Synthesis of the tetracyclic framework of the erythrina alkaloids using a [4 + 2]-cycloaddition/Rh(I)-catalyzed cascade of 2-imidofurans.
Several 2-imido substituted furans were found to undergo a rapid intramolecular [4 + 2]-cycloaddition to deliver oxabicyclo adducts in good to excellent yields. By using a Rh(I)-catalyzed ring opening of the resulting oxabicyclic adduct, it was possible to prepare several highly functionalized tetrahydro-1H-indol-2(3H)-one derivatives which were then used to prepare several erythrina alkaloids. By taking advantage of the Rh(I)-catalyzed reaction, it was possible to convert tert-butyl 3-oxo-5-carbomethoxy-10-oxa-2-azatricyclo[5.2.1.0(1,5)]dec-8-ene-2-carboxylate into the ring opened boronate by reaction with phenylboronic acid. Treatment of the boronate with pinacol/acetic acid afforded the corresponding diol which was used in a successful synthesis of racemic 3-demethoxyerythratidinone. During the course of these studies, several novel rearrangement reactions were encountered while attempting to induce an acid-initiated Pictet Spengler cyclization of a key lactam intermediate. The IMDAF/Rh(I)-catalyzed ring opening cascade sequence was also applied to the total synthesis of (+/-)-erysotramidine as well as the lycorine type alkaloid (+/-)-epi-zephyranthine.
Padwa
Albert
A
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA. chemap@emory.edu
Wang
Qiu
Q
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D002384:Catalysis; D003500:Cyclization; D004895:Erythrina / Q000737:chemistry*; D005663:Furans / Q000737:chemistry*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D015394:Molecular Structure; D012238:Rhodium / Q000737:chemistry*
D000470:Alkaloids; D005663:Furans; D006576:Heterocyclic Compounds, 4 or More Rings; D012238:Rhodium