An Expedient Method for the Umpolung Coupling of Enols with Heteronucleophiles**

Abstract

In this paper, we present an unprecedented and general umpolung protocol that allows the functionalization of silyl enol ethers and of 1,3-dicarbonyl compounds with a large range of heteroatom nucleophiles, including carboxylic acids, alcohols, primary and secondary amines, azide, thiols, and also anionic carbamates derived from CO 2 . The scope of the reaction also extends to carbon-based nucleophiles. The reaction relies on the use of 1-bromo-3,3-dimethyl-1,3dihydro-1λ 3 [d][1,2]iodaoxole, which provides a key α-brominated carbonyl intermediate. The reaction mechanism has been studied experimentally and by DFT, and we propose formation of an unusual enolonium intermediate with a halogen-bonded bromide.

Revisiting the Paradigm of Reaction Optimization in Flow with a Priori Computational Reaction Intelligence

“…4 ‐ CF 3, 4 ‐ CN, 4‐NO 2 ), the trend inverts and a ρ value of +3.33 is obtained. Such a drastic change in behavior reflects the ambivalent nature of both nitrosoarenes 1 and silyl enol ethers 2 [17,41] . The incorporation of strong EWGs in 2 results in an inverse electronic demand by which 2 behaves as the electrophile and 1 as the nucleophile.…”

“…Such a drastic change in behavior reflects the ambivalent nature of both nitrosoarenes 1 and silyl enol ethers 2. [17,41] The incorporation of strong EWGs in 2 results in an inverse electronic demand by which 2 behaves as the electrophile and 1 as the nucleophile. To further confirm this finding, the molecular electrostatic potential (MEP) has been computed, clearly showing a change in the electrophilic and nucleophilic centers (Figure 3C).…”

Revisiting the Paradigm of Reaction Optimization in Flow with a Priori Computational Reaction Intelligence

“…Such a drastic change in behavior reflects the ambivalent nature of both nitrosoarenes 1 and silyl enol ethers 2. [17,41] The incorporation of strong EWGs in 2 results in an inverse electronic demand by which 2 behaves as the electrophile and 1 as the nucleophile. To further confirm this finding, the molecular electrostatic potential (MEP) has been computed, clearly showing a change in the electrophilic and nucleophilic centers (Fig.…”

Silver-Catalyzed Coupling of Ethynylbenziodoxolones with CO2 and Amines to Afford O-β-Oxoalkyl Carbamates

“…Notably, CO 2 has also emerged as an appealing phosgene substitute for the synthesis of organic carbamates . However, only a few methods have been exploited for the preparation of O -β-oxoalkyl carbamates with ketones or their derivatives as the raw materials (Scheme b) . In 2017, our group first developed a n Bu 4 NI-catalyzed coupling of aryl ketones, CO 2 , and amines for constructing O -β-oxoalkyl carbamates by using tert -butyl hydroperoxide as an oxidant .…”

“…Although the mechanism of the silver-catalyzed transformation has not been fully elucidated at this point, on the basis of the experimental results and previous literature, ,, a possible mechanistic pathway was proposed as depicted in Scheme c. Initially, in the presence of DBU, amine 2 can react with CO 2 to give carbamate salt I , , which will undergo a nucleophilic addition to the C–C triple bond of EBX 1 to generate VBX 6 via a vinyl anion II intermediate. Then, under the cooperation of silver catalyst and DBU, VBX 6 will undergo deprotonation to give intermediate III , which leads to the formation of a carbene intermediate IV through α-elimination.…”