Enantioselective Synthesis of 2‐(2‐Arylcyclopropyl)glycines: Conformationally Restricted Homophenylalanine Analogs

Abstract

Dedicated to Professor Wolfgang Steglich on the occasion of his 70th birthdayStarting from simple aromatic aldehydes and acetylfuran, (E)-1-(furan-2-yl)-3-arylprop-2-en-1-ones (2) were synthesized in high yields. Cyclopropanation of the CC bond with trimethylsulfoxonium iodide (Me 3 SO I À ) furnished (furan-2-yl)(2-arylcyclopropyl)methanones 3 in 90 ± 97% yields. Selective conversion of cyclopropyl ketones to their (E)-and (Z)-oxime ethers 5 and oxazaborolidine-catalyzed stereoselective reduction of the CN bond followed by separation of the formed diastereoisomers, furnished (2-arylcyclopropyl)(furan-2-yl)methanamines 6 in optically pure form and high yield. Oxidation of the furan ring of (S,S,S)-, (S,R,R)-, (R,S,S)-, and (R,R,R)-6a afforded the four stereoisomers of a-(2-phenylcyclopropyl) glycine (1a).

Stereospecific Suzuki, Sonogashira, and Negishi Coupling Reactions ofN-Alkoxyimidoyl Iodides and Bromides

“…The common way to make oxime ethers involves a condensation reaction between a ketone and an N -alkoxyamine, which generally results in a mixture of E - and Z -isomers (eq ). − When R 1 and R 2 are similarly sized, such as two aryl groups, the product ratio is typically close to 50:50. These mixtures of geometric isomers, depending on the nature of R 1 and R 2 , can be very difficult to separate.…”

Synthesis of 2,3- and 3,4-Methanoamino Acid Equivalents with Stereochemical Diversity and Their Conversion into the Tripeptide Proteasome Inhibitor Belactosin A and Its Highly Potent Cis-Cyclopropane Stereoisomer

“…Thus, we have successfully developed a general procedure for the preparation of a series of 2,3- and 3,4-methanoamino acid equivalents with cis / trans , d/l , and syn / anti stereochemical diversity. This is, to our knowledge, the first synthetic method for systematically providing chiral 2,3- and 3,4-methanoamino acids with stereochemical diversity. , …”

“…The stereoselective synthesis of cyclopropane derivatives with a desired stereochemistry is often troublesome. ,, To solve this problem, we recently developed chiral units composed of four stereoisomeric cyclopropanes, 1 and 2 , and their enantiomers ent- 1 and ent- 2 (Scheme ), for preparing various cyclopropane derivatives bearing adjacent carbon substituents in a cis or a trans relationship . These units were employed as synthons in this study.…”

Synthesis and Characterization of Novel Aromatic Substituted γ- and δ-Ketoxime Esters

“…We have obtained oxime esters 2a-2j with high yields and the products were synthesized with the reaction between aryl, substituted aryl and heteroaryl γ-and δ-keto esters 1a-1j and hydroxyamine hydrochloride (see Scheme 1). According to these literatures (24,(45)(46)(47)(48), the configuration of the synthesized compounds (2a-2j) in this work were determined by 1 H-NMR spectrum due to the splitting of the methoxy signal as studied in the previous study of our group (24). Two methoxy signals were seen for E/Z mixture.…”

“…We have obtained oxime esters 2a-2j with high yields and the products were synthesized with the reaction between aryl, substituted aryl and heteroaryl γ-and δ-keto esters 1a-1j and hydroxyamine hydrochloride (see Scheme 1). (45)(46)(47). In another work, hydroxyimino derivatives of keto esters were obtained also mainly as E isomer (24).…”