Secondary Phosphine Sulfide-Enabled Iridium-Catalyzed Asymmetric Allylic Substitution.

An iridium-catalyzed asymmetric synthesis of branched allylic phosphine compounds under mild conditions is reported. Products bearing various functional groups can be synthesized with excellent stereoselectivity (up to 99.9 % ee) and regioselectivity. The employment of phosphine sulfides with relatively low deactivation capacity against metal catalysts is crucial for the success of this reaction.

Chiral Diene Ligands in Asymmetric Catalysis.

Asymmetric catalysis has emerged as a general and powerful approach for constructing chiral compounds in an enantioselective manner. Hence, developing novel chiral ligands and catalysts that can effectively induce asymmetry in reactions is crucial in modern chemical synthesis. Among such chiral ligands and catalysts, chiral dienes and their metal complexes have received increased attention, and a great progress has been made over the past two decades. This review provides comprehensive and critical information on the essential aspects of chiral diene ligands and their importance in asymmetric catalysis. The literature covered ranges from August 2003 (when the first effective chiral diene ligand for asymmetric catalysis was reported) to October 2021. This review is divided into two parts. In the first part, the chiral diene ligands are categorized according to their structures, and their preparation methods are summarized. In the second part, their applications in asymmetric transformations are presented according to the reaction types.

Asymmetric Synthesis of Chiral Bicyclo[2.2.1]hepta-2,5-diene Ligands through Rhodium-Catalyzed Asymmetric Arylative Bis-cyclization of a 1,6-Enyne.

A series of novel chiral diene ligands (1R,4S)-L1, which are based on the bicyclo[2.2.1]heptadiene skeleton and are substituted with methyl and an ester group at the bridgehead carbons, were synthesized through rhodium-catalyzed asymmetric arylative bis-cyclization of 1,6-enyne 1 as a key step. The rhodium catalyst with one of the (1R,4S)-L1 ligands was used for the asymmetric bis-cyclization of 1 giving bicyclic product (1S,4R)-2 of 99% ee, which is a synthetic precursor of (1S,4R)-L1 ligands.

Asymmetric Synthesis of Fluorinated Allenes by Rhodium-Catalyzed Enantioselective Alkylation/Defluorination of Propargyl Difluorides with Alkylzincs.

The reaction of propargyl difluorides R1 CF2 C≡CR2 with alkylzincs R3 ZnCl giving axially chiral fluorinated allenes R1 FC=C=CR2 R3 with high enantioselectivity (up to 99 % ee) was found to be catalyzed by a chiral diene/rhodium complex. A key step in the catalytic cycle is selective elimination of one of the enantiotopic fluorides at the ß-position of an alkenyl-Rh intermediate, which is generated by regioselective addition of R3 -Rh onto the triple bond of the starting difluorides.

Asymmetric Synthesis of Alkylzincs by Rhodium-Catalyzed Enantioselective Arylative Cyclization of 1,6-Enynes with Arylzincs.

A chiral diene-rhodium complex was found to catalyze the reaction of 1,6-enynes with ArZnCl to give high yields of 2-(alkylidene)cyclopentylmethylzincs with high enantioselectivity (95-99 % ee). The enantioenriched alkylzincs were readily converted in a one-pot approach into a wide variety of functionalized products by taking advantage of their unique reactivity. The catalytic cylcle involves arylrhodation of alkyne, intramolecular alkenylrhodation of alkene, and transmetalation of the alkyl-rhodium intermediate into alkylzinc.

Rhodium(I)/Chiral Diene-Catalyzed Enantioselective Addition of Boronic Acids to N-Unsubstituted Isatin-Derived Ketimines.

Enantioselective addition of boronic acids to N-unsubstituted isatin-derived ketimines was realized using rhodium(I)/chiral diene catalysts. The reactions can be performed in the presence of catalytic amounts of a base to give adducts in high yield with high enantioselectivity. Preliminary mechanistic information including a computational model to explain the observed enantioselectivity is also provided.

Synthesis of Arylacetaldehydes by Iridium-Catalyzed Arylation of Vinylene Carbonate with Arylboronic Acids.

The one-step synthesis of arylacetaldehydes by carbon-carbon bond formation between formylmethyl and aryl groups has been realized by the reaction of vinylene carbonate with arylboronic acids in the presence of an iridium/bisphosphine catalyst and a catalytic amount of tetrahydroxydiboron.

