Asymmetric synthesis of N-protected amino acids by the addition of organolithium carboxyl synthons to ROPHy/SOPHy-derived aldoximes and ketoximesChiral oxime ethers in asymmetric synthesis. Part 6.1

Abstract

A new asymmetric synthesis of alpha-amino acids is described in which the key step is the highly diastereoselective addition of organolithium carboxyl synthons (2-furyllithium, phenyllithium, vinyllithium) to (R)- and (S)-O-(1-phenylbutyl) oximes to give hydroxylamines, with vinyllithium being the most satisfactory nucleophilic reagent. Subsequent reductive cleavage of the N-O bond in hydroxylamines, followed by N-protection, and oxidative cleavage of the carboxyl precursor gave a range of N-protected amino acids and esters. The method was exemplified by the synthesis of a range of derivatives of non-proteinogenic amino acids such as 4-bromophenylalanine, tert-leucine, norvaline, cyclohexyl- and aryl-glycines, 2-amino-8-oxodecanoic acid (Aoda) and alpha-methylvaline.

Synthesis of ω-Oxo Amino Acids and trans-5-Substituted Proline Derivatives Using Cross-Metathesis of Unsaturated Amino Acids

“…[6][7][8][9][10] A number of approaches to the synthesis of Aoda 1 have been adopted, including the use of chiral pool starting materials, 9,[11][12][13][14] and the use of chiral auxiliary groups. [15][16][17][18] Of most direct relevance to the topic of this paper is the report on the use of radical addition of chiral non-racemic amino acid fragments to enones. 12 However, there is as yet no general approach to a range of simple analogues of 8-oxo-2-aminodecanoic acid in which the position of the ketone and the length of the side-chain can be straightforwardly varied.…”

New total synthesis and structure confirmation of putative (+)-hyacinthacine C3 and (+)-5-epi-hyacinthacine C3

“…The residue was puried by FCC (hexanes/EtOAc 2 : 3) to give an anomeric mixture of isoxazolidine diol 5 (2.23 g, 4.59 mmol, 93%, anomeric ratio ¼ 90 : 10) as a white solid foam. (12). Isoxazolidine 5 (1.46 g, 3.0 mmol, 1 equiv.)…”

“…Finally, the reductive cleavage of the N-O bond of the hydroxylamine group in 13 was carried out with zinc powder in aqueous acetic acid. 12 The reaction proceeded smoothly at room temperature, affording desired pyrrolidine 4 in an excellent 81% yield already aer 30 minutes.…”

Asymmetric Synthesis of Aminocyclopropanes and N‐Cyclopropylamino Alcohols Through Direct Amidocyclopropanation of Alkenes Using Chiral Organozinc Carbenoids

“…62-65°C (EtOAc/ PE), ref. [19] (R)-2-(tert-Butoxycarbonyl)amino-2-(4-methoxyphenyl)ethanol (7): [22] Anhydrous lithium chloride (1.15 g, 27.09 mmol) and sodium borohydride (1.02 g, 27.09 mmol) were added successively to a solution of ester 4 (2.0 g, 6.77 mmol) in dry THF (30 mL) under nitrogen. The reaction mixture was stirred for 4 h and then cooled to 4°C prior to the addition of saturated NH 4 Cl solution (10 mL).…”

“…[18] [ [19] Prepared according to the literature procedure. [20] When the procedure used for the preparation of the ester 4 was employed, racemisation occurred.…”