Methyl Radical Initiated Kharasch and Related Reactions

Abstract

An improved procedure to run halogen atom and related chalcogen group transfer radical additions is reported. The procedure relies on the thermal decomposition of di‐tert‐butylhyponitrite (DTBHN), a safer alternative to the explosive diacetyl peroxide, to produce highly reactive methyl radicals that can initiate the chain process. This mode of initiation generates byproducts that are either gaseous (N2) or volatile (acetone and methyl halide) thereby facilitating greatly product purification by either flash column chromatography or distillation. In addition, remarkably simple and mild reaction conditions (refluxing EtOAc during 30 minutes under normal atmosphere) and a low excess of the radical precursor reagent (2 equivalents) make this protocol particularly attractive for preparative synthetic applications. This initiation procedure has been demonstrated with a broad scope since it works efficiently to add a range of electrophilic radicals generated from iodides, bromides, selenides and xanthates over a range of unactivated terminal alkenes. A diverse set of radical trap substrates exemplifies a broad functional group tolerance. Finally, di‐tert‐butyl peroxyoxalate (DTBPO) is also demonstrated as alternative source of tert‐butoxyl radicals to initiate these reactions under identical conditions which gives gaseous by‐products (CO2).

Dibromo-BODIPY as an Organic Photocatalyst for Radical–Ionic Sequences

“…For comparison, typical initiators were also tested; when 1,1′-azobis­(cyclohexanecarbonitrile) (ACHN) was employed, only the starting material was observed (entry 9). Di- tert -butyl hyponitrite (TBHN) afforded mainly the starting material along with unidentified degradation products (entry 10). When dialuroyl peroxide (DLP) was used as the initiator, acetophenone (debrominated starting material) was isolated in 10% yield along with the unreacted starting material (entry 11).…”

“… a All reactions were performed on 50 mg of 2-bromoacetophenone and 2% mol of PC, at room temperature, in acetonitrile (0.25 M) for 12–13 h or until the starting material was consumed, unless otherwise stated. b Isolated yields. c The reaction was carried out with 5 mol % of ACHN at reflux. d Only the staring material was observed after 2 h of reaction. e A solution of 5a and DTBHN (10 mol %) in EtOAc was refluxed for 30 min according to the literature procedure f DLP was added in 10 mol % portions to a refluxing solution of 5a in 1,2-DCE until completing 30 mol %. g The major product was acetophenone in 10% yield, along with the starting material. h Et 3 B was added in 20 mol % portions at r.t. until completing 60 mol %. i The major product was acetophenone in 60% yield. …”

“… e A solution of 5a and DTBHN (10 mol %) in EtOAc was refluxed for 30 min according to the literature procedure …”

In Situ Generation of Radical Initiators: Air Stable Amine-Borane Complexes Promote Atom Transfer Radical Additions of Alkyl Halides to Alkenes

“…More recently photochemical version of this reaction has gained a major interest either with organometallic complexes (Scheme 1d) or organic photocatalysts (Scheme 1e) [30][31][32][33] Beside recently discovered organic photoredox catalysts, non-metal radical initiators for ATRA reaction have mostly been based on thermal decomposition of peracids (Scheme 1a) 7,34 or AIBN derivatives (Scheme 1b). 35,36 Most of these compounds requires special care for storage and handling as they release alkoxy radicals and/or nitrogen gas, both of which are safety concerns. Additionally, the efficiency of the initiation is often hampered by the compulsory stability of the generated radical.…”

Preparation of Antiproliferative Terpene-Alkaloid Hybrids by Free Radical-Mediated Modification of ent-Kauranic Derivatives

“…The resulting free radical abstracts the X-atom from the alkyl halide and the reaction chain perpetuates. Iodine-ATRA reactions leading to tertiary iodides are often followed by a rapid elimination of HI and conversion to alkenes [18,19]. The azidoalkylation reaction is closely related to the ATRA process but involves an extra azidating agent, usually a sulfonyl azide (Scheme 1, bottom) [20][21][22].…”