Houben-Hoesch-type cyclization

Prof. Hao s synthesis commenced with the copper(I) chloride-catalyzed oxidation of the tryptamine derivative to afford ketone 42 [74], A three-component Strecker-type reaction was designed to react the ketone 42 with tryptamine and TMSCN to finish the first ring closure. After examining a series of both Lewis acid and Bronsted acids, the authors found a catalytic amount of TMSOTf promoted the transformation and afforded nitrile intermediate 43, which is ready for the Houben-Hoesch-type cyclization [75]. Treatment by TfOH (trifluoromethanesulfonic acid) [76] in DCM and the... 

Various intramolecular reactions are widely used to prepare this type of heterocycle. Intramolecular acylation has been used frequently (84AHC(37)i). Houben-Hoesch cyclization of I -(3-cyanoethylpyrrole (4a) gives l-oxo-2,3-dihydropyrrolizine (5a). The methyl group in (4b) selectively activates C-2 so that only the isomer (5b) is formed (66JA1305). 

Hao and colleagues disclosed a rapid total synthesis of ( )-tr onoliimine A via a Strecker/Houben-Hoesch sequence.The three-component Strecker-type reaction of 169, 170, and TMSCN was found to be effectively promoted by TMSOTf to furnish intermediate 171 this intermediate was unstable in basic or neutral environments and thus was treated directly with triflic acid at room temperature to effect the Houben-Hoesch cyclization and give ketone 172. Finally, the addition of hydrazine triggered deprotection of the amine and subsequent cyclization to furnish 173 (130L528). 

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