The development of a practical catalytic Petasus reaction of glycolaldehyde and the asymmetric allylboration of acyl cyanides

• Main Author: Summo, Kathryn Eva
• Language: en_US
• Published: 2016
• Subjects: Organic chemistry
• Online Access: https://hdl.handle.net/2144/19734

Asymmetric nucleophilic boronate reactions have been developed using organic chiral diols, specifically binaphthols, as catalysts. A highly enantioselective allylboration of acyl cyanides under solvent-free conditions was catalyzed by (S)-Br2BINOL. The reaction proceeds through single exchange of boronate with the chiral catalyst, promoted by tert-butanol. Allylation products were obtained in yields up to 97% and enantioselectivities up to 99:1 er. Syn- and anti-crotylborations of benzoyl cyanide were also performed, and the corresponding a-methyl products were isolated in good yields and moderate to good enantioselectivities, with the E-boronate producing a single diastereomer. This methodology represents a new route to enantioenriched homoallylic cyanohydrins through nucleophilic addition of the allyl group to acyl cyanides. The enantioselective Petasis reaction of glycolaldehyde dimer to synthesize b- amino alcohols was also investigated. With commercially available aldehyde dimer, boronic acids, and amines, electron-rich a-arylglycinols were obtained in up to 92% yield and up to 99.5:0.5 er. Direct inject mass spectrometry studies revealed a single exchange between p-methoxyphenylboronic acid and (S)-Br2BINOL, as well as coordination of the imine intermediate to the catalyst-boronate complex. This reaction was further optimized to include electron-deficient boronic acids. Addition of Lewis acidic triethylborate had a two-fold effect on the reactivity; it facilitated both the exchange of boronic acid with catalyst, and the formation of the imine intermediate. Using chloroform as the solvent, and (S)-Ph2BINOL, halogenated phenylboronic acids participated well in the Petasis reaction. This methodology is the first asymmetric Petasis reaction of glycolaldehyde to produce b-amino alcohols. === 2018-12-06T00:00:00Z