Chiral All-carbon Quaternary Center Research Articles

Enantioselective Synthesis of an All-Carbon Quaternary Stereocenter by Chiral Brønsted Acid-Catalyzed Friedel-Crafts-Type Reaction between Pyrroles and 3-Indolylmethanols.

We have developed a chiral phosphoric acid-catalyzed enantioselective Friedel-Crafts alkylation reaction between pyrroles and indolylmethanols. Wide substrate scope was observed, and a chiral all-carbon quaternary center was constructed at the 3 position of indoles in high yields with high to excellent enantioselectivities (up to 99% ee).

Rhodium-Catalyzed Desymmetric Arylation of γ,γ-Disubsituted Cyclohexadienones: Asymmetric Synthesis of Chiral All-Carbon Quaternary Centers.

The desymmetric arylation of prochiral cyclohexadienones with ArZnCl in the presence of an (R)-segphos-rhodium catalyst gave high yields of the corresponding cyclohexenones, which contain a chiral arylated carbon center at the β-position and a chiral all-carbon quaternary center at the γ-position, with high diastereo- and enantioselectivities. This catalytic system was also applied to the arylation of spirocarbocyclic cyclohexadienones and afforded the corresponding cyclohexenones bearing a chiral spiro quaternary carbon with high dr and ee.

Chiral Aluminum Complex Controls Enantioselective Nickel-Catalyzed Synthesis of Indenes: C-CN Bond Activation.

A chiral aluminum complex controlled, enantioselective nickel-catalyzed domino reaction of aryl nitriles and alkynes proceeding by C-CN bond activation was developed. The reaction provides various indenes, bearing chiral all-carbon quaternary centers, under mild reaction conditions in yields of 32 to 91 % and ee values within the 73-98 % range. The reaction mechanism and aspects of stereocontrol were investigated by DFT calculations.

Nickel-Catalyzed Desymmetric Hydrogenation of Cyclohexadienones: An Efficient Approach to All-Carbon Quaternary Stereocenters.

Nickel-catalyzed desymmetric hydrogenation has been achieved. With the Ni(OTf)2/(S,S)-Ph-BPE system, a series of γ,γ-disubstituted cyclohexadienones were transformed to the corresponding cyclohexenones with a chiral all-carbon quaternary center at the γ position in high yields (92-98%) and excellent enantioselectivities (92%-99% ee). This catalytic system can also tolerate the desymmetric reaction of spirocarbocyclic cyclohexadienones to produce the corresponding cyclohexenones bearing a chiral spiro quaternary carbon with high yields (94%-98%) and ee values (96%-99% ee). Furthermore, this methodology provides an efficient and concise synthetic route to the intermediate of natural products cannabispirenones A and B.

Efficient Enantioselective Syntheses of (+)-Dalesconol A and B

We herein report the first enantioselective syntheses of immunosuppressants (+)-dalesconol A and B in a highly efficient and concise manner, which features an efficient palladium-catalyzed enantioselective dearomative cyclization-kinetic resolution cascade to install the chiral all-carbon quaternary center, an effective sterically hindered Stille coupling, a powerful 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidation to furnish all requisite unsaturation, and a tandem hydrolysis-ring closure sequence.

ChemInform Abstract: Nickel(II)‐Catalyzed Asymmetric Michael Addition of Oxindoles with Modified N,N,O‐Tridentate Chiral Phenanthroline Ligands.

Nickel(II)-catalyzed enantioselective Michael addition of N-Boc-oxindole derivatives with methyl vinyl ketone was demonstrated to give the corresponding adducts having chiral all-carbon quaternary centers with up to 87% ee in the presence of axially chiral N,N,O-tridentate phenanthroline ligand.

ChemInform Abstract: Asymmetric Induction at Remote Quaternary Centers of Cyclohexadienones by Rhodium‐Catalyzed Conjugate Hydrosilylation.

AbstractAn enantioselective conjugate hydrosilylation of prochiral γ,γ‐disubstituted cyclohexadienones furnishes cyclohexenones with a chiral quaternary γ‐carbon atom.

Nickel(II)-Catalyzed Asymmetric Michael Addition of Oxindoles with Modified N,N,O-Tridentate Chiral Phenanthroline Ligands

Nickel(II)-catalyzed enantioselective Michael addition of N-Boc-oxindole derivatives with methyl vinyl ketone was demonstrated to give the corresponding adducts having chiral all-carbon quaternary centers with up to 87% ee in the presence of axially chiral N,N,O-tridentate phenanthroline ligand.

Asymmetric Induction at Remote Quaternary Centers of Cyclohexadienones by Rhodium-Catalyzed Conjugate Hydrosilylation.

The enantioselective desymmetrizing conjugate hydrosilylation of prochiral differently γ,γ-disubstituted cyclohexadienone derivatives 2 to furnish the corresponding cyclohexenones 4 with a remote chiral all-carbon quaternary center at the γ position is described. Chiral rhodium-bis(oxazolinyl)phenyl complexes 1 were effective catalysts for this transformation. This catalytic system was extended to the asymmetric transformation of spirocarbocyclic cyclohexadienones 5 to give the corresponding products 6 with high enantiomeric ratios.

Synthesis of triptoquinone H and its C-5 epimer via efficient asymmetric dearomative cyclization

Enantioselective syntheses of triptoquinone H and its C-5 epimer were accomplished for the first time in seven linear steps and 33% overall yield from aldehyde 6 and Wittig salt 5 via a key palladium-catalyzed asymmetric dearomative cyclization. The P-chiral biaryl monophosphorus ligand AntPhos was proved to be efficient for the asymmetric dearomative cyclization to provide the tricyclic compound 8 bearing a chiral all-carbon quaternary center in 85% ee and 87% yield.

