Aryl Propargylic Alcohols Research Articles

Brønsted Acid‐Promoted Benzannulation of o‐Alkynylbenzaldehyde and Alkyne, and the Positive Effect of Propargyl Alcohol

AbstractBromotrimethylsilane‐promoted benzannulation of o‐alkynylbenzaldehydes and alkynes to yield 1‐naphthyl aryl ketones is reported. The reaction conditions are mild, metal‐free, and do not require pretreatment/protection of the substrates. We found that aryl propargyl alcohols were very effective substrates for this reaction, compared with other alkynes. Studies on the reaction scope, monitoring the reaction progress by 1H NMR, and theoretical calculations suggest that isochromenylium (benzopyrilium) ion is the key reaction intermediate.magnified image

Rhodium(II)‐Catalyzed Formal [4+1]‐Cycloaddition of Pyridotriazoles and Propargyl Alcohols: Synthesis of 2,5‐Dihydrofurans

AbstractA rhodium‐catalyzed formal [4+1]‐cycloaddition of pyridotriazoles and aryl propargyl alcohols is reported, providing an effective access to 2‐pyridyl‐substituted 2,5‐dihydrofuran derivatives in moderate to high yields. Mechanistically, the proposed oxonium ylide intermediate in this catalytic alkyne carbocyclization transformation is verified by an interception experiment for the first time.magnified image

Palladium-catalyzed deacetonative coupling of aryl propargylic alcohols with aryl chlorides in water

ABSTRACTA highly efficient and green process for palladium-catalyzed deacetonative coupling of aryl propargylic alcohols with aryl chlorides has been developed. The reaction occurs smoothly in neat water with 2 mol% PdCl2 as catalyst, and various synthetically useful functional groups, including ether, aldehyde, ketone, and heterocyclics, are well tolerated. Moreover, the reaction could proceed through a consecutive Sonogashira/deacetonative process using 2-methyl-3-butyn-2-ol and aryl chlorides as coupling partners, affording the symmetric alkynes in good yields.

Electrophilic Cyclization of Aryl Propargylic Alcohols: Synthesis of Dihalogenated 6,9-Dihydropyrido[1,2-a]indoles via a Cascade Iodocyclization.

A strategy for the synthesis of 6,9-dihydropyrido[1,2-a]indoles through a cascade iodocyclization of 4-(3-methyl-1H-indol-1-yl)-1,1-diphenylbut-2-yn-1-ol derivatives is presented. This reaction was conducted under very mild conditions and in a short time. The reactions are metal-free, are environmentally friendly and give up to 94% yield. Moreover, the obtained halides allow functional group diversification by palladium-catalyzed coupling reactions, which could act as potential intermediates for the synthesis of valuable compounds.

ChemInform Abstract: Synthesis of Carbazoles and Carbazole‐Containing Heterocycles via Rhodium‐Catalyzed Tandem Carbonylative Benzannulations.

Polycyclic aromatic compounds are important constituents of pharmaceuticals and other materials. We have developed a series of Rh-catalyzed tandem carbonylative benzannulations for the synthesis of tri-, tetra-, and pentacyclic heterocycles from different types of aryl propargylic alcohols. These tandem reactions provide efficient access to highly substituted carbazoles, furocarbazoles, pyrrolocarbazoles, thiophenocarbazoles, and indolocarbazoles. While tricyclic heterocycles could be derived from vinyl aryl propargylic alcohols, tetra- and pentacyclic heterocycles were synthesized from diaryl propargylic alcohols. The tandem carbonylative benzannulation is initiated by a π-acidic rhodium(I) catalyst-mediated nucleophilic addition to alkyne to generate a key metal-carbene intermediate, which is then trapped by carbon monoxide to form a ketene species for 6π electrocyclization. Overall, three bonds and two rings are formed in all of these tandem carbonylative benzannulation reactions.

Synthesis of Carbazoles and Carbazole-Containing Heterocycles via Rhodium-Catalyzed Tandem Carbonylative Benzannulations.

Polycyclic aromatic compounds are important constituents of pharmaceuticals and other materials. We have developed a series of Rh-catalyzed tandem carbonylative benzannulations for the synthesis of tri-, tetra-, and pentacyclic heterocycles from different types of aryl propargylic alcohols. These tandem reactions provide efficient access to highly substituted carbazoles, furocarbazoles, pyrrolocarbazoles, thiophenocarbazoles, and indolocarbazoles. While tricyclic heterocycles could be derived from vinyl aryl propargylic alcohols, tetra- and pentacyclic heterocycles were synthesized from diaryl propargylic alcohols. The tandem carbonylative benzannulation is initiated by a π-acidic rhodium(I) catalyst-mediated nucleophilic addition to alkyne to generate a key metal-carbene intermediate, which is then trapped by carbon monoxide to form a ketene species for 6π electrocyclization. Overall, three bonds and two rings are formed in all of these tandem carbonylative benzannulation reactions.

