Transition-Metal- and Light-Free Directed Amination of Remote Unactivated C(sp³)–H Bonds of Alcohols

Abstract

Due to the great value of amino alcohols, new methods for their synthesis are in high demand. Abundant aliphatic alcohols represent the ideal feedstock for the method development toward this important motif. To date, transition-metal-catalyzed approaches for the directed remote amination of alcohols have been well established. Yet, they have certain disadvantages such as the use of expensive catalysts and limited scope. Very recently, transition-metal-free visible-light-induced radical approaches have emerged as new powerful tools for directed remote amination of alcohols. Relying on 1,5-HAT reactivity, these methods are limited to βor δ-amination only. Herein, we report a novel transition-metal-and visible-light-free room-temperature radical approach for remote β-, γ-, and δ-C(sp 3)-N bond formation in aliphatic alcohols using mild basic conditions and readily available diazonium salt reagents.

Photo-induced copper-catalyzed sequential 1,n-HAT enabling the formation of cyclobutanols

“…Taking advantage of the silicon effect for the generation and translocation of α-carbon radicals 27 , 46 , Gevorgyan recently advanced a series of works on the direct γ-amination and γ-vinylation of alcohol derivatives through 1,6-HAT using (halomethyl)silyl auxiliaries (Fig. 1c ) 47 – 50 . Despite this progress, as far as we know, examples of the use of readily available aliphatic halides as the radical precursor under visible-light photocatalysis for intermolecular cascade cyclization en route to four-membered rings are lacking.…”

Mild olefin formation via bio-inspired vitamin B12 photocatalysis

“…This "remote elimination" process would replace a primary alkyl electrophile with hydrogen while also installing an olen adjacent to the original site of the leaving group, functioning as a regioselective halide-directed C-H desaturation reaction, a completely unprecedented transformation and complementary approach to remote functionalization proceeding via HAT to carbon-centered radicals. [34][35][36][37][38][39] Seeking to test this hypothesis, we subjected 1-chlorooctane to our optimized olenation conditions with 5 mol% of cobalt complex C4 added. Gratifyingly, we obtained the internal alkene selectively with quantitative yield under these conditions ( Table 3, entry 1).…”

Recent Progress in the Construction of C−N Bonds via Metal‐Free Radical C(sp3)−H Functionalization

“…In 2019, Gevorgyan's group reported a new approach for the directed remote amination of unactivated C( sp 3 )−H bonds of alcohols. (Scheme ) . Compared with previous methods, which use expensive transition metal catalysts or visible light‐induced radical approaches, this reaction can realize selective remote β‐, γ‐ or δ‐C( sp 3 )−N bond formation in aliphatic alcohols by using mild basic conditions and readily available diazonium salt reagents.…”