Barbier Type Research Articles

Zinc/Bismuth-Mediated Allylation Reaction of Biomass Feedstocks: Synthesis of Furanic Diols

AbstractBiomass-based diols have been synthesized by a Zn/Bi-mediated Barbier-type of reaction from furanic aldehydes and allyl halides to access allylated diols. The allylated diols can be readily converted into alkylated diols by hydrogenation. These furanic diols could be potential replacements for fossil fuel based bisphenol A (BPA) which has an adverse endocrine-disrupting effect on humans. This mild and green protocol provides symmetric and nonsymmetric diols in high yields. A chemoselective reduction of allylic double bonds provides diols with unique substitution.

Synthesis of 12‐epi‐Protopanaxadiol and Formal Synthesis of Ginsenoside Chikusetsusaponin‐LT8

In the context of the total synthesis of protopanaxadiol, two strategies were explored. One strategy from an optically active trienic epoxide, possessing a 5‐membered ring, prepared from (S)‐epoxy‐limonene and (S)‐epoxyfarnesol, which was submitted to Ti‐(III)‐mediated radical cascade to afford an original tetracyclic structure resulting from a 6‐endo‐trig 6‐endo‐trig 8‐endo‐trig process. A second strategy, starting from a Wieland‐Miescher‐type ketone, using a “ring‐by‐ring” synthesis allowed the synthesis of 12‐epi‐protopanaxadiol. In this latter strategy, an efficient sequence of reactions to install the two vicinal C8–C14 quaternary centers involves: i) a Barbier type reaction; ii) an oxidative allylic transposition and iii) a nickel‐catalyzed addition of trimethylaluminium. By using this second strategy, 20‐hydroxydammar‐24‐ene‐3,12‐dione was synthesized which represents a formal synthesis of chikusetsusaponin‐LT8, isolated from Panax japonicus.

An Example of Ketone Olefination via Praseodymium-Mediated Barbier Reaction in the Presence of Diethyl Phosphite

The first example of carbon double-bond formation via praseodymium-mediated Barbier type reaction of ketones and allyl halides in the presence of diethyl phosphite is reported. The reaction is highly α-regioselective and conveniently carried out under mild conditions in a one-pot fashion. From a synthetic point of view, a series of conjugated alkenes were obtained in moderate to good yields in this one-pot reaction with practical reaction conditions.

Studies towards iodine-catalyzed dehydrative-cycloisomerization of pent-4-yne-1,2-diols to di- and tri-substituted furans

An efficient and single-step iodine catalyzed and metal-free synthesis of di and tri-substituted 2-methylfuran derivatives were achieved from 1-popargyl-1,2-diols. Stereospecific synthesis of starting 1,2-diols was achieved by indium mediated Barbier type propargylation on corresponding keto-alcohols or by sodium borohydride mediated reduction of 2-hydroxy-2-propargyl ketones. The furan synthesis proceeded through iodine mediated 5-exo-trig cyclization, dehydration and reductive deiodination. The method was applied to the synthesis of 2-methylfuran fused to phenanthrene, pyrene and acenaphthylene rings.

Proline-Catalyzed Asymmetric α-Amination in the Synthesis of Bioactive Molecules

The direct α-amination of carbonyl compounds using organocatalysts represents a powerful and atom-economical tool for asymmetric C–N bond formation. We describe a complete account of α-functionalization of carbonyl compounds, through iterative sequential α-aminoxylation/amination using electrophilic O and N sources, as well as sequential α-amination/HWE reaction for enantio- and diastereoselective synthesis of both syn- and anti-1,3-aminoalcohols and 1,3-diamines. Additionally this protocol is further extended for the easy construction of alkaloids such as indolizidine, pyrrolizidine, and quinolizidine fused-ring systems just by tuning the chain length of the aldehyde used as a starting material. This methodology provides further scope to extrapolate it for a variety of naturally occurring hydroxylated monocyclic and fused bicyclic pyrrolidine and piperidine based alkaloids such as lentiginosine, epi-lentiginosine, dihydroxypyrrolizidine, (+)-deoxoprosophylline and (–)-deoxoprosopinine alkaloids. Furthermore, we have also uncovered proline-catalyzed anti-selectivity for the synthesis of 1,2-amino alcohols in α-amination of aldehyde and one-pot indium-mediated Barbier type allylation of α-hydrazino aldehydes to accomplish the total synthesis of clavaminols, sphinganine and spisulosine with reduced number of steps and with high overall yields.1 Introduction2 Application in the Total Synthesis of Alkaloids3 Conclusion

