Stereocontrolled syntheses of kainoid amino acids from 7-azabicyclo[2.2.1]heptadienes using tandem radical addition-homoallylic radical rearrangement.
[reaction; see text] N-Boc syn-7-(2-hydroxyethyl)-4-(alkyl or aryl)sulfonyl-2-azabicyclo[2.2.1]hept-5-enes serve as precursors in syntheses of the neuroexcitants 3-(carboxymethyl)pyrrolidine-2,4-dicarboxylic acid 43, alpha-kainic acid 12, alpha-isokainic acid 14, and alpha-dihydroallokainic acid 77. The key step in these syntheses is the intermolecular radical addition of 2-iodoethanol to a N-Boc 2-(alkyl or aryl)sulfonyl-7-azabicyclo[2.2.1]heptadiene 7 to induce nitrogen-directed homoallylic radical rearrangement. Oxidative cleavage of the resulting 2-azabicyclo[2.2.1]hept-5-enes provide straightforward access to polysubstituted pyrrolidines and, in particular, an efficient entry to the kainoid amino acids.
Hodgson
David M
DM
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, UK. david.hodgson@chem.ox.ac.uk
Hachisu
Shuji
S
Andrews
Mark D
MD
D000438:Alcohols / Q000737:chemistry; D000478:Alkylation; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D007455:Iodine / Q000737:chemistry; D007608:Kainic Acid / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011759:Pyrrolidines / Q000737:chemistry; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013455:Sulfur / Q000737:chemistry; D013696:Temperature
D000438:Alcohols; D000596:Amino Acids; D001372:Aza Compounds; D005609:Free Radicals; D007783:Lactones; D011759:Pyrrolidines; D013438:Sulfhydryl Compounds; D013455:Sulfur; D006859:Hydrogen; D007455:Iodine; C032519:pyrrolidine; D007608:Kainic Acid