Cooperative Catalytic Reactions Using Distinct Transition‐Metal Catalysts: Ruthenium‐ and Copper‐Catalyzed Enantioselective Propargylic Alkylation

The enantioselective propargylic alkylation of propargylic alcohols with β‐ketoesters in the presence of a thiolate‐bridged diruthenium complex and a copper complex as co‐catalyst affords the corresponding propargylic alkylated products in excellent yields as a mixture of two diastereoisomers with high enantioselectivity (up to 95 % enantiomeric excess (ee)). The findings reported herein not only open up a new type of enantioselective propargylic substitution reaction, but also a new aspect of cooperative catalytic reactions using distinct transition metals to realize a useful transformation that cannot be achieved by a single catalyst.     

Copper-catalyzed enantioselective propargylic amination of nonaromatic propargylic esters with amines

The enantioselective propargylic amination of propargylic pentafluorobenzoates bearing an alkyl group at the propargylic position with amines in the presence of catalytic amounts of a copper complex and an optically active diphosphine such as BINAP has been found to give the corresponding propargylic amines in good yields with high enantioselectivity.     

Cooperative catalytic reactions using organocatalysts and transition metal catalysts: enantioselective propargylic alkylation of propargylic esters with aldehydes

The enantioselective propargylic alkylation of propargylic esters with aldehydes in the presence of a copper complex and an optically active secondary amine as cocatalysts has been found to give the corresponding propargylic alkylated products in good yields as a mixture of two diastereoisomers with a high enantioselectivity.     

Remarkable effect of N-substituent on enantioselective ruthenium-catalyzed propargylation of indoles with propargylic alcohols

Ruthenium-catalyzed enantioselective propargylation of indoles with propargylic alcohols affords the corresponding beta-propargylated indoles in good yields with a high enantioselectivity (up to 95% ee). A remarkable effect of the nature of the N-substituent of indoles is observed for the enantioselectivity of the propargylated indoles. The preparative method described in this paper may provide a novel protocol for asymmetric Friedel-Crafts alkylation of indoles using propargylic alcohols as a new type of electrophiles.     

Cooperative Catalysis: Enantioselective Propargylic Alkylation of Propargylic Alcohols with Enecarbamates Using Ruthenium/Phosphoramide Hybrid Catalysts

The diastereo‐ and enantioselective propargylic alkylation of propargylic alcohols with E‐enecarbamates in the presence of a catalytic amount of thiolate‐bridged diruthenium complexes bearing an optically active phosphoramide moiety gives the corresponding propargylic alkylated products (up to 97 % ee).     

Total synthesis of cystothiazoles A and B

[structure: see text] Convergent enantioselective syntheses of the antifungal agents cystothiazoles A and B are described. The routes feature an asymmetric crotylation using a propargylic dicobalt hexacarbonyl complex, which provided enhanced diastereoselectivity over the uncomplexed propargylic acetal. The bisthiazole fragment was united with the side chain through a Stille cross-coupling of a terminal (E)-vinylstannane with a 4-trifloyl-substituted thiazole.     

Dimethylzinc-mediated, enantioselective synthesis of propargylic amines

A one-pot, enantioselective synthesis of N-aryl propargylic amines, using alkynylation reagents obtained from dimethylzinc and terminal acetylenes in combination with various aldehydes and o-methoxyaniline as starting materials, has been developed. Enantiopure beta-amino alcohols derived from norephedrine were used as non-covalent chiral auxiliaries, both in stoichiometric or substoichiometric amount. After optimization, propargylic amines were obtained in good to high yields (up to 93%) and with moderate to high enantiomeric excesses (up to 97% ee). The possibility to recover the chiral auxiliary after the reaction was demonstrated.     

Ruthenium-catalyzed enantioselective carbon-carbon bond forming reaction via allenylidene-ene process: synthetic approach to chiral heterocycles such as chromane, thiochromane, and 1,2,3,4-tetrahydroquinoline derivatives

Our previously disclosed ruthenium-catalyzed carbon-carbon bond forming reactions between propargylic alcohols and alkenes via an allenylidene-ene type pathway have been successfully applied to an enantioselective intramolecular cyclization for a variety of chiral heterocycles such as chromane, thiochromane, and 1,2,3,4-tetrahydroquinoline derivatives (up to 99% ee) by use of a suitable optically active diruthenium complex as a catalyst. The methodology described in this paper becomes a novel synthetic approach to chiral heterocycles, the structures of which are widely found in many natural and biologically active compounds.     

Fam-Ti catalyzed enantioselective alkynylation of aldehydes

Ferrocenyl-substituted aziridinylmethanol (Fam-1) has been used as a chiral catalyst with titanium for enantioselective alkynylation of aromatic, heteroaromatic, aliphatic, and alpha,beta-unsaturated aldehydes to give the corresponding propargylic alcohols in up to 96% yield and 96% ee. The ligand can be prepared easily and recycled.     

Pd-Catalyzed annulation of benzene-1,2-diol and propargylic carbonates: a new example of asymmetric catalysis

The palladium-catalyzed cyclization of benzene-1,2-diol with various secondary propargylic carbonates in the presence of (R)-Binap as the chiral ligand afforded the corresponding 2,3-dihydrobenzo-1,4-dioxin derivatives in quite good yields, and also in enantioselectivities of up to 93%. The assumed enantioselective step is the protonation of a palladium-carbene intermediate.     

