William F. Kiesman

Acceleration of Petasis Reactions of Salicylaldehyde Derivatives with Molecular Sieves

Mild reaction conditions for Petasis reactions of substituted salicylaldehydes with various amines and arylboronic acids in the presence of molecular sieves were developed. Molecular sieves (MS) significantly accelerated the reaction rates and drove the reactions to high conversions. The conditions were applied to the synthesis of the core structure of BIIB042, a γ-secretase modulator, without stereochemical erosion of a stereogenic center in the salicylaldehyde intermediate.

Catalytic Asymmetric Petasis Reactions of Vinylboronates

Binaphthol-catalyzed asymmetric Petasis reactions of salicylaldehydes with dibutyl vinylboronates and secondary amines in the presence of 4 Å molecular sieves (MS) afforded products with up to 99% ee in isolated yields of 39-94%. The 99% ee of the product indicated that the reaction by the binaphthol-catalyzed pathway was roughly 500 times faster than the uncatalyzed pathway. NMR experiments ((1)H and (11)B) showed that the amine component played a role in triggering the reaction between the binaphthol catalyst and the vinylboronate in the catalytic reaction sequence. The 4 Å MS enhanced both the rate and enantioselectivity by effective removal of water from the reaction system. A novel rearrangement reaction of the unconjugated allylic amine Petasis reaction product to a conjugated allylic amine was also observed.

Lewis-acid catalysis of the asymmetric Diels–Alder reaction of dimenthyl fumarate and cyclopentadiene

Abstract The effects of Lewis acid catalysts, solvent, catalyst loading, and temperature on the diastereomeric excess in the Diels–Alder reaction of (+)-dimenthyl fumarate and cyclopentadiene were investigated.

Convenient One‐Pot Preparation of Dimethyl Bicyclo[2.2.2]octane‐1,4‐dicarbolylate, a Key Intermediate for a Novel Adenosine A1 Receptor Antagonist

Abstract Dimethyl bicyclo[2.2.2]octane‐1,4‐dicarboxylate (4), a key starting material for a novel adenosine A1 receptor antagonist, was prepared in a one‐pot reaction with convenient workup and improved yield.