Ti-Catalyzed Radical Alkylation of Secondary and Tertiary Alkyl Chlorides Using Michael Acceptors

Abstract

Alkyl chlorides are common functional groups in synthetic organic chemistry. However, the engagement of unactivated alkyl chlorides, especially tertiary alkyl chlorides, in transition-metal-catalyzed C–C bond formation remains challenging. Herein, we describe the development of a TiIII-catalyzed radical addition of 2° and 3° alkyl chlorides to electron-deficient alkenes. Mechanistic data are consistent with inner-sphere activation of the C–Cl bond featuring TiIII-mediated Cl atom abstraction. Evidence suggests that the active TiIII catalyst is generated from the TiIV precursor in a Lewis-acid-assisted electron transfer process.

Titanium and Cobalt Bimetallic Radical Redox Relay for the Isomerization of N-Bz Aziridines to Allylic Amides

“…Our group previously demonstrated that secondary and tertiary alkyl chlorides could be reduced to alkyl radicals by Ti(III) catalysts. 34 Given that we have observed -chloroamides as by-products in the isomerization of aziridines, presumably via a Lewis acid mediated nucleophilic ring opening, we sought to assess the possibility of these chloroamides as key reactive intermediates (Scheme 4). Thus, we carried out two experiments using control substrates: a secondary chloroamide 4a and a tertiary chloroamide 4k (for details, see SI).…”

Shining Light on TiIV Complexes: Exceptional Tools for Metallaphotoredox Catalysis

“…As the chloroalkenes feature high reduction potential ( E red < ‐2.0 V vs. SCE) an inner sphere SET can favour their direct reduction. In order to accomplish the desired transformation, Lin and co‐workers [ 33 ] have reduced the size of the titanium complex, employing Cp*Ti IV Cl 3 (Scheme 5). The favourable interaction of Cp*Ti III Cl with chlorine atoms allowed the generation of secondary and tertiary C‐centered radicals, which then were treated with different Michael acceptors.…”

“…[ 29 ] Cp 2 Ti III Cl is generated by reduction of commercially available Cp 2 Ti IV Cl 2 (stage a , Figure 1). The oxophilic Cp 2 Ti III Cl generally endorses the binding of hard Lewis bases (stage b , typically epoxides), but recent developments demonstrated the possibility to use other substrates such as enones, [ 30 ] nitriles, [ 31 ] N ‐acylaziridines, [ 32 ] chloroalkanes [ 33 ] and cyclopropyl ketones. [ 34 ] The key‐feature provided by the Ti center in titanocenes implies an inner‐sphere electron transfer from Ti III to the coordinated organic moiety (stage c ).…”

Recent Developments in Radical‐Mediated Transformations of Organohalides

“…Inspired by the recent developments within radical chemistry, facilitated the commitment of regular functional groups (e.g., carboxylates, alcohols, alkenes, and alkanes) in carbon–carbon bond making reactions, a novel approach was developed by Lin group for Ti‐catalyzed alkylation of unactivated 2 o and 3 o alkyl chlorides with the optimized reaction conditions (Scheme ). Particularly, tertiary alkyl chlorides were effectively committed for the construction of C–C bond.…”