Cyclopropylimines rearrangements

Although prolonged heating of the pyrroline (192) does not lead to further ring expansion, a second cyclopropylimine rearrangement takes place on heating in the presence of anhydrous hydrobromic acid at 140°C for 10 min, giving after hydrolysis the pyrrolizidinone (193) (equation 128). This sequence opens a route to pyrrolizidines that are of obvious interest in natural product synthesis. 

The aza-di-TT-methane (ADPM) rearrangement of aza-1,4-dienes via radical-cat-ions suggests the possibility that other radical-ion intermediates (e.g., radical-anions) could also be responsible for this rearrangement reaction. In order to test this proposal, the azadiene 101 was irradiated for 20 min in acetonitrile using A,iV-dimethylaniline (DMA) as an electron-donor sensitizer. The reaction leads to formation of the cyclopropylimine 102. Separation of product mixture by column chromatography on silica gel affords the aldehyde 34 (21%) resulting from hydrolysis of the imine 102, (Scheme 18) [70]. 

P.y-Unsaturatod imines and their derivatives undergo ADPM rearrangement upon triplet-sensitized irradiation in the presence of acetone and acetophenone (Scheme 4.31) [45-47]. The alkyl-substituted cyclopropylimines readily underwent hydroxylation on Si02 to afford the corresponding cyclopropanecarbaldehydes... 

Campos, P.J., Soldevilla, A., Sampedro, D., and Rodriguez, M.A. (2001) N-Cyclopropylimine-1 -pyrroline rearrangement. A novel photochemical reaction. Organic Letters, 3, 4087 -089. 

The first 1-ADPM rearrangement of an acyclic derivative, reported five years later, was observed in studies of the sensitized irradiation of the (3,y-unsaturated imine 8 that yielded the corresponding cyclopropylimine 9 exclusively (Sch. 5) [11]. This photoproduct undergoes hydrolysis during isolation to generate the corresponding cyclopropane carbaldehyde 10. 

For more than 30 years, di-7i-methane processes were limited to the three different types of (3,y-unsaturated systems mentioned above. However, recent studies have shown that the rearrangement is applicable to 2-aza-1,4-dienes [13]. Thus, triplet-sensitized irradiation of compound 11 affords the cyclopropylimine 12 and the TV-vinylaziridine 13 (Sch. 6). The photoreaction of 11 represents the first example of a 2-aza-di-7i-methane rearrangement (2-ADPM) that brings about the formation of a heterocyclic product. The reaction has been extended to other 2-azadienes that yield the corresponding cyclopropylimines regioselectively [13b]. 

The 1-ADPM rearrangement of 1-aza- 1,4-dienes affords the corresponding cyclopropylimines regioselectively. However, in order to predict the outcome of the reaction in pyrazinobarrelenes, quinoxalinobarrelenes, and other polycyclic systems, two different factors should be taken into account. One is the possible competition between the DPM and the 1-ADPM rearrangements, and the other is the influence of substitution on the stability of the reaction intermediates. However, in most of the cases studied, the 1-ADPM process takes place preferentially over the DPM reaction [3e]. An example of competition between these two reactions is shown in Sch. 4 for compound 5a [10a]. 

Several related carbene complexes 28 with M = Cr, Mo, or W, have been shown to undergo photocycloadditions with alkenes, in particular acrylates, to furnish a series of 1 -pyrrolines 29 in moderate yields. The mechanism is believed to involve an initial cyclopropanation of the alkene, followed by a light-induced [l,3]-sigmatropic rearrangement of an intermediate N-cyclopropylimine <020M4076>. 

The cyclopropylimine ynoline rearrangement (equation 68) has been exploited by Stevens in alkaloid syntheses. - Wenkert s cyclopropylcarbinyl rearrangement (equation 69) served extremely well in the design of 1,4-dicarbonyl synthons or 3,-y-unsaturated carbonyl compounds which then were expressed in numerous syntheses of terpenoid and alkaloid natural products. Donor-acceptor concepts continue to be express in the applicability of these rearrangements to organic synthesis. 

Af-Cyclopropylimines undergo rearrangement to cyclic imines (pyrrolines) under... 

Cyclopropylimines can be transformed to dihydropyrrols by heating with catalytic amounts of acids having nucleophilic anions (Cloke rearrangement " ). It is very likely that this ring expansion involves an acid-assisted nucleophilic attack followed by reclosure to the heterocycle as depicted in equation 28. 

Two total syntheses of sceletium alkaloid A4 (42) have been reported. The first, which involves a rearrangement of a cyclopropylimine to a pyrroline, is condensed in Scheme 12. The general pattern of the second (Scheme 13) is similar. ... 

Sigmatropic rearrangements of cyclopropylimines <91TL7127> and cyclobutylimines <88H(27)1665> to generate fused bicyclic aziridines have been reported <84CHEC-I(7)47>. The sigmatropic rearrangement of isoxazoles to azirines will be covered in Section 1.01.9.6. Electrocyclic closure of vinyl-nitrenes to azirines will be discussed in Section 1.01.9.5. 

The rearrangement of heterocyclic analogs of vinylcyclopropanes are well-known and have been compiled in several recent reviews. Only a few selected cases dealing with the rearrangements of vinylaziridines, cyclopropylimines, vinyloxiranes and cyclopropylketones are covered in the following section. 

For synthesis of certain alkaloids, the requisite cyclopropylimines were prepared by bisalkylation of the appropriately substituted benzyl cyanide. Cyanides could be selectively reduced in high yield to the corresponding aldehydes by employing diisobutylalmninium hydride. Treatment of these aldehydes with a primary amine completes the synthesis of the imines. Rearrangement " with acids afforded the 2-pyrrolines in high yield (equation 26). 

Scheme 11.2 Thermal rearrangement of Tl l.l-dichloro-2-VCP. (2) unsuhstituted VCP. cyclopropylimine, and (4) cyclopropylcarhaldehyde.

Scheme 11.41 Photochemical rearrangement of N-cyclopropylimines under direct seasitized conditions.

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