29106-33-0Relevant articles and documents
Non-stabilized nucleophiles in Cu-catalysed dynamic kinetic asymmetric allylic alkylation
You, Hengzhi,Rideau, Emeline,Sidera, Mireia,Fletcher, Stephen P.
, p. 351 - 355 (2015/04/27)
The development of new reactions forming asymmetric carbon-carbon bonds has enabled chemists to synthesize a broad range of important carbon-containing molecules, including pharmaceutical agents, fragrances and polymers1. Most strategies to obtain enantiomerically enriched molecules rely on either generating new stereogenic centres fromprochiral substratesor resolving racemicmixtures of enantiomers.Analternative strategy-dynamic kinetic asymmetric transformation-involves the transformation of a racemic starting material into a single enantiomer product, with greater than 50 per centmaximumyield2,3. The use of stabilized nucleophiles (pKaa is the acid dissociation constant) in palladium-catalysed asymmetric allylic alkylation reactions has proved to be extremely versatile in these processes4,5. Conversely, the use of non-stabilized nucleophiles insuch reactions is difficultand remains a key challenge6-9. Herewe report a copper-catalyseddynamic kinetic asymmetric transformation using racemic substrates and alkyl nucleophiles. These nucleophiles have a pKa of ≥ 50, more than 25 orders of magnitude more basic than the nucleophiles that are typically used in such transformations. Organometallic reagents are generatedin situ fromalkenes byhydrometallation and givehighly enantioenriched productsunder mild reaction conditions. The method is used to synthesize natural products that possess activity against tuberculosis and leprosy, and an inhibitor ofpara-aminobenzoate biosynthesis. Mechanistic studies indicate that the reaction proceeds through a rapidly isomerizing intermediate.We anticipate that this approach will be a valuable complement to existing asymmetric catalytic methods.
