The enantioselective addition of Grignard reagents to ketones was promoted by a BINOL derivative bearing alkyl chains at the 3,3′-positions. This is the first asymmetric direct aryl Grignard addition to ketones reported to date. A variety of tertiary diaryl alcohols could be obtained in high yields and enantioselectivities without using any other metal source.

The phosphine oxide-catalyzed asymmetric intramolecular aldol reactions of diketones were investigated. The combination of tetrachlorosilane and a chiral phosphine oxide catalyst promoted the acetyl-selective enolization of diketones, and the subsequent intramolecular aldol reaction occurred in an enantioselective manner. The introduction of two trimethylsilyl groups at the 4- and 4′-positions in BINAP dioxide catalyst improved the enantioselectivity. This reaction provides an effective synthetic method to access β-tertiary-hydroxy cyclohexanones in high yields and with high enantioselectivity.

In this study, we report a new highly diastereoselective domino reaction of imines, enamines, and trichlorosilane. The reaction involves CC bond formation between the imine and enamine followed by the intramolecular reduction of the resulting iminium intermediate by the hydrosilyl group, affording a 1,2-anti-2,3-anti-1,3-diamine in good yield with high diastereoselectivity. Lewis base catalysts such as HMPA increased the chemical yield without decreasing the diastereoselectivity.

The asymmetric addition of lithium acetylides to carbonyl compounds in the presence of a chiral lithium binaphtholate catalyst was developed. A procedure involving the slow addition of carbonyl compounds to lithium acetylides improved the enantioselectivity. This reaction afforded diverse chiral secondary and tertiary propargylic alcohols in high yields and with good to high enantioselectivities.

An application of a hypervalent silicon complex, generated from a chiral phosphine oxide catalyst and silicon tetrachloride, to the enantioselective organocatalytic Morita–Baylis–Hillman reaction is described. A chloride anion liberated from the hypervalent silicon complex smoothly generated a γ-chloro silyl enol ether that subsequently reacted with an aldehyde to afford the Baylis–Hillman adducts in good yields and with good enantioselectivities.

Trichlorosilyl triflate-promoted directed cross-aldol reaction between ketones in the presence of a chiral phosphine oxide as an organocatalyst is described. This is the first enantioselective cross-aldol reaction between simple ketones with good enantioselectivity.

Treatment of an optically pure tartaric acid-derived diiodide and various secondary phosphine oxides with LHMDS provides the corresponding aryl group-modified DIOP dioxides (Ar-DIOPOs). The activities of Ar-DIOPOs as Lewis base catalysts were investigated for several asymmetric transformations using chlorosilane reagents. The p-tolyl-substituted DIOPO (p-tolyl-DIOPO) was most effective for the reductive aldol reaction of chalcone and aldehydes with trichlorosilane, whereas the 2,8-dimethylphenoxaphosphine-derived DIOPO (DMPP-DIOPO) afforded the best enantioselectivity for the phosphonylation of conjugated aldehydes and the chlorinative aldol reaction of an ynone and benzaldehyde.

An efficient method was developed for the enantioselective reductive aldol reaction of α,β-unsaturated ketones with aldehydes in the presence of a Lewis base catalyst; conjugate reduction using a tertiary amine and trichlorosilyl triflate, followed by an aldol reaction with BINAP dioxide (BINAPO) as an organocatalyst, gave the corresponding product in high yield with high stereoselectivity.

Chiral lithium binaphtholate effectively catalyzed the enantioselective alkynylation of ketones using lithium acetylide as an alkynylating agent. This is the first example of the catalytic enantioselective addition of lithium acetylide to carbonyl compounds without the aid of other metal sources.

Chiral lithium 3,3′-diphenylbinaphtholate successfully catalyzed the alkynylation of ketone with trimethoxysilylalkyne, affording chiral tertiary propargylic alcohols in high chemical yields and high enantioselectivities. The present reaction could be extended to the alkynylation of acetylpyridine, which afforded a biologically active pyridyl propargylic alcohol in good enantioselectivity.

