Three-component reductive alkylation of 2-hydroxy-1, 4-naphthoquinones with lactols
Eliana E Kim1, Evans O Onyango1, Jennifer R Pace1
1Department of Chemistry, Dartmouth College, Hanover, NH 03755-3564, USA.
Researchers utilized lactols and hydroxyaldehyde tautomers in a reductive alkylation reaction. This process successfully synthesized various 3-alkylated 2-hydroxy-1,4-naphthoquinone derivatives.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- Lactones are cyclic esters that can be reduced to lactols.
- Lactols exist in equilibrium with their hydroxyaldehyde tautomers.
- 2-hydroxy-1,4-naphthoquinone is a biologically relevant scaffold.
Purpose of the Study:
- To explore the utility of lactols and their tautomers in multi-component reactions.
- To synthesize novel 3-alkylated 2-hydroxy-1,4-naphthoquinone derivatives.
Main Methods:
- DIBAL reduction of lactones (I) to yield lactols (II).
- Equilibration of lactols (II) with hydroxyaldehyde tautomers (III).
- Three-component reductive alkylation using lactols/tautomers and 2-hydroxy-1,4-naphthoquinone.
Main Results:
- Successful synthesis of a series of 3-alkylated 2-hydroxy-1,4-naphthoquinone derivatives (IV).
- Demonstration of a novel synthetic route to functionalized naphthoquinones.
Conclusions:
- Lactols and their hydroxyaldehyde tautomers are effective nucleophiles in reductive alkylation.
- The developed method provides efficient access to substituted 2-hydroxy-1,4-naphthoquinones.
More Related Videos
07:30A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones
Published on: January 21, 2020
09:14Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Related Concept Videos
01:24Preparation of Aldehydes and Ketones from Nitriles and Carboxylic Acids
Reducing carboxylic acid derivatives like acyl chlorides (RCOCl), esters (RCO2R′), and nitriles (RCN) using milder aluminum hydride agents like lithium tri-tert-butoxyaluminum hydride [LiAlH(O-t-Bu)3] and diisobutylaluminum hydride [DIBAL-H]...
02:23Alcohols from Carbonyl Compounds: Reduction
Catalytic hydrogenation is similar to the reduction of an alkene or alkyne by adding H2 across the pi bond in the presence of transition metal catalysts like Raney Ni, Pd–C, Pt, or Ru. Aldehydes and ketones can be reduced by this method, often under mild to moderate heat (25–100°C) and...
01:19Acid Halides to Alcohols: LiAlH4 Reduction
The mechanism proceeds in three steps. First, the nucleophilic hydride ion attacks the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs as a leaving group, generating an aldehyde. A second nucleophilic attack by the hydride yields an alkoxide ion, which, upon protonation, gives a primary alcohol as...
01:09Aldehydes and Ketones to Alkanes: Wolff–Kishner Reduction
01:27Vicinal Diols via Reductive Coupling of Aldehydes or Ketones: Pinacol Coupling Overview
01:17Carboxylic Acids to Primary Alcohols: Hydride Reduction