The present review offers an overview of the current approaches for the photochemical and photocatalytic generation of reactive intermediates and their application in the formation of carbon–carbon bonds. Valuable synthetic targets are accessible, including arylation processes, formation of both carbo- and heterocycles, alpha- and beta-functionalization of carbonyls, and addition reactions onto double and triple bonds. According to the recent advancements in the field of visible/solar light catalysis, a significant part of the literature reported herein involves radical ions and radicals as key intermediates, with particular attention to the most recent examples. Synthetic application of carbenes, biradicals/radical pairs and carbocations have been also reported.

Carbon-Carbon Bond Forming Reactions via Photogenerated Intermediates.

In this review, we summarize the origin and advancements of iridium-catalyzed asymmetric allylic substitution reactions during the past two decades. Since the first report in 1997, Ir-catalyzed asymmetric allylic substitution reactions have attracted intense attention due to their exceptionally high regio- and enantioselectivities. Ir-catalyzed asymmetric allylic substitution reactions have been significantly developed in recent years in many respects, including ligand development, mechanistic understanding, substrate scope, and application in the synthesis of complex functional molecules. In this review, an explicit outline of ligands, mechanism, scope of nucleophiles, and applications is presented.

Iridium-Catalyzed Asymmetric Allylic Substitution Reactions

ConspectusMetal catalyzed allylic substitution is a cornerstone of organometallic and synthetic chemistry. Enantioselective versions have been developed with catalysts derived from transition metals, most notably molybdenum, nickel, ruthenium, rhodium, iridium, palladium, and copper. The palladium- and the iridium-catalyzed versions have turned out to be particularly versatile in organic synthesis because of the very broad scope of the nucleophile and great functional group compatibility. Assets of the iridium-catalyzed reaction are the formation of branched, chiral products from simple monosubstituted allylic substrates, high degrees of regio- and enantioselectivity, and use of modular, readily available chiral ligands. The possibility to use carbon, nitrogen, oxygen, and sulfur compounds as well as fluoride as nucleophiles allows a wide range of chiral building blocks to be prepared.Our Account begins with the presentation of fundamental reaction schemes and chiral ligands. We will focus our discussion ...

Applications of Iridium-Catalyzed Asymmetric Allylic Substitution Reactions in Target-Oriented Synthesis

The divergent total syntheses of complex natural products from a common intermediate have attracted enormous attention in the chemical community in the past few years because it can improve the efficiency of chemical synthesis. A number of powerful and unified strategies have been developed by emulating the natural biosynthesis or through innovative transformations. This review focuses on the total synthesis of natural products by applying divergent strategies and the literature covering from 2013 to June 2017. On the basis of where the diversity comes from, the examples are grouped into three parts and discussed in detail. In each group, the examples that synthesize natural products belonging to the same subfamily are put together to contrast with one another.

Divergent Strategy in Natural Product Total Synthesis.

ConspectusThe catalytic, asymmetric synthesis of complex molecules has been a core focus of our research program for some time because developments in the area can have an immediate impact on the i...

Iridium-Catalyzed Asymmetric Synthesis of Functionally Rich Molecules Enabled by (Phosphoramidite,Olefin) Ligands.

