trans counterpart, the cis-configured scaffold derived from the Castagnoli–Cushman reaction (CCR) is scarce and has not been explored in bioactive compound design. We found that conducting this reaction in DMF (in contrast to conventional toluene or xylene) led to a significantly higher proportion of cis-configured lactams in the diastereomeric product mixture. This allowed us, for the first time, to obtain
与它的反式对应物不同,源自Castagnoli-Cushman反应(CCR)的顺式构型支架十分稀少,尚未在生物活性化合物设计中进行探索。我们发现,在DMF中进行该反应(与常规的甲苯或二甲苯相反)导致非对映体产物混合物中的顺式构型内酰胺的比例明显更高。这使我们第一次获得并充分表征了大量铅样CCR内酰胺的两种立体异构体。已经设计了基于1 H NMR的立体化学分配的简单规则,并将其与为纯顺式和反式获得的单晶X射线结构相关-配置的内酰胺。
The first solvent-free synthesis of privileged γ- and δ-lactams via the Castagnoli–Cushman reaction
A new format for the Castagnoli–Cushman reaction of structurally diverse dicarboxylic acids, amines, and aldehydes in the presence of aceticanhydride as dehydrating agent is described. The reaction is distinctly amenable to parallel format: the combinatorial array of 180 reactions delivered 157 products of >85% purity without chromatographic purification (of this number, 143 compounds had >94% purity)