Functionalizing the γ-position of α-diazo-β-ketoesters

Abstract

Although α-diazo-β-ketoesters are synthetically versatile intermediates, methodology for introducing this functionality into complex molecules is still limited, most frequently involving a carboxylic acid precursor, which is then activated and transformed into a β-ketoester, with the diazo group being subsequently added with a diazo transfer reagent. While introducing this highly functional moiety in a convergent one step process would be ideal, such an objective is limited by the relatively few studies which address functionalization of the α-diazo-β-ketoester at the γ-position. In the present investigation, we evaluate strategies, both new and established, for functionalizing α-diazo-β-ketoesters, particularly with regard to generating compounds prospectively useful in the synthesis of C1-substituted carbapenems. We report the first δ-aldehydo-α-diazo-β-ketoester as well as a method for its oxidation to the corresponding methyl ester, and the formation of a new substituted pyrazole under basic conditions.

Diazocarbonyl and Related Compounds in the Synthesis of Azoles

“…An attempt to prepare carbapenem precursor 206 by treatment of diazo carbonyls 204 with DBU and β -lactam 205 unexpectedly led to the formation of hydroxypyrazoles 207 ( Scheme 49 ) [ 102 ]. From the mechanism standpoint, the 1,5-electrocyclization of enolate 50A likely gave pyrazolium anion 50C, which reacted with imine 50D, which was, in turn, formed by DBU-promoted elimination of acetic acid from β -lactam 205 ( Scheme 50 ).…”