The Photo‐Nazarov Reaction: Scope and Application

The reaction conditions and scope of the photo‐Nazarov reaction of aryl vinyl ketones were investigated. In contrast to the conventional acid‐catalyzed methods, this photolytic electrocyclization proceeds in the neutral or basic conditions. Irradiating substrates bearing various aromatic rings, acid‐sensitive groups, cyclohexenyl, cycloheptenyl, and unsaturated pyran with UV‐light (254 nm) smoothly yielded hexahydrofluorenones and related structures. This photo‐Nazarov reaction could also be applicable to the substrates carrying β‐alkyl groups on the enone, which gave corresponding polycyclic rings containing quaternary centers. These photo‐electrocyclized products may prove useful for synthesizing a variety of natural products and their derivatives. Further application of this mild photo‐Nazarov reaction in the synthesis of taiwaniaquinol B was achieved.     

Enantioselective radical cyclizations: a new approach to stereocontrol of cascade reactions

Stereocontrol in a cascade radical addition-cyclization-trapping reaction was achieved by a new approach, which utilizes a hydroxamate ester moiety as a coordinating chiral Lewis acid tether between two radical acceptors. A remarkable feature of this reaction is the construction of three bonds and tertiary and quaternary stereogenic centers through both inter- and intramolecular carbon-carbon bond-forming processes. The chiral Lewis acid mediated reaction of oxime ethers also proceeded smoothly with good enantio- and diastereoselectivities, indicating the usefulness of the cascade approach for the asymmetric synthesis of various gamma-lactams.     

Synthesis of the Bicyclic Lactone Core of Leonuketal,Enabled by a Telescoped Diels–Alder Reaction Sequence

The Diels–Alder cycloaddition reaction has become established as a fundamental approach for the preparation of complex natural products; however, successful application of the intermolecular Diels–Alder cycloaddition reaction to the synthesis of particularly congested scaffolds remains surprisingly problematic. Inspired by the terpenoid spiroketal natural product leonuketal, a challenging telescoped reaction sequence has been realized to access the core [2.2.2]‐bicyclic lactone ring system and its [3.2.1] isomer. Our four‐step, protecting‐group‐free process required detailed investigation to circumvent the problems of adduct fragmentation and intermediate instability. Successful solution of these practical issues, along with unambiguous structural determination of the target structures, provide useful insights that will facilitate future applications of the Diels–Alder cycloaddition reaction to challenging, highly congested molecular scaffolds and ongoing synthetic efforts towards this natural product.     

Cycle‐Specific Organocascade Catalysis: Application to Olefin Hydroamination,Hydro‐oxidation,and Amino‐oxidation,and to Natural Product Synthesis

United in effort : The combined application of iminium (Im) and enamine (En) catalysts can effect a range of valuable asymmetric transformations including 1,2‐hydroamination, ‐hydro‐oxidation, and ‐amino‐oxidation of olefins (see picture). An enantioselective organocascade catalysis was also applied in the synthesis of a complex natural product.

     

Combining the Power of TiIII‐Mediated Processes for Easy Access to Hydroxylated Polycyclic Terpenoids: Synthesis of Sesterstatin 1 and C–D Rings of Aspergilloxide

A straightforward access to polyhydroxylated terpenoids based on two key titanocene(III)‐mediated reactions is presented: the “head‐to‐tail” Barbier‐type addition of prenyl chlorides to α,β‐unsaturated aldehydes, which allows the introduction of hydroxy groups at desirable positions of the acyclic precursor, and the subsequent bioinspired radical cyclisation. This methodology has been also used in the first total synthesis of pentacyclic sesterstatin 1 and a model compound of the C–D rings of aspergilloxide.     

Unified syntheses of cavicularin and riccardin C: addressing the synthesis of an arene adopting a boat configuration

Concise syntheses of the natural products cavicularin (ten steps) and riccardin C (seven steps) are reported. Key features of the new synthetic route are a convergent strategy to assemble acyclic precursors and a sequence of regioselective reduction and halogenation steps to facilitate Wittig macrocyclisation and transannular ring contraction reactions.     

Strychnine as Target,Samarium Diiodide as Tool: A Personal Story

Strychnine stands out from the group of classical natural products as one of the first complex compounds to be isolated in pure form and an extreme challenge to be structurally characterized. It has played a central role in natural product total syntheses and the surge in the development of innovative synthetic methods for many decades. Recently, we have accomplished one of the shortest formal total syntheses of strychnine (in ten steps and 14% overall yield or even shorter in eight steps and 10% overall yield). The evolution of a productive synthetic strategy, as well as the synthetic challenges tackled, are described here in detail, including examples of related transformations. The successful synthetic strategy was inspired by the premise that the core structure could be derived from simple aromatic indole precursors by a reductive SmI₂‐induced ketyl–aryl coupling. Other key reactions included a diastereoselective reduction and a regioselective elimination protocol. Altogether one of the shortest syntheses of iso‐strychnine and hence of strychnine was established.     

Total Synthesis of Hopeahainol A and Hopeanol

Similar, but different : Possessing almost the same but not identical structures, the recently discovered natural products hopeahainol A ( 1 ) and hopeanol ( 2 ) exhibit important but differing biological properties (see structures). Their first total synthesis has now been achieved through a series of novel cascade reactions and skeletal rearrangements.