Reaction SMILES: [CH3:1][CH:2]1[CH:27]2[O:28][C:26]2([CH3:29])[CH:25]([O:30]C(CC(C)C)=O)[CH2:24][C:22](=[O:23])[N:21]([CH3:37])[C:14]2=[C:15]([Cl:20])[C:16]([O:18][CH3:19])=[CH:17][C:12](=[CH:13]2)[CH2:11][C:10]([CH3:38])=[CH:9][CH:8]=[CH:7][CH:6]([O:39][CH3:40])[C:5]2([OH:45])[NH:41][C:42]([O:44][CH:3]1[CH2:4]2)=[O:43].C(O)=O.O1CCCC1.C(OCC)(=O)C>O>[CH3:1][CH:2]1[CH:27]2[O:28][C:26]2([CH3:29])[CH:25]([OH:30])[CH2:24][C:22](=[O:23])[N:21]([CH3:37])[C:14]2=[C:15]([Cl:20])[C:16]([O:18][CH3:19])=[CH:17][C:12](=[CH:13]2)[CH2:11][C:10]([CH3:38])=[CH:9][CH:8]=[CH:7][CH:6]([O:39][CH3:40])[C:5]2([OH:45])[NH:41][C:42]([O:44][CH:3]1[CH2:4]2)=[O:43]
Reactant: COc1cc2cc(c1Cl)N(C)C(=O)CC(OC(=O)CC(C)C)C1(C)OC1C(C)C1CC(O)(NC(=O)O1)C(OC)C=CC=C(C)C2
Agent: COc1cc2cc(c1Cl)N(C)C(=O)CC(O)C1(C)OC1C(C)C1CC(O)(NC(=O)O1)C(OC)/C=C/C=C(\C)C2
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: COc1cc2cc(c1Cl)N(C)C(=O)CC(O)C1(C)OC1C(C)C1CC(O)(NC(=O)O1)C(OC)C=CC=C(C)C2
Temperature: -57 °C

Procedure:
This example describes preparation of the bridged acetal compound shown in Formula (I), where R1 is CH(CH3)2, reduction of ansamitocins with LiAl(OMe)3H, followed by aqueous formic acid quench. Ansamitocins (3.0 g, 4.72 mmol) were weighed into a three necked flask equipped with a thermometer. Tetrahydrofuran (15 mL) was added to the flask with stirring, and the flask was cooled in a −57° C. cooling bath. Once the contents of the flask reached −35° C., a solution of 0.67 M LiAl(OMe)3H in tetrahydrofuran (56 mL, 37.7 mmol) was added dropwise by syringe using a syringe pump. The temperature of the reaction was maintained between −30° C. and −40° C. throughout the addition. After addition was complete the reaction was stirred for 2 hours at between −34° C. and −37° C. A solution of 88% formic acid (1.85 mL, 2.16 g, 41.5 mmol) in 23 mL of deionized water was added dropwise to the flask at a rate that did not produce excessive frothing, followed by 66 mL of ethyl acetate. The cooling bath was removed and the mixture was allowed to warm to room temperature. The pH of the mixture was checked with pH paper and found to be approximately pH 6. Precipitated aluminum-based byproducts were removed by vacuum filtration and the solvent was removed from filtrate by rotary evaporation under vacuum. Butyl acetate (10 mL) was added to the residue, and the solvent was then evaporated in order to remove residual water. The residue was purified by silica chromatography using dichloromethane:methanol 95:5 (v:v) giving a later eluting band (maytansinol) and an early eluting band. The maytansinol band was collected and solvent was removed by rotary evaporation to give 1.55 g of maytansinol (58% yield by weight). Solvent was removed from the earlier eluting band, and the material was dissolved in a minimum volume of acetonitrile, then purified by preparative reverse phase HPLC. The compound of Formula (I) (retention time 26 min) was recovered, and solvent was removed by rotary evaporation to give 440 mg (15% yield by weight). Characterization of maytansinol: 1H NMR (CDCl3) δ 0.83 (s, 3H), 1.20 (m, 1H), 1.30 (d, 3H, J=6.0 Hz), 1.50 (m, 2H), 1.69 (s, 3H), 2.10 (d, 1H, J=9.4 Hz), 2.52 (d, 1H, J=9.4 Hz), 2.88 (d, 1H, J=5.4 Hz), 3.12 (d, 1H, J=12.7 Hz), 3.2 (s, 3H), 3.36 (s, 3H), 3.46 (m, 2H), 3.54 (d, 1H, J=9.3), 3.64 (br s, 1H), 3.99 (s, 3H), 4.36 (dd, 1H, J=12, 1.0 Hz), 5.53 (dd, 1H, J=15, 9.3 Hz), 6.14 (d, 1H, J=11 Hz), 6.14 (d, 1H, J=11 Hz), 6.27 (s, 1H), 6.44 (dd, 1H, J=15, 11 Hz), 6.81 (d, 1H, J=1.8 Hz), 6.96 (d, 1H, J=1.8 Hz); Characterization of the compound of Formula (I): R1═CH(CH3)2: 1H NMR (CDCl3) δ 0.78 (s, 3H), 0.97 (d, 3H, J=6.9), 1.04 (d, 3H, J=6.7), 1.23 (m, 1H), 1.28 (d, 3H, J=6.4), 1.54 (m, 1H), 1.66 (s, 3H), 1.72 (m, 2H) 2.03 (dd, 1H, J=14, 3.6 Hz), 2.3 (d, 1H, J=14), 2.49 (dd, 1H, J=11.7, 14), 2.92 (d, 1H, J=9.5 Hz), 3.14 (s, 3H), 3.12 (m, 1H), 3.37, (s, 3H), 3.52 (m, 3H), 3.65 (m, 1H), 3.75 (m, 1H), 3.97 (s, 1H), 4.31 (m, 2H), 5.52 (dd, 1H, J=16, 8.7 Hz), 6.13(d, 1H, J=11 Hz), 6.34 (s, 1H), 6.45 (dd, 1H, J=16, 11 Hz), 6.80 (d, 1H, J=1.5 Hz), 6.92 (d, 1H, J=1.5 Hz); MS (M+1 found: 619.3 M+1 calculated: 619.2)