Synthesis of Succinimido[3,4-b]indane and 1,2,3,4,5,6-Hexahydro-1,5-methano-3-benzazocine-2,4-dione by Sequential Alkylation and Intramolecular Arylation of Enolates Derived from N,N,N'N'-Tetramethylbutanediamides and N,N,N'N'-Tetramethylpentanediamides.
The tricyclic title compounds, 4 and 5, were synthesized by initial alkylation of the lithium monoenolates of N,N,N',N'-tetramethylbutanediamide (6) and N,N,N',N'-tetramethylpentanediamide (19) with 2-iodobenzyl chloride in liquid NH(3) at -60 degrees C to afford 2-(2-iodobenzyl)-N,N,N',N'-tetramethylbutanediamide (9) and 2-(2-iodobenzyl)-N,N,N',N'-tetramethylpentanediamide (20) in yields of 88 and 87%, respectively. Treatment of 9 with KNH(2) in liquid NH(3) resulted in formation and intramolecular arylation of the less-substituted alpha-enolate to produce trans-1,2-bis(N,N-dimethylcarboxamido)indane (10a) in 60% yield. Selective hydrolysis of 10a with aqueous Na(2)O(2) gave trans-1-(N,N-dimethylcarboxamido)indane-2-carboxylic acid (17), which was then converted to bridged succinimide 4 by transformation to trans-1-(N,N-dimethylcarboxamido)indane-2-carboxamide (10c) followed by cyclization of this mixed primary/tertiary amide by means of NaH in refluxing THF. Treatment of 20 with KNH(2) in liquid NH(3) led to intramolecular arylation and accompanying ammonolysis to afford trans-1-(N,N-dimethylcarboxamido)-1,2,3,4-tetrahydronaphthalene-3-carboxamide (21b). Conversion of 21b to 5 was similarly effected by means of NaH. Experiments designed to test the mechanistic aspects of the intramolecular arylations provided evidence for competing aryne and SET pathways.
Dandekar
Sushama A.
SA
Department of Chemistry and the Harvey W. Peters Research Center for the Study of Parkinson's Disease and Disorders of the Central Nervous System, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0212.
Greenwood
Stacey N.
SN
Greenwood
Thomas D.
TD
Mabic
Stéphane
S
Merola
Joseph S.
JS
Tanko
James M.
JM
Wolfe
James F.
JF