Direct-Type Aldol Reactions of Fluorenylidene-Protected/Activated Glycine Esters with Aldehydes for the Synthesis ofβ-Hydroxy-α-amino Acid Derivatives
Direct-Type Aldol Reactions of Fluorenylidene-Protected/Activated Glycine Esters with Aldehydes for the Synthesis ofβ-Hydroxy-α-amino Acid Derivatives
复制标题
亚芴基保护/活化甘氨酸酯与醛的直接羟醛反应用于合成β-羟基-α-氨基酸衍生物
DOI：
10.1002/asia.201200081
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Shu Kobayashi
中科院分区：
文献类型：
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作者：
Raphael Rahmani;Masatoshi Matsumoto;Yasuhiro Yamashita;Shu Kobayashi
β-羟基-α-氨基酸的合成在文献中有广泛的记载。[1]事实上，该部分可以在许多天然产物中发现，如万古霉素[2]和乳胞素。[3]得到这些产物的最快速途径之一涉及N-保护的甘氨酸和醛之间的羟醛缩合。米勒和同事[4]报道了使用手性相转移催化剂的甘氨酸席夫碱与醛的羟醛缩合。最近，Shibasaki和同事[5]报道了甘氨酸席夫碱和几种脂肪醛之间成功的直接不对称羟醛缩合反应[6]，具有中等的非对映体和对映体选择性。同年，Maruoka和同事[7]描述了使用相转移催化剂的相同反应，得到具有高非对映体和对映体选择性的相应羟醛加合物。其他小组也报道了类似的羟醛缩合使用甘氨酸席夫碱。[8]作为替代亲核物质，5-烷氧基恶唑，[9] α-异氰基乙酸酯[10]和α-异硫氰酸酰亚胺[11]用于这种类型的反应。[12]此外，已发现酶促通路，但显示出一些底物限制。[13]最近，我们的小组表明，氨基烷烃可以保护和活化，在同一时间通过使用9-芴亚基。[14]该基团允许通过稳定14 π电子系统来强烈活化氮原子的α-位置。[15]基于这一想法，我们开发了一种通过N-保护的亚胺如N-叔丁氧羰基（Boc）或N-二苯基膦酰基（Dpp）亚胺的Mannich型反应来有效合成二胺化合物的方法。这些结果鼓励我们研究芴基保护的甘氨酸席夫碱的直接型羟醛缩合反应。在此，我们描述了使用催化量的官能化碱的高度立体选择性的羟醛缩合反应的发展。
The synthesis of β-hydroxy-α-amino acid has been widely documented in the literature.[1] Indeed, this moiety can be found in numerous natural products such as vancomycin [2] and lactacystin.[3] One of the most rapid routes to these products involves an aldol condensation between an N-protected glycine and an aldehyde. Miller and co-workers [4] reported aldol condensation of a glycine Schiff base with aldehydes using a chiral phase-transfer catalyst. More recently, Shibasaki and co-workers [5] reported the successful direct asymmetric aldol reaction [6] between a glycine Schiff base and several aliphatic aldehydes with moderate diastereoand enantioselectivities. In the same year, Maruoka and coworkers [7] described the same reaction using a phase-transfer catalyst giving the corresponding aldol adduct with high diastereo-and enantioselectivities. Other groups also reported similar aldol condensations using glycine Schiff bases.[8] As alternative nucleophilic species, 5-alkoxyoxazole,[9] α-isocyano acetates,[10] and α-isothiocyanatoimides [11] were used for this type of reaction.[12] Moreover, enzymatic accesses have been found but show some substrate limitations.[13] Recently, our group showed that aminoalkanes could be protected and activated at the same time by using a 9-fluorenylidene group.[14] This group allows a strong activation of the α-position of the nitrogen atom via stabilization of the 14 π electron system.[15] Based on that idea, we have developed an efficient synthesis of diamine compounds by Mannich-type reactions of N-protected imines, such as N-tert-butoxycarbonyl (Boc) or N-diphenylphosphinoyl (Dpp) imines. Those results encouraged us to investigate the direct-type aldol reactions of fluorenylidene-protected glycine Schiff bases. Herein, we describe the development of highly stereoselective aldol reactions using a catalytic amount of functionalized base.