Palladium-catalyzed C—H activation/C—O bond-forming reactions have emerged as attractive tools for organic synthesis. Typically, these reactions require strong chemical oxidants, which convert organopalladium(II) intermediates into the PdIII or PdIV oxidation state to promote otherwise challenging C—O reductive elimination. However, previously reported oxidants possess significant disadvantages, including poor atom economy, high cost, and the formation of undesired byproducts. To overcome these issues, we report an electrochemical strategy that takes advantage of anodic oxidation of PdII to induce selective C—O reductive elimination with a variety of oxyanion coupling partners.

Palladium-Catalyzed C(sp3)-H Oxygenation via Electrochemical Oxidation.

A novel synthesis of azepinone derivatives by using a Rh-catalyzed intramolecular annulation reaction of N-substituted benzamides and α,β-unsaturated aldehydes and ketones is developed.

Mild rhodium(III)-catalyzed cyclization of amides with α,β-unsaturated aldehydes and ketones to azepinones: application to the synthesis of the homoprotoberberine framework.

https://pubs.rsc.org/en/Content/ArticlePDF/2016/NP/C5NP00096C

Synthetic approaches towards alkaloids bearing α-tertiary amines

The main objective of this review is to provide a comprehensive survey of methods used for stereoselective construction of carbon–nitrogen bonds during the total synthesis of nitrogen-containing natural products that have appeared in the literature since 2000. The material is organized by specific reaction in order of decreasing number of applications in natural product synthesis. About 800 total syntheses of natural products with stereogenic carbon–nitrogen bonds described since 2000 have been reviewed.

Cutting-Edge and Time-Honored Strategies for Stereoselective Construction of C-N Bonds in Total Synthesis.

Strain-promoted "click" chemistry is used to post-synthetically modify the pore walls of azide-functionalized mesoporous bio-MOF-100 (N(3)-bio-MOF-100). The reactions proceed in high yield and produce no byproduct. This new method was used to introduce various functional groups into the MOF mesopores, including succinimidyl ester bioconjugation moieties that allow for straightforward coupling of biomolecules to the pore walls.

Strain-promoted "click" modification of a mesoporous metal-organic framework.

Challenging: (+)-gelsemine was synthesized from (R,R)-aziridine 1 in 25 steps with approximately 1 % overall yield. A multistep, one-pot enol-oxonium cyclization cascade was used to construct, simultaneously, the E ring, F ring, C3 stereocenter, and C7 quaternary stereocenter. This synthesis using the enol-oxonium cyclization reaction as a key step to make the cage structure has demonstrated the proposed biosynthetic pathway of the gelsemine family.

Biomimetic total synthesis of (+)-gelsemine.

A systematic investigation of the reductive ring-expansion reaction of cyclic ketoximes fused to aromatic rings with diisobutylaluminum hydride (DIBALH) is described. This reaction regioselectively afforded a variety of five- to eight-membered bicyclic heterocycles or tricyclic heterocycles containing nitrogen neighboring an aromatic ring, including indoline, 1,2,3,4,5,6-hexahydrobenz[b]azocine, 3,4-dihydro-2H-benzo[b][1,4]oxazine, 2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine, 1,2,3,4,5,6-hexahydroazepino[3,2-b]indole, 2,3,4,5-tetrahydro-1H-benzothieno[2,3-b]azepine, 2,3,4,5-tetrahydro-1H-benzothieno[3,2-b]azepine, 5,6-dihydrophenanthridine, and 5,6,11,12-tetrahydrodibenz[b, f]azocine. The reaction mechanism leading to the rearrangement was investigated on the basis of the restricted Becke three-parameter plus Lee−Yang−Parr (B3LYP) density functional theory (DFT) with the 6-31G (d) basis set. It was found that the reaction proceeds through a three-centered transition state via a stepwise mechanism because th...

Regioselective synthesis of heterocycles containing nitrogen neighboring an aromatic ring by reductive ring expansion using diisobutylaluminum hydride and studies on the reaction mechanism

Concise total synthesis of (-)-mersicarpine.

A racemic synthesis of mersicarpine (1) was achieved by the Mizoroki–Heck reaction and a DIBALH-mediated reductive ring-expansion reaction. Based on a first-generation synthesis, a second-generation enantiocontrolled total synthesis of (−)-mersicarpine (1) was achieved by an 8-pot/11-step sequence in 21 % overall yield from commercially available 2-ethylcyclohexanone. Subjection of a ketoester, which was prepared by an asymmetric Michael addition (according to the protocol by d’Angelo and Desmaele), and phenylhydrazine to modified Fischer indole conditions provided a six-membered tricyclic indole. Benzylic oxidation and subsequent oxime formation provided a ketoxime, which was treated with diisobutylaluminum hydride (DIBALH) to construct the characteristic azepinoindole skeleton in good yield. In the DIBALH-mediated reductive ring-expansion reaction, gradually increasing the reaction temperature and in situ-protection of the nitrogen in an oxygen-sensitive azepinoindole with a benzyloxycarbonyl (Cbz) group were crucial for the high-yielding process. With these methodologies, the short-step and efficient synthesis of (−)-mersicarpine was accomplished. Several synthetic efforts are also described.

Enantiocontrolled Total Synthesis of (−)‐Mersicarpine

A systematic investigation of reductive ring expansion reaction of oximes with diisobutylaluminum hydride (DIBAH) was performed. The reaction regiospecifically provided a variety of unsubstituted bicyclic heterocycles 3a-3g or tricyclic heterocycles 3h, 3j-31 that contained nitrogen attached to an aromatic ring.

Regiospecific synthesis of unsubstituted basic skeletons of heterocycles containing nitrogen neighboring an aromatic ring by the reductive ring expansion reaction using diisobutylaluminum hydride

Yusuke Iwama

Papers

Biomimetic total synthesis of (+)-gelsemine.

Regioselective synthesis of heterocycles containing nitrogen neighboring an aromatic ring by reductive ring expansion using diisobutylaluminum hydride and studies on the reaction mechanism

Concise total synthesis of (-)-mersicarpine.

Enantiocontrolled Total Synthesis of (−)‐Mersicarpine

Regiospecific synthesis of unsubstituted basic skeletons of heterocycles containing nitrogen neighboring an aromatic ring by the reductive ring expansion reaction using diisobutylaluminum hydride