Andrea Modi

MULTICOMPONENT DOMINO REACTIONS FOR THE SYNTHESIS OF BIOLOGICALLY ACTIVE NATURAL PRODUCTS AND DRUGS

A main issue in modern synthetic organic chemistry, which deals with the preparation of natural products, pharmaceuticals, diagnostics, agrochemicals, and other important materials, is the improvement of efficiency, the avoidance of toxic reagents, the reduction of waste, and the responsible treatment of our resources. One of the ways to fulfill these goals is the development and use of domino processes, which consist of several bond‐forming reactions and which allow the highly efficient synthesis of complex molecules starting from simple substrates. Herein, the combination of several catalytic bond‐forming transformations is clearly most appropriate. The synthesis of the enantiopure alkaloid (−)‐hirsutine 22, which has a strong inhibitorial effect on influenza A viruses, was accomplished using a biomimetic domino Knoevenagel‐hetero‐Diels Alder‐solvolysis‐hydrogenation process. In a similar way the alkaloids (+)‐dihydrocorynantheine 23 and (−)‐dihydroantirhine 24 as well as heterosteroids 62, D‐homosteroids 65 and 68, and azasteroids 25 are prepared. In addition, novel steroid alkaloids 26 are accessible by a combination of the formation of an iminium salt, a hydride shift, and an alkylation. The anti‐leukemic pentacyclic (−)‐cephalotaxine 27 is obtained by a combination of two Pd‐catalyzed reactions.

Regioselective Silane-Terminated Intramolecular Heck Reaction with Alkenyl Triflates and Alkenyl Iodides

One of the main problems of the Heck reaction using acyclic substrates which lead to Pd intermediates with β- and β′-hydrogens is the lack of selectivity in the formation of the double bond as the last step of the catalytic cycle. The use of allylsilanes as the alkene moiety permits control of the elimination step. Thus, the Pd0-catalysed reaction of 1a−c and 2 leads exclusively to the corresponding bicyclic compounds 11a−c. In contrast, reaction of 7 yields a mixture of 12a, (E)-12b and (Z)-12b.