Enantioselective Allylation Of Aldehydes Research Articles

Enantioselective Synthesis of Atropisomeric Anilides via Pd(II)-Catalyzed Asymmetric C-H Olefination.

Atropisomeric anilides have received tremendous attention as a novel class of chiral compounds possessing restricted rotation around an N-aryl chiral axis. However, in sharp contrast to the well-studied synthesis of biaryl atropisomers, the catalytic asymmetric synthesis of chiral anilides remains a daunting challenge, largely due to the higher degree of rotational freedom compared to their biaryl counterparts. Here we describe a highly efficient catalytic asymmetric synthesis of atropisomeric anilides via Pd(II)-catalyzed atroposelective C-H olefination using readily available L-pyroglutamic acid as a chiral ligand. A broad range of atropisomeric anilides were prepared in high yields (up to 99% yield) and excellent stereoinduction (up to >99% ee) under mild conditions. Experimental studies indicated that the atropostability of those anilide atropisomers toward racemization relies on both steric and electronic effects. Experimental and computational studies were conducted to elucidate the reaction mechanism and rate-determining step. DFT calculations revealed that the amino acid ligand distortion is responsible for the enantioselectivity in the C-H bond activation step. The potent applications of the anilide atropisomers as a new type of chiral ligand in Rh(III)-catalyzed asymmetric conjugate addition and Lewis base catalysts in enantioselective allylation of aldehydes have been demonstrated. This strategy could provide a straightforward route to access atropisomeric anilides, one of the most challenging types of axially chiral compounds.

Axially chiral N,N'-dioxides ethers for catalysis in enantioselective allylation of aldehydes.

A series of axially chiral ethers synthesized from biscarboline N,N'-dioxides, (S)-1a to (S)-1n, was investigated in enantioselectivity addition reactions of allyltrichlorosilane with a series of substituted aldehydes, including bulky substituted aldehydes. High enantioselectivities (up to 96%ee) were achieved using the catalyst (S)-1k at 1 mol % loading.

Silver-Catalyzed Enantioselective Allylation of Aldehydes

Silver-Catalyzed Enantioselective Allylation of Aldehydes

ChemInform Abstract: Syntheses of a Flobufen Metabolite and Dapoxetine Based on Enantioselective Allylation of Aromatic Aldehydes.

AbstractThe enantioselective allylation of aldehydes (I) and (VIII) with pinacolborane (II) in the presence of a chiral BINOL‐phosphoric‐acid‐derived catalyst is the key step in the synthesis of the flubofen metabolite (VII) and dapoxetine (X).

Oxazoline derivatives tagged with tosylated amino acids as recyclable organocatalysts for enantioselective allylation of aldehydes

A series of amino acid-based oxazoline compounds have been prepared and successfully applied to the enantioselective allylation reaction of aldehydes. The fine-tuning of the structure of the oxazolines led to (S,S)-4 as an efficient organocatalyst which gave homoallyl alcohols in good yield (up to 90%) and excellent ee (up to 99%) for a wide range of substrates including aromatic, hetero-aromatic and α,β-unsaturated aldehydes. The chiral organocatalyst was synthesized in three easy steps with an overall 88% yield and successfully recycled for up to three cycles. On the basis of the experimental observations and NMR studies, a probable mechanism was proposed for this reaction.

ChemInform Abstract: Structure Influence of Chiral 1,1′‐Biscarboline‐N,N′‐dioxide on the Enantioselective Allylation of Aldehydes with Allyltrichlorosilanes.

AbstractA new axially chiral biscarboline‐N,N′‐dioxide Lewis base organocatalyst is used in the asymmetric allylation of aldehydes with allyltrichlorosilane (I).

Structure influence of chiral 1,1′-biscarboline-N,N′-dioxide on the enantioselective allylation of aldehydes with allyltrichlorosilanes

A series of new axially chiral 1,1′-biscarboline-N,N′-dioxide Lewis base organocatalysts were examined in the asymmetric allylation of aldehydes with allyltrichlorosilane. The chiral catalysts (R)-1a–e bearing ester groups in 3,3′ position provided good yields of the homoallyl alcohols with excellent enantioselectivities up to 99% for a broad substrate scope that covers aliphatic, aromatic, heteroaromatic, and α,β-unsaturated aldehydes. Solvent effects on the conversion and enantioselectivity were elucidated, and CH2Cl2 proved to be the optimal solvent for the reactions. In addition, the allylation with crotyltrichlorosilane was explored and the result showed that anti-isomer was favored from (E)-crotyltrichlorosilane with complete diastereoselectivity.

Chiral sulfoxides in the enantioselective allylation of aldehydes with allyltrichlorosilane: a kinetic study

The mechanism of the allylation of aldehydes in the presence of allyltrichlorosilane employing the commercially available (R)-methyl p-tolyl sulfoxide as a Lewis base has been investigated. The combination of kinetic measurements, conductivity analysis and quantum chemical calculations indicates that the reaction proceeds through a dissociative pathway in which an octahedral cationic complex with two sulfoxides is involved. The lack of turnover is ascribed to the formation of neutral sulfurane derivatives.

ChemInform Abstract: Chiral Phosphoric Acid Catalyzed Enantioselective Allylation of Aldehydes with Allyltrichlorosilane.

Easily accessible chiral phosphoric acid 1b has been applied as efficient organocatalyst for the asymmetric allylation of aldehydes with allyltrichlorosilane. In the presence of 20 mol% of 1b, the allylation of a broad range of aldehydes proceeded smoothly to give the corresponding homoallylic alcohol with up to 87% ee and 97% yield.

