Catalytic asymmetric diazoacetate cyclopropanation of 1-tosyl-3-vinylindoles. A route to conformationally restricted homotryptamines.
[reaction: see text] Substituted 1-tosyl-3-vinylindoles undergo catalytic asymmetric cyclopropanation with ethyl- and tert-butyldiazoacetate to afford N-protected trans-2-(indol-3-yl)-1-cyclopropanecarboxylic esters in good yield and high enantiomeric excess (81-88% ee). The resulting cycloadducts are demonstrated to be useful intermediates for the synthesis of conformationally restricted, homotryptamine-like analogues such as BMS-505130.
Marcin
Lawrence R
LR
Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA. lawrence.marcin@bms.com
Denhart
Derek J
DJ
Mattson
Ronald J
RJ
D000085:Acetates / Q000737:chemistry; D001391:Azo Compounds / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D003521:Cyclopropanes / Q000138:chemical synthesis*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D014105:Tosyl Compounds / Q000737:chemistry*; D014363:Tryptamines / Q000138:chemical synthesis*; D014753:Vinyl Compounds / Q000737:chemistry*
C502839:2-(5-cyano-1H-indol-3-yl)-1-(N,N-dimethylaminomethyl)cyclopropane; D000085:Acetates; D001391:Azo Compounds; D003521:Cyclopropanes; D007211:Indoles; D014105:Tosyl Compounds; D014363:Tryptamines; D014753:Vinyl Compounds