Synthesis of substituted indoles by metal mediated reactions

Abstract

In view of the extensive natural occurrence and biological importance of the indole nucleus containing heterocyclic compounds a general and facile method for the synthesis of indole derivatives through palladium catalyzed reaction using Terminal alkyne followed by base catalyzed reactions is reported. In this purpose different 2-iodo acetanilide compounds were synthesized from m~substituted aryl amines by iodination reaction (Seheme- I). ~ OC"' ~'" I + I -' R, R, X, X, 4 ~ 3~'l,7,8,9 , CH'COOH,j11",0,lJl 1lO.(,~4-5h ~ ICOCH, , , X, x, " ti, 10,li ~- l.~, R=.(:~,.""'I J X,=X,=!.R,='(:Il, 4, X,=H,R,=-CH, 5.6 X,=lX,=llR,=.('H, 7 X,=H,X,-I,Rl~'(:1 S X,=I,X,=llR,='(:1 9 X,.ll,X,-llR,--C1 10, x,=',X,=H,R,=<:1 II X,-H,X,.II,R,~-CI Nil, .-l- Cu(OAc)"CH,COOH,I, !LA Iwoe 9_IOhr " , " Scheme-} The hctcroannulation reaction was carried out by stirring a mixture of 2-iodo substituted acetanilide and different terminal alkynes in presence of bis(ltiphenylphosphine) palladium (11) chloride as a catalyst, Cu(l) iodide a~ a eo-catalyst and a base lrielhylamine. The condensed product was then subjected to base catalyzed reaction with sodium ethoxide in ethanol to afford the substituted indole (Schemc-2). R,C=CH. ;n:::" x 1 (Ph,P)'pd<.C'Iu,i, X;D;;\'~ I I x, ",-4 ''(Y' '."", +1 n~HCOCH Et,N.DMr, R N HCOCH, ", '0 'H" 4,6.,10 60-80C,6--30hr 12,J3 15,16,t7,t8 lNaOP.t1EtOll X R1 R, Comp, No, 80_8SoC 12hr H -CHj -Ph 12 Ii -Cli] -C(CHu2Cl'b13 x~'~ ! -CH] -Ph 15,20 "" I I -CHJ -C(CH2);,CHJ 16 ,~ ' I -CHl -C(CH ' )lCH, 17 20,21 I -CI -Ph 18,21 Scbeme-2 All the synthesized compounds were chllI'llcterized by lL,ingllOalytical data. obtained from M.P, UV, IR, lHNMR and BC NMR.