The Cyclopropane Ring as a Reporter of Radical Leaving-Group Reactivity for Ni-Catalyzed C(sp³)–O Arylation

Abstract

The ability to understand and predict reactivity is essential for the development of new reactions. In the context of Ni-catalyzed C­(sp3)–O functionalization, we have developed a unique strategy employing activated cyclopropanols to aid the design and optimization of a redox-active leaving group for C­(sp3)–O arylation. In this chemistry, the cyclopropane ring acts as a reporter of leaving-group reactivity, since the ring-opened product is obtained under polar (2e) conditions, and the ring-closed product is obtained under radical (1e) conditions. Mechanistic studies demonstrate that the optimal leaving group is redox-active and are consistent with a Ni­(I)/Ni­(III) catalytic cycle. The optimized reaction conditions are also used to synthesize a number of arylcyclopropanes, which are valuable pharmaceutical motifs.

Enantioselective Conjugate Addition of Catalytically Generated Zinc Homoenolate

“…5 However, such in situ-generated zinc homoenolate has also not been exploited for an enantioselective C-C bond formation. 6,7 Herein, we report on an enantioselective conjugate addition (ECA) of a catalytically generated chiral zinc homoenolate to α,β-unsaturated ketones (Scheme 1c). 8,9 A catalyst generated from Et2Zn and a chiral β-amino alcohol promotes ring-opening addition of cyclopropanols to chalcone and related enones, which displays the feature of ligand-accelerated catalysis and represents a rare example of transition metal-free ECA of organozinc reagents.…”

Development of Nickel-Catalyzed Cross-Coupling of Alcohol Derivatives to Construct Carbon-Carbon Bonds

“…2020 年, Rousseaux 课题组 [80] 开发了镍催化的环丙 醇衍生物与芳基锌试剂的交叉偶联反应, 以中等到优异 的收率得到一系列含季碳中心的环丙烷类衍生物. 该小 组通过不同氧化还原活性离去基团的设计和优化, 得到 不同的偶联产物.…”

Diastereoselective Synthesis of Aryl C‐Glycosides from Glycosyl Esters via C−O Bond Homolysis

“…Redox auxiliaries can transform hydroxyl groups into viable leaving groups via CÀO bond homolysis to form radical intermediates (Scheme 2 A). Typical auxiliaries include xanthates, [23] phosphites, [24] and oxalates [25] activated through electron transfer or light irradiation (Scheme 2 A). These methods, however, have not been applied to glycosylation, possibly due to the instability of the corresponding glycosyl esters.…”

“…Due to fluctuations caused by light irradiation, we recorded the actual temperature of the oil bath for each reaction. In general, electron-deficient aryl bromides gave excellent yields of the corresponding C-glycosyl arenes (19)(20)(21)(22)(23)(27)(28)(29). Performing the synthesis of 17 on a 1.94-gramscale afforded 21 in 82 % isolated yield.…”