Studies of the formation of all-carbon quaternary centres, en route to lyngbyatoxin A. A comparison of phenyl and 7-substituted indole systems.
Copper mediated allylic substitutions and conjugate additions to geranyl, cinnamyl and allylic indole compounds have been investigated with the aim of finding a method for the creation of the all-carbon quaternary centre present in the natural product lyngbyatoxin A. Reaction conditions have been found giving a 68% SN2' selectivity in the copper mediated addition of PhMgBr to geranyl chloride, as well as 99% and 95% SN2' selectivity in the copper catalysed addition of EtMgBr to cinnamyl chloride and acetate, respectively. When the optimised reaction conditions were applied to the corresponding allylic compounds containing a 7-substituted indole moiety, the regioselectivity was reversed giving only the SN2 product. The allylic indole-containing substrates were also found to be unproductive in Pd- or Mo-catalysed SN2'-type substitution reactions. In related studies, copper catalysed conjugate addition of EtMgBr to the tricyclic lactam 6-methyl-pyrrolo[3,2,1-ij]quinolin-4-one gave a maximum of 20% of the 1,4-addition product.
Tønder
Janne E
JE
Department of Chemistry, Technical University of Denmark, Building 201, Kemitorvet, DK-2800 Kgs. Lyngby, Denmark.
Hosseini
Masood
M
Ahrenst
Alex B
AB
Tanner
David
D
D002934:Cinnamates / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D003500:Cyclization; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D007211:Indoles / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry; D018021:Lithium Chloride / Q000737:chemistry; D008235:Lyngbya Toxins / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D008982:Molybdenum / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D013729:Terpenes / Q000737:chemistry
D002934:Cinnamates; D006575:Heterocyclic Compounds, 3-Ring; D007211:Indoles; D007769:Lactams; D008235:Lyngbya Toxins; D009942:Organometallic Compounds; D012997:Solvents; D013729:Terpenes; D010165:Palladium; D003300:Copper; D008982:Molybdenum; C067783:ethyl magnesium bromide; C028419:cuprous chloride; D018021:Lithium Chloride; C019457:lyngbyatoxin A