Five-membered Nitrogen-containing Rings

Five-membered Nitrogen-containing Rings. The addition to alkynes of the azomethine ylide (80), which results from the thermal opening of 2,2-di-methoxycarbonyl-l,3-diphenylaziridine, occurs in both possible orientations giving two isomeric 3-pyrrolines (81). The structure of the products was established by spectroscopic means, and by reduction to known pyrrolidines. 

By a mechanism reminiscent of that above, 4,5-dihydro-l,3,5-oxaza-phospholes (82) undergo a thermal, as well as photochemical, cycloelimination of phosphoric acid ester giving nitrile ylides (83), which participate in cycloadditions.  

Vinyl azides undergo slow cycloaddition with diphenylketen involving loss of nitrogen to give five-membered-ring enamino-ketones (84). The non-concerted mechanism suggested involves nucleophilic attack of the )5-carbon 

Lead tetra-acetate or mercuric oxide oxidation of the hydrazide (85) gives the 1,3-dipole (86) which undergoes cycloaddition, e.g. to form (87).  

Carrie et al. have reported several more cycloadditions of diazo-alkanes to activated olefins. Diazomethane reacts with /3/ -disubstituted-a-acylacrylic esters and nitriles and with 1,1-diacyl- or I-acyl-l-cyano-olefins to give substituted 1-pyrazolines (88). When the 3-acyl substituent is acetyl, isomerization to JV-acetyl-2-pyrazolines (89) may occur. Thermolysis of some of these compounds gives olefins, cyclopropanes, and dihydrofurans. 

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Schemes 3-7 describe the synthesis of cyanobromide 6, the A-D sector of vitamin Bi2. The synthesis commences with an alkylation of the magnesium salt of methoxydimethylindole 28 to give intermediate 29 (see Scheme 3a). The stereocenter created in this step plays a central role in directing the stereochemical course of the next reaction. Thus, exposure of 29 to methanol in the presence of BF3 and HgO results in the formation of tricyclic ketone 22 presumably through the intermediacy of the derived methyl enol ether 30. It is instructive to point out that the five-membered nitrogen-containing ring in 22, with its two adjacent methyl-bearing stereocenters, is destined to become ring A of vitamin Bi2. A classical resolution of racemic 22 with a-phenylethylisocyanate (31) furnishes tricyclic ketone 22 in enantiomerically pure form via diaster-eomer 32.

Miscellaneous Syntheses Starting from a Five-Membered Nitrogen-Containing Ring... 

The formation of pyrrole and its benzo analogs from other heterocyclic systems can occur in any of several general ways. In this section we will consider reactions which change the ring size and composition. In Section 3.06.6, reactions where the five-membered nitrogen-containing ring remains intact will be considered. 

Carbene reactions provide a versatile approach to the synthesis of five-membered nitrogen-containing rings. Of particular importance here are intramolecular insertion of a carbene into C — H and N — H bonds, addition onto multiple carbon-carbon bonds, intermediate formation of ylides as a result of carbene addition onto the heteroatom followed by rearrangement, cycloaddition, and cyclization. 

Several more examples of the application of the dipole-cascade approach to five-membered nitrogen-containing rings from the work of Padwa and co-workers are shown in Scheme 22 (89JA6451 92JA593, 92T7565). 

Studies involving five-membered nitrogen containing rings... 

Some nitrogen containing compounds were identified in the neutral fractions. There were five-membered nitrogen containing ring compounds, including indole, isoxazole, indazole, and carbazoles which do not show basic properties and consequently do not react with 1 M hydrochloric acid in the basic extraction step. A number of phthalate esters were also present in different fractions. 

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