26593-35-1Relevant academic research and scientific papers
Chirally deuterated benzyl chlorides from benzyl alcohols via hexachloroacetone/polymer-supported triphenylphosphine: Synthesis of protected (2S, 3S)-[3-2H, 15N]-tyrosine
Barnett, Derek W.,Refaei, Maryanne S.,Curley Jr., Robert W.
, p. 6 - 11 (2013/03/28)
Chirally deuterated benzyl chlorides were prepared using novel, general hexachloroacetone/polymer-supported triphenylphosphine treatment of chirally deuterated benzyl alcohols. Doubly labeled protected tyrosine was obtained in 62% yield with 86% de at the α-carbon and 82% de at the β-carbon. Key in the synthesis was the alkylation of 15N-labeled (-)-8-phenylmenthylhippurate with R-(-)-4-triisopropylsilyloxybenzyl-α-d chloride. Chirally deuterated benzyl chlorides were prepared in high yield with inversion from benzyl alcohols using solid-phase methods. One of the benzyl chlorides obtained was used in the synthesis of protected tyrosine labeled with 15N and chirally deuterated on the β-position. Copyright
Photochemical generation of highly destabilized vinyl cations: The effects of α- and β-trifluoromethyl versus α- and β-methyl substituents
Van Alem, Kaj,Belder, Geerte,Lodder, Gerrit,Zuilhof, Han
, p. 179 - 190 (2007/10/03)
(Chemical Equation Presented). The photochemical reactions in methanol of the vinylic halides 1-4, halostyrenes with a methyl or a trifluoromethyl substituent at the α- or β-position, have been investigated quantitatively. Next to E/Z isomerization, the reactions are formation of vinyl radicals, leading to reductive dehalogenation products, and formation of vinyl cations, leading to elimination, nucleophilic substitution, and rearrangement products. The vinyl cations are parts of tight ion pairs with halide as the counterion. The elimination products are the result of β-proton loss from the primarily generated α-CH3 and α-CF3 vinyl cations, or from the α-CH3 vinyl cation formed from the β-CH3 vinyl cation via a 1,2-phenyl shift. The β-CF 3 vinyl cation reacts with methanol yielding nucleophilic substitution products, no migration of the phenyl ring producing the α-CF3 vinyl cation occurs. The α-CF3 vinyl cation, which is the most destabilized vinyl cation generated thus far, gives a 1,2-fluorine shift in competition with proton loss. The experimentally derived order of stabilization of the vinyl cations photogenerated in this study, α-CF3 3 3 3, is corroborated by quantum chemical calculations, provided the effect of solvent is taken into account.
Stereoselective route to 15N-labeled-β-deuterated amino acids: Synthesis of (2S,3R)-[3-2H,15N]-phenylalanine
Barnett, Derek W.,Panigot, Michael J.,Curley Jr., Robert W.
, p. 1893 - 1900 (2007/10/03)
(2S,3R)-[3-2H,15N]-Phenylalanine hydrochloride was synthesized utilizing 15N-labeled 8-phenylmenthylhippurate as a chiral glycine equivalent. The key step in the synthesis was the alkylation of the glycine template with (S)-(+)-benzyl-α-d-mesylate. The doubly labeled alkylation product was obtained in 89% yield with 92% de at the α-carbon and 74% de at the β-carbon. The nature of the electrophile employed in the alkylation step significantly affects the stereochemical outcome at the β-carbon. Hydrolysis of the alkylation product under acidic conditions followed by recrystallization from isopropanol yielded the title compound as the hydrochloride salt. Analysis of the (-)-camphanamide derivative of the final product by NMR spectroscopy and HPLC revealed a 76% de at the α-carbon and a 72% de at the β-carbon. The synthetic strategy described represents a simple yet versatile route to chirally deuterated β-methylene unit containing amino acids.
