Highly diastereoselective alkylation of aziridine-2-carboxylate esters: Enantioselective synthesis of LFA-1 antagonist BIRT-377
Highly diastereoselective alkylation of aziridine-2-carboxylate esters: Enantioselective synthesis of LFA-1 antagonist BIRT-377
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DOI：
10.1002/anie.200500923
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Wulff, WD
中科院分区：
文献类型：
--
作者：
Patwardhan, AP;Pulgam, VR;Wulff, WD
叠氮嘧啶是有机化学中重要的合成子，因为它们为光学纯胺、α氨基酸、氨基醇、二胺和各种其他氨基化合物提供了方便的入口，这些化合物在工业和学术研究中都很有用。过去，大多数光学纯的叠氮嘧啶都是由手性池的无环成员衍生而来，然而，通过催化不对称反应直接合成光学纯叠氮嘧啶的方法正在出现本文研究了一种由VAPOL和VANOL配体制备的手性硼刘易斯酸介导的苯并羟基亚胺与重氮化合物反应催化不对称合成叠氮嘧啶的方法。[2-4]这种不对称叠氮化（AZ）被证明适用于一系列亚胺，包括由各种芳基醛以及由伯、仲、叔脂肪醛（90-99% ee）制备的亚胺。n -苄基亚胺的对映选择性低得多。[2d]在α-碳上四取代的α-氨基酸是非常常用的工具，用于控制肽的构象，从而控制其生物和药物特性。四取代α-氨基酸的合成方法有很多，本文对四取代α-氨基酸的合成方法进行了综述有趣的是，偶氮吡啶很少用于合成四取代α-氨基酸，这可能部分是因为偶氮吡啶-2-羧酸的烷基化实际上是一个未知的反应。通常，试图烷基化二羧酸亚氮啶酯会导致开环或自缩合。[6,7]唯一已知的例子包括使用氮吡啶-2-羧酸酯的硫酯，或在氮吡啶上使用氮取代基来螯合金属烯醇酯通过亚胺1与重氮化合物的不对称叠氮化反应，可以预见AZ反应在四取代α-氨基酸合成中的直接应用
Aziridines are important synthons in organic chemistry as they provide convenient entry to optically pure amines, αamino acids, amino alcohols, diamines, and a variety of other amino compounds that are useful both in industrial and academic endeavors. In the past, most optically pure aziridines were derived from acyclic members of the chiral pool, however, methods are emerging for the direct synthesis of optically pure aziridines through catalytic asymmetric reactions.[1] We have developed a process for the catalytic asymmetric synthesis of aziridines from the reaction of benzhydryl imines with diazo compounds mediated by a chiral boron Lewis acid prepared from the VAPOL and VANOL ligands.[2–4] This asymmetric aziridination (AZ) proved general for a range imines including those prepared from a variety of aryl aldehydes and also from primary, secondary, and tertiary aliphatic aldehydes (90–99% ee). Much lower enantioselectivities were observed with N-benzyl imines.[2d] α-Amino acids which are tetrasubstituted at the α-carbon are very popular tools that are used to control conformation in peptides, and hence their biological and pharmaceutical properties. A large number of methods have been developed for the synthesis of tetrasubstituted α-amino acids, and this subject has been reviewed.[5] Interestingly, aziridines have rarely been used for the synthesis of tetrasubstituted α-amino acids and this may be partly due to the fact that the alkylation of aziridine-2-carboxylates is virtually an unknown reaction. Typically, attempts to alkylate aziridine-2-carboxylate esters leads to either ring opening or to self-condensation.[6, 7] The only known examples involve the use of either thioesters of aziridine-2-carboxylates [6] or the use of a nitrogen substituent on the aziridine that can chelate a metal enolate.[7] A direct application of the AZ reaction to the synthesis of tetrasubstituted α-amino acids could be envisioned through the asymmetric aziridination of imine 1 with diazo compound