C3−H Silylation of Furfurylimines: Direct Access to a Novel Biobased Versatile Synthetic Platform Derived from Furfural

Abstract

Herein we report directed iridium-catalyzed C3-H silylation of furfuryl imines, which grants access to versatile synthetic platforms. This transformation was developed on furfuryl derivatives, using imines as directing groups, and trialkylsilanes or bis(trimethylsilyl)methylsilane as silylating agents, in the presence of a hydride scavenger. Subsequently, fluoride-mediated activation strategies were applied to the C3-SiMe(OSiMe3)2 furfural derivatives to achieve a wide range of transformations of the C3-Si bond. Arylation, alkenylation, alkynylation, allylation and alkylation, as well as halogenation and trifluoromethylation were achieved in modest to high yields. A variety of high value-added products were thus easily obtained from the same common C3-silylated furfural-based platform.

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

“…Synthesis of 3-silylated 2-furyl carbinols C3-silylated furfurals 1a-c and 2c are accessible from furfural or 5-methylfurfural [20], respectively, according to our previously reported protocol for selective catalytic C3 silylation [15]. The addition of organolithium [21] or Grignard reagents [22,23] to these substrates was uneventful and allowed for the preparation of 2-furylalkyl (see 3a-c, 4c), -aryl (see 5c, 6c), and -allyl carbinols (see 7c) having furan rings with various triorganosilyl substituents at C3 in a synthetically useful yield and on an appropriate scale (Scheme 2).…”

“…In a flame-dried round-bottom flask under argon was placed the appropriate C3-silylated furfural [15] and dissolved in freshly distilled THF (0.3 M). The solution was cooled to −78 °C, and then n-BuLi (1.2 equiv in hexane) was added dropwise.…”

“…In a flame-dried round-bottom flask under argon was placed the appropriate C3-silylated furfural [15] and dissolved in freshly distilled THF (0.2 M solution). The solution was cooled to 0 °C, and then the Grignard reagent (1.3 equiv in Et 2 O) was added dropwise (the rate of addition was equal to, or lower than 0.125 mL/min).…”

“…We first contemplated the possibility to promote C3-Si bond functionalization through intramolecular activation by alkoxides [15]. It was reported that lithium alkoxides A undergo 1,4-silyl migration (Brook rearrangement) to generate C2-lithiated furans C, which in turn can react in the presence of electrophiles to deliver product D, resulting from the overall C2-Si functionalization (Scheme 3, top) [24,25].…”

“…As part of this effort, exploitation of furfural and corresponding derivatives attracts continuous attention [4][5][6][7]. In this area, we have actively investigated catalytic C-H activation reactions [8][9][10][11][12][13][14], and as part of this work, we have recently developed an iridium-based protocol for the catalytic C3-H silylation of furfurylimines [15]. This method allows to install a C-Si bond poised for further functionalization on the furfural unit, and thereby leads to synthetic platforms useful to access elaborated furans.…”