Department of Chemistry , Barnard College , 3009 Broadway , New York , New York 10027 , United States.
J Org Chem. 2018 Aug 3;83(15):8054-8080. doi: 10.1021/acs.joc.8b00893. Epub 2018 Jul 6.
The rhodium(II)-catalyzed oxidative cyclization of glycal 3-carbamates with in situ incorporation of an alcohol nucleophile at the anomeric position provides access to a range of 2-amino sugars having 1,2-trans-2,3-cis stereochemistry, a structural motif present in compounds of medicinal and biological significance such as the streptothricin group of antibiotics and the Chitinase inhibitor allosamidin. All of the diastereomeric d-glycal 3-carbamates have been investigated, revealing significant differences in anomeric stereoselectivity depending on substrate stereochemistry and protecting groups. In addition, some substrates were prone to forming C3-oxidized dihydropyranone byproducts under the reaction conditions. Allal- and gulal 3-carbamates provided uniformly high stereo- and chemoselectivity, while for glucal substrates, acyclic, electron-withdrawing protecting groups at the 4 O and 6 O positions were required. Galactal 3-carbamates have been the most challenging substrates; formation of their amidoglycosylation products is most effective with an electron-withdrawing 6 O-Ts substituent and a sterically demanding 4 O-TBS group. These results suggest a mechanism whereby conformational and electronic factors determine the partitioning of an intermediate acyl nitrenoid between alkene addition, leading to amidoglycosylation, and C3-H insertion, providing the dihydropyranone byproduct. Along the amidoglycosylation pathway, high anomeric selectivity results when a glycosyl aziridine intermediate is favored over an aziridine-opened oxocarbenium donor.
铑（II）催化的糖醛 3-氨基甲酸酯的氧化环化反应，在糖醛的位引入醇亲核试剂，可得到一系列具有 1,2-反式-2,3-顺式立体化学结构的 2-氨基糖，这种结构基序存在于具有医学和生物学意义的化合物中，如抗生素链丝菌素组和几丁质酶抑制剂 allo 萨米汀。所有的非对映立体异构体的 d-糖醛 3-氨基甲酸酯都进行了研究，结果表明，根据底物的立体化学和保护基的不同，在糖醛的位具有显著的立体选择性差异。此外，一些底物在反应条件下容易形成 C3-氧化的二氢吡喃酮副产物。Allal-和 gulal 3-氨基甲酸酯提供了均匀的高立体和化学选择性，而对于葡萄糖醛酸底物，需要在 4 O 和 6 O 位置上具有非环、吸电子保护基。半乳糖醛酸 3-氨基甲酸酯是最具挑战性的底物；用吸电子的 6 O-Ts 取代基和空间要求高的 4 O-TBS 基团形成它们的酰胺糖基化产物的效果最佳。这些结果表明，构象和电子因素决定了中间体酰基氮烯的分配，该中间体在烯烃加成、导致酰胺糖基化和 C3-H 插入之间进行分配，提供二氢吡喃酮副产物。在酰胺糖基化途径中，当糖基氮丙啶中间体优先于氮丙啶开环的氧杂碳正离子供体时，高的糖醛的位立体选择性结果。
