An Efficient Petasis Boronic–Mannich Reaction of Chiral Lactol Derivatives Prepared from d-Araboascorbic Acid

Abstract

Optically active polyhydroxy trans-1,2-amino alcohols were efficiently synthesized in good to excellent yields by the Petasis boronic-Mannich reaction of an amine, an organoboronic acid, and a chiral lactol, which was prepared from D-araboascorbic acid or its diastereomer. Further transformations of the resulting Petasis products were investigated in detail to obtain chiral building blocks containing three continuous stereogenic centers.

Reactivity and Synthetic Applications of Multicomponent Petasis Reactions

“…Lactols, which are easier to synthesize and handle in comparison with corresponding α-hydroxy aldehydes, were used in several studies as alternative carbonyl components. , A series of polyhydroxy trans -1,2-aminoalcohols 50 were synthesized in good yield from lactol substrates 49 , obtained through the dual protection of d -araboascorbic acid using 3,3-dimethoxypentane and 2,2-dimethoxypropane, respectively (Scheme ). 1,2-Aminoalcohols 50 with three contiguous stereogenic centers and functionalization handles were further tested in regioselective acetal cleavage, alcohol oxidation, and ozonolysis reactions in this study …”

Multicomponent Mannich‐Like Reactions of Organometallic Species

“…Asymmetric versions of the reaction have also been investigated. Diastereoselective reactions have been achieved with N ‐ tert ‐butanesulfinamide and lactol derivatives, whereas enantioselective transformations were achieved with thiourea, binaphthol,, or mixed thiourea/binaphthol organocatalysts. The Petasis reaction has been used in the synthesis of aminophosphonic acid derivatives, α‐pyridinyl amines, pyrrolinol precursors, β,γ‐dehydrohomoarylalanines, tetrahydroisoquinoline precursors, tertiary amines (through a double reaction sequence), benzoxazine derivatives, and quinoxaline precursors, as well as in the total synthesis of cytoxazone, pyrrolizidine natural products, zanamivir, conduramine E, (–)‐steviamine, and legionaminic acid …”

Synthesis of α‐Propargylglycinates Using the Borono‐Mannich Reaction with Pinacol Allenylboronate and Potassium Allenyltrifluoroborate

“…The boronic acid or borono‐Mannich reaction (Petasis reaction) is an important, three‐component reaction, involving a carbonyl component (usually an aldehyde), an amine [primary (1°) or secondary (2 o )] and an organoboronic acid or related derivative (boronate or potassium trifluoroborate) . These reactions work most efficiently when the carbonyl substrate is an α‐hydroxy aldehyde, a glyoxylic acid or a salicylaldehyde , . Reactions involving glyoxylic acid give α‐substituted α‐amino acids while those employing α‐hydroxy aldehydes reliably produce anti ‐1,2‐amino alcohol products in a highly diastereoselective manner .…”

“…These reactions work most efficiently when the carbonyl substrate is an α‐hydroxy aldehyde, a glyoxylic acid or a salicylaldehyde , . Reactions involving glyoxylic acid give α‐substituted α‐amino acids while those employing α‐hydroxy aldehydes reliably produce anti ‐1,2‐amino alcohol products in a highly diastereoselective manner . Asymmetric versions of these reactions using either a chiral Lewis acid or Brønsted acid catalyst are more recent developments .…”