Enantioselective Synthesis of 3,3'-Diaryl-SPINOLs: Rhodium-Catalyzed Asymmetric Arylation/BF3 -Promoted Spirocyclization Sequence.

The enantioselective synthesis of a series of C2 -symmetric 3,3'-diarylated 1,1'-spirobiindane-7,7'-diols (3,3'-diaryl-SPINOLs) was developed by sequential Rh-catalyzed twofold asymmetric conjugate arylation/BF3 -promoted diastereoselective spirocyclization (>20:1 d.r. and >99 % ee for all examples). Some phosphoramidite ligands were prepared from the 3,3'-Ph-SPINOL and applied to several catalytic asymmetric reactions, and the 3,3'-diarylated ligands showed higher enantioselectivities than the privileged nonsubstituted ligands.

Addition of arylstannanes to alkynes giving ortho-alkenylarylstannanes catalysed cooperatively by a rhodium complex and zinc chloride.

The reaction of arylstannanes ArSnR3 with unfunctionalised alkynes was found to proceed in the presence of a rhodium catalyst and a catalytic amount of zinc chloride to give ortho-alkenylarylstannanes with high selectivity in high yields. The catalytic cycle is very unique, consisting of three transmetalation steps, from Sn to Rh, Rh to Zn, and Zn to Sn, in addition to arylrhodation of alkyne followed by 1,4-migration of Rh from 2-arylalkenyl carbon to ortho-alkenylaryl carbon.

Catalytic Asymmetric Conjugate Arylation of γ,δ-Unsaturated ß-Dicarbonyl Compounds.

The first catalytic asymmetric conjugate addition to γ,δ-unsaturated ß-dicarbonyl compounds was developed. With a chiral diene-rhodium(I) µ-chloro dimer as the catalyst in toluene/H2O, asymmetric conjugate arylation of γ,δ-unsaturated ß-dicarbonyl compounds with arylboronic acids proceeded in high efficiency with excellent enantioselectivities. The generated ß-dicarbonyl products are versatile chiral synthons, which can be easily converted to diverse important chiral structures.

Rhodium-Catalyzed Arylzincation of Alkynes: Ligand Control of 1,4-Migration Selectivity.

The addition of arylzinc reagents ArZnCl 1 to alkynes 2 was found to be catalyzed by rhodium complexes in the presence of a catalytic amount of zinc chloride. The selectivity in giving 2-arylalkenylzinc species 3 or ortho-alkenylarylzinc species 4, the latter of which is generated through 1,4-Rh migration from alkenyl to aryl in the catalytic cycle, is controlled by the ligands on rhodium. Ligands cod and binap gave 3 and 4, respectively, with high selectivity.

Asymmetric Synthesis of Axially Chiral 2-Aminobiaryls by Rhodium-Catalyzed Benzannulation of 1-Arylalkynes with 2-(Cyanomethyl)phenylboronates.

Asymmetric benzannulation of 1-arylalkynes, where the aryl group is an ortho-substituted aromatic group, with 2-(cyanomethyl)phenylboronate was catalyzed by a rhodium complex coordinated with a chiral diene ligand to give high yields of axially chiral 2-aminobiaryls with greater than 90 % ee.

Access to Chiral HWE Reagents by Rhodium-Catalyzed Asymmetric Arylation of γ,δ-Unsaturated ß-Ketophosphonates.

Asymmetric arylation of γ,δ-unsaturated ß-ketophosphonates with arylboronic acids is reported. By using the ( R)-diene* ligated rhodium(I) chloride complex as a catalyst under none basic conditions, the corresponding ß-ketophosphonates bearing a δ-chiral center were obtained in high yields (up to 99%) with good to excellent enantioselectivities (up to >99% ee). The enantioenriched products can be readily converted to diverse chiral ß'-aryl enones by the Horner-Wadsworth-Emmons reaction.

Palladium-Catalyzed Asymmetric Allylic Alkylations of Colby Pro-Enolates with MBH Carbonates: Enantioselective Access to Quaternary C-F Oxindoles.

