S,O-acetals as novel "chiral aldehyde" equivalents

Area of Science:

• Organic Chemistry
• Asymmetric Catalysis
• Synthetic Methodology

Background:

• Palladium-catalyzed asymmetric allylic alkylation (AAA) is a powerful tool for C-C bond formation.
• Developing novel chiral building blocks and efficient synthetic routes remains a key challenge in organic synthesis.

Purpose of the Study:

• To investigate palladium-catalyzed asymmetric allylic alkylations (AAA) for the synthesis of chiral aldehyde equivalents.
• To explore the utility of alpha-acetoxysulfones as novel directing groups in asymmetric synthesis.

Main Methods:

• Asymmetric allylic alkylation of allylic geminal dicarboxylates with sodium benzenesulfinate using palladium catalysis.
• Asymmetric dihydroxylation of the resulting alpha-acetoxysulfones.
• Subsequent transformations of the generated diols, including a one-pot protocol.

Main Results:

• Alpha-acetoxysulfones were synthesized in high enantiomeric excess and as single regioisomers.
• Dihydroxylation of alpha-acetoxysulfones afforded syn diols exclusively anti to the acetoxy sulfone in excellent yields and diastereoselectivity.
• Demonstrated the first asymmetric dihydroxylation protocol yielding the equivalent of reaction with a simple enal.
• Developed a one-pot dihydroxylation-deprotective acyl migration protocol for differentially protected 1,2-diols.

Conclusions:

• The study presents a novel and efficient method for generating chiral aldehyde equivalents via palladium-catalyzed AAA.
• The alpha-acetoxysulfone serves as a versatile directing group, enabling highly stereoselective dihydroxylation and subsequent transformations.
• This methodology expands the toolkit for asymmetric synthesis, providing access to valuable 1,2-diol derivatives.