Sodium bicarbonate-catalyzed stereoselective isomerizations of electron-deficient propargylic alcohols to (Z)-enones

Redox isomerization is a synthetically important process because it creates two new functional groups in the product, among which is the isomerization of propargylic alcohols to conjugated enones. Although E-enones have been prepared by this approach, Z-enones could not be accessed. We previously reported DABCO-catalyzed E-selective isomerization of electron-deficient propargylic alcohols to enones and its mechanism. Based on this mechanism, we have now developed the first Z-selective redox isomerization of electron-deficient propargylic alcohol to enone using sodium bicarbonate as a catalyst.     

Studies on the Cu(I)-catalyzed regioselective anti-carbometallation of secondary terminal propargylic alcohols

A highly regioselective Cu(I)-catalyzed anti-carbometallation of secondary terminal propargylic alcohols with 1 degrees alkyl or aryl Grignard reagents affording 2-substituted allylic alcohols was developed. By using this method, optically active allylic alcohols can be prepared from the optically active propargylic alcohols without obvious loss of the enantiopurity. The cyclic organometallic intermediate formed may undergo an iodination or a Pd(0)-catalyzed coupling reaction to afford stereo-defined allylic alcohols.     

Ru(eta3-2-C3H4Me)(CO)(dppf)][SbF6]: a mononuclear 16e - ruthenium(II) catalyst for propargylic substitution and isomerization of HC[triple bond]CCPh2(OH)

The 16e(-) derivative [Ru(eta3-2-C3H4Me)(CO)(dppf)][SbF6] catalyzes: (i) the propargylic substitution reaction of 1,1-diphenyl-2-propyn-1-ol with alcohols to produce propargylic ethers, and (ii) the formal isomerization of 1,1-diphenyl-2-propyn-1-ol into 3,3-diphenyl-2-propenal.     

Copper(I)‐Catalyzed Three‐Component Reaction of Terminal Propargyl Alcohols,Aldehydes, and Amines: Synthesis of 3‐Amino‐2‐pyrones and 2,5‐Dihydrofurans

A novel copper(I)‐catalyzed three‐component reaction for the efficient synthesis of 3‐amino‐2‐pyrones and 2,5‐dihydrofurans from propargyl alcohols, aldehydes, and amines has been developed. The starting materials are easily available and the scope of this method is broad. Through mechanistic studies, it is believed that the three‐component reaction consists of an A³‐coupling to propargylic amine, alkyne–allene isomerization, and intramolecular cyclization of the allenol to form a furan. In case of using ethyl glyoxalate as the aldehyde, a ring‐opening, lactonization, and isomerization process affords the 3‐amino‐2‐pyrones.     

Copper(I)‐Catalyzed Three‐Component Reaction of Terminal Propargyl Alcohols,Aldehydes, and Amines: Synthesis of 3‐Amino‐2‐pyrones and 2,5‐Dihydrofurans

A novel copper(I)‐catalyzed three‐component reaction for the efficient synthesis of 3‐amino‐2‐pyrones and 2,5‐dihydrofurans from propargyl alcohols, aldehydes, and amines has been developed. The starting materials are easily available and the scope of this method is broad. Through mechanistic studies, it is believed that the three‐component reaction consists of an A³‐coupling to propargylic amine, alkyne–allene isomerization, and intramolecular cyclization of the allenol to form a furan. In case of using ethyl glyoxalate as the aldehyde, a ring‐opening, lactonization, and isomerization process affords the 3‐amino‐2‐pyrones.     

Highly chemoselective calcium-catalyzed propargylic deoxygenation

A calcium-catalyzed direct reduction of propargylic alcohols and ethers has been accomplished by using triethylsilane as a nucleophilic hydride source. At room temperature a variety of secondary propargylic alcohols was deoxygenated to the corresponding hydrocarbons in excellent yields. Furthermore, for the first time, a catalytic deoxygenation of tertiary propargylic alcohols was generally applicable. The same protocol was suitable for an efficient reduction of secondary as well as tertiary propargylic methyl, benzyl and allyl ethers. Substrates containing an additional keto-, ester or secondary hydroxyl function were reduced with exceptional chemoselectivity at the propargylic position.     

