Selective Allylation Research Articles

Iridium-Catalyzed, Highly Selective Allylation of Pyrazolones for the Convenient Construction of Adjacent Stereocenters.

This paper describes an iridium-catalyzed allylation of ring-fused pyrazolones that proceeds with excellent regio-, diastereo- and enantio-selectivities. The approach exploits unactivated, racemic allylic alcohols as a source of allyl building blocks. Asymmetric syntheses of a series of biologically relevant, chiral pyrazolones highlight the utility of the methodology. The use of Cu(OTf)2 as a co-catalyst greatly enhances the regioselectivity of the reaction and permits selective syntheses of branched allylation products.

Direct Asymmetric Synthesis of α-Aminoimines from 1,2-Bis-N-Sulfinylimines by Using Allyl Boronic Acids.

A unique direct asymmetric synthesis of α-aminoimines is realized, through rapid and exclusive mono-allylation of chiral bis-N-sulfinylimines using allylboronic acids. The highly selective allylation was possible as electrophilic imine functional group in the product α-aminoimines remained unreactive towards allyl boronic acid nucleophiles. Notably, by varying the geometry and chiral auxiliary, all four isomers of the α-aminoimines were accessed from readily available precursors. A range of allyl nucleophiles, which are tricky to generate by other means possessing highly reactive functional groups also took part in this reaction, expanding the scope further. The applicability of the products α-aminoimines were further demonstrated by accessing a range of structurally diverse chiral cyclic and acyclic 1,2-diamines bearing adjacent stereocenters through addition of a second nucleophile or aza-Prins-type cyclization by exploiting the nucleophilicity of the tethered alkene moiety. Moreover, the leaving group aptitude of sulfinyl auxiliary attached to imine, was exploited to access valuable chiral α-aminonitriles under thermal conditions without employing any reagents. Detailed DFT calculation revealed a chair-like transition state likely operating for the allylboration reaction across imine.

Direct Asymmetric Synthesis of α‐Aminoimines from 1,2‐Bis‐N‐Sulfinylimines by Using Allyl Boronic Acids

AbstractA unique direct asymmetric synthesis of α‐aminoimines is realized, through rapid and exclusive mono‐allylation of chiral bis‐N‐sulfinylimines using allylboronic acids. The highly selective allylation was possible as electrophilic imine functional group in the product α‐aminoimines remained unreactive towards allyl boronic acid nucleophiles. Notably, by varying the geometry and chiral auxiliary, all four isomers of the α‐aminoimines were accessed from readily available precursors. A range of allyl nucleophiles, which are tricky to generate by other means possessing highly reactive functional groups also took part in this reaction, expanding the scope further. The applicability of the products α‐aminoimines were further demonstrated by accessing a range of structurally diverse chiral cyclic and acyclic 1,2‐diamines bearing adjacent stereocenters through addition of a second nucleophile or Prins‐type cyclization by exploiting the nucleophilicity of the tethered alkene moiety. Moreover, the leaving group aptitude of sulfinyl auxiliary attached to imine, was exploited to access valuable chiral α‐aminonitriles under thermal conditions without employing any reagents. Detailed DFT calculation revealed a chair‐like transition state, arising from corresponding allylboroxine species, likely operating for the allylboration reaction across imine.

Palladium-catalyzed (Z)-selective allylation of phosphine oxides with vinylethylene carbonates to construct phosphorus allyl alcohols.

Allylphosphine oxide compounds are important building blocks with broad applications in organic synthesis and pharmaceutical science. Herein, we report an unprecedented palladium-catalyzed allylation of phosphine oxides with vinylethylene carbonates, producing various phosphorus allyl alcohols in excellent yields with high Z-selectivity. In addition, gram-scale synthesis and further functional group transformations demonstrate the practical utility of this synthetic method.

Palladium-Catalyzed para-Selective Allylation of 1-(Cyanomethyl)arenes with Allyl Acetates.

The Pd/PMe3-catalyzed allylation of 1-(cyanomethyl)naphthalenes with allyl acetates proved to be para- rather than α-regioselective. This reaction is thought to proceed through ligand attack of the para-carbon in the arenes, electronically enriched by a cyano-stabilized α-carbanion, to the (π-allyl)palladium and a 1,5-hydrogen shift of the para-hydrogen from the dearomatized intermediate.

An umpolung mechanism of B(pin)-mediated Cu/B rearrangement and origin of regioselectivity for NHC-Cu-catalyzed allylation of imines

An umpolung mechanism of B(pin)-mediated Cu/B rearrangement in copper-catalyzed selective allylation of imines, and the effect of the substituent in the C1 site of allyl and its conformation on the regioselectivity of the reaction.

