A mild and robust direct CH functionalization strategy has been applied to the synthesis of axially chiral biaryls. Such an efficient and stereoselective transformation occurs through an original ...dynamic kinetic resolution pathway enabling the conversion of diastereomeric mixtures of non‐prefunctionalized substrates into atropisomerically pure, highly substituted biaryl scaffolds. The main feature of this transformation is the use of an enantiopure sulfoxide as both chiral auxiliary and traceless directing group. The potential of newly synthesized biaryls as valuable building blocks is further illustrated.
Pd makes it rotate: A CH activation/dynamic kinetic resolution method allows access to axially chiral biaryls. The isomerization step is believed to occur via a palladacyclic intermediate. Chiral induction is achieved using the sulfoxide motif as both “traceless” directing group and chiral source.
Although asymmetric C−H functionalization has been available for the synthesis of structurally diverse molecules, catalytic dynamic kinetic resolution (DKR) approaches to change racemic stereogenic ...axes remain synthetic challenges in this field. Here, a concise palladium‐catalyzed DKR was combined with C−H functionalization involving olefination and alkynylation for the highly efficient synthesis of non‐biaryl‐atropisomer‐type (NBA) axially chiral oragnosilanes. The chemistry proceeded through two different and distinct DKR: first, an atroposelective C−H olefination or alkynylation produced axially chiral vinylsilanes or alkynylsilanes as a new family of non‐biaryl atropisomers (NBA), and second, the extension of this DKR strategy to twofold o,o′‐C−H functionalization led to the multifunctional axially chiral organosilicon compounds with up to >99 % ee.
Powerful DKR: A palladium‐catalyzed atroposelective ortho C−H olefination/alkynylaton combined with dynamic kinetic resolution strategy is developed to construct axially chiral styrene‐type organosilanes with excellent enantioselectivities.
Kinetic resolution, dynamic kinetic resolution and desymmetrization are practical methods to produce enantioenriched products from relatively simple racemic or achiral starting materials, which are ...also sometimes difficult to be accessed by other asymmetric methods. Chiral phosphoric acids, which have been recognized as one of the most powerful chiral organocatalysts to date, have also been extensively applied in the above‐mentioned research fields. In this minireview, we summarized the tremendous development of kinetic resolution, dynamic kinetic resolution and desymmetrization reactions enabled by chiral phosphoric acids since the year of 2016, which were not included in the two previous outstanding reviews by Petersen et al and Dixon et al. A number of examples involving the use of CPA as cooperative catalyst are also included in this review.
Chiral phosphoric acids, as one of the most powerful and versatile chiral organocatalysts, have found extensively applications in the kinetic resolution, dynamic kinetic resolution and desymmetrization reactions, generating a wide range of enantioenriched functional molecules with high enantioselectivities. In this paper, we summarized and reviewed the recent advances (since 2016) in these research fields and provide our own perspective into the future development in this direction.
The radical‐mediated racemization has often hampered the production of optically pure 1,1′‐bi‐2‐naphthols (BINOLs) in transition‐metal‐catalyzed enantioselective oxidative couplings of 2‐naphthols. ...In their Communication on page 10278 ff., S. Akai et al. effectively use this undesired racemization and establish the first lipase/RU‐integrated dynamic kinetic resolution of racemic C1‐ and C2‐symmetric biaryl diols to afford homochiral biaryls in up to 98% yield and up to 98% ee.
The dynamic kinetic resolution of 6‐hydroxypyranones with enals or alkynals through an asymmetric redox esterification is catalyzed by a chiral N‐heterocyclic carbene. The resulting esters are ...obtained in good to high yields and with high levels of enantio‐ and diastereocontrol. The reaction products are further derivatized to obtain functionalized sugar derivatives and natural products.
Sweet products: The dynamic kinetic resolution of 6‐hydroxypyranones with enals or alkynals through an asymmetric redox esterification is catalyzed by a chiral N‐heterocyclic carbene (NHC). The resulting esters are obtained in good to high yields and with high levels of enantio‐ and diastereocontrol.
Enantiomerically pure chiral amines are valuable building blocks for the synthesis of pharmaceutical drugs and agrochemicals. Indeed it is estimated that currently 40 % of pharmaceuticals contain a ...chiral amine component in their structure. Chiral amines are also widely used as resolving agents for diastereomeric salt crystallization. One of the challenges of preparing chiral amines in enantiomerically pure form is the development of cost-effective and sustainable catalytic methods that are able to address the requirement for the entire range of primary, secondary and tertiary amines. In this review we highlight various biocatalytic strategies that have been developed, particularly those based upon asymmetric synthesis or their equivalent therefore (i.e. dynamic kinetic resolution, deracemisation) in which yields and enantiomeric excesses approaching 100 % can be attained. Particular attention is given to the use of monoamine oxidase (MAO-N) from
Aspergillus niger
which has been engineered by directed evolution to provide a tool-box of variants which can generate enantiomerically pure primary, secondary and tertiary amines. These MAO-N variants are combined with non-selective chemical reducing agents in deracemisation processes.
