Solid-Supported Cyclotrimerization Reactions Alexander Deiters North Carolina State University, Department of Chemistry, Raleigh, NC 27695 The following key discoveries have been made, which set the stage for further developments towards unifying reaction conditions for [2+2+2] cyclotrimerization chemistry and its application in target directed synthesis and library synthesis: Chemoselectivity issues have been solved through the application of a solid-support. Reactivity issues have been solved through the application of microwave irradiation. Regioselectivity issues were addressed through regio-directing groups.
Synthesis of an indanone natural product via a chemo- and regioselective solid-supported [2+2+2] cyclotrimerization reaction: O
O O
propyne Cp*RuCl(COD), DCE, r.t.
CH3O
Synthesis of tetrahydroisoquinolines via microwave-mediated solid-supported [2+2+2] cyclotrimerization reactions:
OEt
O
OEt OEt
EtO
CH3O
R
TrtN
CH3
R'
TrtN
Cp*RuCl(COD), MW (300W), 130 oC, 10min toluene
O O
R'
1. K2CO3, MeOH 2.
IBX , DCM (72% over 3 steps)
CH3O
CH3
Microwave-mediated solid-supported [2+2+2] cyclotrimerization reactions: R TrtN
R
N TrtN
CpCo(CO)2, toluene, 300W, 110oC, 10min R
1% TFA HN DCM, rt, 1h
N 87-92%
N
TFA
R
R
HN
DCM
R' 72-89%
