New Tandem Reactions of Metal Carbenoids. Intermolecular Formation of Azomethine Ylide from Methyl 2-Diazo-2-phenylacetate and Schiff Base: Intramolecular 1,3-Dipolar Cycloaddition

Abstract

Rhodium acetate-catalyzed decomposition of methyl 2-diazo-2-phenylacetate in the presence of substituted N-methylbenzylideneamines possessing an activated alkenyl fragment (dipolarophile) in the side chain gives products of intramolecular cycloaddition of intermediate Z,E-and E,Z-azomethine ylides. The cycloaddition is regioselective, and the products are hexahydrochromeno[4,3-b]pyrrole derivatives. The stereoselectivity of the process depends on the temperature. In the temperature range from 20 to 80°C, the major stereoisomer is that with cis junction of the tetrahydropyran and pyrrolidine rings. N-Phenylazomethine ylides generated from methyl 2-diazo-2-phenylacetate and alkyl 4-[2-(phenyliminomethyl)phenoxy]-2-butenoates at 40°C undergo cyclization to aziridines at a higher rate, as compared to the rate of cycloaddition to the internal dipolarophile. N-Phenylazomethine ylides generated by thermolysis of the corresponding aziridine or by the "deprotonation" method react with equal regio-and stereoselectivity to give intramolecular cycloaddition products, hexahydrochromeno[4,3-b]pyrrole derivatives with trans-fused tetrahydropyran and pyrrolidine rings. Analysis of the experimental and calculation data suggests preference of the endo transition state in the cycloaddition of the examined azomethine ylides. Intramolecular 1,3-dipolar cycloadditions of azomethine ylides underlie effective procedures for the synthesis of various fused, bridged, and cage-like polycyclic nitrogen-containing compounds [1]. An important problem is the stereoselectivity of cycloaddition of ylide intermediates, for it determines the efficiency of this approach as applied to a particular synthetic task. Low stereoselectivity often results from configurational heterogeneity of ylide intermediate owing to fairly severe conditions of its generation [2][3][4]. The stereoselectivity problem may be solved by development of such methods for generation of azomethine ylides which would allow their geometry to be controlled. One of these methods is based on reactions of carbenes or carbenoids with compounds possessing a C=N bond and is referred to as "carbene" technique. These reactions occur as a rule under mild conditions, and they make it possible to generate ylides which cannot be obtained by other methods [5].The synthetic sequence intermolecular carbene generation of azomethine ylide-intramolecular cycloaddition almost was not studied as a method of synthesis of nitrogen-containing polycyclic compounds. Only recently, we described examples of such syntheses with the use of difluorocarbene and dichlorocarbene [6][7][8].The goal of the present study was to develop approaches to tandem synthesis of fused heterocycles via the above reaction sequence involving carbenoids generated from diazo compounds. As model system we used azomethine ylides generated by addition of carbene-like species derived from methyl 2-diazo-2-phenylacetate to N-methyl-and N-phenylbenzylideneamines I-IV possessing an activated alkenyl fragment (dipolarophile) in the ortho po...

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

“…In the transition state responsible for formation of the observed products, the dihydropyran ring should adopt a half-chair conformation, while the exo-transition state for the reaction of Z,E-ylide should be destabilized due to ax,ax'-interaction. While studying the reaction of methyl 2-diazo-2-phenylacetate with Schiff bases[18], we also concluded that the endo-transition…”

Intramolecular cycloaddition of azomethine ylides, from imines of O-acylsalicylic aldehyde and ethyl diazoacetate, to ester carbonyl – experimental and DFT computational study

“…Mp = 111-112 °C (EtOH). 1 H NMR (CDCl 3 ): δ = 6.71 (1H, d, J = 16 Hz, CHvCHPh), m,H Ar ),7.95 (1H,d,J = 16 Hz,CHvCHPh),m,H Ar ),8.58 (1H,s,CHvN). 13 C NMR (CDCl 3 ): δ = 116.…”