The transient directing group (TDG) strategy allowed long awaited access to the direct β-C(sp 3 )–H functionalization of unmasked aliphatic aldehydes via palladium catalysis. However, the current techniques are restricted to terminal methyl functionalization, limiting their structural scopes and applicability. Herein, we report the development of a direct Pd-catalyzed methylene β-C–H arylation of linear unmasked aldehydes by using 3-amino-3-methylbutanoic acid as a TDG and 2-pyridone as an external ligand. Density functional theory calculations provided insights into the reaction mechanism and shed light on the roles of the external and transient directing ligands in the catalytic transformation.
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Photoinduced C(sp 3 )–H sulfination empowers the direct and chemoselective introduction of the sulfonyl group
Direct installation of the sulfinate group by the functionalization of unreactive aliphatic C–H bonds can provide access to most classes of organosulfur compounds, because of the central position of sulfinates as sulfonyl group linchpins. Despite the importance of the sulfonyl group in synthesis, medicine, and materials science, a direct C(sp 3 )–H sulfination reaction that can convert abundant aliphatic C–H bonds to sulfinates has remained elusive, due to the reactivity of sulfinates that are incompatible with typical oxidation-driven C–H functionalization approaches. We report herein a photoinduced C(sp 3 )–H sulfination reaction that is mediated by sodium metabisulfite and enables access to a variety of sulfinates. The reaction proceeds with high chemoselectivity and moderate to good regioselectivity, affording only monosulfination products and can be used for a solvent-controlled regiodivergent distal C(sp 3 )–H functionalization.
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- Award ID(s):
- 1920057
- NSF-PAR ID:
- 10341912
- Date Published:
- Journal Name:
- Chemical Science
- Volume:
- 12
- Issue:
- 41
- ISSN:
- 2041-6520
- Page Range / eLocation ID:
- 13914 to 13921
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Direct amination of C(sp3)−H bonds is of broad interest in the realm of C−H functionalization because of the prevalence of nitrogen heterocycles and amines in pharmaceuticals and natural products. Reported here is a combined electrochemical/photochemical method for dehydrogenative C(sp3)−H/N−H coupling that exhibits good reactivity with both sp2and sp3N−H bonds. The results show how use of iodide as an electrochemical mediator, in combination with light‐induced cleavage of intermediate N−I bonds, enables the electrochemical process to proceed at low electrode potentials. This approach significantly improves the functional‐group compatibility of electrochemical C−H amination, for example, tolerating electron‐rich aromatic groups that undergo deleterious side reactions in the presence of high electrode potentials.
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Abstract Direct amination of C(sp3)−H bonds is of broad interest in the realm of C−H functionalization because of the prevalence of nitrogen heterocycles and amines in pharmaceuticals and natural products. Reported here is a combined electrochemical/photochemical method for dehydrogenative C(sp3)−H/N−H coupling that exhibits good reactivity with both sp2and sp3N−H bonds. The results show how use of iodide as an electrochemical mediator, in combination with light‐induced cleavage of intermediate N−I bonds, enables the electrochemical process to proceed at low electrode potentials. This approach significantly improves the functional‐group compatibility of electrochemical C−H amination, for example, tolerating electron‐rich aromatic groups that undergo deleterious side reactions in the presence of high electrode potentials.
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Abstract The Mizoroki–Heck reaction is one of the most efficient methods for alkenylation of aryl, vinyl, and alkyl halides. Given its innate nature, this protocol requires the employment of compounds possessing a halogen atom at the site of functionalization. However, the accessibility of organic molecules possessing a halogen atom at a particular site in aliphatic systems is extremely limited. Thus, a protocol that allows a Heck reaction to occur at a specific nonfunctionalized C(sp3)−H site is desirable. Reported here is a radical relay Heck reaction which allows selective remote alkenylation of aliphatic alcohols at unactivated β‐, γ‐, and δ‐C(sp3)−H sites. The use of an easily installed/removed Si‐based auxiliary enables selective I‐atom/radical translocation events at remote C−H sites followed by the Heck reaction. Notably, the reaction proceeds smoothly under mild visible‐light‐mediated conditions at room temperature, producing highly modifiable and valuable alkenol products from readily available alcohols feedstocks.
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Abstract The Mizoroki–Heck reaction is one of the most efficient methods for alkenylation of aryl, vinyl, and alkyl halides. Given its innate nature, this protocol requires the employment of compounds possessing a halogen atom at the site of functionalization. However, the accessibility of organic molecules possessing a halogen atom at a particular site in aliphatic systems is extremely limited. Thus, a protocol that allows a Heck reaction to occur at a specific nonfunctionalized C(sp3)−H site is desirable. Reported here is a radical relay Heck reaction which allows selective remote alkenylation of aliphatic alcohols at unactivated β‐, γ‐, and δ‐C(sp3)−H sites. The use of an easily installed/removed Si‐based auxiliary enables selective I‐atom/radical translocation events at remote C−H sites followed by the Heck reaction. Notably, the reaction proceeds smoothly under mild visible‐light‐mediated conditions at room temperature, producing highly modifiable and valuable alkenol products from readily available alcohols feedstocks.
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D1SC04245A