Selective N-allylation via SN2ꞌ reaction: Synthesis, characterization, crystal structure, theoretical and biological studies of Ethyl (E)-2-(4-aminobenzene-1-sulphonylimino-thiazol-3-yl-methyl)-3-phenyl acrylate

The title compound ethyl (E)-2-(4-aminobenzene-1-sulphonylimino-thiazol-3-yl-methyl)-3-phenyl acrylate (BH-STZ) was synthesized by an SN2ꞌ reaction between 1:1 ratio of Ethyl 2-(acetoxy phenyl-methyl) acrylate (BH) and 4-amino-N-(1,3-thiazol-2-yl) benzenesulphonamide (STZ). It was characterized by FT-IR, 1H NMR, 13C NMR, DEPT 135, Mass, elemental analysis, and SCXRD. This study investigates the selective allylation of STZ at the secondary amine nitrogen over the primary amine nitrogen. It has been confirmed by the crystal structure of BH-STZ. In the BH-STZ, the hydrogen bonding interaction between primary amine and sulphonyl oxygen (NH.O) forms the β dimer. The photophysical properties (UV absorption and fluorescence emission) of BH-STZ have been studied. The theoretical FT-IR, UV, and SCXRD calculations based on density functional theory correlated well with the experimental results. The HOMO–LUMO energy gap indicated that BH-STZ has good chemical stability and lower hardness. The in vitro antibacterial activity of BH-STZ against a panel of pathogenic bacteria was assayed by the disc diffusion method. These results were compared with molecular docking studies between BH-STZ and the respective target protein from the bacteria. The compound was shown to be non-toxic to normal cells by both in vitro (using bacterial pathogen) and in vivo (using zebrafish) studies.

Resolving m6A epitranscriptome with stoichiometry

A recent study by Hu et al. describes N6-methyladenosine (m6A)-selective allyl chemical labeling and sequencing (m6A-SAC-seq), which allows for quantitative, stoichiometric, and positional analyses of m6A at single-nucleotide resolution across the whole transcriptome level. Information on the m6A stoichiometry will provide additional layers of gene regulatory pathways mediated by m6A modification during diverse molecular, cellular, and physiological events.

Palladium-catalyzed decarboxylative O-allylation of phenols with γ-methylidene-δ-valerolactones

A novel palladium-catalyzed decarboxylative O-allylation of phenols was developed, in which a GMDV was found to be an efficient and selective allylation reagent, affording the target allyl phenyl ethers in up to 92% yields.

Pyridylic anions are soft nucleophiles in the palladium-catalyzed C(sp3)-H allylation of 4-alkylpyridines.

We report a mild palladium-catalyzed method for the selective allylation of 4-alkylpyridines in which highly basic pyridylic anions behave as soft nucleophiles. This method exploits alkylidene dihydropyridines, which are semi-stable intermediates readily formed using a ‘soft-enolization’ approach, in a new mechanistic manifold for decarboxylative allylation. Notably, the catalytic generation of pyridylic anions results in a substantially broader functional group tolerance compared to other pyridine allylation methods. Experimental and theoretical mechanistic studies strongly suggest that pyridylic anions are indeed the active nucleophiles in these reactions, and that they participate in an outer-sphere reductive elimination step. This finding establishes a new pKa boundary of 35 for soft nucleophiles in transition metal-catalyzed allylations.

Study on the Copper-Catalyzed Selective Allylation of Aryl (or Alkyl) Halides

Study on the Copper-Catalyzed Selective Allylation of Aryl (or Alkyl) Halides

Diastereoselectivity Switch in the Pd(0)/InI-Mediated Reactions of β-Lactams with Aldehydes: An Entry into Nonracemic Semiprotected (3E)-2,6-Enediols.

The switch from N-methylimidazole (N-MI) to the Et3N N-ligand efficiently alters diastereoselectivity in Pd(0)/InI-mediated allylations of aldehydes with β-lactam-derived organoindiums. As a result, (3E)-selective allylations and crotylations of a variety of aliphatic and (hetero)aromatic aldehydes with differently substituted chiral ε-amido-allylindiums were developed. Depending on the relative β-lactam configuration, the reactions occur under kinetic or thermodynamic control, with effective remote 1,5- or 1,4,5-asymmetric induction to afford a diversity of previously unavailable (3E)-2,5-syn-2,6-anti-, (3E)-2,5-anti-2,6-anti-, and (3E)-2,5-anti-2,6-syn-substituted enediols, amino alcohols, and homoallylic alcohols in modest to high yields and with moderate to excellent diastereoselectivity. The effect of the N-ligand as well as β-lactam and aldehyde structures on the yield and stereoselectivity was investigated.

