Concise and practical synthesis of C-glycosyl ketones from sugar benzothiazoles and their transformation into chiral tertiary alcohols
Concise and practical synthesis of C-glycosyl ketones from sugar benzothiazoles and their transformation into chiral tertiary alcohols
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DOI：
10.1021/jo051377w
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发表时间：
2005-11-11
影响因子：
3.6
通讯作者：
Marra, A
中科院分区：
文献类型：
--
作者：
Dondoni, A;Catozzi, N;Marra, A
基于使用苯并噻唑作为羰基等价物，通过统一路线制备了 13 种不对称酮的集合，每种酮都具有糖（D-葡萄糖基、D-半乳糖基、D-甘露糖基和 L-岩藻糖基）和糖苷配基部分（苯基、2-噻唑基、TMS-乙炔基、烯丙基和 1-丙烯基）。简而言之，C-糖基苯并噻唑通过将2-锂硫代苯并噻唑加成到糖内酯上并脱氧而容易地制备，并进行一锅反应序列，包括通过WOW对杂环进行N-甲基化，用格氏试剂处理N-甲基苯并噻唑鎓盐，以及HgCl2促进由此形成的苯并噻唑啉的水解。分离得到的酮，产率从 35% 到 80% 不等。用含有苯基、2-噻唑基、TMS-乙炔基或乙炔基作为取代基的各种有机金属处理糖酮，得到手性叔醇。通过粗核磁共振分析观察到，这些加成反应具有高度立体选择性，并且在每种情况下均以高产率分离出单一差向异构体。然而，由于所涉及试剂的复杂性，这些反应的立体化学结果似乎难以通过简单的经典空间模型合理化，因此，考虑糖片段的作用的从头开始研究是可取的。据报道，将含有噻唑环的炔丙醇合成为带有甲酰基和羧酸酯基团的炔丙醇。
A collection of 13 unsymmetrical ketones, each one featuring a sugar (D-glucosyl, D-galactosyl, D-mannosyl, and L-fucosyl) and an aglycone moiety (phenyl, 2-thiazolyl, TMS-ethynyl, allyl, and 1-propenyl) was prepared by a uniform route based on the use of benzothiazole as a carbonyl group equivalent. Succinctly, C-glycosylbenzothiazoles readily prepared by addition of 2-lithiobenzothiazole to sugar lactones and deoxygenation, were subjected to a one-pot reaction sequence involving N-methylation of the heterocyclic ring by WOW, treatment of the N-methylbenzothiazolium salt with a Grignard reagent, and HgCl2-promoted hydrolysis of the benzothiazoline thus formed. The resulting ketones were isolated in yields varying from 35 to 80%. Treatment of the sugar ketones with various organometals containing the phenyl, 2-thiazolyl, TMS-ethynyl, or ethynyl group as a substituent afforded chiral tertiary alcohols. These addition reactions were highly stereoselective as observed by crude NMR analysis and isolation of a single epimer in high yield in each case examined. However, because of the complexity of the reagents involved, the stereochemical outcome of these reactions appears to be difficult to rationalize by simple classical steric models, thus, ab initio studies taking into account the role of the sugar fragment are advisable. An interesting synthetic elaboration of a propargylic alcohol containing the thiazole ring into a propargylic alcohol bearing the formyl and carboxylate groups is reported.