Asymmetric allylic substitution–isomerization to axially chiral enamides <i>via</i> hydrogen-bonding assisted central-to-axial chirality transfer

Sun, Chao; Qi, Xiaotian; Min, Xiao-Long; Bai, Xue-Dan; Liu, Peng; He, Ying

doi:10.1039/d0sc02828b

Cited by 69 publications

(34 citation statements)

References 54 publications

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“…除了以上三种策略以外, 过渡金属催化串联不对称烯丙基取代与烯烃异构化策略最近也被报道. 2020 年何英课题组 [11] 利用金属铱催化不对称烯丙基取代和 [1,3]-H 迁移串联反应, 高效地实现了中心手性向轴手性的转移(图 2b). 该工作初步揭示了金属铱催化的烯丙基取代反应在轴手性化合物的构建方面的潜在应用价值.…”

Section: 引言unclassified

Ir-catalyzed Sequential Asymmetric Allylic Substitution/Olefin Isomerization for the Synthesis of Axially Chiral Compounds

Zhao¹,

Jiang²,

You³

2021

Acta Chimica Sinica

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Axially chiral compounds represent an important class of chiral molecules. In this regard, many methods have been developed to access these compounds. However, efficient methods for the synthesis of axially chiral styrenes are limited to date, mainly due to their relative instability compared to axially chiral biaryl compounds. Iridium-catalyzed asymmetric allylic substitutions have evolved as a powerful tool in constructing C-C or C-X bonds at the allylic position. We developed an efficient sequential strategy to access a series of axially chiral styrenes by iridium-catalyzed allylic substitution and central-to-axial chirality transfer via olefin isomerization. With the iridium complex derived from [Ir(cod)Cl]2 and Alexakis ligand L1 as catalyst, and β-naphthol as nucleophiles, a broad range of axially chiral styrenes were obtained with moderate to excellent yields (28%～97% yields) and enantioselectivity (59%～98% ee). A general procedure for the asymmetric allylation of β-naphthol is described as the following: A flame-dried Schlenk tube was cooled to room temperature and filled with argon. To this flask were added [Ir(cod)Cl]2 (2.6 mg, 0.004 mmol, 2 mol%), (S,S,Sa)-L1 (4.8 mg, 0.008 mmol, 4 mol%), freshly distilled tetrahydrofuran (THF, 0.5 mL) and propylamine (0.5 mL). The mixture was stirred at 50 ℃ for 30 min and then the low-boiling solvents were removed in vacuo to give a pale yellow solid. The solid was stirred at 50 ℃ again under vacuum until it became a powder. After that, β-naphthol 1 (0.22 mmol, 1.1 equiv.), allyl carbonate 2 (0.2 mmol, 1.0 equiv.), 1,4-diazobicyclo(2.2.2)octane (DABCO) (67.3 mg, 0.6 mmol, 3.0 equiv.) and freshly distilled Et2O (2.0 mL) were added to this flask under argon atmosphere. The reaction mixture was stirred at 20 ℃ until the starting material was consumed (monitored by thin layer chromatography, TLC). The crude reaction mixture was diluted with water (5 mL), and extracted with dichloromethane (DCM, 5 mL×3). The organic layers were collected, dried over Na2SO4 and then concentrated in vacuo to afford the crude product. The residue was purified by preparative TLC to afford the product.

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Section: 引言unclassified

Ir-catalyzed Sequential Asymmetric Allylic Substitution/Olefin Isomerization for the Synthesis of Axially Chiral Compounds

Zhao¹,

Jiang²,

You³

2021

Acta Chimica Sinica

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“…It is only in recent years that several approaches emerged for asymmetric access to axially chiral aryl-acyclic alkene scaffolds. These remarkable studies include chiral amines catalyzed addition of carbon anions to ynals 33 , Brønsted acids catalyzed addition of nucleophiles (e.g., sulfinic anions, 5H-oxazol-4-ones, and electrorich aromatic units) to in situ generated allenes 34 – 43 , transition metal-catalyzed cross coupling 44 – 46 , and desymmetrization/kinetic resolution strategies (Fig. 1b ) 47 – 51 .…”

Section: Introductionmentioning

confidence: 99%

Carbene-catalyzed atroposelective synthesis of axially chiral styrenes

et al. 2022

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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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“…These remarkable studies include chiral amines or Brønsted acids catalyzed addition of nucleophiles to ynals 33 and in situ generated allenes [34][35][36][37][38][39][40][41][42][43] , transition metal-catalyzed cross coupling, [44][45][46] and desymmetrization/kinetic resolution strategies (Fig. 1b).…”

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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Asymmetric allylic substitution–isomerization to axially chiral enamides via hydrogen-bonding assisted central-to-axial chirality transfer

Abstract: Axially chiral enamides bearing a N-C axis have been recently studied and were proposed to be valuable chiral building blocks, but a stereoselective synthesis has not been achieved. Here, we...

Cited by 69 publications

References 54 publications

Ir-catalyzed Sequential Asymmetric Allylic Substitution/Olefin Isomerization for the Synthesis of Axially Chiral Compounds

Ir-catalyzed Sequential Asymmetric Allylic Substitution/Olefin Isomerization for the Synthesis of Axially Chiral Compounds

Carbene-catalyzed atroposelective synthesis of axially chiral styrenes

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

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