Increased electron demand in the solvolysis of secondary 2-norbornyl tosylates

Synthesis of Trialkylhydroxylamines by Stepwise Reduction of O-Acyl N,N-Disubstituted Hydroxylamines: Substituent Effects on the Reduction of O-(1-Acyloxyalkyl)hydroxylamines and on the Conformational Dynamics of N-Alkoxypiperidines

“…The strongly retarding effect of the electron-withdrawing group in the reduction of both 1 and 19 is consistent with that of electron-withdrawing groups in solvolysis reactions, − in the hydrolyses of glycosides, and in glycosylation reactions, − and lends support to the intermediacy of an aminoxocarbenium ion intermediate (Figure ) in these reactions. An alternative synthesis of 22 involving alkylation of the sodium salt of N , N -dibenzylhydroxylamine 12 with 2-azidoethyl tosylate was complicated by formation of the nitrone N -(phenylmethylene)­benzylamine N -oxide as determined by mass spectrometry of the crude reaction mixture and gave only 25% yield, consistent with literature observations on the difficulties of alkylation of N , N -dialkylhydroxylamines with all but the most potent electrophiles (Scheme b).…”

“…The filtrate was washed with saturated aq NaHCO 3 , and brine, dried over anhydrous Na 2 SO 4 , concentrated under reduced pressure, and purified by flash column chromatography on silica gel (eluent: 10−30% of ethyl acetate in hexane) to afford 10 (827 mg, 80%) as a colorless oil. IR (neat, cm −1 ) v 1757; 1 1-(4-Chloro-1-piperidinyloxy)-4-phenylbutyl acetate (11). To a stirred solution of 10 (100 mg, 0.35 mmol) at −78 °C under nitrogen in dry CH 2 Cl 2 (2.1 mL) were added sequentially, dropwise DIBAL (0.62 mL 1 M in hexane, 0.62 mmol), pyridine (85 μL, 1.06 mmol), a solution of DMAP (87 mg, 0.71 mmol) in dry CH 2 Cl 2 (1 mL), and finally Ac 2 O (201 μL, 2.13 mmol).…”

“…The reduction of the O -(1-acetoxy-2-β-naphthyloxy)­ethyl N , N -dibenzyl system 1 , however, was strikingly slower and gave only 38% of the hydroxylamine 2 after 7 days at room temperature . We reasoned that the lack of reactivity of 1 under the typical conditions was a manifestation of the electron-withdrawing effect of the ether moiety on the presumed intermediate aminoxocarbenium ion and, thus, related to the well-known strong influence of electron-withdrawing substituents on glycosylation, − and solvolysis reactions in general. − …”

Blue Light Photocatalytic Glycosylation without Electrophilic Additives

“…Encouraged by application of the process to O -tetrahydrofuranyl 2,2,6,6-tetramethylpiperidinoxide, we considered that this process might be adapted to photocatalytic glycosylation through the use of O -glycosyl 2,2,6,6-tetramethylpiperidinoxides , as donors if the highly destabilizing effect of adjacent C–O bonds on cations and oxocarbenium ions − could be overcome. Here, we report the successful reduction of this concept of LED-energized photocatalytic glycosylation in the absence of added electrophiles to practice employing O -glycosyl 2,2,6,6-tetramethylpiperidinoxides (Scheme , R = glycosyl).…”

“…3,10−14 Consequently, we were attracted by recent work on the photocatalytic generation of simple tertiary alkyl, allyl, and benzyl cations from sterically hindered O-alkyl hydroxylamines that proceeds in the absence of stoichiometric additives in which the photocatalytic cycle is closed by reduction of the expelled nitroxyl radical (Scheme 2, R = t-Alkyl). 15 Encouraged by application of the process to O-tetrahydrofuranyl 2,2,6,6-tetramethylpiperidinoxide, 15 we considered that this process might be adapted to photocatalytic glycosylation through the use of O-glycosyl 2,2,6,6-tetramethylpiperidinoxides 16,17 as donors if the highly destabilizing effect of adjacent C−O bonds on cations 18 and oxocarbenium ions 19−23 could be overcome. Here, we report the successful reduction of this concept of LEDenergized photocatalytic glycosylation in the absence of added electrophiles to practice employing O-glycosyl 2,2,6,6-tetramethylpiperidinoxides (Scheme 2, R = glycosyl).…”