PIDA/I₂-Mediated α- and β-C(sp³)–H Bond Dual Functionalization of Tertiary Amines

Abstract

The α,β-C(sp)-H bond dual functionalization of tertiary amines is still a challenging task for both organic and medicinal chemists. Herein a direct, mild, metal-free, and site-specific method mediated by PIDA/I was developed for α,β-C(sp)-H bond dual functionalization of tertiary amines, and this method can provide facile access to α-keto lactams or rarely studied α,α-diiodo lactams. Moreover, this method was used for the effective syntheses of three natural products [obscurumine C (13), obscurumine O (17), and strychnocarpine (18)] and direct preparation of mimics of the in vivo metabolites of two FDA-approved drugs (imatinib and donepezil) in 36-60% overall yield. The method represents a promising protocol for the late-stage α,β-C(sp)-H bond oxidative dual functionalization of tertiary amine-containing drugs and complex natural products.

Concise and Stereoselective Total Syntheses of Annotinolides C, D, and E

“…Critically, with these two targets in hand, we then explored our ability to interconvert them and access additional members. As expected, annotinolide D ( 2 ) could be oxidized into annotinolide E ( 3 ) with KMnO 4 19 in a 4:1 mixture of acetone and H 2 O proving optimal ( Scheme 5 ). We then attempted to convert this new material into annotinolide C ( 1 ) based on the isolation team’s hypothesis that its lactam could rearrange into a lactone.…”

Biocatalytic and chemical derivatization of the fungal meroditerpenoid chevalone E

“…Therefore, we sought to construct the spirolactone moiety using a synthetic chemistry approach. To our delight, irradiation of 10 under the Suárez-modified Hofmann-Löffler-Freytag (HLF) conditions 24,25 smoothly gave the spirolactone 17 in 42% yield (66% brsm.) (Fig.…”

α-C(sp3)-H Arylation of Cyclic Carbonyl Compounds

“…Since C-H bonds are common in organic compounds, C-H functionalization has an extremely broad space of application. Through direct C-H functionalization, the functionalized substrate [1-7], drug intermediates [8][9][10], and bioactive natural products with complex structures [11][12][13][14][15] can be successfully synthesized in a highly effective manner. Therefore, it has been regarded as an "eternal theme" in organic chemistry [16,17].…”