Cationic rhodium(I)/BINAP complex-catalyzed isomerization of secondary propargylic alcohols to alpha,beta-enones

We have developed a cationic rhodium(I)/BINAP complex-catalyzed isomerization of secondary propargylic alcohols to alpha,beta-enones. The asymmetric variant of this reaction, a kinetic resolution of secondary propargylic alcohols, was also developed with good selectivity. The mechanistic study revealed that the isomerization proceeds through intramolecular 1,3- and 1,2-hydrogen migration pathways. [reaction: see text]     

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.     

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.     

Highly efficient synthesis of functionalized dihydronaphthalenes, tetrahydronaphthalenes, and tetrahydroisoquinolines by iron-catalyzed intramolecular Friedel-Crafts reaction of aryl-containing propargylic alcohols

An efficient, convenient, and one-pot procedure for the synthesis of a series of new dihydro- and tetrahydronaphthalenes as well as tetrahydroisoquinolines has been established through Lewis acid-catalyzed intramolecular Friedel-Crafts reaction of aryl-substituted propargylic alcohols.     

Intramolecular Nicholas reaction: stereoselective synthesis of 5-alkynylproline derivatives

The intramolecular Nicholas reaction of propargylic alcohols derived from N, N-acyl-diprotected omega-semialdehydes obtained from glutamic acid provided stereoselectively 5-alkynylproline derivatives. The suitable choice of the N-protecting group (tosyl or benzoyl derivative) permitted control of the stereochemistry during the ring formation. Semiempirical calculations of the species involved in the cyclization support the observed stereochemistry.     

A gold(I)-catalyzed intramolecular reaction of propargylic/homopropargylic alcohols with oxirane

The gold(I)-catalyzed cycloisomerization of epoxy alkynes in the presence of a nucleophile is an efficient protocol to provide ketal skeletons with high stereoselectivity. An intramolecular reaction of propargylic/homopropargylic alcohols with oxirane to produce ketal/spiroketals in moderate yields under mild conditions has been reported. Moreover, the mechanism of this kind of reaction has been discussed on the basis of a series of control and (18)O tracer experiments.     

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.     

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.     

Chemoselective addition of in situ prepared lithium alkynyl borates to aldehydes: a practical and transition metal free approach toward the synthesis of propargylic alcohols

A convenient synthesis of functionalized propargylic alcohols arising from the 1,2-addition of lithium alkynyl-trimethyl borate onto aldehydes under transition metal free mild conditions is reported. The reaction tolerates a wide range of functional groups, is highly chemoselective and the propargylic alcohols are isolated in good to excellent yields.     

Ruthenium-catalyzed propargylic substitution reactions of propargylic alcohols with oxygen-, nitrogen-, and phosphorus-centered nucleophiles

The scope and limitations of the ruthenium-catalyzed propargylic substitution reaction of propargylic alcohols with heteroatom-centered nucleophiles are presented. Oxygen-, nitrogen-, and phosphorus-centered nucleophiles such as alcohols, amines, amides, and phosphine oxide are available for this catalytic reaction. Only the thiolate-bridged diruthenium complexes can work as catalysts for this reaction. Results of some stoichiometric and catalytic reactions indicate that the catalytic propargylic substitution reaction proceeds via an allenylidene complex formed in situ, whereby the attack of nucleophiles to the allenylidene C(gamma) atom is a key step. Investigation of the relative rate constants for the reaction of propargylic alcohols with several para-substituted anilines reveals that the attack of anilines on the allenylidene C(gamma) atom is not involved in the rate-determining step and rather the acidity of conjugated anilines of an alkynyl complex, which is formed after the attack of aniline on the C(gamma) atom, is considered to be the most important factor to determine the rate of this catalytic reaction. The key point to promote this catalytic reaction by using the thiolate-bridged diruthenium complexes is considered to be the ease of the ligand exchange step between a vinylidene ligand on the diruthenium complexes and another propargylic alcohol in the catalytic cycle. The reason why only the thiolate-bridged diruthenium complexes promote the ligand exchange step more easily with respect to other monoruthenium complexes in this catalytic reaction should be that one Ru moiety, which is not involved in the allenylidene formation, works as an electron pool or a mobile ligand to another Ru site. The catalytic procedure presented here provides a versatile, direct, and one-step method for propargylic substitution of propargylic alcohols in contrast to the so far well-known stoichiometric and stepwise Nicholas reaction.     

Preparation of phenyl substituted propargylic alcohol dicobalt hexacarbonyls and their reactions with active methylene compounds in the presence of acid

Eight new complexes with the formula [PhC_2C(OH)R~2R~2]Co_2(CO)_6 were prepared fromphenyl substituted propargylic alcohols and dicobalt octacarbonyl.The reactions of these propargylioalcohol complexes with active methylene compounds,2,4-pentanedione or ethyl acetoacetate,in thepresnce of an acid,HBF_4(40％)+P_2O_5(in excess)or BF_3·Et_2O,at room temperature in dichlorome-thane were investigated.From the 1-alkyl substituted tertiary propargylic alcohol complexes,threenew conjugated ene-yne complexes produced by intramolecular dehydration reaction were isolated inhigh yields(82—95％).On the other hand,four new alkylated complexes were obtained withsatisfactory yields(44—66％)from the secondary propargylic alcohol complexes.The influence ofother acids,phosphorus pentoxide and polyphosphoric acid,on both dehydration reaction andalkylated reaction was also studied.     

