Reaction of Diphenylcyclopropenone with N-Acylamidine Derivatives . Synthetic and Mechanistic Implications

A reatividade de ciclopropenonas frente a derivados de N-acilamidinas foi investigada. Difenilciclopropenona reagiu com N-benzoilacetamidina e com N-(metoxicarbonil)benzamidina formando 1,2-diidro-3 H-pirrol-3-onas em rendimentos moderados, porém alquilfenilciclopropenonas não reagiram com os mesmos nucleófilos investigados. A teoria dos orbitais moleculares de fronteira foi empregada para racionalizar a formação dos produtos.


Introduction
Over the past four decades, the fascinating chemistry of cyclopropenones has attracted considerable attention both in utilization as a synthetic building block 1 and as rare naturally occurring compounds 2 .Our systematic interest in the use of cyclopropenone chemistry in the construction of a wide variety of heterocycles 3 prompted us to study the behavior of cyclopropenones towards N-acylamidine derivatives.Additionally, N-acylamidines can be envisioned as enaminone aza analogs (an "aza-enaminone").Enaminones are versatile nucleophiles toward diphenylcyclopropenone (1) in the synthesis of nitrogen-containing compounds, Scheme 1 3a,d,h .Because of the ambiphilic and ambident proprieties of cyclopropenones, the reactions of this class of compound with nucleophiles is a complex matter 1b-c .Herein we present our results of the reactions of cyclopropenones with N-acylamidine derivatives with emphasis on synthetic and mechanistic implications.
The structure 6 was corroborated by analysis of a longrange heterocorrelation (COLOC) spectrum of derivative 7.This showed a correlation ( 3 J) of the carbonyl C-4 with the methyl group at C-5 as well as the other correlations indicated in structure 7 (Scheme 2) in agreement with the regiochemistry assigned to 6.No such correlations would be observed if a 1,5-dihydro-2H-pyrrol-2-one analogous to 2 had formed.
This reaction proved to be very sensitive to substitution both in the cyclopropenone and in the "aza-enaminone".While diphenylcyclopropenone reacted with N-(methoxycarbonyl)benzamidine ( 8) to afford 9 in good yield, it failed to react with derivatives 10 and 11 under the conditions employed (Scheme 2).In addition, compounds 5 and 8 did not react with methylphenyl-cyclopropenone and isopropylphenylcyclopropenone, showing that formation of the 1,2-dihydro-3H-pyrrol-3-one nucleus is effective only with 1 (1 is more reactive towards nucleophiles than are alkylphenylcyclo-propenones because it has the lower-lying LUMO 5 ).
Recently, we demonstrated that reactivity of cyclopropenones can be rationalized by a frontier orbital approach in combination with the hardness-softness concept 5 .The results of AM1 6 calculations, as implemented in the SPARTAN 4.0 package 7 , are show in Scheme 3. Thus, it would appear that reaction of 1 is kinetically favored for the tautomeric forms of 5 and 8, wherein the terminal imine nitrogen has the largest HOMO coefficient.A slow and irreversible attack at the phenyl-C of 1 followed by an electrocyclic five-membered ring formation results in the regiochemistry observed for compounds 6 and 9.
The present study complements the reported 3h formation of the dihydropyrrolone nucleus from diphenylcyclopropenone and enaminones, furnishing a convenient route to 1,2-dihydro-3H-pyrrol-3-one derivatives and expands the frontier of utilization of cyclopropenones as synthetic building blocks for densely substituted heterocyclic compounds.

Experimental
Melting points were determined on a Hoover-Unimelt apparatus and are uncorrected.Infrared spectra were recorded as KBr discs on a Perkin Elmer FT-IR 1600 instrument.NMR spectra were obtained for 1 H at 300 MHz and for 13 C at 75 MHz using a Varian Gemini 300 or a Bruker AC300P spectrometer.Chemical shifts are reported in δ (ppm) units downfield from reference.HRMS were obtained on a Fisions VG Autospec.N-benzoylacetamidine 8 , N-(methoxycarbonyl)benzamidine 9 and diphenylcyclopropenone 10 were prepared according to known procedures.