Asymmetric Synthesis of α-Trifluoromethylthio-β-Amino Acids under Phase Transfer Catalysis

Abstract

The first asymmetric α-trifluoromethylthiolation of 2-substituted isoxazolidin-5-ones was developed using Maruoka type N-spiro ammonium catalysts under phase-transfer conditions. The resulting products, containing a trifluoromethylthiolated quaternary chiral carbon, were obtained in moderate to good yields and up to 98:2 enantiomeric ratio. Moreover, the easy N− O bond cleavage provided access to undescribed α-trifluoromethylthio-β 2,2 -amino acids, with promising applications in biochemistry and medicinal chemistry. Letter pubs.acs.org/OrgLett

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

“…Hydrolysis of diethyl 2-(perfluorophenyl)malonate ( 3 ) unexpectedly turned out to be quite challenging. Unsubstituted diethyl or dimethyl 2-phenylmalonate can be readily hydrolyzed under basic conditions by heating with aqueous or mixed water–EtOH solutions [ 29 ] or in biphasic water–Et 2 O mixtures [ 30 ] under reflux conditions.…”

Recent Progress in the Asymmetric Syntheses of α‐Heterofunctionalized (Masked) α‐ and β‐Amino Acid Derivatives

“…The asymmetric synthesis of α‐chalcogenated β‐amino acids can be achieved by a variety of different strategies, [ 43–64 ] as outlined in the following chapters.…”

“…With respect to the introduction of various SR‐groups the electrophilic α‐chalcogenation of suited β‐AA precursors is a very powerful approach for this task. [ 43–45 ] In 2006, Davies and co‐workers introduced a highly selective aza‐Michael initiated protocol for the synthesis of the α‐sulfanylated β‐AA 82 (Scheme 16A). [ 43 ] Hereby they made use of the addition of the chiral Li‐amide 43 to Michael acceptor 42 to form the chiral enolate 80 in situ, which can then be trapped with a suited electrophilic S‐transfer reagent giving product 81 .…”

Imbuing an Old Heterocycle with the Power of Modern Catalysis: An Isoxazolidin-5-one Story

“…17) In contrast to the catalytic construction of the five-membered ring, the use of the heterocycle itself as a substrate in catalytic reactions has been less explored until recently. Significant progress has been made in the last five years along this line, [18][19][20][21][22][23][24] making it possible to synthesize structurally diversified β-amino acids otherwise difficult or impossible to obtain. This review focuses on this emerging approach, highlighting the author's work in recent years.…”