Electrocatalysis as a key strategy for the total synthesis of natural products.

Electrochemical strategies have been a powerful approach for the synthesis of valuable intermediates, in particular heterocyclic motifs. Because of the mild nature, a wide range of nonclassical bond disconnections have been achieved via in situ-generated radical intermediates in a highly efficient manner. In particular, anodic electrochemical oxidative strategies have been utilized for the total synthesis of many structurally intriguing natural products. In this review article, we have discussed a number of total syntheses of structurally intriguing alkaloids and terpenoids in which electrochemical processes play an important role as a key methodology.

Pd(0)-Catalyzed Deacylative Allylations (DaA) Strategy and Application in the Total Synthesis of Alkaloids.

Natural product synthesis has been the prime focus for the development of new carbon-carbon bond forming transformations. In particular, the construction of molecules with all-carbon quaternary centers remain one of the most facinating targets. In this regard, transition-metal catalyzed processes have gained imporatnce owing to their mild nature. Towards this, Pd(0)-catalyzed decarboxylative allylations (DcA) is worth mentioning and has emerged as a convenient method for synthesis of molecules even in their enantioenriched form. However, in order to have a flexible approach that facilitate rapid production of derivatives by utilizing commercially available allyl alcohols, the concept of Pd(0)-catalyzed deacylative allylations (DaA) methodology gains popularity. In these reactions, the transfer of an acyl group has a functional role in activating the allylic alcohol (proelectrophile) toward reaction with Pd(0)-catalysts. We present here an Account on newly conceptualized deacylative allylations (DaA) methodology and its applications in the synthesis of various intermediates and building blocks. Further, its potential in the total synthesis of naturally occurring alkaloids have been summarized in this personal account.

Total synthesis of atropisomeric indolosesquiterpenoids via N-N bond formation: dixiamycins A and B.

N-N dimeric indolosesquiterpene alkaloids constitute a class of under-investigated architecturally intriguing natural products. Herein, we report the first chemical oxidation approach to the asymmetric total syntheses of these atropisomeric indolosesquiterpenoids through N-N bond formation. Specifically, dixiamycins A (1a) and B (1b) were prepared through a Cu(i)-mediated aerobic dehydrogenative dimerization from the naturally occurring monomer xiamycin A methyl ester (2b); this preparation also represents the first total synthesis of dixiamycin A (1a). The monomer xiamycin A methyl ester (2b) was synthesized via a late-stage Buchwald Pd(ii)-mediated aerobic dehydrogenative C-N bond formation.

Total syntheses of naturally occurring antiviral indolosesquiterpene alkaloids, xiamycins C-F via Csp3-H functionalization.

Concise total syntheses of naturally occurring antiviral indolosesquiterpene alkaloids, xiamycin C (2a), D (2b), E (2c) and F (2d), have been achieved via a late-stage oxidative δ-Csp3-H functionalization of an advanced pentacyclic enone intermediate 8. This strategy takes advantage of ipso-nitration of naturally occurring abietane diterpenoids to synthesize o-bromo nitroarene derivative 11. A Suzuki-Miyaura coupling of 11 with phenylboronic acid followed by Cadogan's ring closure provided a modular approach to a carbazole ring required for a functionalized pentacyclic core of indolosesquiterpene alkaloids.