A practical approach for the optically pure N-Methyl-α-amino acids

The Facile Production of N-Methyl Amino Acids via Oxazolidinones

“…It was also noted that Reddy et al 22 had shown that N-Boc amino acids would form oxazolidinones. The N-Boc glutamic acid derivative (12) was available in our laboratory and it underwent reaction in the same manner as the N-Cbz amino acids (Scheme 1) to give the oxazolidinone (13) in 60% yield (Scheme 2).…”

“…Some precedent exists for this in the reactions of asparagine reported by Ben-Ishai. 20 Presumably, it is this concern that caused Reddy et al 22 to prepare the t-butyldiphenylsilyl ether of serine.…”

“…These include methods for direct methylation, 1-5 reductive amination, 6-12 alternative methods [13][14][15][16][17][18] and through the generation of oxazolidinones and their subsequent transformation to the N-methyl (alkyl) product. [19][20][21][22][23] In addition, there are strategies involving the use of immonium ions in Diels-Alder/retro-Diels-Alder sequences, 24 the nucleophilic displacement of triflates, 25 the hydroxyamination of chiral enolates 26 and the Mitsunobu reaction. 27 Some of these methods suffer from limitations in the range of amino acids to which they are applicable, some utilize rather long synthetic sequences and some cause at least partial racemisation of the substrate.…”

“…More recently, Reddy et al 22 described the preparation of N-t-butoxycarbonyl (N-Boc) protected oxazolidinones and the production of N-methyl amino acids from N-Cbz and NBoc oxazolidinones by hydrogenolysis. Their results with NCbz compounds (from aliphatic amino acids) contradict the results of Williams and Yuan 23 and Itoh.…”

“…The work described in this paper exploits the oxazolidinone route [19][20][21][22][23] to generate a range of N-methyl amino acids by using simple reproducible chemistry. The reaction plan presented in this paper is depicted by the general diagram in Fig.…”