Carbene-catalyzed atroposelective synthesis of axially chiral styrenes

AbstractAxially chiral styrenes bearing a chiral axis between a sterically non-congested acyclic alkene and an aryl ring are difficult to prepare due to low rotational barrier of the axis. Disclosed here is an N-heterocyclic carbene (NHC) catalytic asymmetric solution to this problem. Our reaction involves ynals, sulfinic acids, and phenols as the substrates with an NHC as the catalyst. Key steps involve selective 1,4-addition of sulfinic anion to acetylenic acylazolium intermediate and sequential E-selective protonation to set up the chiral axis. Our reaction affords axially chiral styrenes bearing a chiral axis as the product with up to > 99:1 e.r., > 20:1 E/Z selectivity, and excellent yields. The sulfone and carboxylic ester moieties in our styrene products are common moieties in bioactive molecules and asymmetric catalysis.

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Carbene-Catalyzed Atroposelective Synthesis of Axially Chiral Styrenes Bearing Acyclic Alkenes

10.21203/rs.3.rs-739850/v1 ◽

2021 ◽

Author(s):

Jia-Lei Yan ◽

Rakesh Maiti ◽

Shi-Chao Ren ◽

Weiyi Tian ◽

Tingting Li ◽

...

Keyword(s):

Asymmetric Catalysis ◽

Rotational Barrier ◽

Bioactive Molecules ◽

Carboxylic Ester ◽

Aryl Ring ◽

Axially Chiral ◽

Sulfinic Acids ◽

Set Up ◽

Key Steps ◽

Asymmetric Solution

Abstract Axially chiral styrenes bearing a chiral axis between a sterically non-congested acyclic alkene and an aryl ring are difficult to prepare due to low rotational barrier of the axis. Disclosed here is an N-heterocyclic carbene (NHC) catalytic asymmetric solution to this problem. Our reaction involves ynals, sulfinic acids, and phenols as the substrates with an NHC as the catalyst. Key steps involve selective 1,4-addition of sulfinic anion to acetylenic acylazolium intermediate and sequential E-selective protonation to set up the chiral axis. Our reaction affords axially chiral styrenes bearing a chiral axis as the product with up to >99:1 e.r., >20:1 E/Z selectivity, and excellent yields. The sulfone and carboxylic ester moieties in our styrene products are common moieties in bioactive molecules and asymmetric catalysis.

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Photocatalytic three-component asymmetric sulfonylation via direct C(sp3)-H functionalization

Nature Communications ◽

10.1038/s41467-021-22690-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Shi Cao ◽

Wei Hong ◽

Ziqi Ye ◽

Lei Gong

Keyword(s):

Asymmetric Catalysis ◽

Organic Synthesis ◽

Photochemical Reaction ◽

Low Cost ◽

Bioactive Molecules ◽

Atom Economy ◽

Mild Conditions ◽

Wide Range ◽

Unsaturated Carbonyl Compound ◽

Direct Functionalization

AbstractThe direct and selective C(sp3)-H functionalization of cycloalkanes and alkanes is a highly useful process in organic synthesis owing to the low-cost starting materials, the high step and atom economy. Its application to asymmetric catalysis, however, has been scarcely explored. Herein, we disclose our effort toward this goal by incorporation of dual asymmetric photocatalysis by a chiral nickel catalyst and a commercially available organophotocatalyst with a radical relay strategy through sulfur dioxide insertion. Such design leads to the development of three-component asymmetric sulfonylation involving direct functionalization of cycloalkanes, alkanes, toluene derivatives or ethers. The photochemical reaction of a C(sp3)-H precursor, a SO2 surrogate and a common α,β-unsaturated carbonyl compound proceeds smoothly under mild conditions, delivering a wide range of biologically interesting α-C chiral sulfones with high regio- and enantioselectivity (>50 examples, up to >50:1 rr and 95% ee). This method is applicable to late-stage functionalization of bioactive molecules, and provides an appealing access to enantioenriched compounds starting from the abundant hydrocarbon compounds.

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Facile axial chirality control by using a precursor with central chirality. Application to the preparation of new axially chiral diphosphine complexes for asymmetric catalysis

Chemical Communications ◽

10.1039/b207399d ◽

2002 ◽

pp. 2546-2547 ◽

Cited By ~ 36

Author(s):

Matthias Lotz ◽

Gernot Kramer ◽

Paul Knochel

Keyword(s):

Asymmetric Catalysis ◽

Axial Chirality ◽

Axially Chiral ◽

Chirality Control

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Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.17.185 ◽

2021 ◽

Vol 17 ◽

pp. 2729-2764

Author(s):

Alemayehu Gashaw Woldegiorgis ◽

Xufeng Lin

Keyword(s):

Phosphoric Acid ◽

Asymmetric Catalysis ◽

Medicinal Chemistry ◽

High Efficiency ◽

Biologically Active ◽

Chiral Compounds ◽

Chiral Phosphoric Acid ◽

Wide Range ◽

Axially Chiral ◽

Acid Catalyzed

In recent years, the synthesis of axially chiral compounds has received considerable attention due to their extensive application as biologically active compounds in medicinal chemistry and as chiral ligands in asymmetric catalysis. Chiral phosphoric acids are recognized as efficient organocatalysts for a variety of enantioselective transformations. In this review, we summarize the recent development of chiral phosphoric acid-catalyzed synthesis of a wide range of axially chiral biaryls, heterobiaryls, vinylarenes, N-arylamines, spiranes, and allenes with high efficiency and excellent stereoselectivity.

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Straightforward synthesis of chiral non-racemic α-boryl isocyanides

Organic & Biomolecular Chemistry ◽

10.1039/d1ob00616a ◽

2021 ◽

Author(s):

Francesco Fini ◽

Alessandro Zanni ◽

Maria Luisa Introvigne ◽

Mattia Stucchi ◽

Emilia Caselli ◽

...

Keyword(s):

Multicomponent Reaction ◽

Bioactive Molecules ◽

Synthetic Sequence ◽

Key Steps

A straightforward concise synthesis of chiral non-racemic aliphatic α-boryl isocyanides, relay intermediates for boron-based bioactive molecules by using multicomponent reaction, is presented. The short synthetic sequence comprises as key steps...

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Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.16.68 ◽

2020 ◽

Vol 16 ◽

pp. 738-755

Author(s):

Valerian Dragutan ◽

Ileana Dragutan ◽

Albert Demonceau ◽

Lionel Delaude

Keyword(s):

Therapeutic Agents ◽

Ruthenium Catalysts ◽

Diels Alder ◽

Bioactive Molecules ◽

Enyne Metathesis ◽

Organic Transformations ◽

Chemically Modified ◽

Key Steps ◽

Powerful Strategy

This account surveys the current progress on the application of intra- and intermolecular enyne metathesis as main key steps in the synthesis of challenging structural motifs and stereochemistries found in bioactive compounds. Special emphasis is placed on ruthenium catalysts as promoters of enyne metathesis to build the desired 1,3-dienic units. The advantageous association of this approach with name reactions like Grignard, Wittig, Diels–Alder, Suzuki–Miyaura, Heck cross-coupling, etc. is illustrated. Examples unveil the generality of such tandem reactions in providing not only the intricate structures of known, in vivo effective substances but also for designing chemically modified analogs as valid alternatives for further therapeutic agents.

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