Auto‐Tandem Catalysis with Frustrated Lewis Pairs for Reductive Etherification of Aldehydes and Ketones

Abstract

Herein we report that a single frustrated Lewis pair (FLP) catalyst can promote the reductive etherification of aldehydes and ketones. The reaction does not require an exogenous acid catalyst, but the combined action of FLP on H , R-OH or H O generates the required Brønsted acid in a reversible, "turn on" manner. The method is not only a complementary metal-free reductive etherification, but also a niche procedure for ethers that would be either synthetically inconvenient or even intractable to access by alternative synthetic protocols.

Size‐Exclusion Borane‐Catalyzed Domino 1,3‐Allylic/Reductive Ireland–Claisen Rearrangements: Impact of the Electronic and Structural Parameters on the 1,3‐Allylic Shift Aptitude

“…[12] Subsequents tudies revealed that the borane I itself was incapable of promoting the 1,3-allylic shift because of the confined space around the Lewis acidic center. However, as our observations [13] suggest,t he allylic transposition (Scheme 2) could proceed by means of either aL ewis acid induced Lewis acid promotion (hydride abstraction from HSiEt 3 with borane I) [16] or hidden proton catalysis [17] (protonationb yt race amount of borane I-watera dduct [11,18] ). Finally,i tw as established that the enhanced steric hindrance around the borane I was ac ritical factor in this reductiveI reland-Claisen reaction.…”

“…However,t he adaptation of borane-promoted hydrosilylation for reductiveI reland-Claisen rearrangement was far from being straightforwardbecause of the substrate inhibition and the extreme water sensitivity of the highly oxo-philic, hard-type boron catalyst. Nevertheless, based on our previousw ork in frustrated Lewis pair hydrogenation [11] and hydrosilylation, [12] we conceived that it is possible to tackle these anticipated constraints of ab orane-catalyzed reductive Ireland-Claisen rearrangement by employing structurally welldesigned, so-called size-exclusion boranes. The enhanced steric shieldinga roundthe boron Lewis acid centerserves to prevent or retard the complexation ability with Lewis basis (including water and carbonyls' oxygen), while retainingt he capacity of cleavage of the silanes and might drive the chemo-and regioselectivity of the hydrosilylation of acrylates.…”

“…The effect of the methoxyg roup was also systematically investigated (Table 2, entries [11][12][13]. Thes ubstituent exertedi ts electron-donating effect in ortho and para positions, resulting in the formation of the 2,3-disubstituted unsaturated 5m,o carboxylic acid derivatives.…”

Applications of alkyl orthoesters as valuable substrates in organic transformations, focusing on reaction media

“…The synthesis of substituted 3-benzoylamino-5-oxo-5,6,7,8tetrahydrocoumarins (427) from 1,3-cyclohexanediones (195,197), hippuric acid (407), and TEOF (5) (or other one-carbon synthetic equivalents, such as diethoxymethyl acetate or N,Ndimethylformamide dimethyl acetal) in acetic anhydride has been described (Scheme 122). 375 In 378 In 2016, estrone 3-secondary ethers (435) were made through the eco-friendly etherication/aromatization reaction of readily accessible dienone (432) with trialkyl orthoformates (127,433,434), as alkylating agent, in a 1 : 5 molar ratio by triic acid (TfOH, 0.5 mmol) in the corresponding alcohol (5 mL) at 100 C for 2 h in 80-87% yields (Scheme 125). The above-mentioned procedure was applied for the generation of three marketed 3-etheried estrogen drugs, quinestrol, quinestradol, and nilestriol, utilizing 19-hydroxyandrost-4-ene-3,17-dione as a commercially available precursor.…”

N‐Phosphine Oxide‐Substituted Imidazolylidenes (PoxIms): Multifunctional Multipurpose Carbenes

“…However,this reactivity of FLPs eventually inhibits their isolation and makes them unstablef or shelf storage, which somewhat limits their utility in organic synthesis. [11] We therefore envisioned as trategy to control the interconversion between CLAs and FLPs by using externals timuli, which should offer an opportunity to use isolable and shelfstable CLAs as precursors for active FLPs under closely controlledr eactionc onditions rather than under ambientc onditions ( Figure 4c). [12] In order to achieve this "frustration revival strategy", we designed PoxIms that undergo significant changes to the spatiale nvironments urrounding their carbene centert hrough rotation of the N-phosphineo xide moiety.…”