A Green Protocol for the Synthesis of α‐Diazo‐β‐hydroxyesters and One‐Pot Conversion to β‐Keto‐Esters and Imidazo[1,2‐a]pyridine‐3‐carboxylates

Abstract

A new solvent cum reagent system comprising of water extract of banana ash and dimethylsulfoxide (WEB‐DMSO) has been engaged for the first time to promote the aldol type condensation reaction of aldehydes with ethyl diazoacetate. The condensation reaction has smoothly undergone producing a range of α‐diazo‐β‐hydroxy esters in good to excellent yields. The solvent system has been reused up to five times without loss of its catalytic activity. Further, two one‐pot sequential reactions have been developed in the same reaction medium. First, the methodology has been extended to synthesize β‐keto esters through Pd catalyzed 1,2‐hydrogen migration. Secondly, β‐keto esters have been converted to imidazo[1,2‐a]pyridine‐3‐carboxylates by using N‐bromosuccinimide and 2‐aminopyridines in a one‐pot fashion.

Diazocarbonyl and Related Compounds in the Synthesis of Azoles

“…An interesting example of using a banana ash extract and dimethylsulfoxide (WEB-DMSO) as solvent cum reagent system for three-step one-pot synthesis of imidazo[1,2- a ]pyridines 180 was reported by Dutta and co-authors in 2019 [ 89 ]. Initially, a WEB-DMSO-promoted aldol condensation of ethyl diazoacetate 82 and aldehyde 178 occurred to give diazo alcohol 181, which was converted to β -ketoester 182 by a Pd-catalyzed 1,2-H shift.…”

Stereoselective Bioreduction of α-diazo-β-keto Esters

“…Therefore, a representative group of in-house made Escherichia coli overexpressed ADHs was evaluated ( Table 2), including the enzymes from Rhodococcus ruber (ADH-A) [38], Thermoanaerobium species (ADH-T) [39], Lactobacillus brevis (LB-ADH) [40,41], Ralstonia species (Ras-ADH) [42,43], Sphingobium yanoikuyae (Sy-ADH), [44,45], and Thermoanaerobacter ethanolicus (Tes-ADH) [46]. Unfortunately, poor activities (<10% conversion, entries [1][2][3][4][5][6] were observed for all these E. coli overexpressed ADHs, except for the Ras-ADH, which led to the formation of a complex mixture of unidentified products [47]. Next, diazo keto esters 2a-i were chemically reduced by employing sodium borohydride (NaBH 4 ) in tetrahydrofuran (THF) as the solvent at 0 • C for only 10 min to give the expected α-diazo-β-hydroxy esters 3a-i in moderate to high yields after column chromatography purification (62-85%, Table 1).…”

“…α-Diazo carbonyl compounds are widely recognized as versatile reagents in organic synthesis and chemical biology [1][2][3][4][5]. The chemistry of α-diazo-β-hydroxy carbonyl compounds attracts particular attention, as these functionalized compounds have been employed in the synthesis of amino acid analogues and heterocycles of biological relevance [6][7][8][9][10][11]. The conventional preparation of α-diazo-β-hydroxy carbonyl compounds relies on the aldol-type addition of a terminal diazo carbonyl compound with aldehydes or ketones mediated by a strong base such as the organometallics of lithium, magnesium, or zinc, DBU, and NaOH [12][13][14][15][16].…”