Stereoselective hydroxyalkylations of (S)‐2‐azetidinecarboxylic acid

Abstract

Key Words: a-Alkylation of amino acids / Self-regeneration of stereogenic centers / Oxazolidinones from amino acids and pivalaldehyde / Azetidine-derived (R,R)-a-amino-P-hydroxy carboxylic acid, X-ray crystal structure of ~~~The enolate generated from S-phenyl (S)-l-benzyl-2-azetidinecarbothioate is converted into racemic products 2 by treatment with electrophiles. The bicyclic oxazolidinone derivative 12 has been prepared from trimethylsilyl (S)-1-(trimethylsily1)-2-azetidinecarboxylate (1 1) and pivalaldehyde without racemization. Addition of 12 to aldehydes and hydrolysis gives the products 13a-h. The structure of the adduct 13h from 4-pyridinecarbaldehyde was determined by X-ray crystal structure analysis, proving that the trigonal centers of the bicyclic enolate and of the aldehyde have combined with relative topicity unlike. Thus, the reaction resembles that of the homologous proline derivative described previously, and the novel products are formally D-allo-threonines with an ethylene bridge between the nitrogen and the adjacent carbon atoms (Scheme 4) and with absolute configuration R,R. The mechanism of the C -C bond-forming reaction is discussed.

Are Oxazolidinones Really Unproductive, Parasitic Species in Proline Catalysis? – Thoughts and Experiments Pointing to an Alternative View

“…2c) [18], and from azetidine-2-carboxylic acid (! 2d) [16b] [19]. The bicyclic oxazolidinones 2a -2d and the monocyclic N-acyl-oxazolidinones 3a (from non-cyclic amino acids) [20] were used for the preparation -through Li-enolates -of a-branched amino acids with self-regeneration of the stereogenic centers…”

“…Decarboxylation also occurs when the desired product 8, prepared from the ketone and silylated proline at room temperature, is distilled under insufficient vacuum 18 ). Contact of the distilled colorless liquid 8 with air or dissolution in aprotic solvents that are not rigorously dry causes precipitation of proline 19 ). However, kept in a freezer and tightly protected from contact with moisture, oxazolidinone 8 is a well-behaved compound, which can be handled with anaerobic syringe techniques; its NMR spectra and part of its IR spectrum are shown in Fig.…”

“…18 ) The use of a special Aldrich Kugelrohr oven is described in an Organic Syntheses procedure for the preparation of 2a [16c]. 19 ) The deliberate hydrolysis is used for analytical purposes to show that no racemization of proline has occurred. The specific rotation of…”

“…According to a literature procedure [19], a vigorously stirred suspension of l-proline (3.50 g, 30.0 mmol) in diethyl(trimethylsilyl)amine (13.3 ml, 70.0 mmol) was heated to 1108 in a distillation apparatus (dried by heat gun at 1.2 mbar) for 2 h under N 2 . As the reaction progressed, Et 2 NH was distilled from the mixture, which became homogeneous.…”

The Structural Chemistry of Aziridino- and Azetidinosilanes

“…[9] which might be employed as substitutes for the rather hazThe taxonomy of related N-silylated aziridines and azetid-ardous free heterocycles. [18] [19] [20] [21] ines is far less developed [10] [11] and no systematic investigation has been made of their properties and structural Results characteristics. [12] This is particularly true for compounds…”