Diazoalkanes, cycloaddition imines

An unusual course of thermolysis occurs in 5-amino- and 5-alkoxytri-azolines, which are formed only as intermediates in the reaction of enamines and enol ethers with azides bearing electron-withdrawing groups it involves cleavage of the N-l/N-2 as well as the C-4/C-5 bonds of the triazoline ring to yield diazoalkanes and imines with one fewer carbon than in the triazolines (amidines and imino ethers) (Scheme 144)233.250 272 431-433 in a cycloelimination reaction, the reverse of diazoalkane-imine cycloaddition. The intermediate formation of a diazonium zwitterion is suggested,233,247 but whether the thermolysis occurs in a one- or two-step reaction is not established. 

Reactions offluorinated dipoles. In recent years, much effort has been devoted to the preparation of tnfluoromethyl-substituted 1,3-dipoles with the goal of using them to introduce trifluoromethyl groups into five-membered nng heterocycles Fluorinated diazoalkanes were the first such 1,3-dipoles to be prepared and used in synthesis A number of reports of cycloadditions of mono- and bis(tnfluo-romethyl)diazomethane appeared prior to 1972 [9] Other types of fluonne-substi-tuted 1,3-dipoles were virtually unknown until only recently However, largely because of the efforts of Tanaka s group, a broad knowledge of the chemistry of tnfluoromethyl-substituted nitrile oxides, nitnle imines, nitnle ylides, and nitrones has been accumulated recently... 

Alkylidene sulfenes (75), generally prepared by the dehydrohalogenation of alkylsulfonyl chlorides, add readily to electron-rich multiple bonds. For example, with enamines, the thietane dioxide (e.g., 76) is formed diazoalkanes yield thiirane dioxides (episulfones) and imines (Schiff bases) afford 1,2-thiazetidine 1,1-dioxides. There are available numerous reviews of sulfenes, including cycloaddition reactions.102... 

Cyclohexadiene 45 was converted to 46 by what has proven to be a general method for preparation of the cyclohexa-2,4-dien-l-one ring system.2 Fragmentation of the aziridinyl imine in 46 at 110 °C gave an intermediate diazoalkane which underwent an intramolecular 1,3-dipolar cycloaddition to give the pyrazoline 47. At 140 °C, pyrazoline 47 expelled N2 and rearranged to the tricyclic ketone 48. The development of this and related bicyclizations29 illustrated a practical synthetic equivalence of an intramolecular diene-carbene 4-1-1 cycloaddition in the cyclohexa-2,4-dien-l-one series. 

The synthesis of longifolene in Scheme 13.25 commences with a Birch reduction and tandem alkylation of methyl 2-methoxybenzoate (see Section 5.5.1). Step C is an intramolecular cycloaddition of a diazoalkane which is generated from an aziridino-imine intermediate ... 

Stanovnik and co-workers (100,101) systematically investigated the cycloaddition reactions of diazoalkanes with unsaturated nitrogen heterocycles, such as azolo-[l,5-fl]pyridines, pyridazin-3(2/7)-ones, and [fo]-fused azolo- and azinopyridazines. The Stanovnik group have studied the further transformations of the products and reviews of this chemistry are available. In a typical example, the reaction of 6-chlorotetrazolo[l,5-/7]pyridazine (37) with 2-diazopropane yields the NH,NH-dihy-dro-pyrazolo[4,3-(i]tetrazolo[l,5-/7]pyridazine 38 (102) (Scheme 8.11). The latter substrate reacts with acetone to produce an azomethine imine 39 that thermally rearranges to give the fused dihydro-1,2-diazepine 40. The azomethine imine obtained with glucose can be trapped with methyl acrylate to furnish the C-nucleoside 41 (103). 

In an earlier survey of the cycloaddition chemistry of diazo compounds with imines (5), it was noted that diazoalkanes react particularly well with both electron-deficient acyclic and strained cyclic imines, such as 27/-azirines, producing... 

The characteristics of the 1,3-dipolar cycloaddition mechanism of azides and other 1,3-dipoles (such as diazoalkanes, azo-methine imines, nitrones, nitrile imines, nitrile oxides) have been described in detail by Huisgen.191 19 According to the author, the addition of a 1,3-dipole (a b c) to a dipolarophile (d e) occurs by a concerted mechanism in which the two new a bonds are formed simultaneously although not necessarily at equal rates (32). As a consequence, a stereoselective cis addition is observed. Thus, the addition of p-methoxyphenyl azide to dimethyl fiynarate (33) yields l-(p-methoxyphenyl)-4,5-froiw-dicarbomethoxy-AMriazoline (34),194 and 4-nitrophenyl azide gives exclusively the respective cis-addition products 35 and 36 on addition to irons- and cis-propenyl propyl ether.196... 

The intermolecular 1,3-dipolar cycloaddition route to bicyclic heterocycles has received considerable attention since 1983. Diazoalkanes, N-oxides, nitrile imines, and nitrile oxides have all been used as the 1,3-dipole component in the synthesis of these heterocycles. 

Stanovnik B, Jelen B, Turk C, Zlicar M, Svete J (1998) 1,3-dipolar cycloadditions of diazoalkanes to pyridazines. Asymmetric 1,3-dipolar cycloaddition of azomethine imines derived from diazoalkane-pyridazine cycloadducts. J Heterocycl Chem 35 1187-1204... 

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