One-step synthesis of substituted dihydro- and tetrahydroisoquinolines by FeCl3.6H2O catalyzed intramolecular Friedel-Crafts reaction of benzylamino-substituted propargylic alcohols

A mild, versatile, and efficient method for the one-step synthesis of substituted dihydro- and tetrahydroisoquinolines has been developed by the FeCl3.6H2O catalyzed intramolecular allenylation/cyclization reaction of benzylamino-substituted propargylic alcohols, representing the first example of the intramolecular Friedel-Crafts reaction of propargylic alcohols.     

Highly Chemoselective Calcium‐Catalyzed Propargylic Deoxygenation

A calcium‐catalyzed direct reduction of propargylic alcohols and ethers has been accomplished by using triethylsilane as a nucleophilic hydride source. At room temperature a variety of secondary propargylic alcohols was deoxygenated to the corresponding hydrocarbons in excellent yields. Furthermore, for the first time, a catalytic deoxygenation of tertiary propargylic alcohols was generally applicable. The same protocol was suitable for an efficient reduction of secondary as well as tertiary propargylic methyl, benzyl and allyl ethers. Substrates containing an additional keto‐, ester or secondary hydroxyl function were reduced with exceptional chemoselectivity at the propargylic position.     

Highly stereoselective palladium-catalyzed dithiocarbonylation of propargylic mesylates with thiols and carbon monoxide

Highly stereoselective dithiocarbonylation of propargylic mesylates with thiols and carbon monoxide has been developed by the use of tetrakis(triphenylphosphine)palladium(0) as the catalyst at 90 degrees C in THF. The reaction affords the corresponding dithioesters in good to excellent yields. For some secondary and tertiary propargylic alcohols with a terminal or internal triple bond, the reaction stereoselectively produces E-dithioesters as products. The dithiocarbonylation is believed to proceed via allenylpalladium and allenyl ester intermediates, and the high stereoselectivity might be rationalized by a mechanism where nucleophilic attack of a Pd(0)L(n) species on the allenyl sp carbon occurs from the less hindered side of an alkyl substituent.     

Atom‐Efficient Gold(I)‐Chloride‐Catalyzed Synthesis of α‐Sulfenylated Carbonyl Compounds from Propargylic Alcohols and Aryl Thiols: Substrate Scope and Experimental and Theoretical Mechanistic Investigation

Gold(I)‐chloride‐catalyzed synthesis of α‐sulfenylated carbonyl compounds from propargylic alcohols and aryl thiols showed a wide substrate scope with respect to both propargylic alcohols and aryl thiols. Primary and secondary aromatic propargylic alcohols generated α‐sulfenylated aldehydes and ketones in 60–97 % yield. Secondary aliphatic propargylic alcohols generated α‐sulfenylated ketones in yields of 47–71 %. Different gold sources and ligand effects were studied, and it was shown that gold(I) chloride gave the highest product yields. Experimental and theoretical studies demonstrated that the reaction proceeds in two separate steps. A sulfenylated allylic alcohol, generated by initial regioselective attack of the aryl thiol on the triple bond of the propargylic alcohol, was isolated, evaluated, and found to be an intermediate in the reaction. Deuterium labeling experiments showed that the protons from the propargylic alcohol and aryl thiol were transferred to the 3‐position, and that the hydride from the alcohol was transferred to the 2‐position of the product. Density functional theory (DFT) calculations showed that the observed regioselectivity of the aryl thiol attack towards the 2‐position of propargylic alcohol was determined by a low‐energy, five‐membered cyclic protodeauration transition state instead of the strained, four‐membered cyclic transition state found for attack at the 3‐position. Experimental data and DFT calculations supported that the second step of the reaction is initiated by protonation of the double bond of the sulfenylated allylic alcohol with a proton donor coordinated to gold(I) chloride. This in turn allows for a 1,2‐hydride shift, generating the final product of the reaction.     

