Organic Synthesis in chiral melts and solid mixtures

大多数有机合成都在溶液中进行，以确保快速转化和良好的热传递。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操作。我们已经将原料和催化剂的低熔点混合物应用于碳水化合物的转化和生物活性杂环的合成。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。熔体的一种成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这一目的。或者，熔体的手性组分作为起始原料，并在熔体条件下转化为手性反应产物。该项目应该导致从简单的前体合成复杂的手性分子的高效、实用、简单和对环境无害的合成。并不是所有原料和催化剂化合物的混合物都形成深度共晶。特别是，生物聚合物很难大量溶解在熔体中。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存在下的机械力化学转化为更高价值的精细化学品。固态转化克服了溶解度的不相容，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具有理想的互补性：巴斯卡兰小组(IIT Madras)在合成复杂的天然产物方面拥有丰富的经验，特别是杂环和碳水化合物。科尼格集团(UR)在物理-有机化学和新反应介质领域拥有专业知识。通过研究生和博士后的交流，将建立新的有机合成方法，包括无溶剂的对映选择性转化，并对反应机理和介质进行研究。

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.