Carbapenem intermediates

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

Several eco-friendly approaches to vinyl-/i-lactams (219-221) bearing a vinyl substituent at various positions on the ring (Scheme 9.71) have recently been described by Manhas [122]. Vinyl-/i-lactams are efficient synthons for a variety of compounds of biomedical interest, e. g. isocephalosporins, carbapenem intermediates and pyrrolidine alkaloids. MORE chemistry techniques allow highly accelerated syntheses using limited amounts of solvent and with efficient stereocontrol, thus achieving high atom economy . 

Fig. 32.29 Ind ustrial synthesis of a carbapenem intermediate by BINAP-Ru-catalyzed hydrogenation.

Although the ketene or acid halide imine methodology has been successfully utilized in the synthesis of optically active monocyclic and bicyclic P-lactams [33, 66], the potential that offers this approach to the synthesis of carbapenem intermediates still seems to be unexploited. With the exception of the above examples, this fact is probably due to the difficulty to obtain 3-alkyl P-lactams in good chemical yields and high stereoselectivity from the corresponding a-unactivated acetic acids or acid chlorides. 

The nitro group is a good leaving group, and allyl nitro compounds are used conveniently for allylation because they can be prepared easily by the reaction of nitromethane with aldehydes and ketones, and used for Pd-catalyzed reactions [15]. As an interesting application, the alkenyl triflate 30 was converted to the allyl nitro derivative 31, which was, without isolation, subjected to the Pd-catalyzed amination with 32 in the presence of tetramethylguanidine (TMG) as a strong amine base to afford the anri-MRS carbapenem intermediate 33 in 34% overall yield [16],... 

Park HS, Alberico E, Alper H. Regio- and stereoselective synthesis of key 1-methyl carbapenem intermediates via hydroformylation using a zwitterionic rhodium catalyst. J. Am. Chem. Soc. 1999 121 11697 11703. 

Figure 6 Carbapenem intermediates derived from methyl (/ )-P-hydroxybutyrate or (J )-P-hy-droxybutyric acid.

---