Intramolecular dihydropyrrole synthesi

As shown above, insertion of alkylidene carbenes is highly regioselective. However, when the normal 1,5-C-H insertion pathway is blocked, 1,4- or 1,6-C-H insertion takes place [Eq. (109)]. Thus, the cyclobutene 121 [192] and the six-membered enol ether 123 [193] were obtained in modest yields. Intramolecular insertion into carbon-carbon double bond provides a method for synthesis of cyclopenten-annulated dihydropyrrole 124, which results from homolytic scission of a methylenecyclopropane intermediate [194]. 

Cyclkation. Generation of oxonium ions and their intramolecular trapping are conveniently performed in the presence of DBU in the context of a tetrahydro-furan/tetrahydropyran synthesis. O-Mesyloximes possessing an active methine undergo cyclization, and this reaction leads to dihydropyrroles and tetrahydropyridines. 

Chiral intermediates for the synthesis of (-)-anisomycin (1) and (+)-anisomycin (anti-1) (153), (R)-2-(p-methoxyphenyl)methyl-2,5-dihydro-pyrrole (142) and its (S)-isomer (+)-187, have been efficiently synthesized from D-tyrosine and L-tyrosine, respectively (Scheme 20) [28]. D-tyrosine was converted to 0-methyl D-tyrosine methyl ester (182) [72-75] which was treated with di-tert-butyl dicarbonate to protect the amino group. Subsequent reduction of the ester group with sodium borohydride in the presence of lithium chloride furnished the alcohol 183. Swern oxidation of 183 followed by chain extension with the anion derived from bis(2,2,2-trifluoroethyl)(ethoxycarbonylmethyl)-phosphonate afforded (Z)-Q ,/0-unsaturated ester (184), which was used immediately without purification to avoid or minimize any possible racemization of the chiral center. Reduction of the ester group of 184 with diisobutylaluminium hydride afforded the alcohol 185 which after mesylation followed by intramolecular cyclization gave the desired 2,5-dihydropyrrole derivative 186. Removal of the tert-butyloxycarbonyl group was achieved by treatment with trifuoroacetic acid to give (-)-142 in 62% overall yield from 182. The (S)-2,5-dihydropyrrole (-l-)-187 was also prepared in the same manner starting from L-tyrosine. Since (-l-)-187 had been transformed into (-l-)-anisomycin (anti-1) (153), (-)-142 could also be transformed to the (-)-anisomycin (1) [26,66]. 

In a completely different context, a cascade Michael/intramolecular addition process involving nitroalkenes and isocyanoesters has been developed, which results in a formal [3 -I- 2] cycloaddition reaction and therefore consisting of a direct and very efficient methodology for the asymmetric synthesis of 2,3-dihydropyrroles (Scheme 7.70). ° The reaction was catalyzed by cinchona... 

Grigg and co-workers have published full details of their studies on the synthesis of substituted pyrrolidines and dihydropyrroles by intramolecular cycloaddition of imines of amino-acid... 

Intramolecular nitrogen attack in propargylated enaminones allows silver-catalyzed access to functionalized pyrroles. This Ag-promoted hydroamination can also be used to obtain A bridgehead pyrroles. Silver nitrate-mediated cyclization of allenylamines, available from Uthiated alkoxy allenes and imines or through reaction of l-(lV-carbamoyl)-alkylcuprates with propargyl substrates, provides access to 2,5-dihydropyrrole derivatives. Iminoallenes can be used for the synthesis of substituted p)moles in moderate yields in the presence of potassium carbonate. ... 

Vinyllithium derivatives 128-131 have been generated through a bromine-lithium exchange with t-BuLi. In the case of 128, used in the synthesis of (-)-wode-shiol, a deprotonation of the alcohol functionality was performed prior lithiation [107]. Intermediates 129 were also used in the synthesis of triquinanes [102,108], meanwhile 130 acted as an intermediate in a synthetic route to (-i)-pericosine B [109]. Dianionic species 131 showed an unexpected intramolecular carbometalla-tion upon addition of TMEDA to give dilithiated dihydropyrroles, which finally reacted with different electrophiles [110]. 

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