Organic Chemistry

Engaging Aldehydes in CuH-Catalyzed Reductive Coupling Reactions: Stereoselective Allylation from 1,3-Diene Pronucleophiles



Recently, CuH-catalyzed reductive coupling processes involving carbonyl compounds and imines has become an attractive alternative to traditional methods for stereoselective addition to carbonyls due to the ability to use readily accessible and stable olefin-derived pronucleophiles as surrogates for organometallic reagents. However, the inability to use aldehydes, which traditionally reduce too rapidly in the presence of copper hydride complexes to be viable substrates, has been a major limitation. We show that by exploiting relative concentration effects through slow addition, we can invert this intrinsic reactivity and achieve the reductive coupling of 1,3-dienes with aldehydes. Using this method, both aromatic and aliphatic aldehydes can be transformed to valuable products with high levels of diastereo- and enantioselectivity and in the presence of many useful functional groups. Furthermore, using a combination of theoretical (DFT) and experimental methods, important mechanistic features of this reaction related to stereo- and chemoselectivity were uncovered.


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Supplementary material

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SI-NMR Spectra-final
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SI-SFC, GC and HPLC Traces-final