Synthesis of Acyclic Aliphatic Amides with Contiguous Stereogenic Centers via Palladium-Catalyzed Enantio-, Chemo- and Diastereoselective Methylene C(sp3)-H arylation.
The enantioselective desymmetrizing C-H activation of α-gem-dialkyl acyclic amides remains challenging because the availability of four chemically identical unbiased methylene C(sp3)-H bonds and increased rotational freedoms of the acyclic systems add tremendous difficulties for chemo- and stereocontrol. We have developed a method for the synthesis of acyclic aliphatic amides with α,β-contiguous stereogenic centers via PdII-catalyzed asymmetric arylation of unbiased methylene C(sp3)-H, in good yields and with high levels of enantio-, chemo- and diastereoselectivity (up to >99 % ee and >20:1 d.r.). Successive application of this method enables the sequential arylation of the gem-dialkyl groups with two different aryl iodides, giving a range of β-Ar1-β'-Ar2-aliphatic acyclic amides containing three contiguous stereogenic centers with excellent diastereoselectivity.
['Han|Ye-Qiang|YQ|', 'Yang|Xu|X|', 'Kong|Ke-Xin|KX|', 'Deng|Yao-Ting|YT|', 'Wu|Le-Song|LS|', 'Ding|Yi|Y|', 'Shi|Bing-Feng|BF|0000-0003-0375-955X']
contiguous stereogenic centers diastereoselectivity enantioselectivity chemoselectivity palladium