Copper(I)‐Catalyzed Enantioconvergent Borylation of Racemic Benzyl Chlorides Enabled by Quadrant‐by‐Quadrant Structure Modification of Chiral Bisphosphine Ligands

Abstract

The first copper(I)-catalyzed enantioselective borylation of racemic benzyl chlorides has been realized by aq uadrant-by-quadrant structure modulation of QuinoxP*type bisphosphine ligands.T his reaction converts racemic mixtures of secondary benzyl chlorides into the corresponding chiral benzylboronates with high enantioselectivity (up to 92 % ee). The results of mechanistic studies suggest the formation of ab enzylic radical intermediate.T he results of DFT calculations indicate that the optimal bisphosphine-copper(I) catalyst engages in noncovalent interactions that efficiently recognize the radical intermediate,a nd leads to high levels of enantioselectivity. Scheme 1. Copper(I)-catalyzed borylation of alkyl electrophiles.

Dual Ni/photoredox-catalyzed asymmetric cross-coupling to access chiral benzylic boronic esters

“…The exclusive selection on aryl iodide was observed in the presence of aryl chloride or triflate group (3x, 3y, 3z) while a mixture was obtained with 1-bromo-4-iodobenzene as a substrate, possibly due to the existing reactivity of aryl bromides. It is worth mentioning that, this method can afford high enantioselectivities not only for the bulky or ortho-substituted aryl substrates as previous reports [29][30][31] , but also for the less sterically hindered components (such as 3g, 3h), thus expanding its application in organic synthesis.…”

“…A palladium-catalyzed asymmetric coupling of bis(pinacolato)diboron (B 2 Pin 2 ) with aryl halides, mainly bearing electron-donating groups, was reported by the Morken group 29 . A nickel- and a copper-catalyzed enantioselective borylation of secondary benzylic chlorides with B 2 Pin 2 , were published by the Fu 30 and Ito 31 group, respectively. However, in these cases, the enantiomeric excess ( ee ) values of the products were generally not ideal (<87%).…”

Catalytic Boration of Alkyl Halides with Borane without Hydrodehalogenation Enabled by Titanium Catalyst

“…From those results, it is reasonable to propose a radical reaction pathway for our current system. It has been well‐demonstrated that Cp 2 Ti III Cl generated in situ from Cp 2 TiCl 2 is an excellent one‐electron transfer reagent, [21] and single‐electron reduction of alkyl halides to radical species is known [7d,e, 8, 16a, 20] . Thus, it is likely that Cp 2 Ti III Cl species is generated in our system and initiate a radical reaction pathway [22] .…”

“…Given the known formation of a radical species from alkyl halides via single‐electron transfer, [7d,e, 8, 16a, 20] we then considered if a radical species is involved in our system. Then, 1 equiv of different radical scavengers, tempo and galvinoxyl, were separately added to our system, interestingly, total suppression of the boration reaction was observed (Scheme 3 e).…”

Recent advances in Cu-catalyzed C(sp3)–Si and C(sp3)–B bond formation

“…Both results suggest a radical pathway (Scheme 78) [142]. Enantioenriched benzylboronates were also synthesized from racemic benzyl chlorides using Cu(CH 3 CN) 4 /(S)-Quinox-t-BuAd 2 as the nonracemic catalytic system [143].…”