Fifteen homoallylic ketones have been synthesized in 26-77% yields on treatment of aromatic, aliphatic, and alpha-amino methyl carboxylates with excess vinylmagnesium bromide and catalytic amounts of a copper salt in THF. Alpha-amino homoallylic ketones derived from N-protected alpha-amino esters possessing aliphatic and alcohol side chains were synthesized in > or =98% enantiomeric purity. [reaction: see text]
N-tert-Butyloxycarbonyl- and N-benzenesulfonyl-beta-hydroxyvalines 1a and 1b were, respectively, synthesized in enantiomerically pure form by a two-step protocol from their enantiomeric N-protected serine methyl esters 2a and 2b. The addition of CH(3)MgBr to 2a and 2b provided diols 3a and 3b, respectively as major products in 83% and 81% yields. Selective oxidation of diols 3a and 3b was performed using a TEMPO, NaClO(2), NaOCl cocktail in 96% and 93% respective yields. This two-step process effectively furnished multigram amounts of enantiopure N-Boc-beta-hydroxyvaline 1a.
Enantiopure (>99% ee) L-N-tert-butyloxycarbonyl-N-methyl-β-hydroxyvaline (2) was synthesized in six steps and 43% overall yield from D-serine methyl ester (5). Methyl (4S)-N-(9-phenylfluoren-9-yl)-oxazolidine-4-carboxylate (7) was prepared in two steps and 73% yield by N-phenylfluorenation of 5 followed by cyclization of N-(PhF)amino alcohol 6 with formaldehyde and catalytic p-toluenesulfonic acid (PhF = 9-phenylfluoren-9-yl). The addition of MeLi to oxazolidine carboxylate 7 produced the tertiary alcohol 8 in 91% yield. Oxazolidines 8 equilibrated with oxazolidine 9 under acidic conditions. Reduction of pure 8 or the mixture of oxazolidines 8 and 9 with NaCNBH3 and hydrochloric acid in anhydrous dioxane afforded N-methyl amino diol 11 in 86%92% yields. Attempts to selectively oxidize N-(PhF)amino diol 11 were unsuccessful; however, hydrogenation of 11 in the presence of di-tert-butyl dicarbonate gave the corresponding N-(Boc)amino diol 12 in 82% yield. Selective oxidation of diol 12 was performed using a cocktail containing TEMPO free radical, NaClO2, and NaOCl to give L-N-Boc-N-methyl-β-hydroxyvaline (2) in 87% yield. Coupling of β-hydroxyvaline 2 and (S)-2-hydroxy-3-methylbutanoate (15) was accomplished by using the methodology of Mitsunobu to provide depsipeptide Boc-(S)-HOMeVal-(R)-Hmb (4) for use as a building block in the synthesis of the cyclic antifungal depsipeptide aureobasidin B.Key words: N-methylated amino acid, serine, depsipeptide, aureobasidin.
A series of enantiomerically pure N-Boc-protected β,β-dialkylserines was synthesized by addition of the appropriate Grignard reagent to N-(Boc)serine methyl ester, followed by TEMPO-catalysed oxidation of the primary alcohol with sodium chlorite and sodium hypochlorite.Key words: amino acid, serine, β,β-dialkylserines, ring-closing metathesis.
Reactions of organo-metal compoundsReactions of organo-metal compounds O 0350 One-Pot Synthesis of Homoallylic Ketones from the Addition of Vinyl Grignard Reagent to Carboxylic Esters. -Optimized reaction conditions allow the preparation of the target compounds without concomitant formation of tertiary alcohol products. -(HANSFORD, K. A.; DETTWILER, J. E.; LUBELL*, W. D.; Org. Lett. 5 (2003) 25, 4887-4890; Dep. Chem., Univ. Montreal, Montreal, Que. H3C 3J7, Can.; Eng.) -Steudel 16-068
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