Pd(II)-catalyzed formal [4+1] cycloaddition reactions of diazoacetates and aryl propargyl alcohols to form 2,5-dihydrofurans.

A Pd(II)-catalyzed formal [4+1] cycloaddition of aryl diazoacetates and aryl propargyl alcohols is reported to afford 2,5-dihydrofuran derivatives as the dominant product over other traditional ones. The auto-tandem catalytic process is proposed to occur via Pd(II)-catalyzed intermolecular oxonium ylide formation and subsequent intramolecular trapping of the ylide with Pd(II)-activated alkynes.

ChemInform Abstract: On the Hydrostannylation of Aryl Propargylic Alcohols and Their Derivatives: Remarkable Differences in Both Regio‐ and Stereoselectivity in Radical‐ and Nonradical‐Mediated Transformations.

Herein, we describe a highly regio- and stereoselective radical-mediated and molecular-oxygen (O2 )-dependent hydrostannylation of phenyl propargylic alcohols and their derivatives. There is a significant steric effect on the stereoselectivity of the tin-radical addition. Further, the uncatalyzed regio- and stereoselective hydrostannylation of aryl propargylic alcohols with nBu3 SnH and Ph3 SnH is also described and occurs with near titration kinetics. Although the uncatalyzed addition with nBu3 SnH gave a remarkable γ-regioselectivity irrespective of the electronic nature of the aryl moiety, addition with Ph3 SnH appears to be driven by the electronic nature of the aryl alkynes.

IrCp*(NCMe)2(PPh2Me)][PF6]2 as Catalyst for the Meyer–Schuster Rearrangement of Arylpropargylic Alcohols under Mild Conditions

AbstractThe novel iridium complex [IrCp*(NCMe)2(PPh2Me)][PF6]2 (I) efficiently catalyzed the Meyer–Schuster rearrangement of selected arylpropargylic alcohols into α,β‐unsaturated aldehydes under mild conditions and without the need of a co‐catalyst. A mechanism involving a (hydroxy)alkenylcarbene intermediate is proposed.

On the hydrostannylation of aryl propargylic alcohols and their derivatives: remarkable differences in both regio- and stereoselectivity in radical- and nonradical-mediated transformations.

Herein, we describe a highly regio- and stereoselective radical-mediated and molecular-oxygen (O2 )-dependent hydrostannylation of phenyl propargylic alcohols and their derivatives. There is a significant steric effect on the stereoselectivity of the tin-radical addition. Further, the uncatalyzed regio- and stereoselective hydrostannylation of aryl propargylic alcohols with nBu3 SnH and Ph3 SnH is also described and occurs with near titration kinetics. Although the uncatalyzed addition with nBu3 SnH gave a remarkable γ-regioselectivity irrespective of the electronic nature of the aryl moiety, addition with Ph3 SnH appears to be driven by the electronic nature of the aryl alkynes.

Palladacycle-Catalyzed Deacetonative Sonogashira Coupling of Aryl Propargyl Alcohols with Aryl Chlorides

An efficient and general protocol for the deacetonative Sonogashira coupling of aryl propargyl alcohols with aryl chlorides is described. The reaction proceeded smoothly with the catalyst system of palladacycle/Xphos. This result represents the first successful deacetonative Sonogashira version for electron-poor, electron-neutral, and even inactive sterically hindered electron-rich aryl chlorides.

Oxygenation of Ruthenium Carbene Complexes Containing Naphthothiophene or Naphthofuran: Spectroscopic and DFT Studies

