Molecular Design of a C₂-Symmetric Chiral Phase-Transfer Catalyst for Practical Asymmetric Synthesis of α-Amino Acids

Abstract

Despite the increasing importance and usefulness of phase transfer catalysis (PTC) in synthetic organic reactions, 1 catalytic asymmetric synthesis utilizing chiral phase-transfer catalysts remains poorly studied. [2][3][4] Yet, since the pioneering work of O 'Donnell et al. in 1989, asymmetric synthesis of R-amino acids by phase-transfer enantioselective alkylation of a prochiral protected glycine derivative 1 using a chiral catalyst has provided an attractive method for the preparation of both natural and unnatural amino acids. 5 Recently, the Corey 6 and Lygo groups 7 independently reported an impressive departure from the previous results in terms of enantioselectivity and general applicability. However, almost all of the elaborated chiral phase-transfer catalysts reported so far have been restricted to cinchona alkaloid derivatives, which unfortunately constitutes a major difficulty in rationally designing and fine-tuning catalysts to attain sufficient reactivity and selectivity for various chemical transformations under phase-transfer catalyzed conditions. 3,4 In this paper, we wish to describe a new, rational approach to this subject, i.e., the molecular design of a C 2 -symmetric chiral quaternary ammonium salt and its successful application to the highly efficient, catalytic enantioselective alkylation of tert-butyl glycinate-benzophenone Schiff base 1 under mild phase-transfer conditions.

Enantioselective syntheses and biological studies of aeruginosin 298-A and its analogs: Application of catalytic asymmetric phase-transfer reaction

“…[24][25][26][27] or other designed catalysts (for representative examples, see refs. [28][29][30][31][32], only a few synthetic applications for complex natural products have been reported (23). Recently, we developed two-center catalysts that promote phase-transfer alkylations and Michael reactions with high substrate generality (14).…”

Quantification of the chiral recognition in electrochemically driven ion transfer across the interface water/chiral liquid

“…The stereoselectivity of chemical and biochemical syntheses [2][3][4] and separations depends on the chiral discrimination of one or the other isomer. Electrochemical reactions can exhibit stereoselectivity when performed in chiral solvents [5], in the presence of chiral supporting electrolytes [5,6], or on electrodes with a chiral surface [7,8].…”

Highly Efficient Catalytic Synthesis of -Amino Acids under Phase-Transfer Conditions with a Novel Catalyst/Substrate Pair

“…Treatment of [OsCl 2 (PPh 3 ) 3 ] (1) [3] with an excess of HC CSiMe 3 in wet benzene produced a yellow precipitate and a brown solution. The yellow precipitate was identified as tal analysis (%) calcd for C 21 H 15 N 3 O 3 Ni: C 60.62,H 3.63,N 10.10;found: C 60.58,H 3.60,N 10 Asymmetric alkylation of 3 under PTC conditions (described for RX BnBr): Finely ground NaOH (2.0 g, 50 mmol), substrate 3 (2.1 g, 5 mmol), and (R)-NOBIN (0.14 g, 0.5 mmol) in anhydrous CH 2 Cl 2 (30 mL) were stirred under Ar for 3 min at 15 ± 20 8C.…”

“…[2c±e] Purely synthetic, chiral, C 2 -symmetrical ammonium salts were recently prepared and shown to be highly efficient in the same set of reactions. [3] Thus, preparative catalytic asymmetric syntheses of very important synthetic targets such as amino acids were developed, and enantioselectivities of up to 92-98 % for the final product were achieved. [2c±e, 3] Unfortunately, N-(diphenylmethylene)glycine esters are expensive, and quaternary ammonium salts are sometimes unstable under basic conditions.…”