Copper-Catalyzed Umpolung of Imines through Carbon-to-Nitrogen Boryl Migration

We report a general strategy for the catalytic umpolung of imines, which was enabled by an unprecedented 1,2-boryl carbon-to-nitrogen migration. Based on the discovery of a rearrangement of an α-borylalkylamido copper intermediate to an α-borylaminoalkyl copper species through 1,2-migration of a boryl group from carbon to nitrogen and copper migration from nitrogen to carbon, we have developed a copper-catalyzed selective allylation of a wide range of aldimines and ketimines with allyl electrophiles in the presence of B2(pin)2 and LiOtBu. We expect this catalytic imine-umpolung strategy may derive useful methodologies for the synthesis of various functionalized amines.

Highly N2-selective allylation of NH-1,2,3-triazoles with allenamides mediated by N-iodosuccinimide

We report a new protocol to synthesize N2-allyl-substituted 1,2,3-triazoles via NIS mediated allylation of allenamides with NH-1,2,3-triazoles.

Palladium-Catalyzed ( Z)-Selective Allylation of Nitroalkanes: Access to Highly Functionalized Homoallylic Scaffolds.

Nitroalkanes undergo decarboxylative allylation in the presence of vinyl-substituted cyclic carbonates, providing a wide variety of functionalized homoallylated compounds with exquisite stereocontrol. This Pd-mediated procedure features operational simplicity, versatile substrate combinations, and also allows for the sequential introduction of different allyl groups in the nitroalkane scaffolds with high levels of stereocontrol through the intermediacy of a ( Z)-configured palladacyclic intermediate. As far as we know, the developed protocol is the first general Pd-mediated methodology toward ( Z)-configured homoallylic nitroalkanes with attractive functional group diversity.

Scalable Sn-Catalyzed Regioselective Allylation of 1-Methyl-l-α-rhamnopyranoside

A robust selective allylation of 1-methyl-l-α-rhamnose was developed using di-n-butyltin oxide (n-Bu2SnO) as the catalyst. Proton sponge was found to be the optimal base for high regioselective control. The optimized condition afforded the 3-O-allylated rhamnose in excellent regioselectivity (>20:1) and 82% isolated yield on a 50 g scale. A scalable isolation/purification process was developed which afforded the desired product in 72% yield with 1530 ppm of Sn. The residual Sn level can be further reduced to <20 ppm by treatment with scavengers. This catalytic system also showed outstanding potential in the selective benzylation of the same substrate.

Enantioselective and Regiodivergent Addition of Purines to Terminal Allenes: Synthesis of Abacavir.

The rhodium-catalyzed atom-economic asymmetric N-selective intermolecular addition of purine derivatives to terminal allenes is reported. Branched allylic purines were obtained in high yields, regioselectivity and outstanding enantioselectivity utilizing a Rh/Josiphos catalyst. Conversely, linear selective allylation of purines could be realized in good to excellent regio- and E/Z-selectivity with a Pd/dppf catalyst system. Furthermore, the new methodology was applied to a straightforward asymmetric synthesis of carbocyclic nucleoside abacavir.

Enantioselective and Regiodivergent Addition of Purines to Terminal Allenes: Synthesis of Abacavir

AbstractThe rhodium‐catalyzed atom‐economic asymmetric N‐selective intermolecular addition of purine derivatives to terminal allenes is reported. Branched allylic purines were obtained in high yields, regioselectivity and outstanding enantioselectivity utilizing a Rh/Josiphos catalyst. Conversely, linear selective allylation of purines could be realized in good to excellent regio‐ and E/Z‐selectivity with a Pd/dppf catalyst system. Furthermore, the new methodology was applied to a straightforward asymmetric synthesis of carbocyclic nucleoside abacavir.

ChemInform Abstract: Catalytic Enantioselective Assembly of Homoallylic Alcohols from Dienes, Aryldiazonium Salts, and Aldehydes.

A highly selective multicomponent carbonyl allylation reaction of 1,3-butadienes, aryldiazonium tetrafluoroborates, and aldehydes has been established under the combined catalysis of palladium acetate and chiral anion phase transfer to render the favorable assembly of chiral Z-configured homoallylic alcohols in high yields and with excellent levels of enantioselectivity.

ChemInform Abstract: Stereoselective Synthesis of C13—C28 Fragment of Marinomycin A.

Synthesis of the C13–C28 fragment of marinomycin A, consisting of all the five stereocenters, was achieved by asymmetric synthesis, starting from l -malic acid. The simple convergent approach utilized cross metathesis of two key olefinic fragments for the introduction of the C20–C21 double bond. Two of the five stereocenters, C19 and C27, were realized from l -malic acid, while, C17 and C23 are introduced by Sharpless asymmetric epoxidation and C25 by a selective allylation reaction.