The aryl propargylic alcohol 1-[2-(thiophen-3-yl)phenyl]prop-2-yn-1-ol (1a) is readily prepared from 2-(thiophen-3-yl)benzaldehyde. In the presence of visible light, treatment of 1a with one-half mole equivalent of [Ru]Cl ([Ru]=Cp(dppe)Ru) (dppe=1,2-bis(diphenylphosphino)ethane) and NH4PF6 in O2 affords the naphtha[2,1-b]thiophene-4-carbaldehyde (4a) in high yields. The cyclization reaction of 1a proceeds through the formation of the carbene complex 2a that contains the naphtha[2,1-b]thiophene ring, which is isolated in a 1:1 stoichiometric reaction. The C-C bond formation between the inner carbon of the terminal triple bond and the heterocyclic ring is confirmed by structure determination of 2a using single-crystal X-ray diffraction analysis. Facile oxygenation of 2a by O2 yields the aldehyde product 4a accompanied by the formation of phosphine oxide of dppe. Oxygen is most likely activated by coordination to the ruthenium center when one PPh2 unit of the dppe ligand dissociates. This dissociated PPh2 unit then reacts with the coordinated oxygen nearby to generate half-oxidized dppe ligand and an unobserved oxo-carbene intermediate. Coupling of the oxo/carbene ligands followed by demetalation then yields 4a. Presumably the resulting complex with the half-oxidized dppe ligand continuously promotes cyclization/oxygenation of 1a to yield the second aldehyde molecule. In alcohol such as MeOH or EtOH, the oxygenation reaction affords a mixture of 4a and the corresponding esters 5a or 5a'. Four other aryl propargylic alcohols 1b-e, which contain thiophen-2-yl, isopropenyl, fur-3-yl, and fur-2-yl, respectively, on the aryl ring are also prepared. Analogous aldehydes 4b-e are similarly prepared from 1b-e, respectively. For oxygenations of 1b, 1d, and 1e in alcohol, mixtures of aldehyde 4, ester 5, and acetal 8 are obtained. The carbene complex 2b obtained from 1b was also characterized by single-crystal X-ray diffraction analysis. The UV/Vis spectra of 2a and 2b consist of absorption bands with a high extinction coefficient. From DFT calculations on 2a and 2b, the visible light is found to populate the LUMO antibonding orbital of mainly Ru=C bonds, thereby weakening the Ru=C bond and promoting the oxygenation/demetalation reactions of 2.

Stereoselective Synthesis of 1,3-Dienes from Propargylic Alcohols by LiAlH4/AlCl3

Herein we report that LiAlH4/AlCl3 is a very efficient reagent for the reductive dehydration of aryl propargylic alcohols in tetrahydrofuran solvent at reflux to give 1,3-dienes with good yields and high E selection. The reaction conditions are mild and easy to operate, and a variety of aryl functional groups, such as bromo, fluoro, butyl, and methoxyl groups, are tolerated. With our protocol, useful (E,E)-1,3-dienes can be synthesized. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

Copper-Catalyzed Regioselective Reaction of Internal Alkynes and Diaryliodonium Salts

The copper-catalyzed highly regioselective reaction of internal alkynes with diaryliodonium salts was achieved for the first time. α-Arylketones were obtained in moderate to good yields from arylpropargylic alcohols or aryl alkyl alkynes under mild conditions. It was found that the two kinds of substrates underwent two different arylation-oxygenation pathways under different reaction conditions based on deuterated experiments, controlling experiments, and spectroscopic analysis of reaction intermediates.

A novel convenient approach towards pyrrolo[1,2-b]pyridazines through a domino coupling–isomerization–condensation reaction

A novel Pd/Cu catalyzed domino reaction for the synthesis of functionalized pyrrolo[1,2-b]pyridazines from readily accessible (hetero)aryl propargyl alcohols and 1-amino-2-bromopyrroles was developed. This cascade process involves a Sonogashira cross-coupling reaction, an isomerization and an intramolecular condensation.

ChemInform Abstract: Tandem Amination/Cycloisomerization of Aryl Propargylic Alcohols with 2‐Aminopyridines as an Expedient Route to Imidazo[1,2‐a]pyridines.

AbstractImidazo[1,2‐a]pyridines are prepared in a new tandem route from aryl propargylic alcohols (I) and 2‐aminopyridines in the presence of ZnCl2 and CuCl.

Tandem Amination/Cycloisomerization of Aryl Propargylic Alcohols with 2‐Aminopyridines as an Expedient Route to Imidazo[1,2‐a]pyridines

AbstractA new tandem route leading to imidazo[1,2‐a]pyridines has been explored through the direct amination of aryl propargylic alcohols with 2‐aminopyridines and their subsequent intramolecular cycloisomerization. A ZnCl2/CuCl system has been developed to promote this transformation, which resulted in various imidazo[1,2‐a]pyridines in moderate to good yields.

ChemInform Abstract: Facile Synthesis of Diiodinated Dihydronaphthalenes and Naphthalenes via Iodine Mediated Electrophilic Cyclization.

AbstractA variety of dihydronaphthalenes is readily prepared by electrophilic iodocyclization of aryl propargyl alcohols.

ChemInform Abstract: Electrophilic Carbocyclization of Aryl Propargylic Alcohols: A Facile Synthesis of Diiodinated Carbocycles and Heterocycles.

AbstractThe presence of a trace of water is essential for the reaction.

Iron(III) Chloride–Promoted Isomerization of Propargyl Alcohols to α,β-Unsaturated Carbonyl Compounds

Aryl propargyl alcohols bearing a terminal alkynyl moiety can undergo a facile iron(III) chloride–promoted transformation to the corresponding α,β-unsaturated aldehyde in good yield and excellent stereoselectivity.