Cooperative Ni/Cu-Catalyzed Asymmetric Propargylic Alkylation of Aldimine Esters

A novel Ni/Cu dual catalysis gives rise to fundamentally new cooperative reactivity and enables the regio- and enantioselective propargylic alkylation reaction. A diverse set of α-quaternary propargylated amino ester derivatives were synthesized in good yields with excellent enantioselectivity (up to 99 % ee). This work highlights the power of cooperative catalysis, which can be expected to have broad implications in homogeneous catalysis beyond the highly valuable synthetic intermediates.     

Cooperative Ni/Cu‐Catalyzed Asymmetric Propargylic Alkylation of Aldimine Esters

A novel Ni/Cu dual catalysis gives rise to fundamentally new cooperative reactivity and enables the regio‐ and enantioselective propargylic alkylation reaction. A diverse set of α‐quaternary propargylated amino ester derivatives were synthesized in good yields with excellent enantioselectivity (up to 99 % ee). This work highlights the power of cooperative catalysis, which can be expected to have broad implications in homogeneous catalysis beyond the highly valuable synthetic intermediates.     

Kinetic Resolution of Tertiary Propargylic Alcohols by Enantioselective Cu−H‐Catalyzed Si−O Coupling

A broad range of tertiary propargylic alcohols were kinetically resolved by catalyst‐controlled enantioselective silylation. This non‐enzymatic kinetic resolution is catalyzed by a Cu?H species and makes use of the commercially available precatalyst MesCu/(R,R)‐Ph‐BPE and a simple hydrosilane as the resolving reagent. Both alkyl,aryl‐ as well as dialkyl‐substituted propargylic alcohols participate, and especially high selectivity factors are achieved when the alkyne terminus carries a TIPS group, which also enables facile post‐functionalization in this position (s up to 207).     

Zn(ODf)2: preparation and application in asymmetric alkynylation of aldehydes

A new Lewis acid, Zn(ODf)2, was first prepared from commercially available 3,3,4,4-tetrafluoro[1,2]oxathietane 2,2-dioxide in four steps with 56% yields and also was applied to catalyze highly enantioselective alkynylation of aldehydes in the presence of ligand (1S,2S)-3-(tert-butyldimethylsilyloxyl)-2-N,N-dimethylamino-1- (p-nitrophenyl)-propane-1-ol or ligand (-)-N-methylephedrine to afford the corresponding propargylic alcohols in high yields with up to 99% ee.     

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%).     

Formal chemoselective synthesis of leucascandrolide A

A chemoselective synthesis of the macrocyclic core of leucascandrolide A has been achieved, utilizing highly enantioselective allylmetalations, an enantioselective Noyori reduction of a propargylic ketone and olefin metatheses as the key steps.     

Synthetic efforts toward the macrolactone core of Leucascandrolide A

A chemoselective synthesis of 1, the macrocyclic core of leucascandrolide A, has been achieved by utilizing highly enantioselective allylmetalations, an enantioselective Noyori reduction of a propargylic ketone, and olefin metatheses as the key steps.     

Chiral Brønsted Acid Catalyzed Enantioconvergent Propargylic Substitution Reaction of Racemic Secondary Propargylic Alcohols with Thiols

Despite the significant progress of the enantioselective reaction using chiral catalysts, the enantioselective nucleophilic substitution reaction at the chiral sp³-hybridized carbon atom of a racemic electrophile has not been largely explored. Herein, we report the enantioconvergent propargylic substitution reaction of racemic propargylic alcohols with thiols using chiral bis-phosphoric acid as the chiral Brønsted acid catalyst. The substitution products were formed in high yields with high enantioselectivities in most cases. The cation-stabilizing effect of the sulfur functional group introduced at the alkynyl terminus is the key to achieving the efficient enantioconvergent process, in which chiral information originating from not only the racemic stereogenic center but also the formed contact ion pair is completely eliminated from the present system.     

Construction of Chiral Tri‐ and Tetra‐Arylmethanes Bearing Quaternary Carbon Centers: Copper‐Catalyzed Enantioselective Propargylation of Indoles with Propargylic Esters

Copper‐catalyzed enantioselective propargylation of indoles with propargylic esters and sequential Huisgen cycloaddition with azides lead to the construction of chiral triarylmethanes, bearing a quaternary carbon center, with high to excellent enantioselectivities. The result described herein can be used in the enantioselective preparation of a tetraarylmethane.     

Kinetic resolution of secondary alcohols using amidine-based catalysts

Kinetic resolution of racemic alcohols has been traditionally achieved via enzymatic enantioselective esterification and ester hydrolysis. However, there has long been considerable interest in devising nonenzymatic alternative methods for this transformation. Amidine-based catalysts (ABCs), a new class of enantioselective acyl transfer catalysts developed in our group, have demonstrated, inter alia, high efficacy in the kinetic resolution of benzylic, allylic, and propargylic secondary alcohols and 2-substituted cycloalkanols, and thus provide a viable alternative to enzymes.