Synthesis of 1,2,5- and 1,2,3,5-substituted pyrroles from substituted aziridines via Ag(I)-catalyzed intramolecular cyclization

An efficient synthesis of 1,2,5- and 1,2,3,5-substituted pyrroles has been achieved from the sequential reactions including a ring-opening of 1-(aziridin-2-yl)propargylic alcohols by various nucleophiles under mild condition followed by an intramolecular cyclization using Ag(I) 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.     

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.     

Palladium-catalyzed intermolecular coupling of 3-substituted propargylic carbonates with phenols: Synthesis of 2-substituted benzofuran derivatives

We accomplished the synthesis of 2-substituted benzofuran derivatives by the palladium-catalyzed reaction of 3-substituted propargylic carbonates with phenols. The 2-substituted benzofuran derivatives were obtained through the intermolecular coupling of the 3-substituted propargylic carbonates with phenols, and sequential intramolecular cyclization reaction.     

Synthesis of quinazoline based chiral ligands and application in the enantioselective addition of phenylacetylene to aldehydes

Five novel 4-phenylquinazolinols were synthesised in three steps. Their application as ligands in the titanium tetraisopropoxide promoted catalytic enantioselective addition of phenylacetylene to a variety of aldehydes gave propargylic alcohols. Under the optimised reaction conditions, the best enantioselectivity was obtained using l-lactic acid derived 4-phenylquinazolinol and apart from the cyclohexylcarbaldehyde derivative, 16 propargylic alcohols were then synthesised in moderate to excellent enantiomeric excess from 53% to 97%.     

Task-specific ionic liquid and CO2-cocatalysed efficient hydration of propargylic alcohols to α-hydroxy ketones

The hydration of propargylic alcohols is a green route to synthesize α-hydroxy ketones. Herein a CO₂-reactive ionic liquid (IL), [Bu₄P][Im], was found to display high performance for catalyzing the hydration of propargylic alcohols in the presence of atmospheric CO₂, and a series of propargylic alcohols could be converted into the corresponding α-hydroxy ketones in good to excellent yields. In the IL/CO₂ reaction system, CO₂ served as a cocatalyst by forming α-alkylidene cyclic carbonates with propargylic alcohols, and was released via the rapid hydrolysis of the carbonates catalysed by the IL. This is the first example of the efficient hydration of propargylic alcohols under metal-free conditions.     

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.     

Biradicals from benzoenyne-allenes. Application in the synthesis of 11H-benzo[b]fluoren-11-ols, 1H-cyclobut[a]indenes, and related compounds

New synthetic pathways to 11H-benzo[b]fluoren-11-ols, 1H-cyclobut[a]indenes, and related compounds via biradicals generated from benzoenyne-allenes were developed. Treatment of the diacetylenic propargylic alcohols 13, derived from condensation between benzophenones and the lithium acetylide of 1-(2-ethynylphenyl)-2-phenylethyne, with thionyl chloride produced the 11-chloro-11H-benzo[b]fluorene 14 and, after hydrolysis, the corresponding 11H-benzo[b]fluoren-11-ols 15. The transformation involved a sequence of reactions, including a biradical-forming C2-C6 cyclization (Schmittel cyclization) reaction of the chlorinated benzoenyne-allene intermediates followed by an intramolecular radical-radical coupling to form the formal Diels-Alder adducts. Interestingly, in the case of the diacetylenic propargylic alcohol 26, obtained from dibenzosuberenone (25), an intramolecular [2 + 2] cycloaddition reaction of the chlorinated benzoenyne-allene intermediate occurred, furnishing the 1H-cyclobut[a]indene 27 exclusively. The dramatic change of the reaction pathway could be attributed to the emergence of a steric strain due to the nonbonded interactions with the chloro substituent along the pathway toward the formal Diels-Alder adduct 31. On the other hand, the non-chlorinated benzoenyne-allene, derived from prototropic isomerization of the diacetylenic hydrocarbon 60, underwent a formal Diels-Alder reaction to furnish the 11H-benzo[b]fluorene-type hydrocarbon 61 exclusively.     

Iron-catalyzed ene-type propargylation of diarylethylenes with propargyl alcohols

The diarylalkenyl propargylic complex framework has been found in many natural products and medicinal regents. Herein, we have disclosed an unprecedented FeCl(3) catalyzed ene-type reaction of propargylic alcohols with 1,1-diaryl alkenes which enabled us to furnish a diarylalkenyl propargylic complex framework in moderate to high chemical yields (up to 98%).