Enantioselective Oxidation by a Chiral Acylaminyl Oxide

Abstract

of the alkylation can be determined, either 'H-NMR spectroscopically at the stage of the alkylation product (6) or polarimetrically or NMR spectroscopically with chiral shift reagents at the stage of the a-methyl-a-aminocarboxylate (7) or a-methyl-a-amino acid.We obtained 3,6-dihydropyrazine (3) by reaction of cyclo-(L-Ala-L-Ala) (2)I2I with trimethyloxonium tetrafluoroborate. This reaction proceeds without racemization. The lithiation of (3) to (4) can be smoothly performed at -70 "C (in tetrahydrofuran) with butyllithium or lithium diisopropylamide (LDA). Double metalation at C-3, which would lead to an antiaromatic 8 T electron system, does not take place[31. The alkylation products (6) are hydrolyzable with 0.5 N hydrochloric acid even at room temperature. The esters ( I ) and (7) can be separated, for instance, by distillation.In the alkylation (4) + (6), the R-configuration is induced at C-6, i. e. the alkyl moiety prefers the trans-position to the methyl group at C-3. For example, (R)-( -)-a-methylphenylalanine['"I is obtained from (6a) via the ester (7a). In (6a) the R-configuration at C-6 is recognizable in the 'H-NMR spectrum: 3-H absorbs at relatively high field strengths (6=3.17) because it is situated in the shielding anisotropic region of the phenyl group, which probably lies in a .rr-complex fashion over the hetero~ycle[~l. We attribute the high asymmetric induction to the fact that one of the two diastereotopic sides of the probably planar anion of (4) is relatively strongly shielded by the methyl group. Experimental(2): After washing with ether, the crude product obtained according to is ca. 90% optically pure. Crystallization twice from water yielded almost optically pure (2); [ a J g = 26.4" (c=1.3, H20); after drying in a vacuum over P205, m.p. 289 "C.(3): A mixture of (2) (14.2 g, 0.1 mol) in anhydrous CH2C12 (300 ml) and trimethyloxonium tetrafluoroborate was vigorously stirred or shaken for 34 h at room temperature15]. A buffer solution, consisting of NaH2P04 (40.0 g, 0.3 mol) and Na2HP04 (113.7 g, 0.8 mol) in 500 ml water, was added to the ice-cold mixture, the organic phase was separated off and the aqueous phase extracted three times with CH2C12. The combined extracts were dried over MgSO, and then evaporated to dryness at 10 torr; yield 14.9 g (88%) of almost optically pure (3), b.p. Alkylation of (3) to (6): A solution of butyllithium (10 mmol, 6.4 ml of a 1.55 N solution in hexane) (or 10 mmol lithium diisopropylamide in a little THF) is cooled to -70 "C and then added dropwise to a solution of (3) (1.7 g, 10 mmol) in anhydrous T H F (20 ml) at -70 "C. The mixture is stirred for 10 min at this temperature, treated with a solution of (5) (10 mmol) in THF (10 mmol) and stirring continued for 2-10 h. The mixture is allowed to warm to room temperature, the solvent removed at 10 torr, the residue treated with 10 ml water (and if necessary 5 g common salt), extracted three times with 30 ml of ether or CH2C12, the extracts combined, dried over MgSO, and worked-up in the usual way. Diastereo...

Some physical and chemical aspects of spin trapping of organometallic radicals by quinones: optically active radical complexes

“…To the best of our knowledge, isolation and direct identification of a pure optically active radical has not been heretofore achieved. A few of the previous studies have involved optically active radical intermediates (23)(24)(25)(26) by inferring from product analysis or by observing different optical rotation values for the solution containing both the presumed chiral radical and the parent optically active reactant.…”

Acyl nitroxides. Part 4. Estimation of OH bond dissociation energies for N-t-butylhydroxamic acids

“…The failure to obtain data for the N-hydroxycarbamates is puzzling. Analogy with the discussion so far would tend to suggest that the strengths of the 0 -H bonds in (10) and (1 1) might have been found to be between those of (4a) and (12). Whether intramolecular hydrogen bonding might be especially important in these hydroxy-compounds, and impede atom transfer to (l), is not clear.…”

“…Because of the rather wide error limits in these experiments, no attempt has been made to study the temperature dependence of K for any of the equilibria. In any case, it might reasonably be expected that hydrogen bonding effects will be similar in 0- (14) most of the systems studied, and from the high reactivity of the acyl nitroxides in hydrogen abstraction reactions [9][10][11][12] it is at least clear that we are dealing with nitroxides which have an unusually high affinity for hydrogen, Hydrogen bonding in the hydroxamic acids will be discussed further below, but with the above reservation in mind, Table 4 has been prepared as a summary of the hydroxamic acid 0-H bond dissociation energies obtained from the experimental AG (CCI,) values by addition to the 0-H bond strength (71.8 kcal mol-I) for One problem, removed as the investigation developed, was the original choice of benzene as solvent. Weak radical sohation by benzene has often been and at least one specific instance concerns nitroxides.…”

Acyl nitroxides

“…Other oxidations may be effected often in high yield [18,19]. Especially interesting are those of allylic and benzylic alcohols; here, the near quantitative oxidations of vitamin A alcohol 9 to retinal [20], and of hydrobenzoin to benzil without cleavage to benzoic acid, are good examples. the interesting result that reaction via an eight-membered ring transition state (n = 2) was found to be more favourable than that via the more familiar 6-membered ring.…”

“…Indeed, no intramolecular radical processes appear to show the enormous rate enhancements frequently encountered in intramolecular ionic reactions [22]. In our [~]2SICHCl3 )= -1.9" 8% enantiorner~ excess |opf~colly pure) benzil [20]. Although the selectivity was small, and substantial improvements seemed unlikely in view of the relative remoteness of X and Y in a linear hydrogen atom transfer X-H + Y" ~ X" + HY, consideration was given to means of This brief paper has concentrated on the structure and chemistry of acyl nitroxides.…”