Azetidinone trithiocarbone

Sulopenem (CP-70429 see Tables 1 and 7) has been prepared via this reaction as the key step (G=0/C=S reductive coupling). The total synthesis utilizes L-aspartic acid to generate the chiral precursor 78 of the C-2 side chain, a modified chiron 76 (X = C1) to improve the preparation of the trithiocarbonate intermediate 79, a chemoselective oxalofluoride-based azetidinone N-acylation to give 80 (a procedure that avoids sulfoxide O-acylation), and mild final deprotection conditions of hydroxyl and carboxyl functions. In particular, the chloroallyl ester 81 has been selected, owing to its smooth cleavage by a palladium-mediated transesterification procedure (Scheme 42) <1992JOC4352>. 

Transfer into a single-necked round-bottomed flask (100 mL), 4-acetoxy-2-azetidinone (1.32 g, 10.2 mmol) and a magnetic stirrer bar. Pour acetone (1 mL) and water (3.5 mL) into the flask under a stream of nitrogen and equip the flask with a pressure-equalizing addition funnel (50 mL) containing a solution of potassium ethyl trithiocarbonate (2.25 g, 1.28 mol-eq.) in water (12 mL). 

In particular, oxoamide-trithiocarbonate 243a (obtained by acylation of the IH-azetidinone 103a) reacted with triethyl phosphite under high dilution condi-... 

The chloracetic methine linked to the azetidinone nitrogen, which in compound 304 reacted as an electrophile, upon deprotonation can react as a nucleophile in other cyclization strategies. Very recently the conversion of trithiocarbonates 308a, b to penem 309 (a precursor of Pfizer s clinical candid-... 

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