Unprecedented Regioselectivity Research Articles

Ni-Catalyzed Regioselective Hydrocarboxylation of Alkynes with CO2 by Using Simple Alcohols as Proton Sources

A mild and user-friendly Ni-catalyzed regioselective hydrocarboxylation of alkynes with CO2 (1 bar) is described. This protocol is characterized by a wide scope while obviating the need for sensitive organometallic species and by an unprecedented regioselectivity pattern using simple alcohols as proton sources.

Widening the scope of the corrole sulfonation

The sulfonation reaction has been particularly useful to prepare amphiphilic derivatives of 5,10,15-tris(pentafluorophenyl)corrole, but it has been limited to this corrole. We have studied the scope of this reaction, using 5,10,15-triphenylcorrole as the prototypical example of corrole structure. The reaction protocol has been modified to avoid the corrole aggregation, which limited its reactivity in the neat chlorosulfonic acid. Surprisingly, the reaction shows an unprecedented regioselectivity for corrole derivatives, affording 3 as the main product, but also corrole 5, which is the first example of monosubstituted corrole on pyrrole B. By modulating the corrole:chlorosulfonic acid reagent ratio, it has been possible to obtain the antipodal disubstituted product 6, demonstrating again a not usual regioselectivity for corrole substitution. These results allow the preparation of novel amphiphilic corrole derivatives, which open up their potential applications in different fields.

Controlled Acid‐Mediated Regioselective O‐Desilylations for Multifunctionalization of Cyclodextrins

AbstractA highly valuable tri‐/tetra‐functionalization method is reported for cyclodextrin (CD) chemistry by taking advantage of the acid‐sensitivity of the O‐silyl ether group and also the geometry of CD macrocycles. The controlled acid‐mediated O‐desilylations from the easily accessible per‐3,6‐O‐silylated CD derivatives provide unprecedented regioselectivity to differentiate not only primary O‐silyl groups from secondary groups, but also O‐silyl groups of the same type with identical chemical reactivity. This methodology differs from other conventional monofunctionalization methods of natural CDs, which only allow for a direct twofold differentiation of hydroxyl groups in a CD, because the current method permits the synthesis of tri‐ and tetra‐functionalized CDs in a short reaction sequence. Most importantly, the developed method has been found to be applicable to all α‐, β‐, and γ‐CDs and the obtained CD intermediates are versatile. Furthermore, we demonstrate that these processes are practical and can be carried out on multigram scales.

Supramolecular Encapsulated Rhodium Catalysts for Branched Selective Hydroformylation of Alkenes at High Temperature

AbstractThis study reveals that, in contrast to expectations, supramolecular encapsulated rhodium catalysts can be used at industrially relevant temperatures (75–80 °C), providing highly active catalysts. The unprecedented regioselectivity for the branched aldehydes can be retained if high carbon monoxide (CO) concentrations are used.

Unprecedented Meta-Substitution of Calixarenes: Direct Way to Inherently Chiral Derivatives

Electrophilic aromatic substitution in the calix[n]arene series is a well-established procedure leading exclusively to para-substituted derivatives. An unprecedented regioselectivity of the mercuration reaction leading to the meta-substituted calix[4]arenes is described. These compounds represent a new type of substitution pattern in classical calixarene chemistry and open the door for the straightforward synthesis of inherently chiral receptors based on calixarenes.

Molecular Diversity of the Three‐Component Reactions of N‐Benzylbenzimidazolium Salts, Aromatic Aldehydes, and Active Methylene Compounds

AbstractThe three‐component reactions of in‐situ‐formed N‐benzylbenzimidazolium salts, aromatic aldehydes, and active methylene compounds in the presence of triethylamine showed very interesting molecular diversity. The reactions with Meldrum's acid or barbiturate in acetonitrile gave a series of the novel zwitterionic salts in high yields. Under similar reaction conditions, the reactions with malononitrile or ethyl cyanoacetate produced functionalized pyrrolo[1,2‐a]benzimidazoles in good yields with an unprecedented regioselectivity.

ChemInform Abstract: Reactions of Triene-Conjugated Diazo-Compounds: Reaction Paths from o-(1,3-Dienyl)aryldiazomethanes to 3,8-Methano-1,2-diazocines and to Pyrrolo[2,1-a]phthalazines via Intramolecular [3 + 2] and 1,1-Cycloaddition Reactions.