Indium‐Mediated Domino Allylation‐Lactonisation Approach: Diastereoselective Synthesis of β‐Carboline C‐3 Tethered α‐Methylene γ‐Butyrolactones

AbstractA facile and convenient tandem approach has been devised towards the diastereoselective synthesis of β‐carboline C‐3 tethered α‐methylene γ‐butyrolactones via indium‐promoted Barbier Type allylation reaction followed by in situ intramolecular lactonisation protocol. Interestingly, no additive was required for this transformation and the products were obtained with syn stereochemistry.

A Tandem Approach towards Diastereoselective Synthesis of Quinoline C‐3 Tethered γ‐Lactones

AbstractA convenient approach has been developed for the facile synthesis of novel quinoline and α‐methylene γ‐butyrolactones based molecular hybrids. The tandem synthesis of quinoline C‐3 tethered lactone derivatives was achieved via indium‐mediated Barbier Type allylation followed by in situ intramolecular lactonisation approach.

Photocatalytic Barbier reaction - visible-light induced allylation and benzylation of aldehydes and ketones.

We report a photocatalytic version of the Barbier type reaction using readily available allyl or benzyl bromides and aromatic aldehydes or ketones as starting materials to generate allylic or benzylic alcohols. The reaction proceeds at room temperature under visible light irradiation with the organic dye 3,7-di(4-biphenyl)1-naphthalene-10-phenoxazine as a photocatalyst and DIPEA as sacrificial electron donor. The proposed cross-coupling mechanism of a ketyl- and an allyl or benzyl radical is supported by spectroscopic investigations and cyclic voltammetry measurements.

Stereoselective Synthesis of Dipeptidyl Peptidase‐4 (DPP‐4) Inhibitor, (R)‐Sitagliptin

AbstractAn operationally simple and efficient strategy for a highly potent Dipeptidyl Peptidase‐4 (DPP‐4) inhibitor, sitagliptin has been developed employing readily available precursors. The chiral β‐amino acid core of sitagliptin has been constructed through a Barbier type allylation of chiral sulfinyl imine or a Mannich type addition of diethyl malonate. This approach is more convenient, exquisitely selective and practical.

Waste management in zinc promoted allylation of aldehyde

The waste zinc material in Zn(0) promoted Grignard–Barbier type allylation of aldehydes has been successfully utilized as a reusable material for the adsorption of various dyes and also converted into the corresponding hexagonal wurtzite phase of ZnO.

ChemInform Abstract: CuI Catalyzed Barbier Type Allylation of Aldehyde in Presence of S1,S2‐Dipyridin‐2‐yl Ferrocene‐1,1′‐dicarbothioate as Ligand.

AbstractThe introduced method gives very good yields of allylated product (III) of both aromatic as well as aliphatic aldehyde within a short time.

Total synthesis of decytospolides A, B and a formal synthesis of aspergillide A starting from d-mannitol via tandem/domino reactions by Grubb’s catalysts

A simple, short, efficient, and concise approach for the synthesis of decytospolides A, B and partial synthesis of aspergillide A was achieved from d-mannitol. The key steps employed in this approach are a Barbier type allylation, an epoxide opening by Grignard reagent, a chelation controlled reduction, tandem or domino (olefin cross-metathesis/intramolecular oxa-conjugate cyclization by Hoveydas–Grubb’s 2nd generation and olefin cross-metathesis/SN2 reaction with Grubb’s 2nd generation catalyst) processes.