Strategies on the construction of enantiomerically pure silicon‐stereogenic silanes generally relies on desymmetrization of prochiral and symmetric substrates. However, dynamic kinetic asymmetric ...transformations of organosilicon compounds have remained underdeveloped and unforeseen owing to a lack of an effective method for deracemization of the static silicon stereocenters. Here we report the first Rh‐catalyzed dynamic kinetic asymmetric intramolecular hydrosilylation (DyKAH) with “silicon‐centered” racemic hydrosilanes that enables the facile preparation of silicon‐stereogenic benzosiloles in good yields and excellent enantioselectivities. The special rhodium catalyst controlled by non‐diastereopure‐type mixed phosphine‐phosphoramidite ligand with axial chirality and multiple stereocenters can induce enantioselectivity efficiently in this novel DyKAH reaction. Density functional theory (DFT) calculations suggest that the amide moiety in chiral ligand plays important role in facilitating the SN2 substitution of chloride ion to realize the chiral inversion of silicon center.
An unprecedented (SiMOS‐Phos) ligand‐controlled Rh‐catalyzed hydrosilylation of “silicon‐centered” racemic hydrosilanes was developed for the highly efficient and enantioselective construction of silicon‐stereogenic centers of benzosiloles (up to 96 : 4 er). This achievement was obtained by using an original synthetic strategy involving dynamic kinetic asymmetric transformations.
An efficient chiral 4-aryl-pyridine-N-oxide (ArPNO) nucleophilic organocatalyst was rationally designed, synthesized, and applied to the acylative dynamic kinetic resolution of azoles, aldehydes, and ...anhydride. The restriction of the pyridine’s C-4 position, where the dialkylamino group should be always present when using chiral pyridine-N-oxide as an acyl transfer catalyst, was overcome, thereby allowing structural diversity at this position. In the presence of 5 mol % 3,5-dimethylphenyl-derived ArPNO catalyst, the corresponding 2,5-disubstituted tetrazole hemiaminal esters were obtained in up to 93% yields, >20:1 rr, and 99% ee. Other N-heteroaromatics, including substituted pyrazole, imidazole, purine, benzimidazole, and benzotriazole, were also suitable substrates. Mechanistic studies by control experiments and density functional theory calculations indicated that an acyloxypyridinium cation was formed, and the nucleophilic substitution of azole hemiaminal with the acyloxypyridinium cation was the rate-determining step. Furthermore, the nucleophilic ability of oxygen in pyridine-N-oxide was higher than that of nitrogen in pyridine. This work provides an effective method for the utilization of the C-4 position of the pyridine ring, allowing the development of more varied chiral 4-substituted pyridine-N-oxides as efficient nucleophilic organocatalysts.
A Z‐selective rhodium‐catalyzed hydrothiolation of 1,3‐disubstituted allenes and subsequent oxidation towards the corresponding allylic sulfones is described. Using the bidentate ...1,4‐bis(diphenylphosphino)butane (dppb) ligand, Z/E‐selectivities up to >99:1 were obtained. The highly atom‐economic desymmetrization reaction tolerates functionalized aromatic and aliphatic thiols. Additionally, a variety of symmetric internal allenes, as well as unsymmetrically disubstituted substrates were well tolerated, thus resulting in high regioselectivities. Starting from chiral but racemic 1,3‐disubstituted allenes a dynamic kinetic resolution (DKR) could be achieved by applying (S,S)‐Me‐DuPhos as the chiral ligand. The desired Z‐allylic sulfones were obtained in high yields and enantioselectivities up to 96 % ee.
Zelectivity: The title reaction permits the synthesis of valuable allylic thioethers and sulfones in excellent Z selectivity. By using unsymmetrically 1,3‐disubstituted allenes, good to high regioselectivities were obtained. Asymmetric hydrothiolation of racemic allenes with (S,S)‐Me‐DuPhos meets the criteria of a dynamic kinetic resolution. Me‐DuPhos=2′,5′,2′′,5′′‐tetramethyl‐1,2‐bis(phospholanyl)benzene.
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