Iron-Catalyzed Chemoselective Azidation of Benzylic Silyl Ethers
Iron-Catalyzed Chemoselective Azidation of Benzylic Silyl Ethers
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铁催化苄基甲硅烷基醚的化学选择性叠氮化
DOI：
10.1002/chem.201202984
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Y. Monguchi
中科院分区：
文献类型：
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作者：
Y. Sawama;S. Nagata;Y. Yabe. K. Morita;Y. Monguchi
硅醚传统上用于保护醇，并且由于硅氧基的离去基团能力较低，在大多数亲核试剂存在下是稳定的。[1]碳亲核试剂，例如烯丙基硅烷[2]和烯醇乙酸酯[3]，可以在合适的路易斯酸存在下与甲硅烷基醚反应。此外，还开发了硅醚在离子液体中的溴化、硫氰化和异硫氰化反应。 [4]尽管叠氮化物很重要，因为例如它们可以通过胡伊斯根反应转化为三唑[5]，并通过还原转化为胺[6]，但用于甲硅烷基醚叠氮化的方法很少；这种转化可以通过在 PPh3 和 2, 3-二氯-5, 6-二氰基苯醌 [7] 或 2, 4, 6-三氯 ACHTUNGTRENNUNG [1, 3, 5] 三-ACHTUNGTRENNUNGazine [8] 存在下使用 nBu4NN3 作为叠氮源来完成。在这些报道中，未受保护的（游离）醇[9]比甲硅烷基醚对叠氮阴离子的亲核攻击更具反应性，并且伯醇在仲醇和叔醇存在下优先转化为相应的伯叠氮产物。我们现在展示了一种新型的铁催化甲硅烷基醚叠氮化反应，该反应条件允许在伯苄基甲硅烷基醚存在下化学选择性转化仲和叔苄基甲硅烷基醚。此外，仲和叔苄基甲硅烷基醚相对于相应的游离苄醇更有效地进行叠氮化，并且许多反应性官能团，例如烷基氯，[10]，a，b-不饱和酯，[11]和醛，[12]在叠氮化条件下是稳定的。我们的研究小组一直致力于开发一种有效的方法来制备药用叠氮衍生物[13]，我们想知道在亲核取代条件下通常稳定的甲硅烷基醚的直接叠氮化是否可能。幸运的是，AuCl3 (5 mol%) 在 4 当量 TMSN3 存在的 (CH2Cl) 2 溶液中于室温下促进了 1-苯基乙醇 TBS 醚 (1a) 的理想叠氮化
Silyl ethers are traditionally used for the protection of alcohols and are stable in the presence of most nucleophiles, owing to the low leaving-group ability of the siloxy groups.[1] Carbon nucleophiles, such as allylsilanes [2] and enol acetates,[3] can react with silyl ethers in the presence of suitable Lewis acids. Furthermore, the bromination, thiocyanation, and isothiocyantion of silyl ethers in an ionic liquid were also developed.[4] Although azides are important because, for example, they can be transformed into triazoles by the Huisgen reaction [5] and into amines by reduction,[6] there are only a few methods for the azidation of silyl ethers; this transformation can be accomplished by the use of nBu4NN3 as an azido source in the presence of PPh3 and either 2, 3-dichloro-5, 6-dicyanobenzoquinone [7] or 2, 4, 6-trichloroACHTUNGTRENNUNG [1, 3, 5] tri-ACHTUNGTRENNUNGazine.[8] In these reports, nonprotected (free) alcohols [9] are more reactive than silyl ethers toward nucleophilic attack of the azide anion and primary alcohols are preferentially converted into the corresponding primary azido products in the presence of secondary and tertiary alcohols. We now demonstrate a novel iron-catalyzed azidation of silyl ethers, the reaction conditions allowing chemoselective transformation of secondary and tertiary benzylic silyl ethers in the presence of primary benzylic silyl ethers. Moreover, secondary and tertiary benzylic silyl ethers undergo azidation more efficiently relative to that of the corresponding free benzylic alcohols, and many reactive functional groups, such as alkyl chlorides,[10] a, b-unsaturated esters,[11] and aldehydes,[12] were stable under the azidation conditions. Our research group has been focusing on the development of an efficient method for preparing pharmaceutically useful azido derivatives [13] and we wondered whether the direct azidation of silyl ethers, which are normally stable under nucleophilic-substitution conditions, was possible. Fortunately, AuCl3 (5 mol%) facilitated the desirable azidation of 1-phenylethanol TBS ether (1a) in the presence of 4 equivalents of TMSN3 in (CH2Cl) 2 at room temperature