1,4‐Addition of TMSCCl₃ to Nitroalkenes: Efficient Reaction Conditions and Mechanistic Understanding

Abstract

Improved synthetic conditions allow preparation of TMSCCl3 in good yield (70 %) and excellent purity. Compounds of the type NBu4X [X=Ph3SiF2 (TBAT), F (tetrabutylammonium fluoride, TBAF), OAc, Cl and Br] act as catalytic promoters for 1,4-additions to a range of cyclic and acyclic nitroalkenes, in THF at 0–25 °C, typically in moderate to excellent yields (37–95 %). TBAT is the most effective promoter and bromide the least effective. Multinuclear NMR studies (1H, 19F, 13C and 29Si) under anaerobic conditions indicate that addition of TMSCCl3 to TBAT (both 0.13 M) at −20 °C, in the absence of nitroalkene, leads immediately to mixtures of Me3SiF, Ph3SiF and NBu4CCl3. The latter is stable to at least 0 °C and does not add nitroalkene from −20 to 0 °C, even after extended periods. Nitroalkene, in the presence of TMSCCl3 (both 0.13 M at −20 °C), when treated with TBAT, leads to immediate formation of the 1,4-addition product, suggesting the reaction proceeds via a transient [Me3Si(alkene)CCl3] species, in which (alkene) indicates an Si⋅⋅⋅O coordinated nitroalkene. The anaerobic catalytic chain is propagated through the kinetic nitronate anion resulting from 1,4 CCl3− addition to the nitroalkene. This is demonstrated by the fact that isolated NBu4[CH2−NO2] is an efficient promoter. Use of H2C−CH(CH2)2CH−CHNO2 in air affords radical-derived bicyclic products arising from aerobic oxidation.

Efficient Preparation of TMSCCl2Br and Its Use in Dichlorocyclopropanation of Electron‐Deficient Alkenes

“…% tetramethylpiperidinyloxide (TEMPO) to provide acceptable yields. This behaviour is attributed to aerobic triggered competing radical reactions, which we have noted before . Control reactions (absence of anionic promotors and use of other radical traps) indicated that the TEMPO does act as an inhibitor in this case…”

“…With 1 now accessible cleanly and in large quantities, its reactivity and potential as a cyclopropanation reagent was explored. Cyclic nitroolefin ( 2 a ) was picked as the model alkene for the reaction, as nitroolefins have been reported as potent Michael acceptors for TMSCCl 3 ,. Table outlines the effects of different promotors on its cyclopropanation reaction with 1 .…”

“…The motifs 9 a – h are also accessible using our previously reported anionic promotor pool methodology where using 5 mol. % NBu 4 OAc typically furnishes the 1,4‐addition products in <30 min at room temperature ,. When NBu 4 OAc was used at 5 mol.…”

“…In seeking a user‐friendly approach to dichlorocyclopropanation we had settled on use of TMSCCl 3 and recently could demonstrate both its high yield synthesis and its use in the conjugate addition of trichloromethyl units ( A , Scheme ) . However, under the published conditions, base‐induced closure of A to the dichlorocyclopropanes B could lead to poor yields or the formation of alternative (elimination) by‐products…”

1,4‐Addition of TMSCCl3 to (E)‐Fumaric Esters and Thermal Rearrangement of the Adducts to 3,4‐Dichloropent‐2‐enedioates

“…Trichloro(trimethylsilyl)methane2 is an attractive heat‐ and air‐stable reagent that provides a milder equivalent of the [CCl 3 ] – carbanion for use in 1,2‐ and 1,4‐additions to π‐systems such as aldehydes and ketones,3 imines4 acrylates5 and nitroalkenes 6. In 2014 we were able to contribute an improved synthesis of TMSCCl 3 that enabled us to expand the scope of 1,4‐additions to nitro olefins,7 yet the use of other Michael acceptors with this reagent remains rather underexplored. While additions of trichloromethyl radicals to electron‐rich alkenes have been known since the pioneering work of Kharasch in the late 1940s,8 additions of “ · CCl 3 ” units to electron‐deficient alkenes appear limited to acrylonitrile and methyl acrylate.…”