Desymmetrization of prochiral diaryl sulfoxides by an asymmetric sulfoxide-magnesium exchange.
Desymmetrization of prochiral diaryl sulfoxides by an asymmetric sulfoxide-magnesium exchange.
复制标题
DOI：
10.1002/chem.201103928
复制
发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
T. Hampel;Simon Ruppenthal;D. Sälinger;R. Brückner
中科院分区：
文献类型：
--
作者：
T. Hampel;Simon Ruppenthal;D. Sälinger;R. Brückner
具有立体生成的S原子的对映体纯或富含亚硫醚是非常重要的。2010年美国销量第二高的药物就是这种结构性的主题。S-手性亚硫醚也被用于不对称合成，既可以作为手性信息的化学计量载体，也可以作为过渡金属催化反应和有机催化的配体。常见的方法包括拆分外消旋物质、硫化物的不对称氧化、精制已有的亚硫醚以及硫亲电试剂的亲核取代反应。通过非手性底物的去对称化制备非外消旋产物具有广泛的吸引力，原因有两个：1)前手性或介观构型的化合物通常容易通过双向合成获得。2)如果在去对称化之后进行动力学拆分，则可能发生特别高的对映体过量。图1描述了所选择的前手性单亚硫醚，其中硫原子通过两个侧链官能团之一的酶促单官能化而成为立体中心。最近，我们通过不对称的溴-镁交换反应使前手性二溴醇5去对称化(方案1；6+iPrBr)。在对潜在机制进行理论推导时，我们想知道类似的反应是否会降低...
Enantiomerically pure or enriched sulfoxides with a stereogenic S-atom are of great importance. The second highest selling drug in the USA in 2010 features this structural motif. S-chiral sulfoxides are also used in asymmetric synthesis, either as stoichiometric carriers of chiral information or as ligands in transition-metal catalyzed reactions and organocatalysis. Common accesses to such sulfoxides include the resolution of racemic material, the asymmetric oxidation of sulfides, the elaboration of already existing sulfoxides, and nucleophilic substitutions at sulfur electrophiles. The preparation of non-racemic products by the desymmetrization of achiral substrates is quite generally appealing for two reasons: 1) Prochiral or meso-configured compounds are often readily accessible by bidirectional synthesis. 2) Particular high enantiomeric excesses are possible if the desymmetrization is followed by a kinetic resolution. Figure 1 depicts selected prochiral monosulfoxides, in which the sulfur atom became a stereocenter through enzymatic monofunctionalizations of one of the two side-chain functional groups. Recently we desymmetrized the prochiral dibromo alcohol 5 by an asymmetric bromine–magnesium exchange (Scheme 1; ! 6 + iPrBr). Theorizing about the underlying mechanism we wondered whether a similar reaction de-