7610
J. Org. Chem. 1993,58, 7610-7612
Mn(II1)-PromotedHomolytic Methylmalonylation of Pyrrole and Indole Derivatives. A Simple Route to a-Methyl-2-Pyrrole-and a-Methyl-3-IndoleaceticAcids
Scheme I Mn+
Enrico Baciocchi' and Ester Muraglia Dipartimento di Chimica and Centro CNR per lo Studio dei Meccanismi di Reazione, Universitb "La Sapienza", PJe A. Moro 5, 00185 Rome, Italy
+
T0C02R w-. HC, C02R
7,C02R A
H
+ 'C, C0,R
+
M(n-l)+
H++
T,CO,R
.c,
C02R
-
H
Received July 29, 1993
The Mn(II1)- and Ce(1V)-induced homolytic malonylation of homocyclic aromatic compounds have been extensively studied.1 Very likely these reactions occur as described in Scheme I (R = H, alkyl, R' = alkyl). As expected, they are more efficient with electron-rich substrates (toluene, anisole, methoxynaphthalene) than with benzene. So far, however, the logical extension of these reactions to the electron-rich pentatomic heteroaromatics has been possible only for furan and thiophene derivatives.l*JJI2With the still more electron-rich pyrrole the procedure has been unsuccessful, due to the fact that the oxidative conditions of these reactions are not compatible with this substrate. Recently, the homolytic alkylation of pyrrole with electrophilic carbon radicals has been accomplished under milder conditions such as H20z/Fe+2/alkyl iodide in DMSO38 and BEtalOdalkyl halides in DMS0.sb These are very efficient procedures which, however, to generate the malonyl radical require the use of the halomalonates. We have felt, therefore, it worthwhile to explore the possibility that the oxidative conditions of M n + t and Ce+4promoted reactions could a t least be applied to pyrroles and indoles substituted by strong electron-withdrawing groups: which are expected to be less easily oxidizable than unsubstituted pyrrole. We have mainly concentrated our attention on the methylmalonyl radical, since the methylmalonyl group can easily be converted into the a-methylacetic group by one-pot hydrolysis and decarboxylation. Thus, this approach could provide us with a simple method for the synthesis of a number of a-methyl2-pyrroleacetic acids, directly starting from a dialkyl methylmalonate. The results of this study are reported herewith.
Results and Discussion Pyrroles 1-7, when reacted with diethyl methylmalonate (5-fold excess), Mn(OAc)3*2HzO, and sodium acetate in
-
T,cofi
-H*
A+r
