CONSPECTUS
The reaction of substituted allylmetal on prostereogenic carbonyl compound can give rise to up to two racemic diastereomers (syn and anti). Classically, when anti selectivity was observed from pure E-isomers while the Z-isomers exhibit syn-selectivity, the empirical Zimmerman – Traxler model is used. In this model, chair-like transition states are predicted to dominate over boat-like arrangements and the incoming aldehyde alkyl (aryl) residue occupies a pseudo-equatorial rather than a pseudo-axial position to avoid potential 1,3-diaxial steric interactions. However, the stereochemical outcome of the reaction of γ,γ-disubstituted allylzinc species with carbonyl compounds reaction may be completely different as two gauche interactions are generated. Would the two gauche interactions present in the transition state where the aldehyde substituent occupies a pseudo-equatorial position be preferred to a transition state in which the same substituent of the aldehyde occupies a pseudoaxial position? In this study, we could show that reaction of γ,γ-disubstituted allylzinc species with carbonyl compounds proceeds through a chair-like transition state and the substituent of the incoming aldehyde residue prefers to occupy a pseudo-axial rather than into a pseudo-equatorial position to avoid these two gauche interactions. Our experimental results were supported by theoretical calculations on model systems. This new stereochemical outcome has been extended to the formation of α-alkoxyallylation of aldehydes through the formation of the rather uncommon (E)-γ,γ-disubstituted alkoxyallylzinc species. This method could also be used to transform aromatic ketones as well as α-alkoxyaldehydes and ketone into functionalized adducts in which three new carbon-carbon bonds and two to three stereogenic centers, including an all-carbon quaternary stereocenter, were created in an acyclic systems in a single-pot operation from simple alkynes. Increasing the size of substituents on the zinc atom decreases the diastereoselectivity since 1,3-diaxial interactions are now produced with the axial substituent.
SummaryThis personal account summarizes our recent developments in gold-catalyzed direct substitutions on propargylic (allylic, benzylic) alcohols, with various nucleophiles (and bi-nucleophiles) based on the σ- and/or π-acidity of gold(III) complexes. Synthetic developments are also briefly described.
The use N-sulfonyl-protected hydroxylamines as bi-nucleophiles in iron-catalyzed propargylic substitutions allows the selective one-pot synthesis of four classes of substituted isoxazoles or isoxazolines from the same propargylic alcohols (21 examples) by simply tuning the nature of the base. By using an iron(III) catalyst and a base such as triethylamine (3 equiv), isoxazoles 3 are obtained in good isolated yields (56-95%), whereas N-sulfonyl-protected isoxazolines 6 are selectively obtained (77-93% yield) by using iron and gold catalysts in the presence of a catalytic amount of pyridine (10 mol%).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.