Practical synthesis of C1–8 fragment of autolytimycin via a chelation-controlled diastereoselective addition of diisopropenylzinc to α-methoxy aldehyde

The C1–8 fragment of autolytimycin was synthesized via a reliable 10-step route capable of delivering 41% overall yield at multi-gram scale. As a key step, a chelation-controlled isopropenylation of α-oxygenated aldehydes was established with a reagent combination of diisopropenylzinc, magnesium halide, and a dichloromethane/toluene mixed solvent. Cram-chelate isopropenylation products dominated for aldehydes with a small α-substituents, such as –OMe and –OBn groups, while the Felkin product could be obtained with a bulky –OTBS group.