Ruthenium- and platinum-catalyzed sequential reactions: selective synthesis of fused polycyclic compounds from propargylic alcohols and alkenes

A simple method for the preparation of fused polycyclic compounds by an intramolecular cyclization of propargylic alcohols bearing an alkene moiety at a suitable position has been developed, where the presence of both Ru and Pt catalysts promotes a sequence of catalytic cycles in the same medium. This sequential system can be applied to an intermolecular reaction between a propargylic alcohol and an alkene to obtain the corresponding bicyclo[3,1,0]hex-2-ene derivative. These sequential reactions provide a conceptually new type of cycloaddition system between propargylic alcohols and alkenes.     

A general procedure for the synthesis of enones via gold-catalyzed Meyer-Schuster rearrangement of propargylic alcohols at room temperature

Meyer-Schuster rearrangements of propargylic alcohols take place readily at room temperature in toluene with 1-2 mol % PPh(3)AuNTf(2), in the presence of 0.2 equiv of 4-methoxyphenylboronic acid or 1 equiv of methanol. Good to excellent yields of enones can be obtained from secondary and tertiary alcohols, with high selectivity for the E-alkene in most cases. A one-pot procedure for the conversion of primary propargylic alcohols into β-arylketones was also developed, via Meyer-Schuster rearrangement followed by Pd-catalayzed addition of a boronic acid.     

Ruthenium-catalyzed carbon-carbon bond formation between propargylic alcohols and alkenes via the allenylidene-ene reaction

A novel ruthenium-catalyzed carbon-carbon bond formation between propargylic alcohols and alkenes via the allenylidene-ene reaction has been found to afford the corresponding 2,4-disubstituted-1-hexen-5-ynes in moderate yields. The finding described here discloses a new reactivity of allenylidene complexes. As a synthetic application, intramolecular cyclization of propargylic alcohols bearing an alkene moiety has been developed to give the corresponding syn-substituted chromanes in high yields with an excellent diastereoselectivity.     

Gold- and silver-catalyzed reactions of propargylic alcohols in the presence of protic additives

A wide range of primary, secondary and tertiary propargylic alcohols undergo a Meyer-Schuster rearrangement to give enones at room temperature in the presence of a gold(I) catalyst and small quantities of MeOH or 4-methoxyphenylboronic acid. The syntheses of the enone natural products isoegomaketone and daphenone were achieved using this reaction as the key step. The rearrangement of primary propargylic alcohols can readily be combined in a one-pot procedure with the addition of a nucleophile to the resulting terminal enone, to give β-aryl, β-alkoxy, β-amino or β-sulfido ketones. Propargylic alcohols bearing an adjacent electron-rich aryl group can also undergo silver-catalyzed substitution of the alcohol with oxygen, nitrogen and carbon nucleophiles. This latter reaction was initially observed with a batch of gold catalyst that was probably contaminated with small quantities of silver salt.     

Carbon dioxide triggered and copper-catalyzed domino reaction: efficient construction of highly substituted 3(2H)-furanones from nitriles and propargylic alcohols

A novel carbon dioxide triggered and copper-catalyzed domino reaction for the efficient synthesis of highly substituted 3(2H)-furanones from readily available nitriles and propargylic alcohols has been developed. Carbon dioxide is a prerequisite for achieving the present catalytic transformation, and one of the oxygen atoms of carbon dioxide is incorporated into the 3(2H)-furanones. Nitriles not only act as the reaction solvent but also as the reactant; copper salts play dual roles of activating both the propargylic alcohols and nitriles.     

