Fluorinated Amine Stereotriads via Allene Amination

Abstract

The incorporation of fluorine into organic scaffolds often improves the bioactivity of pharmaceutically relevant compounds. C–F/C–N/C–O stereotriad motifs are prevalent in antivirals, neuraminidase inhibitors, and modulators of androgen receptors, but are challenging to install. An oxidative allene amination strategy using Selectfluor rapidly delivers triply functionalized triads of the form C–F/C–N/C–O, exhibiting good scope and diastereoselectivity for all syn products. The resulting stereotriads are readily transformed into fluorinated pyrrolidines and protected α-, β-, and γ-amino acids.

Chemo‐ and Enantioselective Intramolecular Silver‐Catalyzed Aziridinations

“…These aziridines could also be transformed into (2-aziridinyl)acetic acids by carbamate cleavage and oxidation of the primary alcohol. [22] …”

Oxidative allene amination for the synthesis of nitrogen-containing heterocycles

“…The presence of fluorine in drugs often leads to improved pharmacological properties; indeed, C(sp 3 )-F bonds are embedded in aminated triads that occur in anti-virals, neuraminidase inhibitors and modulators of androgen receptors (Figure 1, vide infra). [63][64][65][66][67][68][69][70] Oxidative allene amination provides convenient access to fluorinated triads in good-to-excellent dr (Scheme 7) 71 via reaction of 32 with Selectfluor R , 72 followed by reduction with hydride, Grignard or cyanide nucleophiles to furnish 34-44 in moderate-to-excellent dr. Our ability to install fluorine at quaternary carbons in 37-42 was particularly noteworthy, as this is challenging to achieve via fluoride ring-openings of typical epoxides or aziridines. © ARKAT USA, Inc Scheme 6.…”

Oxidative Cyclization of Sulfamates onto Pendant Alkenes

“…These reactions reliably yield valuable six-membered oxathiazinane heterocycles with pendant unsaturation. The oxathiazinane moiety is a masked 1,3-amino alcohol, a motif found in myriad biologically active compounds (Figure ), and can be used as a synthetic intermediate for a variety of transformations. − Our protocol, catalytic in palladium and reliant on Cu­(OAc) 2 /O 2 as stoichiometric oxidants, offers convenient access to these important synthetic intermediates (Scheme ).…”