Practical catalytic asymmetric synthesis of diaryl-, aryl heteroaryl-, and diheteroarylmethanols.
Practical catalytic asymmetric synthesis of diaryl-, aryl heteroaryl-, and diheteroarylmethanols.
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DOI：
10.1021/ja9046747
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发表时间：
2009-09-02
影响因子：
15
通讯作者：
Walsh, Patrick J.
中科院分区：
文献类型：
--
作者：
Salvi, Luca;Kim, Jeung Gon;Walsh, Patrick J.
对映体富集的二芳基、芳基、杂芳基和二芳基甲醇具有重要的生物学和药用特性。介绍了以易得芳基溴为原料，一锅催化不对称合成这些化合物的方法。因此，溴化锂与市售芳基溴化物和n-BuLi交换，然后与ZnCl2盐分解生成ArZnCl。另一种相当于n-BuLi的物质被加入到混合有机锌ArZnBu中。在对映体富集的氨基醇基催化剂的存在下，ArZnBu加到醛上生成基本上是外消旋的二芳基甲醇。低对映体选择性归因于氯化锂促进的背景反应。为了抑制这一背景反应，在醛加成之前引入了螯合二胺TEEDA（四乙二胺）。在此条件下，得到了对映体富集的二芳基甲醇，ee为> ~ 90%。烯醛的芳基化反应生成的烯丙醇的ee为81-90%。然而，当应用于杂芳基溴时，该方法是不成功的，这是由于在盐复分解条件下杂芳基锂的分解。为了避免这一问题，用EtZnCl进行了分解，使得盐的分解可以在低温下进行。得到的EtZn（ArHetero）中间体（ArHetero=2-和3-噻吩基、2-苯并噻吩基、3-呋喃基和5-吲哚基）被成功地添加到醛和杂芳基醛上，对映选择性在81-99%之间。这是催化和高度对映选择性合成二异芳基甲醇的第一个例子。以类似的方式，二茂铁溴制得FcZnEt，二茂铁基加入到苯甲醛和杂芳醛中形成二茂铁基配体前体，产率为86-95%，ee为96-98%。还发现，在环氧醛的芳基化和异芳基化之后，可以在一锅过程中进行非对映选择性环氧化，以提供具有高对映性和非对映选择性的环氧醇。
Enantioenriched diaryl-, aryl heteroaryl- and diheteroarylmethanols exhibit important biological and medicinal properties. One-pot catalytic asymmetric syntheses of these compounds beginning from readily available aryl bromides are introduced. Thus, lithium-bromide exchange with commercially available aryl bromides and n-BuLi was followed by salt metathesis with ZnCl2 to generate ArZnCl. A second equivalent of n-BuLi was added to form the mixed organozinc, ArZnBu. In the presence of enantioenriched amino alcohol-based catalysts, ArZnBu adds to aldehydes to afford essentially racemic diarylmethanols. The low enantioselectivities were attributed to a LiCl-promoted background reaction. To inhibit this background reaction, the chelating diamine TEEDA (tetraethylethylene diamine) was introduced prior to aldehyde addition. Under these conditions, enantioenriched diarylmethanols were obtained with >90% ee. Arylations of enals generated allylic alcohols with 81–90% ee. This procedure was unsuccessful, however, when applied to heteraryl bromides, which was attributed to decomposition of the heteroaryl lithium under the salt metathesis conditions. To avoid this problem, the metathesis was conducted with EtZnCl, which enabled the salt metathesis to proceed at low temperatures. The resulting EtZn(ArHetero) intermediates (ArHetero=2- and 3-thiophenyl, 2-benzothiophenyl, 3-furyl, and 5-indolyl) were successfully added to aldehydes and heteroaryl aldehydes with enantioselectivities between 81–99%. These are the first examples of catalytic and highly enantioselective syntheses of diheteroarylmethanols. In a similar fashion, ferrocenyl bromide was used to generate FcZnEt and the ferrocenyl group added to benzaldehyde and heteroaromatic aldehydes to form ferrocene-based ligand precursors in 86–95% yield with 96–98% ee. It was also found that the arylation and heteroarylation of enals could be followed by diastereoselective epoxidations to provide epoxy alcohols with high enantio- and diastereoselectivities in a one-pot procedure.
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影响因子：
4.9
作者：
Bolm, C;Muñiz, K
通讯作者：
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7.3
作者：
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作者：
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