Nickel, Haney

The synthesis of bufotenine itself followed closely upon the proof of its structure. Hoshino and Shimodaira reduced the ethyl ester of 5-ethoxy-indole-3-acetic acid by the Bouveault-Blanc procedure to the corresponding primary alcohol, which was treated with phosphorus tribromide and then dimethylamine, to give the ethyl ether of bufotenine, which was demethylated with aluminum chloride (130). In a later synthesis, 2,5-dimethoxybenzyl cyanide (XXIII) was alkylated by Eisleb s method with dimethylaminoethyl chloride in the presence of sodamide to give l-(2,5-dimethoxyphenyl)-3-dimethylaminopropyl cyanide (XXIV), which was then hydrogenated over Haney nickel to yield 2-(2,5-di-methoxyphenyl)-4-dimethylaminobutylamine (XXV R = Me). De-methylation of this with hydrobromic acid, followed by oxidation of the product (XXV R = H) with potassium ferricyanide yielded bufotenine (XIX) via the related quinone (109). 

Enchaining radical cyclizations steps to provide polycyclic compounds is the simplest approach. Because the 5-exo cychzation is the most straightforward mode of cychzation, polyquinanes have been the object of many studies [20]. Roimd-trip strategies as defined by Haney and Curran [21], from a vinyl radical such as 8 have been developed by Takasu et al. [22] and revisited by Tripp et al. (Scheme 3) [23]. Mixtures of diastereomers 9 are obtained from hnear precursor 7. The same group has examined the intramolecular addition of a vinyl radical onto a dienoate to produce [4 -l-1]- or [4 + 2]-annulated compounds [24]. Tandem 5-exo-trig cyclizations have also been shown to yield tricyclo[6.2.1.0 ]undecan-4-one and related polycyclic compounds, using a nickel-catalyzed electroreduction [25]. 

Nlckel-uliinilnum allny (1 1 Kiinry nickel allny). Suppliers W. K. (irnce Co.. Haney Ciiliilysi Division Mnishnw. 

Caution Part A must be conducted in a hood due to the noxious odor of dimethyl sulfide. In Pari B, the usual precautions associated with the pyrophoric reagent Haney nickel must be observed [see Note 8). 

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