Ruthenium-catalyzed propargylic substitution reaction of propargylic alcohols with thiols: a general synthetic route to propargylic sulfides

A novel cationic methanethiolate-bridged diruthenium complex [Cp*RuCl(mu2-SMe)2RuCp*(OH2)]OTf (1e) has been disclosed to promote the catalytic propargylic substitution reaction of propargylic alcohols bearing not only terminal alkyne group but also internal alkyne group with thiols. It is noteworthy that neutral thiolate-bridged diruthenium complexes (1a-1c), which were known to promote the propargylic substitution reactions of propargylic alcohols bearing a terminal alkyne group with various heteroatom- and carbon-centered nucleophiles, did not work at all. The catalytic reaction described here provides a general and environmentally friendly preparative method for propargylic sulfides, which are quite useful intermediates in organic synthesis, directly from the corresponding propargylic alcohols and thiols.     

Base-catalyzed stereoselective isomerization of electron-deficient propargylic alcohols to E-enones

We have developed highly stereoselective methods to isomerize electron-deficient propargylic alcohols to E-enones under mild conditions (EWG = electron-withdrawing group). Among weak bases we screened, catalytic (10-20 mol %) 1,4-diazabicyclo[2.2.2]octane (DABCO) was found to be effective in most cases. When the substrate is conjugated with an amide, the addition of sodium acetate catalyzed the isomerization.     

Rh‐Catalyzed Reaction of Propargylic Alcohols with Aryl Boronic Acids–Switch from β‐OH Elimination to Protodemetalation

It is known that Rh‐catalyzed reaction of propargylic alcohols with aryl metallic reagents undergoes S_N2’‐type reaction affording allenes via a sequential arylmetalation and β‐OH elimination process. Here we report a Rh/Ag‐cocatalyzed reaction of propargylic alcohols with organoboronic acids affording stereo‐defined (E)‐3‐arylallylic alcohols via arylmetalation and protodemetalation with a high regio‐ and stereoselectivity under very mild conditions. The reaction exhibits a good substrate scope and the compatibility with synthetically useful functional groups with no racemization for optically active propargylic alcohols. Such a reaction may also be extended to homopropargylic alcohols with a remarkable regioselectivity and exclusive E‐stereoselectivity.     

Gold‐ and Silver‐Catalyzed Reactions of Propargylic Alcohols in the Presence of Protic Additives

A wide range of primary, secondary and tertiary propargylic alcohols undergo a Meyer–Schuster rearrangement to give enones at room temperature in the presence of a gold(I) catalyst and small quantities of MeOH or 4‐methoxyphenylboronic acid. The syntheses of the enone natural products isoegomaketone and daphenone were achieved using this reaction as the key step. The rearrangement of primary propargylic alcohols can readily be combined in a one‐pot procedure with the addition of a nucleophile to the resulting terminal enone, to give β‐aryl, β‐alkoxy, β‐amino or β‐sulfido ketones. Propargylic alcohols bearing an adjacent electron‐rich aryl group can also undergo silver‐catalyzed substitution of the alcohol with oxygen, nitrogen and carbon nucleophiles. This latter reaction was initially observed with a batch of gold catalyst that was probably contaminated with small quantities of silver salt.     

Studies on Cu(I)-catalyzed synthesis of simple 3-substituted 1,2-allenes and optically active 2-substituted secondary 2,3-allenols

The sequential treatment of terminal alkynes or propargylic alcohols with n-BuLi and MOMCl afforded the corresponding propargylic methyl ethers, which would react with primary alkyl Grignard reagents under the catalysis of CuBr to afford 3-substituted 1,2-allenes or 2-substituted secondary 2,3-allenols, respectively. The reaction may be applied to the synthesis of optically active 2-substituted secondary 2,3-allenols with up to >99% ee without any protection to the free hydroxyl group in the starting 4-hydroxy-2-alkynyl methyl ethers.