Synthesis, Inhaltsverzeichnis Synthesis 2014; 46(11): 1475-1480DOI: 10.1055/s-0033-1340955 paper © Georg Thieme Verlag Stuttgart · New York Solvent-Free Synthesis of a Secondary N-Benzhydrylamine as a Chiral Reagent for Asymmetric Deprotonation of Bicyclic N-Benzylamino Ketones Aneta Nodzewska* Institute of Chemistry, University of Bialystok, Hurtowa 1, 15-399 Bialystok, Poland Fax: +48(85)7470113 eMail: annodz@uwb.edu.pl , Katarzyna Sidorowicz Institute of Chemistry, University of Bialystok, Hurtowa 1, 15-399 Bialystok, Poland Fax: +48(85)7470113 eMail: annodz@uwb.edu.pl , Michal Sienkiewicz Institute of Chemistry, University of Bialystok, Hurtowa 1, 15-399 Bialystok, Poland Fax: +48(85)7470113 eMail: annodz@uwb.edu.pl › Institutsangaben Artikel empfehlen Abstract Artikel einzeln kaufen Alle Artikel dieser Rubrik Abstract Several chiral secondary N-benzhydrylamines were synthesized in good yields (68–92%) without racemization by the direct alkylation of amines with benzhydryl chloride under solvent-free conditions. Using the solvent-free conditions (R)-N-benzhydryl-1-phenylethylamine was obtained with the highest yield (92%), purified on ion-exchange resin, and converted to its hydrochloride salt. The resulting chiral amine hydrochloride was transformed into lithium amide/lithium chloride mixture used in asymmetric deprotonations of N-benzyl analogues of tropinone and granatanone followed by aldol reactions giving products in high diastereomeric purities (up to 96%) and enantiomeric excesses of 77 to 96%. Key words Key wordsaldol reaction - N-alkylation - asymmetric synthesis - amines - enantioselectivity Volltext Referenzen References 1a O’Brien P. J. Chem. Soc., Perkin Trans. 1 1998; 1439 1b Simpkins NS, Weller MD. Asymmetric Deprotonations using Chiral Lithium Amide Bases. In Topics in Current Stereochemistry. Vol. 26. Gawley RE. Wiley-VCH; Weinheim: 2010 2a Majewski M, Nowak P. J. Org. Chem. 2000; 65: 5152 2b Inoue M, Lee N, Kasuya S, Sato T, Hirama M, Moriyama M, Fukuyama Y. J. Org. 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In the presence of deuterated solvent, for example, MeOD, only the NH hydrogen is substituted by deuterium and is invisible in the NMR spectrum in contrast to Ph2CH {1H NMR (400 MHz, MeOD): δ = 7.45–7.08 (m, 15 H, ArH), 4.56 [s, 1 H, CH(Ph)2], 3.64 (q, J = 6.7 Hz, 1 H, CHMe), 1.36 (d, J = 6.7 Hz, 3 H, CH3)}. Signal from Ph2CH is observed in the NMR spectrum of Li-3, obtained in the reaction of amine 3 with n-BuLi in THF-d 8 under typical reaction condition (0 °C, 30 min) in NMR tube {1H NMR (400 MHz, THF-d 8): δ = 7.38–6.92 (m, 15 H, ArH), 4.81 [s, 1 H, CH(Ph)2], 3.74 (q, J = 6.4 Hz, 1 H, CHMe), 0.95 (d, J = 6.6 Hz, 3 H, CH3)}. 22a Brzezinski K, Lazny R, Sienkiewicz M, Wojtulewski S, Dauter Z. Acta Crystallogr., Sect. E 2012; 68: o149 22b Lazny R, Wolosewicz K, Dauter Z, Brzezinski K. Acta Crystallogr., Sect. E 2012; 68: o1367 23a Lazny R, Nodzewska A, Sidorowicz K, Kalicki P. Beilstein J. Org. Chem. 2012; 8: 1877 23b Lazny R, Wolosewicz K. 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