FUNCTIONALIZATION OF BENZYLIC CARBON-HYDROGEN BONDS - MECHANISM AND SCOPE OF THE CATALYTIC SYNTHESIS OF INDOLES WITH [RU(DMPE)2]

A unique route for the synthesis of indoles from o-tolyl isocyanides u sing Ru(dmpe)2(H)(naphthyl) and Ru(dmpe)2H2 as catalysts has been exam ined. The scope of this method for indole preparation has been examine d with a variety of o-tolyl isocyanides, including 3-, 4-, and 5-R-o-t olyl isocyanides (where R = methyl, methoxy, or fluoro), 2,6-xylyl iso cyanide, 2,6-diethylphenyl isocyanide, 2-ethylphenyl isocyanide, o-tol yl isocyanide, and 6-ethyl-o-tolyl isocyanide. The mechanism of indole formation has been investigated using kinetic and isotope effect expe riments to differentiate key product-determining steps of the cycle. R esults are consistent with a mechanism involving irreversible CNR coor dination prior to intramolecular oxidative addition of the o-methyl C- H bond. Competitive isotope effect studies using d0- and ha,alpha,alph a,alpha',alpha',alpha',3,5-d8-labeled 4-tert-butyl-2,6-xylyl isocyanid es indicate virtually no isotope effect (k(H)/k(D) = 1.08) when the se lection of which bond to active is intermolecular. Use of 4-tert-butyl -2,6-xylyl-alpha,alpha,alpha-d3 isoCYanide shows that C-H activation i s faster than C-D activation (k(H)/k(D) = 2.6) in an intramolecular co mpetition, where the choice of C-H and C-D bonds to activate is within one xylyl isocyanide. The reaction with 2,6-diethylphenyl isocyanide to give 3-methyl-7-ethylindole is first order in [Ru(dmpe)2(H)(naphthy l)] and zero order in [CNR]. While hindered 2,6-disubstituted phenyl i socyanides eliminate free indoles catalytically, less hindered isocyan ides give stable indole N-H oxidative addition adducts with [Ru(dmpe)2 ]. The resulting cis and trans N-H activated complexes are thermodynam ically the most stable species in solution. N-H addition products were also formed with substituted indoles, pyrrole, pyrazole, indazole, an d pyrrolidine. Blocking the N-H position of indole with a methyl group results in C-H oxidative addition of ruthenium at the 2-position of t he ring. trans-RuH(3-methylindole-N)(dmpe)2 crystallizes in orthorhomb ic space group Pnnm (No. 58) with, a = 17.263(10) angstrom, b = 10.668 (10) angstrom, c = 13.524(10) angstrom, V = 2491(6) angstrom3, and Z = 4. trans-RuH(5-methoxyindole-N) (dmpe)2 crystallizes in monoclinic sp ace group P2(1)/c (No. 15) with, a = 9.065(2) angstrom, b = 16.379(3) angstrom, c = 19.196(5) angstrom, beta = 92.06(4)-degrees, V = 2848(2) angstrom3, and Z = 4. trans-RuH(5-fluoroindole-N)(dmpe)2 Crystallizes in monoclinic space group P2(1)/c(No. 15) with, a = 8.854(4) angstrom , b = 16.45(1) angstrom, c = 18.873(8) angstrom, beta = 93.95(4)-degre es, V = 2743(5) angstrom3, and Z = 4. cis-RuH(N-methylindole-C2)(dmpe) 2 Crystallizes in monoclinic space group P2(1)/c (No. 15) with, a = 15 .08(l) angstrom, b = 10.173(8) angstrom, c = 18.09(2) angstrom, beta = 114.49(7)-degrees, V = 2526(8) angstrom3, and Z = 4.