Highly Enantioselective Synthesis of α-Alkyl-alanines via the Catalytic Phase-Transfer Alkylation of 2-Naphthyl Aldimine tert-Butyl Ester by Using O(9)-Allyl-N(1)-2‘,3‘,4‘-trifluorobenzylhydrocinchonidinium Bromide

Abstract

Systematic investigations to develop an efficient enantioselective synthetic method for alpha-alkyl-alanine by catalytic phase-transfer alkylation were performed. The alkylation of 2-naphthyl aldimine tert-butyl ester, 1E, with RbOH and O(9)-allyl-N-2',3',4'-trifluorobenzylhydrocinchonidinium bromide, 6, at -35 degrees C showed the highest enantioselectivities, up to 96% ee.

Asymmetric Synthesis and Conformational Analysis by NMR Spectroscopy and MD of Aba‐ and α‐MeAba‐Containing Dermorphin Analogues

“…The use of only CH 2 Cl 2 as a solvent in the enantioselective alkylation also did not lead to further improvements (entry 9, 60 % ee; entry 10, 70 % ee). Finally, the commercially available catalyst used by the Maruoka group, 22, [36] was applied in the phase-transfer catalysis reaction of 9 b with o-cyanobenzyl bromide. Unfortunately, this did also not improve the enantioselectivity (entry 11, 40 % ee).…”

Convenient Conditions for the Enantioselective Synthesis of α‐Methyl‐α‐amino Acids with the Use of Cinchona Ammonium Salts as Phase‐Transfer Organocatalysts

“…[24] Thus, under these reaction conditions, 50 % aqueous KOH, [14] [c] Configuration assigned on the basis of the relative reported retention times of the (R/S) isomers. [15] [d] A 87 % ee was reported with the use of catalyst 7 (K 2 CO 3 /KOH, toluene, r.t.). [14] toluene/chloroform, 0°C, a 82 % ee for corresponding AMAA derivative (S)-10aa was obtained (Table 1, Entry 1).…”

“…(Table 1, compare Entries 1 and 7). However, when the alkylation substrate was changed to 2-naphthyl aldimine alanine tert-butyl ester 7c, [15] the enantioselectivity for (S)-10ca rose from 82 up to 87 % ee ( Table 1, compare Entries 1 and 8).…”

“…They obtained even higher enantioselectivities in the α-alkylation of a 2-naphthyl aldimine Schiff base of alanine tert-butyl ester 6 (Ar = 2-naphthyl, R 1 = Me, R 2 = tBu) and achieved 95 % ee for the benzylation reaction. [15] Other non-Cinchona catalysts have been used for the enantioselective synthesis of AMAA derivatives by alkylation of alanine-derived imines 6 under PTC conditions, such as metal-salen complexes, [16,17] binaphthol derivatives, [18] and C 2 -symmetric ammonium salts. [19][20][21] under PTC conditions with the use of common, simple, and inexpensive cinchonidine and cinchonine ammonium salts 2a,d or 4 as organocatalysts can be considerably improved.…”

Neue Entwicklungen bei asymmetrischen Phasentransferreaktionen

“…Dementsprechend wurden zahlreiche Untersuchungen zur Entwicklung wirklich effizienter Synthesemethoden durchgeführt, wozu die Phasentransferkatalyse einzigartige Beiträge geleistet hat. [2,3] Auf der Grundlage der früheren Arbeit von Jew und Park [40] berichteten Nµjera et al über die asymmetrische Alkylierung des 2-Naphthylaldimin-Alanin-tert-butylesters 39 mit den von Cinchona-Alkaloiden abgeleiteten quartären Ammoniumsalzen 1 c und 2 c als Katalysatoren. Die Alkylierungen von 39 verliefen in Gegenwart der starken Base Rubidiumhydroxid (RbOH) bei À20 8C mit den hçchsten Enantioselektivitäten (Schema 29).…”