Aluminum compounds nitrile synthesis

Intramolecular electrophilic substitution of a pyrrole by a nitrile under acidic conditions generates a dihydropyrrolizine after hydrolysis of the iminium ion intermediate. This type of cyclization has received considerable attention. Braunholtz et al. demonstrated that improved yields (70%) in the cyclization step were effected with a melt of the chlorides of aluminum, potassium, and sodium, but the conditions were extremely critical. Meinwald and Meinwald used this method for their preparation of the dihydropyrrolizinone (50). This confirmed the structure of the major component of the hairpencil secretion of the male tropical butterfly Lycorea ceres ceres. None of the isomeric 2-methyl compound was formed during this synthesis [Eq. (17)]. It is suggested that the 3-methyl group of pyrrole activates the adjacent 2-position sufficiently to promote regiospecific intramolecular electrophilic substitution. 

Malonate and related activated methylene compounds have also been used as the nucleophile in conjugate addition/Michael reactions. Taylor and co-workers have developed a new methodology that utilizes (salen)aluminum complexes such as 43 as a catalyst to effect the enantioselective conjugate addition to a,p-unsaturated ketones by a variety of nucleophiles.25 For example, nitriles, nitroalkanes, hydrazoic acids, and azides have found utility in this reaction. Additionally, cyanoacetate (42) has been demonstrated to undergo a highly enantioselective conjugate addition to 41. The Krapcho decarboxylation is then necessary to produce cyanoketone 44, an intermediate in the synthesis of enantioenriched 2,4-cw-di substituted piperidine 45. 

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