Iridium‐Catalyzed Enantioselective Indole Cyclization: Application to the Total Synthesis and Absolute Stereochemical Assignment of (−)‐Aspidophylline A

Jiang, Shizhi; Zeng, Xiangbo; Xiao, Liang; Lei, Ting; Yang, Yu‐Rong

doi:10.1002/ange.201511549

Cited by 54 publications

(5 citation statements)

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“…In 2016, Yang and co-workers realized this concept by application of the Carreira Ir catalyst system. 405 After identification of a suitable Lewis acid promoter, reactions proceeded in good yields and with high enantioselectivity, albeit with moderate diastereoselectivity.…”

Section: Applications Of Ir-catalyzed Asymmetric Allylic Substitution...mentioning

confidence: 99%

Iridium-Catalyzed Asymmetric Allylic Substitution Reactions

et al. 2018

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In this review, we summarize the origin and advancements of iridiumcatalyzed 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. Ircatalyzed 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.

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Section: Applications Of Ir-catalyzed Asymmetric Allylic Substitution...mentioning

confidence: 99%

Iridium-Catalyzed Asymmetric Allylic Substitution Reactions

et al. 2018

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“…Based on a dearomatization reaction, Yang et al accomplished the first enantioselective total synthesis of the alkaloid (−)-aspidophylline A (Scheme 32). 51 An enantioselective type II allylic alkylation of an indole followed by an in situ nucleophilic addition at the resultant iminium ion gave a 5:1 mixture of inseparable diastereomers. Following an oxidative degradation, a diastereomerically pure ketone was obtained, which was an excellent starting material for eight further steps to the target.…”

Section: Accounts Of Chemical Researchmentioning

confidence: 99%

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

Helmchen

2017

Acc. Chem. Res.

271

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Metal 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 on reactions promoted by phosphoramidite ligands, though numerous chiral ligands have been employed. The subsequent section presents a brief overview of reaction mechanism and experimental conditions. Two versions of the iridium-catalyzed allylic substitution have emerged. In type 1 reactions (introduced in 1997), linear allylic esters are commonly used as substrates under basic reaction conditions. In type 2 reactions (introduced in 2007), environmentally friendly branched allylic alcohols can be reacted under acidic conditions; occasionally, derivatives of allylic alcohols have also been applied. A unique feature of the type 2 reactions is that highly electrophilic allylic intermediates can be brought to reaction with weakly activated alkenes. The subsequent text is ordered according to the strategies followed to transform allylic substitution products to desired targets, most of which are natural products or drugs. Syntheses starting with an intermolecular allylic substitution are discussed first. Some fairly complex targets, for example, the potent nitric oxide inhibitor (-)-nyasol and the drug (-)-protrifenbute, have been synthesized via less than five steps from simple starting materials. Most targets discussed are cyclic compounds. Intermolecular allylic substitution with subsequent ring closing metathesis is a powerful strategy for their synthesis. Highlights are stereodivergent syntheses of Δ-tetrahydrocannabinols (THC), wherein iridium- and organocatalysis are combined (dual catalysis). The combination of allylic alkylation with a Diels-Alder reaction was utilized to synthesize the ketide apiosporic acid and the drug fesoterodine (Toviaz). Sequential allylic amination, hydroboration and Suzuki-Miyaura coupling generates enones suitable for conjugate addition reactions; this strategy was employed in syntheses of a variety of alkaloids, for example, the poison frog alkaloid (+)-cis-195A (pumiliotoxin C). Intramolecular substitutions offer interesting possibilities to build up stereochemical complexity via short sy...

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“…This precedent set the stage for application of dearomative methods for future syntheses of akuammiline natural products. Mac-Millan 345 and Yang 346 developed unique approaches employing catalytic enantioselective methods for dearomatization of the indole moiety based on sequential Diels-Alder cycloaddition/ amination (352 / 353) and Ir-catalyzed allylic substitution reaction (355 / 356), respectively. Both syntheses are discussed in greater details in a previous review.…”

Section: Reviewmentioning

confidence: 99%