The reaction paths followed by the triene-conjugated diazo-compounds 7, which have α,β aromatic and γ,δ; e,ζ olefinic unsaturation, depend strongly on the nature of the substituents R1 and R2. Those with R1,R2 = (CH2)3, 7a–e, react at room temperature via an intramolecular (3 + 2) cycloaddition reaction of unprecedented regioselectivity to give the bridged benzodiazocines 18a–e in high yield. Those with R1 = Me and R2 = Ph, 7f and 7g, react at 80 °C to give the hydrocarbons 19f,g and, via new chemistry, the pyrrolo[2,1-a]phthalazines 24f,g. The structures of compounds 18a, 19a and 24f have been determined by X-ray crystallography.

Catalytic Asymmetric Synthesis of Allylic Aryl Ethers

[reaction: see text] The reaction of trichloroacetimidate derivatives of (Z)-2-alken-1-ols with phenol nucleophiles in the presence of the palladium(II) catalyst [COP-OAc]2 provides 3-aryloxy-1-alkenes in high yields and high enantiomeric purity (typically 63-90% yield and 90-97% ee). The reaction is exemplified by 20 examples. The method employs 1 mol % of the commercially available catalysts (S)- or (R)-[COPOAc]2, produces the branched isomer with unprecedented regioselectivity, and is compatible with the presence of base-labile functionality in either reactant.

Hydroformylation of Internal Alkenes by Encapsulated Rhodium

This is an outstanding report with unprecedented regioselectivity for hydroformylation of internal alkenes. The use of encapsulated rhodium gives extremely high regioselectivity, whereas a standard rhodium catalyst (not encapsulated) gives nearly a 1:1 mixture of isomers. When the reaction is performed at 25 °C, the highest regio­selectivity is obtained, and the selectivity decreases with an increase in temperature due to isomerization pathways capable at the elevated temperatures.

Catalytic Asymmetric Ring Opening of 2,3‐Substituted Norbornenes with Organometallic Reagents: A New Formal Aza Functionalization of Cyclopentadiene.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Regio‐ and Diastereoselective Conjugate Addition to 4,4‐Dimethylcyclohexadienones

AbstractConjugate addition of vinyl cuprate and dimethyl malonate to 4,4‐dimethylcyclohexa‐2,5‐dienones has allowed facile access to mono‐ and bis‐adducts in satisfactory yields. While the high diastereoselectivity of such processes to afford trans‐bis‐adducts was predictable, an unprecedented regioselectivity was observed with 2,4,4‐trimethylcyclohexa‐2,5‐dienone, with the first addition occurring exclusively at the C‐5 carbon atom (distal from the methyl group) and with the second addition of a bulky nucleophile such as dimethyl malonate even prevented. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Catalytic Asymmetric Ring Opening of 2,3-Substituted Norbornenes with Organometallic Reagents: A New Formal Aza Functionalization of Cyclopentadiene

An unprecedented regioselective and anti stereoselective asymmetric ring opening of 1,3-cyclopentadiene-heterodienophile cycloadducts, including also 2,3-diazabicyclo[2.2.1]heptenes, with hard alkylmetals and copper-phosphoramidite catalysts, is reported. The induced ring opening, in conjunction with C-C bond formation, gives a catalytic and practical access to new heterofunctionalized cyclopentenes in an enantioenriched form (up to 86% ee). [reaction: see text]

Buttressing Effects on Haloarene Deprotonation: A Merely Kinetic or Also Thermodynamic Phenomenon?

(2,6-Dichlorophenyl)- and (2,6-dibromophenyl)trialkylsilanes undergo hydrogen/metal interconversion preferentially at the 4- rather than 3-position. However, the organometallic species generated by such a "meta metalation" are thermodynamically less stable (i.e., more basic) than those that would result from an ordinary "ortho metalation". This was demonstrated by equilibration experiments based on permutational halogen/metal interconversion. A new buttressing effect can explain the unprecedented regioselectivity. It is supported by X-ray structures that reveal marked deformations of the benzene ring in halophenylsilanes. [structure: see text]

Palladium(II) complexes, as synthetic peptidases, regioselectively cleave the second peptide bond "upstream" from methionine and histidine side chains.

