solution in THF, 25 mL, 25 mmol, 1.6 equiv.) was added. The mixture was heated at 50 °C for 1 hour at which point additional TBAF (25 mL) was added, and heating continued for 2 hours. Upon cooling, the reaction mixture was partitioned between saturated aqueous NH₄Cl (150 mL) and Et₂O (150 mL) and the aqueous layer extracted with Et₂O (150 mL, 3X). The combined organic layers were washed with 1M HCl (500 mL), water (500 mL), brine (500 mL), and dried (MgSO₄). The solvent was removed in vacuo to afford a yellow solid which was re-dissolved in AcOH:MeCN:THF (1:1:1 v/v/v, 150 mL). Me₄NBH(OAc)₃ (16.5 g, 62.7 mmol, 4 equiv.) was added portion-wise to the rapidly stirring solution. The reaction mixture was stirred for 1.5 hours then carefully poured into saturated aqueous NaHCO₃ (250 mL) and Et₂O (200 mL). The aqueous layer was extracted with Et₂O
(200 mL, 3X) and the combined organic layers carefully washed with saturated aqueous NaHCO₃ (250 mL, 5X), brine (250 mL), and dried (MgSO₄). The solvent was removed in vacuo and the crude material purified by silica gel flash chromatography⁸ (gradient from 2:1 to 1:1 hexanes:Et₂O) to afford compound 4 (3.1 g, 72% over 3 steps) as a white solid; m.p.: 165 °C (Et₂O); TLC (Et₂O:hexanes, 5:1 v/v): Rf = 0.13; 1H NMR (600 MHz, CDCl₃) δ 5.28 (dd, J = 4.5, 2.5 Hz, 1 H), 3.79 (dd, J = 10.4, 5.0 Hz, 1 H), 2.20 (s, 1 H), 2.15 – 2.10 (m, 1 H), 2.03 – 1.97 (m, 2 H), 1.86 – 1.77 (m, 3 H), 1.72 – 1.71 (m, 1 H), 1.67 – 1.58 (m, 5 H), 1.45 – 1.36 (m, 2 H), 1.15 – 1.13 (m, 2 H), 1.04 (d, J = 6.4 Hz, 3 H), 0.99 (d, J = 6.6 Hz, 3 H), 0.93 (J = 6.5 Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ 142.5, 117.0, 74.3, 73.1, 50.3, 46.7, 45.1, 36.3, 34.8, 34.7, 32.6, 32.1, 23.8, 21.9, 21.9, 21.5, 20.5, 15.3; IR (film) nmax 3371, 2929, 1638, 1469, 1368, 1326,
1227, 1034, 988 cm-1. HRMS (m/z): [M+Na]+ calcd. for C₁₈H₂₈O₂Na, 299. 1981; found, 299.1969.

Maimone, T. J.; Shi, J.; Ashida, S.; Baran, P. S. J. Am. Chem. Soc. 2009, 131, 17066-17067.