Carbon has the unique ability to bind four atoms and form stable tetravalent structures that are prevalent in nature. The lack of one or two valences leads to a set of species-carbocations, carbanions, radicals and carbenes-that is fundamental to our understanding of chemical reactivity. In contrast, the carbyne-a monovalent carbon with three non-bonded electrons-is a relatively unexplored reactive intermediate; the design of reactions involving a carbyne is limited by challenges associated with controlling its extreme reactivity and the lack of efficient sources. Given the innate ability of carbynes to form three new covalent bonds sequentially, we anticipated that a catalytic method of generating carbynes or related stabilized species would allow what we term an 'assembly point' disconnection approach for the construction of chiral centres. Here we describe a catalytic strategy that generates diazomethyl radicals as direct equivalents of carbyne species using visible-light photoredox catalysis. The ability of these carbyne equivalents to induce site-selective carbon-hydrogen bond cleavage in aromatic rings enables a useful diazomethylation reaction, which underpins sequencing control for the late-stage assembly-point functionalization of medically relevant agents. Our strategy provides an efficient route to libraries of potentially bioactive molecules through the installation of tailored chiral centres at carbon-hydrogen bonds, while complementing current translational late-stage functionalization processes. Furthermore, we exploit the dual radical and carbene character of the generated carbyne equivalent in the direct transformation of abundant chemical feedstocks into valuable chiral molecules.
The first stereoconvergent cyclopropanation reaction by means of photoredox catalysis using diiodomethane as the methylene source is described. This transformation exhibits broad functional group tolerance and it is characterized by an excellent stereocontrol en route to trans-cyclopropanes regardless of whether E- or Z-styrene substrates were utilized.
An efficient approach to (Rp) planar-chiral tri- and tetracyclic ortho-condensed aromatic ferrocenes was developed through the enantioselective cationic Au(i)-catalyzed cycloisomerization, in the presence of bidentate phosphine ligand (R)-DTBM-Segphos, from readily available ortho-alkynylaryl ferrocenes under very mild conditions (11 examples, up to 92% yield and 93% ee).
An enantiopure helical ferrocene (R p )-5 with five ortho-condensed aromatic rings was synthesized using a PtCl 2catalyzed cycloisomerization of planar-chiral 2-ethynyl-1-(4-phenanthrenyl)ferrocene (R p )-6f, prepared in 3 steps from known enantiopure sulfinyl ferrocenyl boronic acid (S S ,S p )-7, as the source of planar chirality. This pentacyclic helical ferrocene showed a very high optical rotation value and strong circular dichroism (CD) signals.
Tertiary diarylmethanols are highly bioactive structural motifs. A new strategy to access chiral tertiary diarylmethanols through copper‐catalyzed direct alkylation of (di)(hetero)aryl ketones by using Grignard reagents was developed. The low reactivity and the similarity of the enantiotopic faces of bis‐aromatic ketones were partially overcome, which resulted in moderate to good yields and enantioselectivities.
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