Highly Versatile β-C(sp³)–H Iodination of Ketones Using a Practical Auxiliary

Abstract

The first example of palladium(II)-catalyzed β-C(sp3)–H iodination of a wide range of ketones using a commercially available aminooxyacetic acid auxiliary has been achieved. This L, X-type directing group overcomes the limitations of the transient directing group approach for C(sp3)–H functionalization of ketones. Practical advantages of this method include simple installation of the auxiliary without chromatography, exceptional tolerance of α-functional groups, as well as alkenes and alkynes, and rapid access to diverse sterically hindered quaternary centers.

Versatile Alkylation of (Hetero)Aryl Iodides with Ketones via β-C(sp3)–H Activation

“…Very recently, we reported a practical aminooxyacetic acid auxiliary for β -C(sp 3 )–H iodination. 6 The weakly coordinating carboxyl motif in this bidentate directing group was found to be crucial for assembling the reactive palladium complex. Herein, we report a new aminooxyacetic acid auxiliary that successfully addressed all the limitations of β -C(sp 3 )–H arylation of ketones.…”

“…We were pleased to observe that using the optimal directing group ( DG1 ) for β -C(sp 3 )–H iodination 6 afforded the desired arylated product in 10% yield. However, the yield failed to be further improved after an extensive screening of conditions with DG1 .…”

Iridium‐Catalyzed β‐Alkynylation of Aliphatic Oximes as Masked Carbonyl Compounds and Alcohols

“…Ketoximes have been used as directing group in C(sp 3 )−H functionalization in the context of C−H oxygenation, amidation, amination, arylation, and iodination with different transition metals as catalysts. We envisioned that the alkynylation of oximes derived from aldehydes, ketones, or alcohols could significantly broaden the scope of the functionalization of C(sp 3 )−H bonds.…”

Distal γ‐C(sp3)−H Olefination of Ketone Derivatives and Free Carboxylic Acids

“…Recently, we have designed L,X‐type covalent and transient directing groups to enable a wide range of C(sp 3 )−H activation reactions with both ketones and aldehydes . In particular, a new aminooxy acetic acid directing group enabled C(sp 3 )−H iodination and (hetero)arylation of ketones with a broad substrate scope and superior reactivity. However, most transformations with this DG target the β‐C(sp 3 )−H bond, with only one example of γ‐C(sp 3 )−H (hetero)arylation .…”