A Catalytic, Enantioselective Sulfamate Tethered Aza-Michael Cyclization

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• Chiral molecules are crucial in pharmaceuticals and materials science.
• Developing efficient methods for synthesizing enantiomerically pure compounds is a significant challenge in organic chemistry.
• Sulfamates are versatile functional groups that can be utilized in various synthetic transformations.

Purpose of the Study:

• To report the first examples of enantioselective cyclization reactions involving tethered sulfamates and α,β-unsaturated carbonyl compounds.
• To introduce a novel chiral bifunctional guanidine catalyst for promoting these cyclization reactions.
• To explore the scope and limitations of the developed methodology with various substrates.

Main Methods:

• Utilized a newly developed chiral bifunctional guanidine catalyst.
• Performed enantioselective cyclization reactions between tethered sulfamates and pendant α,β-unsaturated esters, ketones, and thioesters.
• Examined a range of primary and secondary sulfamates and sulfamides.

Main Results:

• Achieved excellent yields and enantiomeric ratios for the cyclization products using primary sulfamates and sulfamides.
• Demonstrated the feasibility of kinetic resolutions with secondary sulfamates.
• Successfully synthesized oxathiazinanes, which serve as valuable chiral synthons.

Conclusions:

• The developed catalytic system provides an operationally simple and effective route to enantiomerically enriched oxathiazinanes.
• The new chiral guanidine catalyst is highly effective in promoting enantioselective cyclization reactions.
• The synthesized oxathiazinanes are versatile building blocks for further asymmetric synthesis.