Apomitomycin Eschenmoser coupling reaction

The mitomycins are a class of antitumor antibiotics that has been the target of numerous synthetic efforts. The Eschenmoser reaction was a key coupling step in the synthesis of a mitomycin intermediate, apomitomycin (153). Thiopyrrolidinone (149) was alkylated with the aryl bromoacetate (150), and the intermediate a-thioiminium salt was heated with DBU (Scheme 32). The desired condensation product (151) was obtained in excellent yield, although epimerization about the pyrrolidine ring had occurred to produce a 1 1 mixture of the cis and trans substituted diastereomers. Note that, in contrast to a-alkyl-substituted electrophiles, which require conversion to triflates for complete thioamide alkylation, the more reactive benzylic bromide in (150) gave efficient alkylation. The key intermediate (151) was cy-clized in the presence of sodium hydride and copper(I) bromide to yield a single product (152) in nearly quantitative yield. Epimerization to the more stable trans isomer occurred under the cyclization conditions. This intermediate was readily converted to the final product (153). 

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See also in sourсe #XX -- [ ]

See also in sourсe #XX -- [ ]

See also in sourсe #XX -- [ ]

See also in sourсe #XX -- [ ]

See also in sourсe #XX -- [ ]

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