Asymmetric synthesis of beta-pyridyl-beta-amino acid derivatives
The conjugate additions of homochiral lithium (R)-N-benzyl-N-α-methyl-4-methoxybenzylamide to tert-butyl 3-(3-pyridyl)- and tert-butyl 3-(4-pyridyl)-prop-2-enoates proceed in 84% de, and after subsequent recrystallisation and oxidative N-deprotection furnish the (S)-3-(3-pyridyl)- and (S)-3-(4-pyrid...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2002
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| Summary: | The conjugate additions of homochiral lithium (R)-N-benzyl-N-α-methyl-4-methoxybenzylamide to tert-butyl 3-(3-pyridyl)- and tert-butyl 3-(4-pyridyl)-prop-2-enoates proceed in 84% de, and after subsequent recrystallisation and oxidative N-deprotection furnish the (S)-3-(3-pyridyl)- and (S)-3-(4-pyridyl)-β-amino acid derivatives in 97% ee and 98% ee respectively. Conjugate additions of lithium N-benzyl-N-α-methyl-4-methoxybenzylamide to tert-butyl 3-(2-pyridyl)prop-2-enoates proceed with low levels of diastereoselectivity unless the 3-(2-pyridyl) ring is substituted. Application of this methodology allows the asymmetric synthesis of (R)-tert-butyl 3-(2-chloro-3-methoxymethoxy-6-pyridyl)-3-aminopropanoate, the protected β-amino ester component of kedarcidin, in 97% ee. |
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