Palladium(II) complexes promote hydrolysis of natural and synthetic oligopeptides with unprecedented regioselectivity; the only cleavage site is the second peptide bond upstream from a methionine or a histidine side chain, that is, the bond involving the amino group of the residue that precedes this side chain. We investigate this regioselectivity with four N-acetylated peptides as substrates: neurotransmitter methionine enkephalin (Ac-Tyr-Gly-Gly-Phe-Met) and synthetic peptides termed Met-peptide (Ac-Ala-Lys-Tyr-Gly-Gly-Met-Ala-Ala-Arg-Ala), His-peptide (Ac-Val-Lys-Gly-Gly-His-Ala-Lys-Tyr-Gly-Gly-Met(OX)-Ala-Ala-Arg-Ala), in which a Met is oxidized to sulfone, and HisMet-peptide (Ac-Val-Lys-Gly-Gly-His-Ala-Lys-Tyr-Gly-Gly-Met-Ala-Ala-Arg-Ala). While maintaining protein-like properties, these substrates are suitable for quantitative study since their coordination to Pd(II) ion can be determined (by NMR spectroscopy), and the cleavage fragments can be separated (by HPLC methods) and identified (by MALDI mass spectrometry). The only peptide bonds cleaved were the Gly3-Phe4 bond in methionine enkephalin, Gly4-Gly5 bond in Met-peptide, Gly3-Gly4 in His-peptide, and Gly3-Gly4 and Gly9-Gly10 bonds in HisMet-peptide. We explain this consistent regioselectivity of cleavage by studying the modes of Met-peptide coordination to the Pd(II) ion in [Pd(H(2)O)(4)](2+) complex. In acidic solution, the rapid attachment of the Pd(II) complex to the methionine side chain is followed by the interaction of the Pd(II) ion with the peptide backbone upstream from the anchor. In the hydrolytically active complex, Met-peptide is coordinated to Pd(II) ion as a bidentate ligand - via sulfur atom in the methionine side chain and the first peptide nitrogen upstream from this anchor - so that the Pd(II) complex approaches the scissile peptide bond. Because the increased acidity favors this hydrolytically active complex, the rate of cleavage guided by either histidine or methionine anchor increased as pH was lowered from 4.5 to 0.5. The unwanted additional cleavage of the first peptide bond upstream from the anchor is suppressed if pH is kept above 1.2. Four Pd(II) complexes cleave Met-peptide with the same regioselectivity but at somewhat different rates. Complexes in which Pd(II) ion carries labile ligands, such as [Pd(H(2)O)(4)](2+) and [Pd(NH(3))(4)](2+), are more reactive than those containing anionic ligands, such as [PdCl(4)](2)(-), or a bidentate ligand, such as cis-[Pd(en)(H(2)O)(2)](2+). When both methionine and histidine residues are present in the same substrate, as in HisMet-peptide, 1 molar equivalent of the Pd(II) complex distributes itself evenly at both anchors and provides partial cleavage, whereas 2 molar equivalents of the promoter completely cleave the second peptide bond upstream from each of the anchors. The results of this study bode well for growing use of palladium(II) reagents in biochemical and bioanalytical practice.

An unusual regioselectivity in the Pd-catalyzed cross coupling of alkynes. A correction

Palladium catalyzed additions of terminal alkynes to alkynoates can lead from preferential to exclusive CC bond formation at the α-carbon and, in the case of ethyl 3-dimethylphenylsilylpropiolate, complete selectivity for α-attack, an unprecedented regioselectivity that requires revision of the earlier assignment of regioselectivity.

Reactions of triene-conjugated diazo-compounds: reaction paths from o-(1,3-dienyl)aryldiazomethanes to 3,8-methano-1,2-diazocines and to pyrrolo[2,1-a]phthalazines via intramolecular (3 + 2) and 1,1-cycloaddition reactions

The reaction paths followed by the triene-conjugated diazo-compounds 7, which have α,β aromatic and γ,δ; e,ζ olefinic unsaturation, depend strongly on the nature of the substituents R1 and R2. Those with R1,R2 = (CH2)3, 7a–e, react at room temperature via an intramolecular (3 + 2) cycloaddition reaction of unprecedented regioselectivity to give the bridged benzodiazocines 18a–e in high yield. Those with R1 = Me and R2 = Ph, 7f and 7g, react at 80 °C to give the hydrocarbons 19f,g and, via new chemistry, the pyrrolo[2,1-a]phthalazines 24f,g. The structures of compounds 18a, 19a and 24f have been determined by X-ray crystallography.

One-step synthesis of 2,3-dihydronaphtho[2,3-b]thiophene-4,9-diones by a new regioselective [3 + 2] photoaddition of photogenerated 2-mercapto-1,4-naphthoquinone with alkenes

2,3-Dihydronaphtho[2,3-b]thiophene-4,9-diones are formed in one-step reactions in 6–41 % yields by an unprecedented regioselective (3 + 2] photoaddition of 2-mercapto-1,4-naphthoquinone, generated by the photochemical decarbonylation of 5-hydroxynaphth[2,1-d]-1,3-oxathiol-2-one, with alkenes.