Palladium-catalyzed asymmetric three-component reaction between glyoxylic acid, sulfonamides and arylboronic acids for the synthesis of α-arylglycine derivatives

Abstract

A palladium-catalyzed asymmetric three-component synthesis of α-arylglycine derivatives starting from glyoxylic acid, sulfonamides and arylboronic acids is reported. This novel, operationally simple method offers access to the α-arylglycine scaffold in good yields and enantioselectivities. The utilization of α tailored catalyst system enables the enantioselective synthesis of the desired α-arylglycines despite a fast racemic background reaction. The obtained products can be directly employed as building blocks in peptide synthesis.

Palladium-Catalyzed Enantioselective Three-Component Synthesis of alpha-Arylglycine Derivatives from Glyoxylic Acid, Sulfonamides and Aryl Trifluoroborates

“…]17 -20] Recently, we were able to extend these transformations to a palladium-catalyzed enantioselective synthesis of -arylglycine bearing a free carboxylic acid functionality directly from the parent glyoxylic acids (Scheme 1c). [21] We could show, that the desired arylglycine can be synthesized in good to excellent enantioselectivities. However, depending on the nature/substitution pattern of aryl boronic acid, some of the arylglycine products could only be obtained in very low enantioselectivities.…”

“…11 Scheme 3. Reaction Scope -Aryl Trifluoroborates (Yields and e.r in parentheses refer to our previous study with the corresponding boronic acids [21] )…”

“…As already demonstrated in our previous work, the Pbf-protected arylglycine products can be directly used as building blocks for peptide synthesis. [21] This is exemplified in the preparation of the dipeptide 17 via a standard peptide coupling of arylglycine 10a with L-valine methyl ester hydrochloride, followed by TFA-mediated removal of the Pbfprotecting group.…”

“…Synthesis of dipeptide 17 from arylglycine 10a. [21] Finally, we utilized our method for the preparation of a protected version of parahydroxphenylglycine, a common structural motif in vancomycin, teicoplanin, feglymycin and amoxicillin. Therefore the OBn-protected aryl trifluoroborate was subjected to our standard reaction conditions, affording the desired N,O-protected (S)-arylglycinederivative 10k in 38% yield and enantiomeric ratio of 88:12.…”

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

“…In parallel, we have developed palladium-catalyzed three-component reactions between arylboronic or carboxylic acids, amides or sulfonamides and different aldehyde components as attractive and broadly applicable alternative to the classical Petasis borono-Mannich reaction ( Scheme 1b ) [ 17 – 21 ]. Recently, we were able to extend these transformations to a palladium-catalyzed enantioselective synthesis of α-arylglycine bearing a free carboxylic acid functionality directly from the parent glyoxylic acids ( Scheme 1c ) [ 22 ]. We could show that the desired arylglycine can be synthesized in good to excellent enantioselectivities.…”