NHC-Catalyzed Atroposelective Acylation of Phenols: Access to Enantiopure NOBIN Analogs by Desymmetrization

Lu, Shenci; Poh, Si Bei; Rong, Zi‐Qiang; Zhao, Yu

doi:10.1021/acs.orglett.9b02425

Cited by 74 publications

(30 citation statements)

References 69 publications

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“…In the con ned arena of axially chiral molecule synthesis, NHC catalysis were previously used by us 52,53 and others 30,[54][55][56][57][58][59][60][61][62][63][64] to mediate cycloaddition 30,52,[54][55][56][57][58] , desymmetrization 53,[59][60][61] or kinetic resolution [62][63][64] to construct molecules bearing the chiral axis between two rigid rings. In our present study, nucleophilic 1,4-addition of sulfur atom of sul nic acid to an NHC-activated ynal set up the chiral axis.…”

Section: Introductionmentioning

confidence: 99%

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

Jia

Maiti

Ren

et al. 2021

Preprint

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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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Section: Introductionmentioning

confidence: 99%

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

Jia

Maiti

Ren

et al. 2021

Preprint

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“…At the onset of these studies the acylative desymmetrization of biaryl phenols using a small molecule catalyst had not been demonstrated . In recent independent publications, Wang and Zhao disclosed the desymmetrization of biaryl amino alcohol derivatives via NHC‐catalyzed acylation . Despite both giving excellent product enantioselectivity, the scope was limited to amino‐alcohol substrates, and the process required high catalyst loadings (10–20 mol % azolium salt precatalysts) and either a co‐oxidant or excess acylating agent (2.5 equiv) for optimal results.…”

Section: Introductionmentioning

confidence: 99%

“…[19] In recent independent publications,W ang and Zhao disclosed the desymmetrization of biaryl amino alcohol derivatives via NHC-catalyzed acylation. [20] Despite both giving excellent product enantioselectivity,t he scope was limited to amino-alcohol substrates,a nd the process required high catalyst loadings (10-20 mol %a zolium salt precatalysts) and either aco-oxidant or excess acylating agent (2.5 equiv) for optimal results.I sothioureas have been extensively exploited as mild, readily available chiral Lewis bases. [21] They are recognized as effective catalysts for the acylative kinetic resolution (KR) of point chiral primary, [22] secondary, [23] and tertiary alcohols, [24] and the acylative desymmetrization of diols.…”

Section: Introductionmentioning

confidence: 99%

Isothiourea‐Catalyzed Atropselective Acylation of Biaryl Phenols via Sequential Desymmetrization/Kinetic Resolution

et al. 2020

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Axially chiral phenols are attractive targets in organic synthesis. This motif is central to many natural products and widely used as precursors to, or directly, as chiral ligands and catalysts. Despite their utility few simple catalytic methods are available for their synthesis in high enantiopurity. Herein the atropselective acylation of a range of symmetric biaryl diols is investigated using isothiourea catalysis. Studies on a model biaryl diol substrate shows that the high product er observed in the process is a result of two successive enantioselective reactions consisting of an initial enantioselective desymmetrization coupled with a second chiroablative kinetic resolution. Extension of this process to a range of substrates, including a challenging tetraorthosubstituted biaryl diol, led to highly enantioenriched products (14 examples, up to 98:2 er), with either HyperBTM or BTM identified as the optimal catalyst depending upon the substitution pattern within the substrate. Computation has been used to understand the factors that lead to high enantiocontrol in this process, with maintenance of planarity to maximize a 1,5‐S⋅⋅⋅O interaction within the key acyl ammonium intermediate identified as the major feature that determines atropselective acylation and thus product enantioselectivity.

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“…They also described the preparation of both enantiomers by the use of different lipases. [11a] Very recently, the N ‐heterocyclic‐carbene‐catalyzed atroposelective acylation of σ‐symmetric 2'‐amino‐1,1'‐biphenyl‐2,6‐diols was reported . However, to the best of our knowledge, the atroposelective desymmetrization of σ‐symmetric biaryl diols 1 by enzymatic esterification has yet to be reported.…”

Section: Introductionmentioning

confidence: 99%

Enantiodivergent Synthesis of Axially Chiral Biphenyls from σ‐Symmetric 1,1'‐Biphenyl‐2,6‐diol Derivatives by Single Lipase‐Catalyzed Acylative and Hydrolytic Desymmetrization

2020

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The enzymatic acylative desymmetrization of σ‐symmetric 2'‐halo‐1,1'‐biphenyl‐2,6‐diols was achieved for the first time using commercially available Burkholderia cepacia lipase immobilized on diatomaceous earth to give (S)‐mono esters. The hydrolytic desymmetrization of the corresponding diacetates was also achieved using the same lipase to give (R)‐mono esters. Our results, therefore, demonstrate that a single lipase can conduct the enantiodivergent synthesis of axially chiral biphenyl compounds in high chemical and optical yields.

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NHC-Catalyzed Atroposelective Acylation of Phenols: Access to Enantiopure NOBIN Analogs by Desymmetrization

Cited by 74 publications

References 69 publications

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

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

Isothiourea‐Catalyzed Atropselective Acylation of Biaryl Phenols via Sequential Desymmetrization/Kinetic Resolution

Enantiodivergent Synthesis of Axially Chiral Biphenyls from σ‐Symmetric 1,1'‐Biphenyl‐2,6‐diol Derivatives by Single Lipase‐Catalyzed Acylative and Hydrolytic Desymmetrization

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