ChemInform Abstract: Bismuth Chloride Mediated Allylation of Carbonyl Compounds in Aqueous Media: A Mechanistic Investigation

Abstractthe reactive species is CH2=CHCH2BiBr2

Bismuth chloride mediated allylation of carbonyl compounds in aqueous media: a mechanistic investigation

The bismuth chloride mediated, aluminum promoted aqueous Barbier type coupling of allyl unit with carbonyl compounds which gives the corresponding homoallyl alcohol is studied. The transient in situ generated allylbismuth(III) bromide intermediate was studied by 1H NMR and GCMS for mechanistic study of allylation. The role of solvent, temperature, and additives in their formation is also studied. The results show that the most reactive intermediate species is CH2CHCH2BiBr2 which mediates allylation of aldehydes and ketones with different substituents with good yields.

Rapid access to homoallylic alcohols via Pd(OAc)2 catalyzed Barbier type allylation in presence of DMAP

DMAP was found to accelerate significantly the rate of Pd(OAc)2 catalyzed Barbier type allylation of carbonyl compounds by allylbromide using SnCl2·2H2O as reducing agent. Both aldehyde as well as ketones produced excellent yields within a short reaction time in the presence of 3mol% of Pd(OAc)2 and 12mol% of DMAP at room temperature. Aldehydes could be allylated within 5–10min whereas, in case of ketones, the reaction completes in 45–120min.

An efficient synthesis of homoallylic amides via magnesium mediated Barbier type allylation of imines

An efficient method for the synthesis of homoallylic amides by the reaction of Mg foil, allyl bromide and imines in THF at room temperature is reported. This Barbier type allylation provides a straightforward and new method for the preparation of homoallylic amides.

Indium-mediated regioselective mono-allylation of 1,5-dicarbonyl compounds and dehydrative cyclization to 2,3-dihydro-4H-pyran-4-ones and 3,4-dihydro-2H-[1,4]oxazines

An indium-mediated Barbier type mono-allylation of 1,5-dicarbonyl compounds and a subsequent acid-catalyzed dehydrative cyclization afforded 2,3-dihydro-4H-pyran-4-ones and 3,4-dihydro-2H-[1,4]oxazines.

ChemInform Abstract: Tin‐Mediated Barbier Type Allylation in Ionic Liquids.

Abstract The Barbier type allylation of carbonyl compounds is a useful organic transformation as the resultant homoallylic alcohols are important building blocks for many biologically active molecules. Tin mediated Barbier allylation of different carbonyl compounds in room temperature ionic liquid, [BMIM][BF 4 ] afforded the corresponding homoallylic alcohols in good to excellent yields. The ionic liquid was successfully recycled and reused in allylation reactions.

Facile synthesis of γ-alkenylbutenolides from Baylis–Hillman adducts: consecutive in-mediated Barbier allylation, PCC oxidation, isomerization, and Zn-mediated Barbier allylation

Alkenylbutenolides were synthesized regioselectively in good to moderate yields from Baylis–Hillman adducts via a consecutive indium-mediated Barbier type reaction between Baylis–Hillman bromide and aldehyde, PCC oxidation of the homoallylic alcohol, double bond isomerization, and zinc-mediated Barbier type alkenylation protocol.

Tin mediated Barbier type allylation in ionic liquids

The Barbier type allylation of carbonyl compounds is a useful organic transformation as the resultant homoallylic alcohols are important building blocks for many biologically active molecules. Tin mediated Barbier allylation of different carbonyl compounds in room temperature ionic liquid, [BMIM][BF4] afforded the corresponding homoallylic alcohols in good to excellent yields. The ionic liquid was successfully recycled and reused in allylation reactions.