Chiral Allyl Ethers Research Articles

Novel Pd(PN,S)-complexes: Highly active catalysts designed for asymmetric allylic etherification

• A highly modular approach has been developed for the synthesis of chiral PN,S-ligands. • The ligands were used in Pd-catalyzed asymmetric allylic etherification. • High yields (up to 95%) could be obtained at unprecedentedly low catalyst loadings (0.2 mol%). • The excess of the reagents were significantly decreased compared to literature examples. • The main factors affecting activity and enantioselectivity have been investigated. Six novel thioether-aminophosphine type ligands with a general formula (Ar 1 ) 2 PN(R 1 )CHR 2 (CH 2 ) n CH(R 3 )SAr 2 has been synthesized. The modular structure of the ligands and the new methodologies developed for their preparation enabled the systematic variation of their bridge length (n = 0 or 1), the substitution pattern of the backbone (R 2 , R 3 = H or Me) as well as the P-, N- and S-substituents (Ar 1 = Ph or 3,5-Me 2 C 6 H 3 , R 1 = Et or i Pr and Ar 2 = Ph, 4-MeC 6 H 4 , or 4-MeOC 6 H 4 , respectively). The ligands proved to be effective in Pd-catalyzed asymmetric allylic etherification reactions providing the products in high yields (up to 95%) and with good enantioselectivities (up to 86%) using unprecedentedly low (0.2 mol%) loadings of the chiral Pd-catalyst. Based on these findings, a new scalable protocol has been developed for the preparation of chiral allylic ethers. Furthermore, the Pd(II) coordination chemistry of the ligands was thoroughly investigated by 1D and 2D NMR methods as well as by X-ray crystallography with special attention to the conformation of the chelate ring and the stereoselectivity of the sulfur coordination. Based on these studies, the main factors determining activity and selectivity of the catalytic system have been identified.

Formation of Chiral Allylic Ethers via an Enantioselective Palladium-Catalyzed Alkenylation of Acyclic Enol Ethers.

This report details a palladium-catalyzed process to access highly functionalized, optically active allylic aryl ethers. A number of electron-deficient alkenyl triflates underwent enantioselective and site-selective coupling with acyclic aryl enol ethers in the presence of a chiral palladium catalyst. This transform provides chiral allylic ether products in high yields and excellent enantiomeric ratios, furnishing a unique disconnection to incorporate heteroatoms at a stereocenter. Finally, the applicability of the products to target synthesis was demonstrated through the formation of a chiral allylic alcohol and the generation of a flavone-inspired product.

Transition State Gauche Effects Control the Torquoselectivities of the Electrocyclizations of Chiral 1-Azatrienes.

Hsung et al. have reported a series of torquoselective electrocyclizations of chiral 1-azahexa-1E,3Z,5E-trienes that yield functionalized dihydropyridines. To understand the origins of the torquoselectivities of these azaelectrocyclizations, we modeled these electrocyclic ring closures using the M06-2X density functional. A new stereochemical model that rationalizes the observed 1,2 stereoinduction emerges from these computations. This model is an improvement and generalization of the "inside-alkoxy" model used to rationalize stereoselectivities of the 1,3-dipolar cycloaddition of chiral allyl ethers and emphasizes a stabilizing hyperconjugative effect, which we have termed a transition state gauche effect. This stereoelectronic effect controls the conformational preferences at the electrocyclization transition states, and only in one of the allowed disrotatory electrocyclization transition states is the ideal stereoelectronic arrangement achieved without the introduction of a steric clash. Computational experiments confirm the role of this effect as a stereodeterminant since substrates with electropositive groups and electronegative groups have different conformational preferences at the transition state and undergo ring closure with divergent stereochemical outcomes. This predicted reversal of stereoselectivity for the ring closures of several silyl substituted azatrienes have been demonstrated experimentally.

ChemInform Abstract: Diastereofacial Selectivity in Intermolecular Nitrone Cycloadditions to Chiral Allyl Ethers. Application of Chiral Synthesis of Coniine.

ChemInform Abstract: Diastereofacial Selectivity in Intermolecular Nitrone Cycloadditions to Chiral Allyl Ethers. Application of Chiral Synthesis of Coniine.

ChemInform Abstract: Catalytic Asymmetric Synthesis of Branched Chiral Allylic Phenyl Ethers from (E)‐Allylic Alcohols.

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Enantioselective Allylic Etherification Using a Novel COP Catalyst

Asymmetric allylic substitution ­reactions can provide rapid access to chiral allylic ethers. However, these reactions are often plagued by poor branched/linear ratios which need to be controlled through the appropriate choice of both substrate and catalyst. Extending on previous work with (Z)-allylic alcohols (Org. Lett. 2007, 9, 911), the authors present a highly enantioselective allylic substitution of (E)-2-alken-1-ols with phenols giving complete branched ­selectivity. Key to this new transformation was the development of a novel COP-type palladium catalyst.

Catalytic Asymmetric Synthesis of Branched Chiral Allylic Phenyl Ethers from (E)‐Allylic Alcohols

The first di-μ-amidate dipalladium complexes and a new di-μ-carboxylate dipalladium complex of the COP (cobalt oxazoline palladacycle) palladium(II) catalyst family are reported and characterized crystallographically. The di-μ-amidate complex 3 or its enantiomer (ent-3) are the first asymmetric catalysts that allow commercially available, or readily accessible, (E)-2-alkene-1-ols to be transformed to enantioenriched branched allylic aryl ethers upon reaction of their trichloroacetimidate derivatives with phenols. The 3-aryloxy-1-alkene products are formed in high enantiomeric purity (typically 90-98% ee) and useful yields (61-88%).