The pyrroloindoline alkaloids attract wide interest from the fields of chemistry, biosynthesis, and biology. From a structural perspective, they can be divided into several classes that vary in the substituent on C3a of the pyrroloindoline core, including heteroatoms, arenes, aliphatic groups, and another pyrroloindoline motif. Accordingly, a series of strategies have been developed for the synthesis of the above pyrroloindoline classes. Notably, a structurally complex aliphatic side chain linked to the C3a position is rather rare. The drimentine alkaloids (1–4, Scheme 1), which exhibit anticancer, antibacterial, antifungal, and anthelmintic properties, possess the latter substitution mode. A stereocontrolled method to form the C10b–C12 bond of the drimentine scaffold is highly desired for the synthesis of these compounds. Indotertine A (5, Scheme 1) with an unprecedented, but biosynthetically relevant, skeleton was recently discovered. The biosynthetic relationship between 3 and 5 is postulated in Scheme 1. Acidic activation of the germinal diamine moiety of 3 may generate an iminium species 6, which could undergo an iminium–olefin cyclization followed by a proton elimination of the cationic intermediate 7. Herein, we report the first total synthesis of drimentines A, G, and F (1–3), exploiting a photocatalyzed radical conjugate addition to address the problem of the C10b–C12 bond formation; a synthesis of indotertine A (5), guided by the above biosynthetic hypothesis, is also described. We first undertook a retrosynthetic analysis of drimentine G (Scheme 2). Disassembly of the diketopiperazine motif at the amide bonds followed by cleavage of the exocyclic C=C bond simplifies this molecule to core structure 8. Disconnection of the C10b–C12 bond leads to a pair of precursors (9 and 10) for an intermolecular radical conjugate addition. The former is readily available from bis(Boc-l-tryptophan) methyl ester (Boc= tert-butoxycarbonyl), whereas the latter could be derived from commercially available (+)-sclareolide (11). Scheme 1. Representative drimentine alkaloids and the postulated biosynthetic relationship between drimentine F and indotertine A.

Total Synthesis of Indotertine A and Drimentines A, F, and G

The first total syntheses of taiwaniadducts B, C, and D have been accomplished. Two diterpenoid segments were prepared with high enantiopurity, both through Ir-catalyzed asymmetric polyene cyclization. A sterically demanding intermolecular Diels–Alder reaction promoted by Er(fod)3 assembled the scaffold of taiwaniadducts B and C. A carbonyl-ene cyclization forged the cage motif of taiwaniadduct D at a late stage, providing over 200 mg of this compound.

Total Synthesis of Taiwaniadducts B, C, and D

The first and asymmetric total synthesis of longeracinphyllin A, a hexacyclic Daphniphyllum alkaloid, has been accomplished. A tetracyclic intermediate was prepared through silver-catalyzed alkyne cyclization and Luche radical cyclization. A phosphine-promoted [3 + 2] cycloaddition reaction was exploited to construct the sterically congested E ring bearing vicinal tertiary and quaternary centers. The cyclopentenone motif was assembled by using intramolecular Horner–Wadsworth–Emmons olefination. Raney Ni reduction delivered the tertiary amine from a thioamide precursor at a late stage.

Total Synthesis of Longeracinphyllin A

We report the total syntheses of daphenylline (1), daphnipaxianine A (5), and himalenine D (6), three Daphniphyllum alkaloids from the calyciphylline A subfamily. A pentacyclic triketone was prepared by using atom-transfer radical cyclization and the Lu [3+2] cycloaddition as key steps. Inspired by the proposed biosynthetic relationship between 1 and another calyciphylline A type alkaloid, we developed a ring-expansion/aromatization/aldol cascade to construct the tetrasubstituted benzene moiety of 1. The versatile triketone intermediate was also elaborated into 5 and 6 through a C=C bond migration/aldol cyclization approach.

Total Syntheses of Daphenylline, Daphnipaxianine A, and Himalenine D

Hybridaphniphylline B (1) is a Daphniphyllum alkaloid possessing 11 rings and 19 stereocenters. Here we report the first total synthesis of 1 featuring a late-stage intermolecular Diels–Alder reaction of a fully elaborated cyclopentadiene and asperuloside tetraacetate. The diene was prepared on the basis of a scalable route to daphnilongeranin B (4). Claisen rearrangement of an allyl dienol ether was exploited as a key step; the subtle variation of the substrate and use of protic solvents suppressed the undesired Cope rearrangement. Daphniyunnine E (6) and dehydrodaphnilongeranin B (7), two congeners of 4, were also synthesized. The dienophile arose from (+)-genipin through glycosylation and lactonization. A one-pot protocol was developed for the diene formation and Diels–Alder reaction; one of the cycloadducts was converted into 1 through reductive desulfurization and global deacetylation.

Wenhao Zhang

Papers

Total Synthesis of Indotertine A and Drimentines A, F, and G

Total Synthesis of Taiwaniadducts B, C, and D

Total Synthesis of Longeracinphyllin A

Total Syntheses of Daphenylline, Daphnipaxianine A, and Himalenine D

Total Synthesis of Hybridaphniphylline B