Organic Synthesis in chiral melts and solid mixtures

大多数有机合成在溶液中进行，以确保快速转化和良好的传热。然而，使用深共晶熔体混合物作为反应介质对于某些应用具有优势，例如非常高的底物浓度和易于执行。我们已经应用了低熔点的原料和催化剂的混合物转化碳水化合物和生物活性杂环化合物的合成。我们现在的目标是将熔融混合物反应的范围扩大到不对称合成。熔体的一种组分充当手性有机催化剂或手性碱，从而控制反应的立体化学结果。氨基酸和金鸡纳生物碱被设想用于此目的。或者，熔体的手性组分用作起始材料，并在熔体条件下转化为手性反应产物。该项目将导致从简单的前体高效、简单和环境友好地合成复杂的手性分子。并非所有的起始材料和催化剂化合物的混合物都形成深共晶。特别地，生物聚合物难以大量溶解在熔体中。因此，我们研究了大量天然产物在固态和试剂，催化剂或清除剂化合物的存在下转化为更高价值的精细化学品的机械化学转化。固态转化克服了溶解度的不相容性，并可能提供不同的选择性和产物分布。参与拟议研究的两个小组的专业知识是理想的互补性：Baskaran小组（IIT Madras）在合成复杂的天然产物，特别是杂环和碳水化合物方面拥有丰富的经验。柯尼希集团（UR）的专长是物理有机化学和新反应介质领域。通过研究生和博士后的交流，将建立无溶剂的有机合成新协议，包括对映选择性转化，并研究反应机理和介质。

Most organic syntheses are performed in solution to ensure rapid conversion and good heat transfer. However, the use of deep eutectic melt mixtures as reaction media has advantages for some applications, such as very high substrate concentration and ease of performance. We have applied low melting mixtures of starting materials and catalysts for the conversion of carbohydrates and the synthesis of bioactive heterocycles. We now aim to expand the scope of melt mixture reactions to asymmetric synthesis. One component of the melt acts as chiral organocatalyst or chiral base and thereby controls the stereochemical outcome of the reaction. Amino acids and cinchona alkaloids are envisaged for this purpose. Alternatively a chiral component of the melt serves as starting material and is converted into chiral reaction products under melt conditions. The project should lead to efficient, practically simple and environmentally benign syntheses of complex chiral molecules from simple precursors. Not all mixtures of starting materials and catalyst compounds form deep eutectics. In particular biopolymers are difficult to dissolve in melts in larger quantities. We therefore investigate the mechanochemical conversion of bulk natural products in the solid state and the presence of reagents, catalysts or scavenger compounds into higher value fine chemicals. The conversion in the solid state overcomes incompatibilities in solubility and may provide different selectivites and product distributions.The expertise of both groups participating in the proposed research is ideally complementary: The Baskaran group (IIT Madras) has ample experience in the synthesis of complex natural products, in particular heterocycles and carbohydrates. The expertise of the König group (UR) is in the area of physical-organic chemistry and new reaction media. By the exchange of graduates students and postdocs new protocols for organic synthesis, including enantioselective transformations, without solvents will be established and the reaction mechanisms and media investigated.