Total synthesis of salacinol. Ephedrine as a chiral auxiliary. Stereocontrol in the ethyl aluminum dichloride-induced cyclization of chiral gamma,delta-unsaturated methyl ketones to form cyclopentanones: Approaches toward the synthesis of bisabosqual A.

摘要

The total synthesis of salacinol (1.1) was completed in 4 steps from known intermediates. 1,1,1,3,3,3-Hexafluoroisopropanol, an unusual solvent inorganic synthesis, was used efficiently in the key step of the synthesis, improving the yield of this step from 33 to 94%, proving to be superior to the more commonly used solvents in polarity and low nucleophilicity.; The formation of ephedrine- and pseudoephedrine-derived acylketene hemicacetal oxazolines (2.9) was studied, as well as their application as chiral auxiliaries.; The stereoselectivity of EtAlCl2-induced cyclizations of chiral gamma,delta-unsaturated ketones (3.10a-e and 3.37a-b) was studied. The cyclization takes place mainly from the expected face. The selectivity is modest for 3.10d (60:40) in which the large substituent is a primary alkyl group and the medium substituent is a methyl group and excellent for 3.37b (93:7) in which the large substituent is a cyclohexyl group and the medium substituent is a methyl group. The cyclization of 3.37a is anomalous, suggesting that the phenyl group has more than a simple steric effect.; The synthesis of the core of bisabosqual A (4.1) was accomplished. HCl-catalyzed deprotection and cyclization of 4.55 affords tricycle 4.56 cleanly. Epoxidation of 4.56 affords tetracycle 4.59 with the wrong stereochemistry at the tertiary alcohol. Selective elimination of the tertiary alcohol to give the exocyclic methylene compound, alkene cleavage to form the ketone with OsO4 and NaIO4 and addition of MeMgBr from the least hindered face affords tertiary alcohol 4.63 with the tetracyclic core of bisabosqual A (1).