Fanning Kate N, Jamieson Andrew G, Sutherland Andrew
WestChem, Department of Chemistry, Joseph Black Building, University of Glasgow, Glasgow, UKG12 8QQ.
Org Biomol Chem. 2005 Oct 21;3(20):3749-56. doi: 10.1039/b510808j. Epub 2005 Sep 9.
A highly diastereoselective synthesis of (2S,3S)-beta-hydroxy-alpha-amino acids has been developed from enantiopure alpha-hydroxy acids using a MOM-ether-directed, palladium(II)-catalysed, aza-Claisen rearrangement of allylic acetimidates to effect the key step. This highly stereoselective process gave allylic amides in diastereomeric ratios of up to 14 : 1. Problems associated with the isolation of 1,3-products (anti-Claisen) from sterically demanding substrates via an insitu palladium(0)-catalysed rearrangement process were overcome by the addition of a re-oxidant, p-benzoquinone, leading to cleaner reactions and improved yields of the 3,3-products (Claisen). The target beta-hydroxy-alpha-amino acids are an important class of natural products that are also components of more complex organic compounds with significant biological properties.
已开发出一种从对映体纯的α-羟基酸出发，通过甲氧基甲基醚导向、钯（II）催化的烯丙基乙酰亚胺酸的氮杂克莱森重排来实现关键步骤，从而高度非对映选择性地合成（2S，3S）-β-羟基-α-氨基酸的方法。这种高度立体选择性的过程以高达14:1的非对映体比例得到烯丙基酰胺。通过添加再氧化剂对苯醌，克服了通过原位钯（0）催化的重排过程从空间位阻较大的底物中分离1,3-产物（反式克莱森）相关的问题，从而使反应更纯净，并提高了3,3-产物（克莱森）的产率。目标β-羟基-α-氨基酸是一类重要的天然产物，也是具有显著生物学特性的更复杂有机化合物中的组成部分。
