Imine compounds intramolecular cycloadditions

Intramolecular cycloadditions of N-aryl imines [269] have also found widespread use in the synthesis of tri- and tetracyclic compounds like octahydro-acridine derivatives [270-273]. In these studies tricarbonylchromium comple-... 

Scheme 29 describes a plausible mechanism for the formation of the products which fit the observed coulometric (n 0.45 F/mol) and preparative results. The intramolecular cyclization process involves a dimerization between a radical cation 52a and the ketene imine 52 to form the intermediate radical cation 52b which then cyclizes to the radical 52c which can abstract a hydrogen atom leading to 54 or can be further oxidized and transformed through a cyclization and deprotonation reaction to 53 which involves 1 F/mol. However, it seems that the [2 -1- 3]-cycloaddition between the parent compound 52 and the cation 52d giving rise to 55 is the fastest reaction as compared with the intramolecular cyclization of 52d to 53. This can also explain the low consumption of electricity. 

To form the stereocenter at C-3 a direct reduction-alkynylation sequence was applied, that provided the diastereomeric homopropargylic alcohols 83 in a ratio of syn anti=76l2A, The major isomer syn-S3 was isolated in 55% yield. The key step of the synthesis was an intramolecular imidotitanium-al-kyne [2+2] cycloaddition/acyl cyanide condensation. With this sequence the pyrrolidine ring was formed and all the carbon atoms of the alkyl side chain were established in acrylonitrile 84. The reduction of the imine double bond proceeded stereoselectively and the nitrile group was removed reductively en route to the target compound. 

In a series of papers, Laude and co-workers (144-149) examined 1,3-dipolar cycloaddition reactions of mtinchnone imines derived from Reissert compounds. For example, mtinchnone imine 241 undergoes a smooth intramolecular 1,3-dipolar cycloaddition with the tethered alkyne unit to afford pyrrole 242 after extrusion of HNCO (144). 

The formation and intramolecular dipolar cycloaddition of azomethine ylides formed by carbenoid reaction with C=N bonds has recently been studied by the authors group.84 Treatment of 2-(diazoace-tyl)benzaldehyde O-methyl oxime (176) with rhodium(II) octanoate in the presence of dimethyl acetylenedicarboxylate or N-phenylmaleimide produced cycloadducts 178 and 179, respectively. The cycloaddition was also carried out using p-quinone as the dipolarophile. The major product isolated corresponded to cycloadduct 180. The subsequent reaction of this material with excess acetic anhydride in pyridine afforded diacetate 181 in 67% overall yield from 176. The latter compound incorporates the basic dibenzofa, d -cyclohepten-5,10-imine skeleton found in MK-801,85 which is a selective ligand for brain cyclidine (PCP) receptors that has attracted considerable attention as a potent anticonvulsive and neuro-protective agent.86,87... 

The Weinreb group has used an intramolecular imino Diels-Alder cycloaddition as the key step in a total synthesis of the fungal neurotoxin slaframine (74) (equation 25). Thus, thermolysis of acetate (71) produced an intermediate A -acyl imine (72) which underwent [4 + 2] cycloaddition to afford bicyclic lactam (73) as a 1.8 1 mixture of epimers. Both compounds were converted to the natural product in a few steps. 

Because all of the work with munchnone imines that has been reported since the review by Gingrich and Baum was described by one research group and involves only cycloaddition chemistry, it is collected in this section. In a series of papers, Laude and co-workers " " examined 1,3-dipolar cycloaddition reactions of munchnone imines derived from Reissert compounds. For example, treatment of the readily assembled Reissert compounds 358 and 360 with HBF4 forms the munchnone imines 359 and 361, respectively (Fig. 4.119). " " Both 359 and 361 undergo smooth intramolecular 1,3-dipolar cycloaddition with the tethered alkyne unit to afford pyrroles 362 and 363, respectively, after extrusion of HNCO (Fig. 4.120). " " ... 

Neooctams, such as the unsubstituted parent compound (191), are easily obtained in cycloadditions. Isocyanates [125,126], sulphonyl isocyanates (43) [29,127] and especially chlorosulphonyl isocyanate (189) [128] react with alkenes to form variously-substituted j3-lactams [129—135]. Synthesis of compound (191) is an example of this reaction which has been discussed in detail [52]. The same compound (192) can be obtained in the photolytic rearrangement of the pyrazolone (194) [136]. Compound (196) is neooctam-5,7-diene, obtained from the azocine (195) and hydrogen bromide [137]. Lactam (196)is a partly saturated form of (199). The latter is an unstable neooctam derivative, formed in an intramolecular ketene-imine cycloaddition reaction (see (198))... 

It is well known that alkyl azides also behave as 1,3-dipoles in intramolecular thermal cycloaddition reactions. The formation of two carbon-nitrogen bonds leads to triazolines, which are usually not stable. They decompose after the loss of nitrogen to aziridines, diazo compounds, and heterocyclic imines. There are a limited number of examples reported in which the triazoline was isolated [15]. The dipolar cycloaddition methodology has been extremely useful for the synthesis of many natural products with interesting biological activities [16], In recent years, the cycloaddition approach has allowed many successful syntheses of complex molecules which would be difficult to obtain by different routes. For instance, Cha and co-workers developed a general approach to functionalized indolizidine and pyrrolizidine alkaloids such as (-i-)-crotanecine [17] and (-)-slaframine [18]. The key step of the enantioselective synthesis of (-)-swainsonine (41), starting from 36, involves the construction of the bicyclic imine 38 by an intramolecular 1,3-dipolar cycloaddition of an azide derived from tosylate 36, as shown in Scheme 6 [ 19). 

---