On the Reactivity of α-( Triphenylphosphoranylidene )-benzylphenylketene with Nitrogen Compounds . Synthetic and Mechanistic Implications

A reatividade do ilídeo de fósforo estabilizado derivado da difenilciclopropenona, o α(trifenilfosforanilideno)-benzilfenilceteno, frente a compostos nitrogenados polifuncionalizados foi investigada. Em particular, a reação do α-(trifenilfosforanilideno)-benzilfenilceteno com o azodicarboxilato de etila pode se constituir como um novo método de síntese de N-acil-carbamatos densamente substituidos.


Introduction
While the reactivity of diphenylcyclopropenone (1)  with nucleophiles has been well documented, 1 studies of the behavior of its derivative α-(Triphenylphosphoranylidene)-benzylphenylketene (2, α-TPBPK) with such reagents are scarce. 2Otherwise, phosphorus ylides have been intensively used in organic synthesis, mainly in olefination reactions. 3Stabilized triphenylphosphonium ylides have attracted attention and new methods of preparation, 4 their behavior under pyrolysis conditions 5 and structural elucidation 6 still demand investigation.When carrying out a transformation with stabilized triphenylphosphonium ylides their nucleophilicity has been the prime consideration. 7ecently, we reported the study of the reaction of triphenylphosphoranylidenesuccinic anhydride with a broad spectrum of nitrogen nucleophiles and a new method of synthesis of phosphonioum salts was described. 8Our continued interest in the chemistry of cyclopropenones and their derivatives 1 as well as in the reactivity of phosphorus ylides stabilized by electrophilic functions 8 prompted us to study the behavior of α-TPBPK toward nitrogen compounds.In this work we present our results concerning the reactivity of α-TPBPK with such derivatives with emphasis on synthetic and mechanistic implications.

Results and Discussion
The ambiphilic α-TPBPK 2 is readily prepared by the reaction of diphenylcyclopropenone with triphenylphosphine.As expected, this solid is stable only under anhydrous conditions, but alternatively it can be generated in situ. 2 Thus, equimolar amounts of triphenylphosphine and diphenylcyclopropenone (1) were reacted under inert atmosphere and then the nucleophile was introduced (see Experimental).Among the broad spectrum of nitrogen nucleophiles available, we selected ones whose reactivity toward diphenylcyclopropenone was known.Thus, we began our study with 2-amino-4-methylpyridine 3, 9 pyridinium N-imine 4 10 and N-benzoylacetamidine 5 1 (examples of reactivity towards 1 are shown in Scheme 1).
α-TPBPK reacted with 2-amino-4-methylpyridine (3) to afford a crystalline solid along with almost quantitative recovery of triphenylphosphine.Although the IR spectrum of the product suggested the presence of amide NH and C=O groups, and proton NMR integration indicated that this material was a 1:1 adduct, the chemical shifts of the pyridinic ring ruled out the formation of 6 (δ H 3 6.15, δ H 5 6.37 and δ H 6 7.60, and 8.30, 6.80 and 8.10 for 6, Cunha and Kascheres J. Braz.Chem.Soc. respectively 9 ).Additionally, the NMR spectrum contained a low field N-H proton (δ10.20,D 2 O exchangeable) as a broad signal and an olefinic proton as a sharp singlet at δ 7.82, indicating a cis relationship of the phenyl groups as in 6, where this absorption appears at δ 8.0. 9To accommodate these spectral features structure 11 was proposed (Scheme 2).Also, the hydrogen chemical shifts mentioned above for the nitrogen-containing ring of 11 with an exocyclic carbon-nitrogen double bond are in agreement with a model compound previously reported by us (11a, Scheme 2), whose X-ray structure was obtained. 11It should be pointed out that 11 is not converted into 6 under reflux in chloroform or nitromethane.Under basic conditions (K 2 CO 3 ), α-phenylcinnamic acid is the sole isolated compound.When α-TPBPK was reacted with pyridinium N-imine (4), generated in situ by reaction of N-aminopyridinium iodide 12 with K 2 CO 3 , compound 12 was isolated in modest yield (Scheme 2).The pyridinium ring 13 and the N-αphenylcinnamoyl moiety 9 in 12 could be defined by comparison with analogues described in the literature.We next studied the reaction of 2 with N-benzoylacetamidine (5).In this case, a mixture of products 13-15 was obtained in contrast to the reaction of this nucleophile 1 with 1.As in the reaction of 2 with 3, triphenylphosphine was recovered in the reaction of 2 with 4 and 5. From a mechanistic viewpoint, the formation of 11-15 may be visualized as occurring through attack of the nitrogen nucleophile at the electrophilic carbon of the ketene portion of 2, followed by triphenylphosphine elimination and proton transfer (Scheme 3).
To provide insight into the behavior of α-TPBPK toward nitrogen compounds without transferable hydrogen, 2 was treated with azobenzene and N-(p-methoxyphenyl)benzaldimine, but only complex mixtures were formed.However, with diethyl azodicarboxylate 16 a clean reaction took place, wherein the N-acyl carbamate (17) was formed in excellent yield.This is a very interesting result since densely substituted N-acyl carbamates are versatile intermediates in the synthesis of nucleoside analogues and their preparation is not a trivial task. 14ontrary to the other reactions described above, triphenylphosphine oxide was the co-product, and the phenyl groups are positioned trans in 17, as indicated by the chemical shift of the olefinic hydrogen as a sharp singlet at δ 7.20 (in 6, 9 11 and 12 the phenyl groups are positioned cis and the olefinic proton appears at δ 8.0, δ 7.82 and δ 7.82, respectively).However, the formation of 17 is not well understood and its mechanism is under study.
The results of the present work, together with those obtained previously with triphenylphosphoranylidenesuccinic anhydride, 8 provide an interesting spectrum of reactivity for phosphorus ylides stabilized by electrophilic functions, and also expand the frontiers of applications of cyclopropenone derivatives in synthesis.Particularly, the formation of 17 provides a new route to polysubstituted N-acyl carbamates.Studies involving the preparation of unsymmetrical cyclopropenones and their reactions with diethyl azodicarboxylate are under investigation to establish the mechanism, scope and limitations of this new synthetic protocol.

Experimental
Melting points were measured 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.Unless otherwise stated, all spectra were run in CDCl 3 solutions.Chemical shifts are reported in δ (ppm) units downfield from reference.Elemental analyses were performed on a Perkin Elmer 2401 Elemental Analysis by Instituto de Química, Universidade Estadual de Campinas, Brazil.N-aminopyridinium iodide, 12 N-benzoylacetamidine 15 and diphenylcyclopropenone 16 were prepared according to known procedures.All reactions were performed under a positive pressure of argon with oven-dried glassware (120 °C).Benzene and CH 2 Cl 2 were distilled from Nabenzophenone and CaH 2 , respectively.