Quebrachamine total synthesis

The total synthesis of ( + )-quebrachamine has been achieved by a modification of the route used for the synthesis of aspidospermine (Section II,C ref. 27a). Condensation of the intermediate XXX-J with phenyl hydrazine gave dl-IX which on borohydride reduction yielded (+ )-quebrachamine (I). 

A simple application of this reaction scheme to the total synthesis of the alkaloids eburnamonine XXXVI, quebrachamine, vincadine and epivincadine XXXVII [64], is illustrated by figure 2. 

The large synthetic scope of the copper-catalyzed asymmetric cyclopropanation is illustrated by the use of Evans bis(oxazoline) with CuOTf which allows efficient transformation of a cyclic enol ether the context of a total synthesis of (+ )-quebrachamine... 

A total synthesis of tricyclic ketone (Chart 11.3) cyclized in hot acetic acid to give the indolenine indole forms, reduction of which under the correct conditions gave the desired racemic penta- or tetracyclic alkaloid. The tricyclic ketone was prepared in nine steps from butyraldehyde. 

Very recently, Hoveyda and coworkers reported a very elegant total synthesis of the Aspidosperma alkaloid (-i-)-quebrachamine (139) through a highly enantioselective alkene RCM promoted by molybdenum based catalyst (141) [88, 89]. In this study... 

Fig. 37), the late-stage enantioselective alkene RCM required the closure reaction onto one of two sterically hindered vinyl groups at a congested quaternary carbon in the presence of a potentially problematic tertiary amine moiety. Through an extensive screen of chiral catalysts, gratifyingly, the desired tetracycle (142) was obtained in 84% yield and 96% ee, which allowed the completion of total synthesis of (+)-quebrachamine (139). 

Kozmin SA, Iwama T, Huang Y, Rawal VH. An efficient approach to Aspidosperma alkaloids via [4-1-2] cycloadditions of aminosiloxydienes stereocontrolled total synthesis of ( )-tabersonine. Gram-scale catalytic asymmetric syntheses of (-l-)-tabersonine and (-l-)-16-methoxytahersonine. Asymmetric syntheses of (-l-)-aspidospermidine and (-)-quebrachamine. J. Am. Chem. Soc. 2002 124(17) 4628-4641. 

SCHEME 24.40. Total synthesis of the (-h)-quebrachamine using ARCM. 

Coldham I, Burrell AJM, White LE, Adams H, Oram N. Highly efficient synthesis of tricyclic amines by a cycliza-tion/cycloaddition cascade total syntheses of aspidosper-mine, aspidospermidine, and quebrachamine. Angew. Chem. Int. Ed. 2007 46(32) 6159-6162. 

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