ortho-Dialkylamino arylboranes as efficient reagents for difluorocarbene trapping

Abstract

A readily accessible reagent bearing ortho-oriented amino and boryl groups efficiently traps difluorocarbene.

Difluorocarbene-Mediated Cascade Cyclization: The Multifunctional Role of Ruppert–Prakash Reagent

“…When the nucleophile and electrophile reside in the same molecule, an interesting homologation cyclization process may occur with difluorocarbene acting as a C1 ring-building synthon. For instance, Dilman et al disclosed that difluorocarbene can be trapped by frustrated Lewis pairs, affording cyclic zwitterionic phosphonium salts useful for difluorocarbene transfer reactions (Scheme a) . Furthermore, cyclization of o -hydroxyaryl ketones and o -mercatoaryl ketones via difluorocarbene insertion have enabled rapid construction of CF 2 -containing five-membered heterocycles (Scheme b, c) .…”

In silico reaction screening with difluorocarbene for N-difluoroalkylative dearomatization of pyridines

“…Although N-heterocycles that bear two fluorine atoms at the βand γ-positions are prevalent in pharmaceuticals such as the DPP-4 (dipeptidyl peptidase) inhibitors gosogliptin or gemigliptin (Fig. 4a), the analogous α,αdifluorinated N-heterocyclic motif has not been used for these applications, presumably due to the lack of synthetic methods [24][25][26][27][28][29][30][31][32][33][34][35] . In this context, we sought to realize the multicomponent reaction of a C=N bond, a C=O bond and a difluorocarbene to afford N-α,α-difluorooxazolidines A1 (Fig.…”

“…The pyridine scope was also investigated with i-butyraldehyde as the coupling partner. A series of bioactive nicotine derivatives underwent the cycloaddition, and substrates with a variety of functionalities such as ester, nitro, nitrile, ketone, amide, bromide and boronic ester groups are well tolerated (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). The cycloadditions proceeded preferentially at the less-hindered carbon atom adjacent to the nitrogen atom on the pyridine substrates.…”

Deconstrutive Difunctionalizations of Cyclic Ethers Enabled by Difluorocarbene to Access Difluoromethyl Ethers

“…Subsequently, Ngai et al reported a distinct radical approach for catalytic C-H difluoromethoxylation of (hetero)arenes using difluoromethoxylative reagents [11][12] (Figure 1B, left). Of note, as an important and special fluorine-containing intermediate in organic synthesis [13][14][15][16][17][18][19][20][21][22][23][24] , difluorocarbene has been combined with various alcohols or thiolsto synthesize difluoromethyl ethers [25][26][27][28] or thioethers [29][30] (Figure 1B, right). Despite the progress achieved in recent years on the synthesis of difluoromethyl ethers, their efficient synthetic methods are still rare and the development of a general and practical strategy for their construction is still highly appealing, especially in terms of complexity and versatility of difluoromethoxy compounds.…”

“…Given the prevalence of alkyl ethers and inspired by our previous work on the deconstructive functionalization of tertiary amines by difluorocarbene [49][50][51][52] , we envisage that the electron-deficient 53 difluorocarbene might interact with the lone pair electrons [54][55][56][57] of the oxygen atom in alkyl ether, thus forming a zwitterionic intermediate, which might experience a nucleophilic attack by a third component on the carbon atom that is adjacent to the oxygen in cyclic ethers to procure difluoromethyl ethers via ether editing. If successful, we will significantly expand the substrate scope for difluoromethyl ethers by developing a three-component reaction with readily accessible starting materials, meanwhile we will increase the diversity of difluoromethoxy compounds and provide a versatile pool for medicinal chemistry.…”