CARBENOID CHEMISTRY - REACTION OF PYRROLE DERIVATIVES WITH ETHYL DIAZOACETATE

Reaction of IV-methylpyrrole (NMP) with ethyl diazoacetate (EDA) produced monoacetate adducts 2 and 4, with a wide range of copper promoting agents. Minor amounts of diacetate adducts (20a-c) were also formed (about one-tenth the amount of monoacetates). The relative amounts of 2 and 4 varied according to promoting agent (2/4 ratio ranged from 16/1 to 3/2). The regiochemistry of the reactions served to characterize the relative reactivity of the metal-carbenoid reagents. The least discriminant agents were Cu(OTf)2 and Cu(BF4)2, and the most discriminant ones (for a substitution) were certain copper(II) 1, 3-diketone, salicylaldehyde, and salicylaldimine chelates (5a, 5c, 6c, 6g, and 6h). Certain copper(II) chelates of these classes also furnished optimal yields of 2 (5g, 6b, 6d, 6e, 6g-i, and 8). Other pyrrolic compounds were also studied with a limited number of promoting agents [generally Cu(acac)2, copper bronze, and/or Cu(OTf)2]. Pyrrole gave 2- and 3-acetates (13 and 14), with no N-H insertion product 15. N-Isopropylpyrrole gave 2- and 3-acetates, but N-ieri-butylpyrrole gave only 3-acetate. With a specific promoting agent, the N-substituted pyrroles showed an increasing proportion of β substitution with increasing steric bulk of the N group (tert-butyl > isopropyl > methyl > hydrogen). Reaction of 1, 2- and 1, 3-dimethylpyrroles with EDA afforded mixtures of three isomeric monoacetates; the C-methyl substituent exhibited an ortho-directing influence. In the reaction of NMP with EDA, employing certain copper(I) and copper(II) halides, a carbethoxycarbene trimer, triethyl (£)-aconitate, was identified; this represents a “propene” trimerization pathway for: CHCO2C2H5 as opposed to the more common “cyclopropane” pathway. On the basis of the variation of α/β isomer ratio with promoting agent and the substituent effects, the mechanism of the reaction of N-H and N-alkyl pyrroles with EDA is depicted as an electrophilic substitution (rather than insertion) process leading directly to acetate adducts (i.e., not involving distinct homopyrrole intermediates). © 1979, American Chemical Society. All rights reserved.