Diastereoselective addition of 2-alkoxy-2-fluoroacetate to N-(tert-butylsulfinyl)imines: Synthesis of α-alkoxy-α-fluoro-β-amino acids

A diastereoselective Mannich-type reaction of 2-alkoxy-2-fluoroacetate and N-(tert-butylsulfinyl)imines is reported. This protocol provides a straightforward route to & alpha;-alkoxy-& alpha;-fluoro-& beta;-amino acids in good yields and moderate to high diastereoselectivities. This approach uses readily accessible starting materials and is operationally simple. Additionally, the stereochemistry of the current reaction was different from that of the known addition of comparable nonfluorinated 2-alkoxycarboxylic esters to N-sulfinyl imines. An open transition state (rather than a closed one) is proposed to explain the stereochemical outcome.

Automated summary

A diastereoselective Mannich-type reaction of 2-alkoxy-2-fluoroacetate and N-(tert-butylsulfinyl)imines is reported, providing a straightforward route to α-alkoxy- α-fluoro- β-amino acids in good yields and moderate to high diastereoselectivities. This approach uses readily accessible starting materials and is operationally simple. The stereochemistry of the current reaction differs from that of the known addition of comparable nonfluorinated 2-alkoxycarboxylic esters to N-sulfinyl imines, suggesting an open transition state explanation.