Phenolate-induced intramolecular ring-opening cyclization of N-tosylaziridines: access to functionalized benzoxacycles

Abstract

Phenolate-induced, diastereo- and regioselective intramolecular exo-tet ring-opening cyclization of N-tosylaziridines has been achieved for the first time. The N-tosylaziridine substrates bearing a tethered (ortho-(tert-butyldimethylsiloxy))aryl substituent, prepared directly from the corresponding olefins under Sharpless aziridination conditions, furnished functionalized 2,3-dihydrobenzofuran, chroman, and 1-benzoxepane derivatives in excellent yields when treated with tetrabutylammonium fluoride (TBAF) at room temperature. Our ability to synthesize benzoxacycle-based N-tosyl-protected amino alcohols, that are otherwise difficult to obtain by traditional synthetic routes, has opened the door to diversify the chemistry of β-amino alcohols. We also succesfully performed the Baeyer-Villiger oxidation of a salicylaldehyde ether bearing a tethered N-tosylaziridine moiety with m-CPBA followed by tandem saponification and 6-exo-tet aziridine ring-opening cyclization, furnishing the corresponding trans-3,4-disubstituted-1,4-benzodioxane derivative. Overall, the study has unveiled a new entry to the synthesis of benzoxacycles and has also broadened the impact of aziridines as synthetic building blocks.

TBAF-Catalyzed O-Nucleophilic Cyclization of Enaminones: A Process for the Synthesis of Dihydroisobenzofuran Derivatives

“…Initially, enaminone 2b was generated via a conjugate addition ( 1a to 2b ). Subsequently, the hydrogen atom on the nitrogen of enaminone was removed by fluoride anion ( A to B ) . Then, the in situ generated oxygen anion attacked the alkyne moiety ( B to C , 5-exo-dig), which might be activated by the cation−π interaction, to furnish C .…”

“…It was also widely used as a reagent for the cleavage of silyl ethers . In recent years, TBAF has been extensively used as basic catalyst, fluorinated reagent, or used for reduction reactions, elimination reaction, cyclization reaction, , etc . However, the above properties or applications were more focused on the contribution of the fluoride anion in TBAF.…”

Exploiting the reactivities ofortho-alkynyl aryl ketones: opportunities in designing catalytic annulation reactions

“…18 Interestingly, when R 1 was an n -butyl group, conjugated aldehyde 8 was obtained in 92% yield under mild conditions. Based on the control experiments, the authors proposed that the hydrogen atom on the nitrogen of enaminone was removed by fluoride anion, 19 followed by the in situ 5- exo-dig /cation–π interaction to generate intermediate Int4-3 , which underwent a protonation process to offer the target molecule. This procedure is considered to suggest that the cation–π interaction and basicity offered by TBAF might be indispensable for the isomerization of enaminone and the formation of a carbon–oxygen bond.…”

Controlling Cyclization Pathways in Palladium(II)-Catalyzed Intramolecular Alkene Hydrofunctionalization via Substrate Directivity

“…Substrates 1a-1s were prepared according to adapted literature procedures. [1][2][3][4][5][6][7] according to General Procedure A. Purification using silica gel column chromatography with 1:1 hexane:EtOAc as the eluent gave the product as a light-yellow solid (224 mg, 62% yield). 1 H NMR (600 MHz, CDCl3) δ 10.00 (s, 1H), 8.80 (dd, J = 4.3, 1.6 Hz, 1H), 8.76 (dd, J = 7.4, 1.5 Hz, 1H), 8.16 (dd, J = 8.2, 1.7 Hz, 1H), 7.55-7.49 (m, 2H), 7.46 (dd, J = 8.3, 4.2 Hz, 1H), 5.77 (ddd, J = 6.2, 4.9, 4.0 Hz, 2H), 4.28 (s, 1H), 3.30-3.27 (m, 2H), 3.16 (q, J = 6.7 Hz, 2H), 2.93 (s, 3H), 2.20 (td, J = 7.2, 5.1 Hz, 2H), 1.69-1.63 (m, 2H), 1.57 (dq, J = 10.0, 7.2 Hz, 2H); 13 C NMR (150 MHz, CDCl3) δ 170.0, 148.…”

“…To initiate our investigation, we elected to use alkenyl amine 1c as our pilot substrate, which we hypothesized would react via 6-exo-trig cyclization (Table 1). Using Pd(OAc)2 as precatalyst and MeCN as solvent, we evaluated a series of carboxylic acid additives (entries [1][2][3][4][5][6] and found that sterically bulky aliphatic acids led to slightly better yields, with 1-AdaCO2H being the best among those tested (entry 1). Another key finding was that polar aprotic solvents, such as MeCN and PhCN, outperformed nonpolar solvents, and that acidic protic solvents, such as HFIP and TFE, led to diminished yields (entries [7][8][9][10][11].…”