Restricted Rotation in Aryl Olefins. II. Preparation and Resolution of Certain β-Chloro-β-(2,4,6-trimethyl- and 2,4,6-triethyl-3-bromophenyl)-acrylic Acids

Adams, Roger; Anderson, A. W.; Miller, Marc

doi:10.1021/ja01851a028

Cited by 18 publications

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“…The resolution of enantiomers of biphenyls, first observed by Christie and Kenner 192 on 6,6′dinitro-2,2′-diphenic acid (1), proved that the molecules must be twisted to remove planar symmetry. The resolution of a number of other sterically hindered biphenyls, [205][206][207][208] anilines, [209][210][211][212][213] and styrenes [214][215][216][217][218] soon followed. The ability of compounds to possess chirality due to restricted rotation was labeled atropisomerism 219 (from Greek; a meaning not and tropos meaning turn or rotate).…”

Section: Historical Account Of Molecular Propellers and Gearsmentioning

confidence: 99%

Artificial Molecular Rotors

et al. 2005

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Section: Historical Account Of Molecular Propellers and Gearsmentioning

confidence: 99%

Artificial Molecular Rotors

et al. 2005

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“…Axial chirality refers to separable stereoisomers that occur due to the restricted rotation around a single bond (chirality axis). There are many classes of recognized axially chiral compounds such as chiral biaryls, N-aryl carbazoles, styrenes, − allenes, and so on. Among them, synthetically occurring axially chiral biaryls and their derivatives are recognized as some of the important entities of chiral ligands, − organocatalysts, , and other useful reagents in asymmetric synthesis. , Axial chirality is also widely observed in natural products , and biologically active molecules , (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

Recent Progress toward the Construction of Axially Chiral Molecules Catalyzed by an N-heterocyclic Carbene

2021

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Axial chirality widely exists in natural products, pharmaceutical compounds, and other functional molecules; these axially chiral compounds also find wide utility as catalysts or ligands in organic synthetic chemistry. Nevertheless, whereas significant progress has been made toward the synthesis of enantioenriched axially chiral molecules over the past two decades, the strategies involving organocatalysis have only started to emerge recently. Nheterocyclic carbene (NHC) organocatalysts have been recognized to be powerful tools for the rapid construction of complex molecular architectures. However, previous works have mainly focused on the assembly of point chirality and only recently has it been realized that the asymmetric synthesis of axial chirality could be achieved by using NHCs as organocatalysts. This Perspective highlights the developments and advances in the synthesis of axially chiral scaffolds catalyzed by NHCs. The aim of this Perspective is to provide an overview of this area and serve as a stepping stone for future investigations.

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“…Adams and co-workers have prepared and resolved to enantiomers two pairs of β-chlorocinnamic acids: the α-Me4a and α-H 4b with 3-bromo-2,4,6-trimethyl substituents; i.e., the aryl group is 3-bromomesityl. The optical activity results from hindered rotation around the Ar−Cbond due to the steric interaction of the o -Me substituents with the double-bond substituents, which lead to atropisomerism.…”

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“…Two practical problems that may complicate the study are the possibility of a substitution via elimination−addition and the possibility of a racemization of the precursor due to a low rotational barrier. Both problems are reduced with the α-Me compound ArC(Cl)C(Me)CO 2 Me (Ar = 3-Br-2,4,6-Me 3 C 6 H) since the barrier in the acids is relatively high and there is no vinylic hydrogen available for elimination 4a…”

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Nucleophilic Substitution of Methyl β-Chloro-(3-bromo-2,4,6-trimethyl)cinnamate

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Rappoport

1997

J. Org. Chem.

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We are looking for probes for delineating the mechanism of bimolecular nucleophilic vinylic substitution proceeding by an initial nucleophilic attack on the double bond (the "addition-elimination" route). 1 With mildly activated systems the stronger evidence for a multistep route via an intermediate carbanion (eq 1) (i.e., A being an intermediate and not a transition state) is the element effect (the relative rates k when X ) F, Cl, Br, e.g., k Br / k Cl ), 2 which is not always available.-Halocinnamates belong to this class of compounds. Methyl -chlorocinnamates (ArC(Cl))CHCO 2 Me, Ar ) Ph, p-ClC 6 H 4 , p-Tol) undergo elimination with MeO -/ MeOH, 3a-c but with PhS -, substitution takes place, giving the retained substitution product. 3d This and the formation of the isomeric E/Z substitution products in the addition of PhS -/H + to the corresponding methyl propiolates (ArCtCCO 2 Me) exclude an elimination-addition route, except when Ar ) p-O 2 NC 6 H 4 when the substitution gives E/Z substitution products mixture.Adams and co-workers have prepared and resolved to enantiomers two pairs of -chlorocinnamic acids: the R-Me 4a and R-H 4b with 3-bromo-2,4,6-trimethyl substituents; i.e., the aryl group is 3-bromomesityl. The optical activity results from hindered rotation around the Ar-Cdbond due to the steric interaction of the o-Me substituents with the double-bond substituents, which lead to atropisomerism. We reasoned that if a carbanion A with a finite lifetime is formed by attack on C giving a carbanion, the locked geometry may be relaxed, leading to a racemized product, whereas if the reaction is concerted (i.e., A is a transition state) this will not happen. Since the activation by a carboxyl is low and the negative charge on a carboxylate may complicate the study, the corresponding esters seem to be suitable substrates. Such an approach was applied by Cabaret, Welvart, and co-workers in a related system. 5 Two practical problems that may complicate the study are the possibility of a substitution via eliminationaddition and the possibility of a racemization of the precursor due to a low rotational barrier. Both problems are reduced with the R-Me compound ArC(Cl)dC(Me)-CO 2 Me (Ar ) 3-Br-2,4,6-Me 3 C 6 H) since the barrier in the acids is relatively high and there is no vinylic hydrogen available for elimination. 4a In a study of this ester, we found that dechlorocarbomethoxylation reaction with a loss of both the Cl and the CO 2 Me groups led to an acetylene and not to a substitution product. 6 This was apparently due to the excessive steric hindrance to approach to the vinylic carbon.Consequently, in the present work, we prepared the R-H analog. It is known that racemization of the acid takes place in n-BuOH with a half-life of 206 min at reflux. Moreover, the system is a priori prone to R,elimination. However, according to Adams, 4 the isomer studied is the E isomer where the hydrogen and chlorine are cis to one another so that E2 elimination may be difficult.The study of this system therefore imposes s...

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Restricted Rotation in Aryl Olefins. II. Preparation and Resolution of Certain β-Chloro-β-(2,4,6-trimethyl- and 2,4,6-triethyl-3-bromophenyl)-acrylic Acids

Cited by 18 publications

References 0 publications

Artificial Molecular Rotors

Artificial Molecular Rotors

Recent Progress toward the Construction of Axially Chiral Molecules Catalyzed by an N-heterocyclic Carbene

Nucleophilic Substitution of Methyl β-Chloro-(3-bromo-2,4,6-trimethyl)cinnamate

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