Asymmetric synthesis of .alpha.-amino acids. I. A new approach

Abstract

A new approach has been demonstrated for the asymmetric synthesis of a-amino acids from a-keto acids using chiral reagents which are regenerated by the synthesis. The chiral reagents used were the N-amino-2-hydroxymethylindolines (9-9 and (9-16. The synthesis, resolution, and assignment of absolute configuration for these reagents is described. The application of ( 9 -9 and (9-16 to the asymmetric synthesis of a-amino acids depends on their combination with a-keto acids to form chiral hydrazono lactones (see Chart IX). Reduction of the C=N unit in these lactones (23,24, and 25) affords the corresponding hydrazino lactones (29,30, and 31) which are transformed to a-amino acids by hydrogenolysis of the N-N linkage and ester hydrolysis. By this process o-alanine and D-butyrine have been synthesized from pyruvic acid and a-ketobutyric acid using the reagent ( 3 -9 in optical purities of 80 and 90%, respectively. As a result of these studies, a solid basis exists for the design of chiral indoline reagents of still greater eficiency in the asymmetric synthesis of a-amino acids.(13) For another asymmetric synthesis of aspartic acid (optical purity ca. 88 %), involving the addition OF a-methylbenzylamine to maleic acid followed by catalytic hydrogenolysis, see A. P. Terent'ev, R. A.

Bioorganic Chemistry

“…There was thus a need for a more general method where the asymmetric reagent will not be sacrificed and which insures the recovery of the starting material. To overcome these problems, E. J. Corey and collaborators (12) from Harvard University in 1970 proposed the methodology depicted in Fig. 2.7.…”

“…in biological systems: tetrahydrofolic acid. In some bacteria, homocysteine can be converted back to methionine by methylation with methylcobalamin (the methyl derivative of vitamin B 12 ), in the presence of other required compounds or cofactors. This latter methylation reaction is of interest because it can occur, at a reduced rate, in the absence of any enzymes, and a simpler model system has been developed to mimic this reaction (see details in Chapter 6).…”

Synthesis of N4‐substituted[1,3,4]oxadiazinan‐2‐ones derived from norephedrine

“…Ultimately, the ratio of diastereomeric N-nitrosamines is unimportant as this stereochemical element is removed in the subsequent reduction. Reduction of the N-nitrosamines was accomplished with lithium aluminum hydride [7]. This process afforded the corresponding β-hydrazino-alcohols in quantitative conversion.…”

Chiral N‐Acylhydrazones: Versatile Imino Acceptors for Asymmetric Amine Synthesis

“…More recently, Leighton has explored chiral strain-activated allylsilane reagents [57] [Equation (8)], and Kobayashi has reported nucleophilic catalysis of allyltrichlorosilane addition [Equation (7)] using chiral sulfoxides; [58] both afford highly enantioselective addition to N-acylhydrazones. (6) (7) (8) In the additions of allylchlorosilanes to N-acylhydrazones, coordination of the N-acyl oxygen atom to the silicon may play an important role, as illustrated in two similar transition states proposed by Kobayashi and Leighton (Figure 6). …”

“…[6,7] Related chiral hydrazones were exploited by Corey for asymmetric amine synthesis by reductive amination. [8] Applications of chiral hydrazones have broadened in recent years; new developments include allene anion additions to SAMP hydrazones, [9] chiral umpolung reactiv-ity [10] and [2+2] cycloadditions [11] employing formaldehyde hydrazones, and asymmetric catalysis with hydrazone chelate complexes. [12] …”