An Efficient Protocol for the Palladium-catalyzed Asymmetric Decarboxylative Allylic Alkylation Using Low Palladium Concentrations and a Palladium(II) Precatalyst.

Enantioselective catalytic allylic alkylation for the synthesis of 2-alkyl-2-allylcycloalkanones and 3,3-disubstituted pyrrolidinones, piperidinones and piperazinones has been previously reported by our laboratory. The efficient construction of chiral all-carbon quaternary centers by allylic alkylation was previously achieved with a catalyst derived in situ from zero valent palladium sources and chiral phosphinooxazoline (PHOX) ligands. We now report an improved reaction protocol with broad applicability among different substrate classes in industry-compatible reaction media using loadings of palladium(II) acetate as low as 0.075 mol % and the readily available chiral PHOX ligands. The novel and highly efficient procedure enables facile scale-up of the reaction in an economical and sustainable fashion.

ChemInform Abstract: Catalytic Asymmetric Synthesis of 3,3′‐Diaryloxindoles as Triarylmethanes with a Chiral All‐Carbon Quaternary Center: Phase‐Transfer‐Catalyzed SNAr Reaction.

Catalytic asymmetric synthesis of unsymmetrical triarylmethanes with a chiral all-carbon quaternary center was achieved by using a chiral bifunctional quaternary phosphonium bromide catalyst in the SNAr reaction of 3-aryloxindoles under phase-transfer conditions. The presence of a urea moiety in the chiral phase-transfer catalyst was important for obtaining high enantioselectivity in this reaction.

Organocatalytic asymmetric vinylogous Michael addition of 3-alkylidene oxindoles to α-substituted β-nitroacrylates: facile construction of a chiral all-carbon quaternary center

A highly enantioselective vinylogous Michael addition reaction of 3-alkylidene oxindoles to α-substituted β-nitroacrylates has been developed by using a cinchona alkaloid-squaramide bifunctional organocatalyst, which provides a series of chiral products bearing all-carbon quaternary stereocenters in excellent yields with high enantioselectives (up to 97%).

Catalytic asymmetric synthesis of 3,3'-diaryloxindoles as triarylmethanes with a chiral all-carbon quaternary center: phase-transfer-catalyzed S(N)Ar reaction.

Catalytic asymmetric synthesis of unsymmetrical triarylmethanes with a chiral all-carbon quaternary center was achieved by using a chiral bifunctional quaternary phosphonium bromide catalyst in the S(N)Ar reaction of 3-aryloxindoles under phase-transfer conditions. The presence of a urea moiety in the chiral phase-transfer catalyst was important for obtaining high enantioselectivity in this reaction.

A facile asymmetric synthesis of Δ3-2-Hydroxybakuchiol, Bakuchiol and ent-Bakuchiol

A facile asymmetric synthesis of Δ3-2-Hydroxybakuchiol, Bakuchiol, and ent-Bakuchiol is described through one common intermediate bearing a chiral all-carbon quaternary carbon center, which involves stereoselectively unconjugated alkylation of the α,β-unsaturated imide bearing Evans' auxiliary, Takai–Utimoto reaction, Negishi reaction, and Heck reaction as key steps.

Stereoarrays with an All‐Carbon Quaternary Center: Diastereoselective Desymmetrization of Prochiral Malonaldehydes

Tamed by chelation: The MgBr2 chelation of prochiral malonaldehydes allows diastereoselective monoaddition reactions with allyl stannane nucleophiles (see scheme; PG=protecting group, TBDMS=tert-butyldiphenylmethylsilyl, Tr=trityl). In the same pot, addition of a second nucleophile proceeds in high diastereoselectivity to generate nonsymmetric products with up to five contiguous stereogenic centers, including a chiral all-carbon quaternary center.

Efficient construction of a chiral all-carbon quaternary center by asymmetric 1,4-addition and its application to total synthesis of (+)-bakuchiol

The conjugate addition of lithium divinylcuprate to (4 S,2′ E)-3-(6′-TBDPS-3′-methylhex-2′-enoyl)-4-phenyloxazolidin-2-one proceeded efficiently to create a chiral all-carbon quaternary center with a high diastereoselectivity ( R: S = 95:5). The absolute configuration of the newly generated chiral center was confirmed by applying this methodology to the total synthesis of (+)-bakuchiol.

Highly Enantioselective Hydrovinylation of α-Alkyl Vinylarenes. An Approach to the Construction of All-Carbon Quaternary Stereocenters

The highly enantioselective hydrovinylation of alpha-alkyl vinylarenes was realized by using nickel complexes of chiral spiro phosphoramidite ligands. The method provided a new approach to the construction of chiral all-carbon quaternary centers.

A Copper‐Catalyzed Method for the Facially Selective Addition of Grignard Reagents to Cyclopropenes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A copper-catalyzed method for the facially selective addition of grignard reagents to cyclopropenes.

A Cu-catalyzed method for the addition of Grignard reagents to 1-alkyl-3-hydroxymethylcyclopropenes and their MOM ethers is described. The face of addition is syn relative to the hydroxymethyl and alkoxymethyl groups. Excellent diastereoselectivity is observed for a range of alkyl, alkenyl, and alkynylmagnesium halides. The addition reactions create chiral all-carbon quaternary centers, and the cyclopropylmetals that are generated can be reacted with electrophiles to produce highly functionalized cyclopropanes.