ChemInform Abstract: Synthesis of Axially Chiral Bipyridine N,N′‐Dioxides and Enantioselective Allylation of Aldehydes

AbstractReview: 26 refs.

Synthesis of axially chiral bipyridine N,N'-dioxides and enantioselective allylation of aldehydes

N-oxides possessing the pyridine framework are strong Lewis bases that can activate the C–Si bond of allylhalosilanes to such an extent that they catalyze reactions with aldehydes. N-oxides embedded in chiral scaffolds are usually capable of highly selective chirality transfer to the derived products. Our goal was to develop a general synthetic method allowing the preparation of structurally varied N,N'-dioxides suitable for enantioselective organocatalysis. The underlying synthetic strategy was based on [2 + 2 + 2]-cyclotrimerization of suitably substituted diynes with nitriles catalyzed by Co-complexes to generate the desired bipyridines, their further oxidation and resolution of which furnished the corresponding chiral N,N'-dioxides. The prepared compounds were used in catalytic allylation of aromatic aldehydes to homoallyl alcohols with high enantioselectivity (up to 96 % ee). Enantioselectivity, enantiodiscrimination, and the reaction mechanism are controlled by the choice of solvent.

ChemInform Abstract: Chiral Diphenylthiophosphoramides: A New Class of Chiral Ligands for the Silver(I)-Promoted Enantioselective Allylation of Aldehydes.

Abstract Chiral C2-symmetric diphenylthiophosphoramides 1 and 2 were prepared in high yields from the reaction of diphenylthiophosphinic chloride with (1R,2R)-(−)-1,2-diaminocyclohexane and (1R,2R)-(+)-1,2-diphenylethylenediamine, respectively. Another novel chiral ligand 4 was prepared from reaction of diphenylthiophosphinic chloride with (R)-(+)-1,1′-binaphthyl-2,2′-diamine using butyllithium as a base. They were used as catalytic chiral ligands in the silver(I)-promoted enantioselective allylation reaction of aldehydes with allyltributyltin.

ChemInform Abstract: New Pathway to C2‐Symmetric Atropoisomeric Bipyridine N,N′‐Dioxides and Solvent Effect in Enantioselective Allylation of Aldehydes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Improved Cr-Catalyzed Enantioselective Allylation of Aldehydes

The authors’ aim was to develop a scalable method for allylation which would allow recovery of the chiral ligand. The described procedure improved the practicality of a reaction they developed earlier (J. Am. Chem. Soc. 2004, 126, 12248). Under the above conditions, the 2-iodoallylation reaction gave B on a 30 g scale, and ligand A was recovered in 83% yield (X = I). It is noteworthy that the catalytic allylation reaction affords exceptional selectivity in cases where the aldehyde is already chiral (D and E; with matched ligand).

New Pathway to C2‐Symmetric Atropoisomeric Bipyridine N,N′‐Dioxides and Solvent Effect in Enantioselective Allylation of Aldehydes

AbstractThe [2+2+2] cyclotrimerization of 1,7,9,15‐hexadecatetrayne with nitriles catalyzed by dicarbonylcyclopentadienylcobalt(I) opened a new pathway for the synthesis of C2‐symmetrical bis(tetrahydroisoquinolines) that were used as starting material for the preparation of axially chiral bipyridine N,N′‐dioxides. The N,N′‐dioxides (1 mol%) were found to be highly catalytically active and enantioselective (up to 83% ee) for the asymmetric allylation of aldehydes with allyl(trichloro)silane in various solvents. In addition, a dramatic solvent effect was observed where the use of different solvents induced opposite chiralities of the product with the same enantiomer of the catalyst, e.g., 65% ee (S) in acetonitrile (MeCN) vs. 82% ee (R) in chlorobenzene.

Catalytic enantioselective allylation of aldehydes using β-amido functionalized allylstannanes with chiral In(OTf) 3/ i-Pr-pybox complexes

The enantioselective allylation of aldehydes using a variety of β-amido functionalized allyltributylstannanes proceeded smoothly with good to high yields and enantioselectivities in the presence of 10 mol % of a chiral catalytic complex prepared from In(OTf) 3 and 2,6-bis[( S)-4-isopropyloxazolin-2-yl]pyridine {( S)- i-Pr-pybox}, providing the corresponding chiral γ-hydroxy amides.

Enantioselective Allylation of Aldehydes with Allyltrichlorosilane Promoted by New Chiral Dipyridylmethane N‐Oxides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A Simple Approach to Unsymmetric Atropoisomeric Bipyridine N,N′‐Dioxides and Their Application in Enantioselective Allylation of Aldehydes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Enantioselective allylation of aldehydes with allyltrichlorosilane promoted by new chiral dipyridylmethane N-oxides

New chiral dipyridine N-monoxides and N,N′-dioxides, which possess an isopropylidene backbone between two pyridine rings, have been prepared from naturally occurring monoterpenes. Their utility as organocatalysts has been demonstrated in the enantioselective addition of allyltrichlorosilane to aldehydes. Enantioselectivities up to 85% ee have been obtained.

A Simple Approach to Unsymmetric Atropoisomeric Bipyridine N,N′‐Dioxides and Their Application in Enantioselective Allylation of Aldehydes

AbstractThe [2+2+2] cyclotrimerization of 1‐isoquinolinyl‐1,7‐octadiyne with benzonitrile catalyzed by CpCo(CO)2 opened a new pathway for a synthesis of unsymmetrical axially chiral bipyridine N,N′‐dioxides. The N,N′‐dioxide 3a was found to be highly catalytically active and enantioselective for the asymmetric allylation of aldehydes with allyltrichlorosilane. The allylation took place with even 1 % of the catalyst with an enantioselectivity up to 87 % ee.