Intramolecular 1,3-Dipolar Cycloaddition of Azomethine Ylides Generated from Ethoxycarbonylcarbenoids and Schiff Bases

Abstract

Decomposition of ethyl diazoacetate in the presence of copper, copper acetylacetonate, or copper trifluoroacetylacetonate and ethyl 4-[2-(R-imino)phenoxymethyl]-2-butenoate leads to formation of chromeno-[4,3-b]pyrrole-2,3-dicarboxylic acid derivatives. The reactions involve intermediate formation of azomethine ylides which undergo regio-and stereoselective intramolecular cycloaddition at the C=C bond to afford chromeno[4,3-b]pyrroles. The steric structure of the product depends on the configuration of intermediate ylide and nature of the substituent at the ylide nitrogen atom.Metal carbenoids generated by catalytic decomposition of α-diazocarbonyl compounds are effective intermediates in the synthesis of various polycyclic systems. Several methods for building up nitrogen-and oxygen-containing polycyclic skeletons with participation of ylides have been developed in the framework of the general metal carbenoid strategy. These include cyclization of metal carbenoids to give azomethine or carbonyl ylides (cycloaddition), cyclization of metal carbenoids with formation of onium ylides (sigmatropic rearrangement), and intermolecular generation of cyclic iminium ylides (intermolecular cycloaddition) [1-7]. One more possible approach to heteropolycyclic systems via ylides generated from carbenes is based on intermolecular generation of azomethine ylide-intramolecular cycloaddition; it was implemented only with difluoro-and dichlorocarbenes [8][9][10][11].In the present work we extended this approach to ylides generated from ethoxycarbonylcarbenoids and Schiff bases Ia-Ic derived from O-substituted salicylaldehydes containing a dipolarophilic olefin fragment in the side chain.Ethyl diazoacetate was slowly added to a boiling solution of Schiff base Ia in benzene containing a catalytic amount of copper. As a result, two compounds were formed: hexahydrochromenopyrrole IIa (34%; product of intramolecular cycloaddition of intermediate azomethine ylide IVa at the C=C bond) and tetrahydrochromenopyrrole IIIa (26%) (Scheme 1). Monitoring of the reaction course by thin-layer chromatography showed that initially compound IIa is formed exclusively. Tetrahydrochromenopyrrole IIIa appears in the reaction mixture later, the conversion of initial Schiff base Ia being incomplete. By special experiment we found that compound IIIa is formed by dehydrogenation of IIa during decomposition of ethyl diazoacetate in the presence of copper. Under analogous conditions, from Schiff base Ib we obtained only hexahydrochromenopyrrole IIb. It should be emphasized that intramolecular cycloaddition of ylides IVa and IVb is strictly stereoselective. Using the reaction of Schiff base Ib with ethyl diazoacetate as an example, we examined the effect of the catalyst on the yield of product IIb. The best results were obtained with copper acetylacetonate (Table 1). Surprisingly, decomposition of ethyl diazoacetate in the presence of copper and N-tert-butyl-substituted Schiff base Ic afforded stereoisomeric chromenopyrrole IIc in which the ethoxycarbonyl group...

One-Carbon Ring Expansion of Azetidines via Ammonium Ylide [1,2]-Shifts: A Simple Route to Substituted Pyrrolidines

“…With diazoacetophenone 2c , the only isolable product was pyrroline 5a , formed in modest yields (entry 10). Apparent dehydrogenation products of this sort were also obtained from the reaction of 2c with azetidines 1b , c (entries 11 and 12) . Variation of the azetidine exocyclic nitrogen substituent, replacing N -benzyl with N -pentyl or N -allyl, had little effect on the overall efficiency of the process.…”

Reactivity of sarcosine and 1,3-thiazolidine-4-carboxylic acid towards salicylaldehyde-derived alkynes and allenes

“…Compound 4 (5.96 g, 94%) was obtained as a low melting solid. IR (film, cm À1 ): 2120, 1222; 1 H NMR (CDCl 3 ) 7.54e7.57 (1H, m, AreH), 7.28e7.32 (1H, m, AreH), 7.00e7.04 (2H, m, AreH), 5…”

“…4 A similar approach involving the generation of azomethine ylides from ethoxycarbonylcarbenoids and Schiff bases of O-alkynyl salicylaldehydes is known. 5 On the other hand, it has been demonstrated that the reaction of imines derived from O-alkenyl salicylaldehydes and acid chlorides mediated by PhP(2-catechyl) leads to chromeno [4,3-b]pyrrole derivatives via intramolecular cycloaddition of phosphorus-containing 1,3-dipoles. 6 Despite the existing methods for the synthesis of chromeno [4,3b]pyrrole derivatives, there still is demand for strategies to achieve wider structural diversity.…”

Nonconcerted Cycloaddition of 2H-Azirines to Acylketenes: A Route to N-Bridgehead Heterocycles

“…Because of our research interest concerning the chemistry of azirines and the synthesis of nitrogenated heterocycles via reactions of diazo compounds with imines, ,,,, we envisioned the possibility of assembling a new heterocyclic system, 5-oxa-1-azabicyclo[4.1.0]­hept-3-ene 1 , by the reaction of azirines 2 with acylketenes 3 , according to the retrosynthetic sequence described in Scheme .…”