Merging Electron Transfer Activation with 1,2-Metalate Migration: Deoxygenative Silylation of Amides

Abstract

A direct deoxygenative silylation of amides with silylboronate reagents is developed in the presence of SmI2/Mg, affording a variety of high value-added α-aminosilane compounds in moderate to excellent yields with good functional group compatibility. The key to the success of this strategy lies in the merging of activation of amides induced by electron transfer with 1,2-metalate migration. The addition of Xantphos ligand can improve the reaction efficiency. The reactions are operationally simple and proceed under mild conditions, the raw materials are easily available and the products are highly valuable.

Making Full Use of TMSCF3: Deoxygenative Trifluoromethylation/Silylation of Amides

“…Notably, this reaction behavior of TMSCF 3 is much different from that disclosed in previous reports. − Therefore, further optimization efforts were made to enhance the selective formation of 2a . Based on some seminal reports and our own studies that the use of catalytic amounts of an additive may greatly influence the reductive property of SmI 2 , we subsequently proceeded to screen a variety of additives. Under otherwise identical conditions, the use of 5.0 mol % of hexamethylphosphoramide (HMPA) or protic solvents such as methanol as an additive resulted in complete inhibition of the formation of the desired product (entries 2–3).…”

“…Based on the above results and our previous investigation, we tentatively proposed that the amide is first reduced in an SET process by SmI 2 to generate a Sm(III)-coordinated ketyl radical anion I , , which is reduced further to a Sm(II)-coordinated radical II ,, via a SET from Sm (Scheme d). The intermediate II could also be viewed as a resonance structure of Sm(III)-coordinated anion III (a carbenoid equivalent), which may generate an α-aminocarbene intermediate IV by deoxygenation .…”

“…Therefore, the development of effective deoxygenative methodologies of amides to various densely functionalized amines should find widespread use across academia and industry . Over the past decades, several attractive strategies have been developed for deoxygenative activation of an amide, i.e., through electrophilic activation by using Tf 2 O, transition-metal-catalyzed hydride transfer, , and single-electron-transfer (SET) activation by SmI 2 . − The amido group is first selectively transformed into active intermediates, such as iminium ion (Scheme b-i) − or α-aminocarbene/carbenoid equivalent, , followed by the reaction with a coupling partner to generally afford a deoxygenative monofunctionalization product . Considering the increased nucleophilicity and electrophilicity of α-aminocarbenes compared with N,N -dimesityl imidazolylidene (NHC), with a much less explored reactivity distinct from the well-developed carbene chemistry in organic synthesis, we envisioned that combining Sm–SmI 2 -mediated amide activation with the synthetically versatile TMSCF 3 reagent may lead to the efficient synthesis of fluorine-containing densely functionalized amines that are otherwise difficult to attain.…”

Deoxygenative alkynylation of amides via CO bond cleavage

“…26 Subsequently, a series of deoxygenative functionalization of amides induced by SmI 2 /Sm were developed. 27–32 In 1997, Ogawa group reported a single example of SmI 2 /Sm-mediated deoxygenative alkynylation of amides using HMPA. 33 We attempted the deoxygenative alkynylation of other amides and alkynes under these conditions, but the results showed that other types of amides and alkynes are not applicable to this SmI 2 system.…”