Diastereoselective synthesis of unsaturated 1,4-amino alcohols as a biologically important moiety

The diastereoselective synthesis of unsaturated 1.4-amino alcohols can be achieved using chial allylic ethers with a hydroxyl group attached to the pi-system and chlorosulfonyl isocyanate. The enantioselectivity of the CSI reaction with the chiral allylic and benzylic ethers was examined in various solvents and temperatures. Based on these results, it was proposed that the CSI reaction is a competitive reaction of a SNi (retention) and a SN1 mechanism (racemization) according to the stability of the carbocation intermediate. This means that there is a greater proportion of retention with the less stable the carbocation intermediate and vise versa.

Regio‐ and Enantioselective Iridium‐Catalyzed Intermolecular Allylic Etherification of Achiral Allylic Carbonates with Phenoxides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Regio- and enantioselective iridium-catalyzed intermolecular allylic etherification of achiral allylic carbonates with phenoxides.

An enantioselective and regioselective iridium-catalyzed allylic etherification is described. The reaction of sodium and lithium aryloxides with achiral (E)-cinnamyl and terminal aliphatic allylic electrophiles in the presence of 2 mol % of an iridium-phosphoramidite complex provides chiral allylic aryl ethers in high yields and excellent levels of regio- and enantioselectivity. Lithium aryloxides containing a single substituent at an ortho, meta, or para position as well as sterically hindered phenoxides were tolerated. Reactions in THF displayed the most suitable balance of rate, regio-, and enantioselectivity. High ee's were also observed for the products from the reaction of alkyl (E)-allylic carbonates.

Stereoselection in Reactions of Chiral Allyl Ethers: The Case of 1,3-Dipolar Cycloaddition

Stereoselection in Reactions of Chiral Allyl Ethers: The Case of 1,3-Dipolar Cycloaddition

Stereoselection in Reactions of Chiral Allyl Ethers: The Case of 1,3-Dipolar Cycloaddition

Stereoselection in Reactions of Chiral Allyl Ethers: The Case of 1,3-Dipolar Cycloaddition

The Importance of Electrostatic Interactions in the Stereoselective 1,3-Dipolar Cycloadditions of Nitrones to Chiral Allyl Ethers: An Experimental and Force Field Approach

The 1,3-dipolar cycloaddition of formaldehyde N-benzylnitrone with β′-alkoxy- and γ-alkoxy-α,β-unsaturated esters was investigated. The stereochemical outcome of these reactions was nicely rationalized on the basis of an interpretation of the inside alkoxy theory emphasizing the electrostatic interactions in the reaction TS. The force field approach previously developed for evaluating the stereoselection in nitrile oxide cycloadditions to chiral alkenes was successfully extended to nitrones′ reactions.

Models for Stereoselective Additions to Chiral Allylic Ethers: Osmium Tetroxide Bis-hydroxylations

Density functional calculations (Becke3LYP/6-31G(d)) on the (3 + 2) transition structures of osmium tetroxide mediated dihydroxylations of chiral allylic ethers show that the stereoselectivity is c...

Electrostatic effects in 1,3-dipolar cycloaddition reactions to chiral allyl ethers: a rationale for the experimentally observed diastereoselectivities

Semiempirical (PM3) and ab initio (RHF/3-21G) transition structures for 1,3-dipolar cycloadditions of 5 different dipoles to alkenes were analyzed; the differences in 1,3-dipole charge distribution offer a rationale for the different stereoselectivities experimentally observed in the reactions with chiral allyl ethers.

Zirconium-catalyzed ethylmagnesiation of hydroxylated terminal alkenes; a catalytic and diastereoselective carbon-carbon bond-forming reaction

Zirconocene dichloride catalyzes the addition of ethylmagnesium halides to chiral allylic and homoallylic alcohols and ethers in an efficient manner. These transformations proceed with high levels of regio- and stereocontrol; with the appropriate choice of the neighboring heteroatom substituent (alcohol vs ether), either of the two diastereotopic faces of a chiral alkene can be selectively functionalized. Experimental data described indicate that the regio- and stereoselective outcomes of catalgic carbomagnesation of acyclic substrates are unique

Conformational preferences of C1-oxygenated acyclic chiral alkenes: evidence for the C-C eclipsed conformer

Three forms of conformational minima were found for 3-buten-2-ol by ab initio MO methods, including the conformers where the allyl methyl group eclipses the C1 bond. The computational results are corroborated by a VT NMR study of a variety of C1-oxygenated chiral alkenes. The experimenal study indicates that chiral allylic alcohols and ethers with a formula of (E)-RCH=CHCH(OP)R'can have either two or three stable rotamers depending on the size of the allylic substituent, R'. When R'is a methyl group, the coupling constant, 3 J ab is smaller than when R'is a bulky group, indicating a three-rotamer equilibrium

Diastereofacial selectivity in intermolecular nitrone cycloadditions to chiral allyl ethers. application to chiral synthesis of coniine

Diastereofacial selectivity in intermolecular nitrone cycloadditions to chiral allyl ethers. application to chiral synthesis of coniine

Diastereofacial selectivity in intermolecular nitrone cycloadditions to chiral allyl ethers. Application to Chiral Synthesis of Coniine

The intermolecular cycloadditions of a cyclic nitrone to chiral allyl ethers take place with erythro selectivity, where the degree of selectivity achieved is dependent upon the size of the alkyl substituent attached to the allylic chiral center, and these reactions are applied to the synthesis of optically active alkaloid coniine.

ChemInform Abstract: Determination of the Enantiomeric Purity of Chiral Allyl Alcohols and Allyl Ethers by 195Pt NMR Spectroscopy.

ChemInform Abstract: Determination of the Enantiomeric Purity of Chiral Allyl Alcohols and Allyl Ethers by 195Pt NMR Spectroscopy.