p-Methoxyacetophenone dimethyl ketal and .alpha.,p-dimethoxystyrene. Efficient and useful reagents for 1,2- and 1,3-diol protection

Abstract

2419General Procedure. Diisobutylaluminum hydride (1.0 M, hexanes) was added portionwise to a 0.3 M toluene solution of the unsaturated lactone (7.0 mmol) cooled to -78 O C (dry ice-CH30H bath) until TLC analysis judged the reaction complete.It was then poured into a rapidly stirred mixture of ice (25 g) and acetic acid (7 mL). Chloroform (50 mL) was added and the twephase system stirred vigorously for 10 min. Another 100-mL portion of chloroform was added and vigorous stirring continued until two distinct layers formed when the stirring was halted (typically 3 0 4 min). The layers were separated, and the organic layer was washed with bicarbonate (2 X 100 mL) and brine (75 mL). Drying and removal of the solvents afforded a colorless oil which was used without purification.The crude lactol and triethylsilane (1.22 g, 10.5 mmol) in dichloromethane (25 mL) were cooled under nitrogen. Dropwise addition of boron trifluoride etherate (0.95 mL, 7.7 mmol) gave a solution which was stirred until TLC indicated that no lactol was present and then quenched by addition of ca. 10 mL of aqueous bicarbonate. The cooling bath was removed and the solution allowed to warm to room temperature with vigorous stirring. After the mixture was transferred to a separatory funnel, ether (100 mL) was added and the whole washed with bicarbonate (20 mL) and brine (20 mL). Drying and removal of the solvents afforded an oil which was chromatographed (silica gel, hexanes-EtOAc). 695 cm-'; NMR (CDClJ 6 1.74 (m, 3 H), 2.20 (m, 4 H), 4.34 (m, 2 H), 4.55 (dd, J = 5, 9 Hz), 5.52 (m, 1 H), 7.40 (s, 5 H).2: IR (film) 2980,2895, 1065; NMR (CDClJ 6 1.52-2.42 (m, 4 H), 3.704.18 (m, 2 H), 4.68-4.94 (m, 1 H), 7.03-7.30 (m, 5 H); ' % NMR 143.315,128.146,126.954, 125.492,80.527,68.446,34.534, 25.919. The boiling point [105-107 "C (15 mmHg)] was identical with the literature13 boiling point.

Lewis Acid Catalysed [4+2] Heterocycloadditions between Ketone Enol Ethers and β-Ethylenic α-Oxo Esters

“…Methyl enol ethers 2bϪd and 2f were prepared according to reported procedures. [13,14] The silyl enol ethers 2e, [7b] 2g, 2h, 2j, 2k and 2l [15] were prepared by Duboudin's modified procedure [16] starting from the appropriate chlorosilane and ketone (NaI/Et 3 N/MeCN/20°C). Spectroscopic data of adducts 3a/4a, 3d/4d and 3e/4e were described in a previous paper by our group.…”

Total Synthesis and Structural Elucidation of the Antifungal Agent Papulacandin D

“…Unfortunately, formation of the acetal 21 was capricious (0−95%) and proceeded with partial but variable desilylation. Attempts to convert the crude tetraol 14 into the corresponding acetals with anisaldehyde, 2,4-dimethoxybenzaldehyde, or 4-methoxyacetophenone also proceeded in variable yet low yields. Saponification of the tetraacetate 17 gave the crude tetraol 14 which was directly condensed with 1,1,3,3-tetraisopropyl-1,3-dichlorodisiloxane. , 1 H NMR spectroscopy of the crude reaction mixture was consistent with partial de- tert -butylsilylation, and chromatography gave a spiroketal tentatively assigned as the adduct 22 in only modest yield (50%).…”

Chiral synthesis of polyketide-derived natural products. Part 6. Chemical correlation of chiral synthons, derived from D-glucose for the synthesis of erythromycin A, with chemical cleavage products the natural antibiotic

“…1.0 Hz), 2.49 (0.7 H, dd, J8.0, 14.0 Hz), 2.75 (0.7 H, dd, J6.0, 14.0 Hz), 2.81-3.00 (0.3 H, m), 3.14 (0.7 H, dd, J 3.0, 8.0 Hz), 3.18 (0.3 H, t, J6.5 Hz), 3.29 (0.7 H, dd, J 1.5,lO.O Hz), 3.34 (0.3 H, dd, J2.5, 10.0 Hz), 3.76, 3.77, 3.79 (total 6 H, each s), 4.34-4.69 (5 H, m), 5.03 (0.7 H,br s), 5.30 (0.7 H, d, J 1.5 Hz), 5.82 (0.3 H, dd, J 1.5,9.5 Hz), 6.73-6.81 (4 H, m), and 7.18-7.37 (9 H, m); v,,,. (CHCI,) 1 610 cm-'.…”

“…In order to prove unequivocally the structures and configurations of the two synthesized segments, (3) and (4), for the synthesis of erythromycin A (1) from D-glucose ( Z ) , chemical cleavage of dihydroerythronolide A (5) at the lactone and the 5,6-vicinal diol positions was examined via selective protection of hydroxy groups, lithium aluminium hydride reduction, and lead tetra-acetate oxidation. The two segments derived from (5), (2R,3S,4S,5R,6R,7R) -1hydroxy-5,6-isopropylidenedioxy-3,7-bis-(4-methoxybenzyloxy) -2,4,6-trimethylnonane (3) and (2S,3R,4S) -3,5-isopropylidenedioxy-2,4dimethylpentanal (4), were completely identical in their spectral data with the respective synthesized segments.…”