Late-stage functionalization
of C–H bonds (C–H LSF)
can provide a straightforward approach to the efficient synthesis
of functionalized complex molecules. However, C–H LSF is challenging
because the C–H bond must be functionalized in the presence
of various other functional groups. In this Perspective, we evaluate
aromatic C–H LSF on the basis of four criteriareactivity,
chemoselectivity, site-selectivity, and substrate scopeand
provide our own views on current challenges as well as promising strategies
and areas of growth going forward.
Functionalized enantiopure
organosilanes are important building
blocks with applications in various fields of chemistry; nevertheless,
asymmetric synthetic methods for their preparation are rare. Here
we report the first organocatalytic enantioselective synthesis of
tertiary silyl ethers possessing “central chirality”
on silicon. The reaction proceeds via a desymmetrizing carbon–carbon
bond forming silicon–hydrogen exchange reaction of symmetrical
bis(methallyl)silanes with phenols using newly developed imidodiphosphorimidate
(IDPi) catalysts. A variety of enantiopure silyl ethers was obtained
in high yields with good chemo- and enantioselectivities and could
be readily derivatized to several useful chiral silicon compounds,
leveraging the olefin functionality and the leaving group nature of
the phenoxy substituent.
Carbon–heteroatom (C–X) cross-coupling is a common method for bond-forming reactions in chemistry but the more electronegative the heteroatom X is, the more challenging the bond formation becomes. Although reductive elimination from Cu(III) intermediates to form C–X bonds is generally a facile reaction, oxidative addition of Cu(I) into the carbon–(pseudo)halide bond of aryl (pseudo)halides is energetically challenging. Therefore, cross-coupling reactions of aryl halides with a variety of nucleophiles is currently out of reach for methods based on copper. Here we present a strategy to bypass the high-barrier oxidative addition step to aryl halides by the generation of aryl radicals from triplet states. Photoinduced energy transfer to, or direct excitation of, aryl halides even enables the use of aryl chlorides as electrophilic coupling partners. This strategy allows for the use of alcohols, amines and fluoride as nucleophiles and expands the scope of copper-mediated cross-coupling chemistry.
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