Yohimbane alkaloids

Wender and Aube have independently described the use of the Bischler-Napieralski reaction in the synthesis of Yohimban alkaloids. Aube s approach involved the cyclization of indole 50 followed by reduction of the resulting dihydroisoquinoline... 

The iron-mediated [2 + 2 + 1]-cycloaddition to cyclopentadienones has been successfully applied to the synthesis of corannulene [24] and the yohimbane alkaloid ( )-demethoxycarbonyldihydrogambirtannine [25]. A [2 + 2 + l]-cydoaddition of an alkene, an alkyne and carbon monoxide mediated by pentacarbonyliron, related to the well-known Pauson-Khand reaction [26], has also been described to afford cyclopentenones [27]. 

In a previously described approach, a largely similar strategy was employed in order to generate enantio-selectively (—)-allo-yohimbane [84]. Yohimbane alkaloids such as reserpine and yohimbine were of long-standing interest from pharmacological and synthetic points of view, and the first enantio-selective (—)-alloyohimban synthesis was reported some time ago by Isobe et al. [88]. 

The process has been applied to the synthesis of derivatives of the yohimbane alkaloid... 

Complex examples of the diene-alkyne [4+2] cycloaddition reaction have been illustrated in syntheses of a yohimban alkaloid and vitamin D analogs (Scheme 3-21). A representative procedure for the synthesis of a vitamin D analog is provided below. 

The known yohimbane alkaloids have been correlated with the key compounds on p. K9 by chemical and chiroptical means [1 ]. ORD/CD of the four yohimbane types [5]. 

The route employed to prepare indanone 51 involved the cycloaddition-hydrolysis-aldol sequence shown in Scheme 3.9. Accordingly, condensation of cyclopentenone 52 with ynamine 53 (84) afforded the bicyclic enamine 54 which was converted to indanones 51 and 55 by hydrolytic cyclobutane ring opening followed by intramolecular aldol condensation. Interestingly, treatment of 54 with aqueous formic acid yielded indanone 51 which has stereochemistry complementary to that at C(15) and C(20) in reserpine. In contrast, hydrolysis of this substance with aqueous hydrochloric acid afforded the trans-fused indanone 55. Subsequent to this work, the Ficini group found that esterification of 51 followed by photochemically induced addition of methanol afforded adduct 56 which has four of the reserpine stereocenters in place (23). While no further work on this problem has been reported, these preliminary investigations demonstrate a novel use of [2 -h 2] photocycloaddition chemistry in potential approaches to yohimbane alkaloid synthesis. 

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