Owing to the innovative applications of fluorinated compounds in many areas of technology and medicine, methods for the preparation of C-F quaternary fluorine containing compounds are in extremely high demand. Here, we report the discovery of a general procedure for an SN 2 reaction catalyzed by Pd/Ding-SKP-type ligands, and that occurs between Colby pro-enolates with MBH carbonates to afford the corresponding products featuring two consecutive stereogenic carbons, including a C-F quaternary stereogenic center. The reactions readily occur at ambient temperatures with high chemical yields and in excellent chemo-, diastereo- and enantioselective manners. This practically attractive stereochemical outcome, coupled with the operational simplicity and structural generality, bodes well for the synthetic application of this process in the preparation of a novel class of biologically relevant fluorine-containing compounds.

Rhodium-Catalyzed Enantioposition-Selective Hydroarylation of Divinylphosphine Oxides with Aryl Boroxines.

The rhodium-catalyzed hydroarylation of divinylphosphine oxides (RP(O)(CH=CH2 )2 ) with aryl boroxines ((ArBO)3 ) gives the corresponding monoarylation products (RP(O)(CH=CHAr)CH2 CH3 ) in high yields. One of the two vinyl groups in the phosphine oxide undergoes oxidative arylation while the other one is reduced to an ethyl moiety. These reactions proceed with high selectivity in terms of the enantiotopic vinyl groups in the presence of (R)-DTBM-segphos/Rh to give the P-stereogenic monoarylation products with high enantioselectivity.

Dynamic Kinetic Resolution in Rhodium-Catalyzed Asymmetric Arylation of Phospholene Oxides.

The reaction of 2,5-dihydro-1H-phosphole 1-oxide 1 with ArB(pin) 3 in the presence of a chiral (R)-segphos-rhodium catalyst under highly basic conditions (10 equiv of KOH) gave high yields of (1S,3S)-3-arylphospholane 1-oxide 4 with high diastereoselectivity as well as high enantioselectivity. Equilibration of 1 with its 2,3-dihydro isomer 2, which is chiral and racemic, by base-catalyzed olefin isomerization followed by kinetic resolution of 2 with the chiral rhodium catalyst realized the present dynamic kinetic resolution.

Enantioselective Access to Bicyclo[3.2.1]octadienone Skeleton: Total Syntheses of (+)-Engelharquinone and Its Epoxide.

The first enantioselective total syntheses of engelharquinone (2) and its epoxide 3 have been achieved. The key steps include (1) catalytic asymmetric 1,4-addition of a naphthylboronic acid derivative to a masked naphthoquinone derivative by using a chiral Rh-complex and (2) thiolate-promoted stereospecific construction of the bicyclo[3.2.1]octadienone scaffold.

Aryloxymethyltrifluoroborates for Rhodium-Catalyzed Asymmetric Conjugate Arylation. o-Methoxyarylation through 1,4-Rhodium Shift.

Reaction of potassium aryloxymethyltrifluoroborates 1 with α,ß-unsaturated carbonyl compounds 2 in the presence of a chiral diene-rhodium catalyst in H2O at 100 °C introduced 2-methoxyaryl groups at the ß-position of 2 with high enantioselectivity in high yields. The reaction is assumed to proceed through 1,4-Rh shift from aryloxymethyl-Rh intermediate to 2-methoxyaryl-Rh. The high availability of phenol derivatives makes this asymmetric conjugate arylation synthetically useful.

Rhodium-Catalyzed Asymmetric Arylation/Defluorination of 1-(Trifluoromethyl)alkenes Forming Enantioenriched 1,1-Difluoroalkenes.

The reaction of 1-(trifluoromethyl)alkenes (CF3CH=CHR) with arylboroxines (ArBO)3 in the presence of a chiral diene-rhodium catalyst gave high yields of chiral 1,1-difluoroalkenes (CF2=CHC*HArR) with high enantioselectivity (≥95% ee). The reaction is assumed to proceed through ß-fluoride elimination of a ß,ß,ß-trifluoroalkylrhodium intermediate that is generated by arylrhodation of the 1-(trifluoromethyl)alkene.

Palladium-Catalyzed Asymmetric Arylation of Trifluoromethylated/Perfluoroalkylated 2-Quinazolinones with High Enantioselectivity.

Asymmetric arylation of 4-fluoroalkyl-2-quinazolinone derivatives with arylboronic acids proceeded smoothly in the presence of a cationic palladium catalyst (1 mol %) coordinated with a chiral phosphinooxazoline (phox) ligand to create the corresponding fluorine-containing arylated dihydroquinazolinones in high yields and with greater than 99 % ee.