Dynamic kinetic asymmetric allylic amination and acyl migration of vinyl Aziridines with imido carboxylates
Dynamic kinetic asymmetric allylic amination and acyl migration of vinyl Aziridines with imido carboxylates
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DOI：
10.1002/anie.200700835
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Stiles, Dylan T.
中科院分区：
文献类型：
--
作者：
Trost, Barry M.;Tandrick, Daniel R.;Stiles, Dylan T.
钯催化的不对称烯丙基烷基化反应（AAA）已被证明是制备合成有用物质的一种通用方法。[1]乙烯基环氧化物在相关的动态动力学不对称转化（DYKAT）中显示出广泛的用途，其中外消旋起始材料转化为对映体富集的产物。[2]直到最近才报道了乙烯基氮丙啶与异氰酸酯的环加成反应，得到手性咪唑烷酮。[3]尽管这种方法以高ee提供了有价值的手性邻位二胺部分[4]，但由于难以区分所得胺，其合成实用性受到限制。在最近对酰亚胺亲核试剂的研究中，我们发现了一种原子经济型[5] DYKAT，可通过使用容易进行原位酰基迁移的酰亚胺羧酸酯有效制备有用的正交保护的手性邻二胺。通过与乙烯基环氧化物的DYKAT反应的类比，[6]我们首先研究了使用二膦配体3将邻苯二甲酰亚胺不对称加成到母体乙烯基氮丙啶1上[Eq.①]。加入催化乙酸，这在之前与异氰酸酯的环加成中是有益的，[3]使ee增加（47至82%ee），同时产率下降（99至55%）。而使用催化三乙胺则在提高ee的同时提供了实际产率。高对映体选择性的合理合理化是一个非对映体η3-烯丙基PdII络合物的Curtin-Hammett动力学胺化，该络合物来自通过π-σ-π机理快速相互转化的对。
The palladium-catalyzed asymmetric allylic alkylation (AAA) has proven to be a versatile method for the preparation of synthetically useful materials.[1] Vinyl epoxides have shown a broad utility in related dynamic kinetic asymmetric transformations (DYKATs), wherein a racemic starting material is converted into an enantioenriched product.[2] Only recently has the cycloaddition of vinyl aziridines with isocyanates to afford chiral imidazolidinones been reported.[3] Although this methodology provides the valuable chiral vicinal diamine moiety [4] in high ee, its synthetic utility has been limited owing to the difficult differentiation of the resulting amines. In recent studies with imide nucleophiles, we discovered an atom-economical [5] DYKAT for the efficient preparation of useful orthogonally protected chiral vicinal diamines through use of imido carboxylates that undergo a facile in situ acyl migration. Application of the AAA enabled the formal synthesis of the potent PKC inhibitor balanol and its cis diastereomer.By analogy to the DYKAT reactions with vinyl epoxides,[6] we first examined the asymmetric addition of phthalimide to the parent vinyl aziridine 1 with the use of diphosphine ligand 3 [Eq.(1)]. The addition of catalytic acetic acid, which was beneficial in the previous cycloadditions with isocyanates,[3] gave an increase in ee (47 to 82% ee) with a concomitant drop in yield (99 to 55%). The use of catalytic triethylamine instead provided a balance in improving the ee while affording a practical yield. A reasonable rationalization for the high enantioselectivity is the Curtin–Hammett kinetic amination of one diastereomeric η3-allyl PdII complex from a pair which rapidly interconvert through a π–σ–π mechanism.