Visible-light-mediated, nitrogen-centered radical amination of tertiary alkyl halides under metal-free conditions to form α-tertiary amines

Abstract

A mild and operationally convenient amino-functionalization of a range of tertiary alkyl halides by reaction with iminoiodinanes (PhI[double bond, length as m-dash]NNs) and I2 has been developed. According to the mechanistic experiments described within, the reaction is speculated to proceed through a light-promoted, N-centered radical pathway involving a N,N-diiodosulfonamide reactive species. This method of direct N-incorporation offers an attractive alternative to the production of α-tertiary amines, a synthetically challenging structural class found in a variety of bioactive molecules.

Visible-Light, Iodine-Promoted Formation of N-Sulfonyl Imines and N-Alkylsulfonamides from Aldehydes and Hypervalent Iodine Reagents

“…In addition to traditional approaches of aldehyde/sulfonamide condensation, methods involving the non-dehydrative reaction of aldehydes with isocyanate analogues have been reported ( Scheme 1 , method B) [ 44 , 45 , 46 ]. Resulting from our research group’s interest in the utilization of N-centered radical (NCR) precursors for C–N bond formation [ 47 , 48 , 49 ], we have recently reported a mild alternative for imine formation that uses iodine and pre-formed iminoiodinane reagents in the presence of light ( Scheme 1 , method C), which addresses many of the shortcomings of traditional methods [ 49 ]. NCR-mediated reactions have seen substantial advances recently, due to the advent of visible-light photoredox catalysis and the development of predictable NCR precursors [ 50 , 51 , 52 ], but there have been very few reports that have utilized NCR species for carbonyl activation [ 49 , 53 , 54 , 55 ].…”

Hypervalent Iodine(III)-Mediated Decarboxylative Ritter-Type Amination Leading to the Production of α-Tertiary Amine Derivatives

“…Among the methods for preparing α-tertiary amine derivatives, introducing an amino functional group into a tertiary carbon centers, that is, the formation of a C–N bond at a tertiary carbon center, has been recognized as one of the most straightforward approaches and has attracted considerable attention in the past decades. In this context, efficient synthetic methods for amination at a tertiary carbon center, including radical C–H amination ,, and C–H amination by an imino-λ 3 -bromane and a metal nitrenoid, have recently been developed. Most recently, the azidation of tertiary carbon centers and the hydroamination of alkenes have also emerged as powerful and useful methods.…”

Sulfonylimino Group Transfer Reaction Using Imino-λ3-iodanes with I2 as Catalyst Under Metal-free Conditions

“…From blank experiments and previously related results involving the amidyl radical species from imino-λ 3 -iodane 2a with I 2 [34,35,36,40], we proposed the reaction mechanism of imination (Scheme 4). Initially, ( N -tosylimino)-phenyl-λ 3 -iodane 2a reacted with I 2 to produce N , N -diiodotosylamide 6 (or related species) followed by generation of the amidyl radical 7 and iodine radical under the reaction conditions.…”

“…To clarify the mechanism of metal-free sulfonylimino group transfer reaction, we have performed several blank experiments (Scheme 3). Based on the previously reported experiment, a amidyl radical precursor like N , N -diiodotosylamide or a related species might be generated from ( N -tosylimino)-phenyl-λ 3 -iodane 2a with I 2 [34,35,36,40]. A radical mechanism is plausible because performing the reaction under dark conditions results in relatively low yields of product 3a (Table 1, entry 20).…”