Enantioselective N‐Heterocyclic Carbene Catalyzed Bis(enoate) Rauhut–Currier Reaction

Bae, Song Mi; Zhang, Changhe; Gillard, Rachel M.; Lupton, David W.

doi:10.1002/ange.201907111

Cited by 5 publications

(5 citation statements)

References 91 publications

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“…Notably, the use of 2‐methyl indole and N ‐methyl indole significantly reduced the enantioselectivity (entries 3 y and 3 z ) and Boc‐protected indole failed to give the desired product 3 aa due to a lack of nucleophilicity at the C‐3 position. It is very important to mention that the substrate's E/Z ‐ratio does not affect the enantioselectivity and yield of annulation reaction due to therapid isomerization of iminium intermediate [14] . The relative stereochemistry ( 1,2‐cis, 2,3‐cis, 3,4‐trans ) and absolute configuration (1 R,2R,3S,4R ) of the bicyclic enone 3 r were unambiguously established through single‐crystal X‐ray analysis, and all products were assumed by analogy (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Enantioselective Desymmetrization Triggered by Iminium‐Enamine Activation: Access to Complex Cyclohepta[b]indoles

Magham

Thopate

Samad

et al. 2023

Chemistry A European J

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The expeditious construction of complex molecules having multiple stereocentres is highly desirable in organic chemistry. In the present communication, we report the development of an organocatalytic asymmetric desymmetrization of prochiral enal-tethered cyclohexadienones via the C3-selective FriedelÀ Crafts alkylation of indoles triggered by LUMO-lowering iminium activation/HOMO-raising enamine activation. The reaction provides access to bicyclic enones, which further undergo acid-mediated intramolecular annulation from C2-position to afford highly strained cyclohepta [b]indoles with five contiguous stereocentres and three new CÀ C bonds in excellent enantioselectivity and diastereoselectivity.

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Section: Resultsmentioning

confidence: 99%

Enantioselective Desymmetrization Triggered by Iminium‐Enamine Activation: Access to Complex Cyclohepta[b]indoles

Magham

Thopate

Samad

et al. 2023

Chemistry A European J

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“…Thus, we felt that chiral NHCs had potential with substrates traditionally unviable with phosphine catalysis, leading us to examine the cycloisomerization of bis -cinnamate 34 which can be prepared in three steps. As suspected, this substrate required one of the most nucleophilic triazolium-derived NHCs, which allowed the reaction to proceed smoothly, giving lactone 35 in 87% yield and 93:7 er (Figure C) . A similar approach was examined with the amide version of this substrate (i.e., 36 ).…”

Section: Polarity Inversion Using N-heterocyclic Carbenesmentioning

confidence: 99%

Enantioselective Catalysis by the Umpolung of Conjugate Acceptors Involving N-Heterocyclic Carbene or Organophosphine 1,4-Addition

2023

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Conspectus Conjugate acceptors are one of the most common electrophilic functional groups in organic synthesis. While useful in a diverse range of transformations, their applications are largely dominated by the reactions from which their name is derived (i.e., as an acceptor of nucleophiles in the conjugate position). In 2014, we commenced studies focused on their ability to undergo polarity inversion through the conjugate addition of Lewis base catalysts. The first step in this process provides an enolate, from which the well-developed Rauhut–Currier (RC) and Morita–Baylis–Hillman (MBH) reactions can occur; however, tautomerization to provide a species in which the β-carbon of the conjugate acceptor can now act as a donor is also possible. When we commenced studies on this topic, reaction designs with this type of species, particularly when accessed using N-heterocyclic carbenes (NHCs), had been reported on only a handful of occasions. Despite a lack of development, conceptually it was felt that reactions taking advantage of polarity switching by Lewis base conjugate addition have a number of desirable features. Perhaps the most significant is the potential to reimagine a ubiquitous functional group as an entirely new synthon, namely, a donor to electrophiles from the conjugate position. Our work has focused on catalysis with both simple conjugate acceptors and also those embedded within more complicated substrates; the latter has allowed a series of cycloisomerizations and annulation reactions to be achieved. In most cases, the reactions have been possible using enantioenriched chiral NHCs or organophosphines as the Lewis base catalysts thereby delivering enantioselective approaches to novel cyclic molecules. While related chemistry can be accessed with either family of catalyst, in all cases reactions have been designed to take advantage of one or the other. In addition, a fine balance exists between reactions that exploit the initially formed enolate and those that involve the polarity-inverted β-anion. In our studies, this balance is addressed through substrate design, although catalyst control may also be possible. We consider the chemistry discussed in this Account to be in its infancy. Significant challenges remain to be addressed before our broad aim of discovering a universal approach to the polarity inversion of all conjugate acceptors can be achieved. These challenges broadly relate to chemoselectivity with substrates bearing multiple electrophilic functionalities, reliance upon the use of conjugate acceptors, and catalyst efficiency. To address these challenges, advances in catalyst design and catalyst cooperativity are likely required.

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“…In 2019, Lupton and co-workers exploited the high nucleophilicity of N -heterocyclic carbenes to achieve intramolecular RC reaction of bis(enoate) substrates ( Scheme 27 ) [ 189 ]. The addition of NHC resulted in the formation of an enolate, which then cyclized to form the lactone, with a new C–C bond between the α-position of one activated alkene and the β-position of the second alkene.…”

Section: Rauhut–currier Reactionmentioning

confidence: 99%

Organocatalytic Name Reactions Enabled by NHCs

et al. 2020

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Giving reactions the names of their discoverers is an extraordinary tradition of organic chemistry. Nowadays, this phenomenon is much rarer, although already named historical reactions are still often developed. This is also true in the case of a broad branch of N‑heterocyclic carbenes catalysis. NHCs allow many unique synthetic paths, including commonly known name reactions. This article aims to gather this extensive knowledge and compare historical reactions with current developed processes. Furthermore, this review is a great opportunity to highlight some of the unique applications of these procedures in the total synthesis of biologically active compounds. Hence, this concise article may also be a source of knowledge for scientists just starting their adventure with N‑heterocyclic carbene chemistry.

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Enantioselective N‐Heterocyclic Carbene Catalyzed Bis(enoate) Rauhut–Currier Reaction

Cited by 5 publications

References 91 publications

Enantioselective Desymmetrization Triggered by Iminium‐Enamine Activation: Access to Complex Cyclohepta[b]indoles

Enantioselective Desymmetrization Triggered by Iminium‐Enamine Activation: Access to Complex Cyclohepta[b]indoles

Enantioselective Catalysis by the Umpolung of Conjugate Acceptors Involving N-Heterocyclic Carbene or Organophosphine 1,4-Addition

Organocatalytic Name Reactions Enabled by NHCs

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