[reaction: see text] An overall stereoconservative protection and deprotection method of amino and carboxyl groups is presented. N-Phthaloyl N'-alkyl secondary amides of alpha-amino acids can be generated from corresponding N-phthaloyl amino acids by coupling reaction of N-alkylamines using mixed anhydride method. These secondary amides can be transformed by thermal rearrangement of intermediate nitrosoamides to O-alkyl esters with retention of configuration and excellent yields.

Asymmetric alkylation of (S)‐Boc‐BMI (1a, BMI = 2‐tert‐butyl‐3‐methylimidazolidin‐4‐one) and its α‐methyl derivative 1b with 2‐fluoroallyl tosylate, subsequent mild acidic deprotection of the products 2a and 2b, and basic hydrolysis of the thus formed N‐methylamides 4a and 4b gave (S)‐2‐amino‐4‐fluoropent‐4‐enoic acid (5a) and (S)‐2‐amino‐4‐fluoro‐2‐methylpent‐4‐enoic acid (5b). Basic hydrolysis of compound 4a was accompanied by partial racemization, which was overcome by applying a new stereoconservative deamidation procedure. The alkylated cis‐configured product 2a formed under kinetic control epimerized on refluxing with 2 n NaOH to give the thermodynamically more stable trans isomer 9. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

An unprecedented cascade of reactions after acid-catalyzed hydrolysis of tert-butyl (2S,5S)-2-tert-butyl-5-(2-fluoroallyl)-3-methyl-4-oxoimidazolidine-1-carboxylate 3a leading to pipecolic acid derivative 5 is presented. The vinylfluoro group is shown to be an acetonyl cation equivalent under acidic conditions. Interestingly, vinylchloro and vinylbromo groups do not show such transformation under the same conditions. The pipecolic acid derivative 5 produced in this way is further used to synthesize (2R,4R,6S)-6-tert-butyl-4-hydroxypiperidine-2-carboxylic acid 9.

This paper describes a method for the racemization of unwanted (S)-1 isomer arising from the resolution of (±)-1. The process of racemization involves thiyl radical-mediated reversible hydrogen abstraction at the chiral center, in the presence of AIBN in water. The racemized isomer was subsequently resolved by L-(+)-tartaric acid to get (R)-1, a histamine H 3 receptor pharmacophore. We foresee that such an approach of racemization will be industrially useful for recycling waste (S)-1 enantiomer.

Acids. -A highly efficient and stereoselective protection/deprotection and amidation/ deamidation protocol for chiral α-amino acids is presented. It leads to important building blocks for synthetic peptides. -(SHENDAGE, D. M.; FROEHLICH, R.; HAUFE*, G.; Org. Lett. 6 (2004) 21, 3675-3678; Org.-Chem. Inst., Westfael. Wilhelms Univ., D-48149 Muenster, Germany; Eng.) -Steudel 05-180