Synthesis of gem-difluorocarba-D-glucose:: A step further in sugar mimesis
Synthesis of gem-difluorocarba-D-glucose:: A step further in sugar mimesis
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DOI：
10.1002/anie.200461244
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发表时间：
2004-01-01
影响因子：
16.6
通讯作者：
Sinay, P
中科院分区：
文献类型：
--
作者：
Deleuze, A;Menozzi, C;Sinay, P
由于吡喃糖苷 [20] 的可及性以及 Harrity 和同事 [21] 最近的结果表明六羰基二钴簇 [22] 在类似情况下可以充当 EDG，我们预计我们应用于二氟烯烃 2 的 TIBAL 介导的还原重排可能会为我们的目标分子 1 提供方便的进入（方案 2）。方案 3 描述了化合物 2 的前体 ynopyranose 6 的合成。已知的[20]偕二溴烯烃3首先通过原位产生的炔属阴离子的甲基化转化为炔烃4。乙酰解[23]，然后水解生成的端基乙酸酯，并氧化半缩醛，得到相应的内酯 5。根据 Motherwell 等人的说法，二氟亚甲基化[24]提供了所需的偕二氟烯烃前体 6。正如预期的那样，令我们高兴的是，关键的重排是通过两步一锅法进行的，首先涉及八羰基二钴与炔烃 6 的络合，[25]，然后是还原性 TIBAL 诱导的 2 重排。[17]粗化合物 7 与 CAN（硝酸高铈铵）[26] 解络，经过三步，仅一步色谱纯化，得到醇 8，收率 75%。然后，通过控制三键还原、还原性臭氧分解和脱苄基作用，可以轻松获得 5a-gem-二氟碳-α-d-吡喃葡萄糖 1 [27]（方案 4）。正如之前所观察到的，[15]重排发生时构型保留。假定瞬态的减少
accessibility of ynopyranosides [20] and the recent results of Harrity and co-workers [21] who showed that dicobalt hexacarbonyl clusters [22] could act as EDGs in a similar situation, we anticipated that our TIBAL-mediated reductive rearrangement applied to the difluoroalkene 2 might provide a convenient entry to our target molecule 1 (Scheme 2). Synthesis of the ynopyranose 6, the precursor of compound 2, is depicted in Scheme3. The known [20] gemdibromoalkene 3 was first converted into alkyne 4 through methylation of the acetylenic anion generated in situ. Acetolysis,[23] followed by hydrolysis of the generated anomeric acetate, and oxidation of the hemiacetal afforded the corresponding lactone 5. Difluoromethylenation according to Motherwell et al.[24] provided the desired gem-difluoroalkene precursor 6.As anticipated and much to our delight, the key rearrangement was performed through a two-step one-pot procedure that involved first, the complexation of the alkyne 6 by dicobalt octacarbonyl,[25] followed by the reductive TIBAL-induced rearrangement of 2.[17] Decomplexation with CAN (ceric ammonium nitrate)[26] of the crude compound 7 afforded alcohol 8 in 75% yield over three steps and only one purification step by chromatography. The 5a-gem-difluorocarba-α-d-glucopyranose 1 [27] was then easily obtained by controlled reduction of the triple bond, reductive ozonolysis, and debenzylation (Scheme4). As previously observed,[15] the rearrangement occurs with retention of configuration. The reduction of the putative transient