Chiral dinitrones were synthesized by the condensation of a C2-symmetrical chiral dihydroxylamine with various aldehydes. The electronic and steric properties of the dinitrones can be modified by changing the aldehyde component. The activity of dinitrones as Lewis base catalysts was examined for the asymmetric allylation of aldehydes with allyltrichlorosilanes. Using DMPU as an additive in chloroform, the reaction proceeded at room temperature to afford allylated products in good yields and good enantioselectivities.(1S,2S,NZ,N′Z)-N,N′-Dibenzylidenecyclohexane-1,2-diamine N,N′-dioxideC20H22N2O2[α]D30=+279.8 (c 1.0, CHCl3)Source of chirality: (S,S)-1,2-cyclohaxanediamineAbsolute configuration: (1S,2S)(1S,2S,NZ,N′Z)-N,N′-Bis(naphthalene-1-ylmethylene)cyclohexane-1,2-diamine N,N′-dioxideC28H26N2O2[α]D22=-56.6 (c 1.0, CHCl3)Source of chirality: (S,S)-1,2-cyclohaxanediamineAbsolute configuration: (1S,2S)(1S,2S,NZ,N′Z)-N,N′-Bis(naphthalene-2-ylmethylene)cyclohexane-1,2-diamine N,N′-dioxideC28H26N2O2[α]D19=+578.6 (c 1.0, CHCl3)Source of chirality: (S,S)-1,2-cyclohaxanediamineAbsolute configuration: (1S,2S)(1S,2S,NZ,N′Z)-N,N′-Bis(4-chlorobenzylidene)cyclohexane-1,2-diamine N,N′-dioxideC20H20Cl2N2O2[α]D31=+223.6 (c 1.0, CHCl3)Source of chirality: (S,S)-1,2-cyclohaxanediamineAbsolute configuration: (1S,2S)(1S,2S,NZ,N′Z)-N,N′-Bis(4-nitrobenzylidine)cyclohexane-1,2-diamine N,N′-dioxideC20H20N4O6[α]D26=+418.4 (c 0.4, CHCl3)Source of chirality: (S,S)-1,2-cyclohaxanediamineAbsolute configuration: (1S,2S)(1S,2S,NZ,N′Z)-N,N′-Bis(4-methoxybenzylidine)cyclohexane-1,2-diamine N,N′-dioxideC22H26N2O4[α]D22=+185.8 (c 0.34, CHCl3)Source of chirality: (S,S)-1,2-cyclohaxanediamineAbsolute configuration: (1S,2S)(1S,2S,NZ,N′Z)-N,N′-Bis(3,4,5-trimethoxybenzylidene)cyclohexane-1,2-diamine N,N′-dioxideC26H34N2O8[α]D22=+111.9 (c 1.0, CHCl3)Source of chirality: (S,S)-1,2-cyclohaxanediamineAbsolute configuration: (1S,2S)(R)-1-(3,4,5-Trimethoxyphenyl)but-3-en-1-olC13H18O4Ee = 87%[α]D31=+32.2 (c 2.9, CHCl3)Source of chirality: enantioselective synthesisAbsolute configuration: (R)

N-Acylated β-amino enones reductively cyclize by treatment with trichlorosilane and a chiral Lewis base catalyst to afford optically active 4H-1,3-oxazines, which can be transformed to other chiral compounds without racemization.

Lewis bases such as Ph3PO and HMPA catalyze the 1,4-reduction of α,β-unsaturated ketones with trichlorosilane, and because the 1,2-reduction of aldehydes scarcely proceeded under the conditions, one-pot reductive aldol reactions with aldehydes were successfully achieved; preliminary studies using a chiral Lewis base revealed a high potential for enantioselective catalysis.

The enantioselective ring opening of meso-epoxides with tetrachlorosilane in the presence of diisopropylethylamine using chiral phosphine oxide BINAPO as the catalyst affords the corresponding chlorohydrins in high enantioselectivities of up to 90% ee.(1S,2S)-2-Chloro-1,2-diphenylethanolC14H13ClOEe = 90%[α]D25=+19.7 (c 1.0, EtOH)Source of chirality: asymmetric synthesisAbsolute configurations: (1S,2S)

Lewis bases such as Ph3PO and HMPA catalyze the 1,4-reduction of α,β-unsaturated ketones with trichlorosilane, and because the 1,2-reduction of aldehydes scarcely proceeded under the conditions, one-pot reductive aldol reactions with aldehydes were successfully achieved; preliminary studies using a chiral Lewis base revealed a high potential for enantioselective catalysis.

N-Acylated β-amino enones reductively cyclize by treatment with trichlorosilane and a chiral Lewis base catalyst to afford optically active 4H-1,3-oxazines, which can be transformed to other chiral compounds without racemization.

Treatment of an optically pure tartaric acid-derived diiodide and various secondary phosphine oxides with LHMDS provides the corresponding aryl group-modified DIOP dioxides (Ar-DIOPOs). The activities of Ar-DIOPOs as Lewis base catalysts were investigated for several asymmetric transformations using chlorosilane reagents. The p-tolyl-substituted DIOPO (p-tolyl-DIOPO) was most effective for the reductive aldol reaction of chalcone and aldehydes with trichlorosilane, whereas the 2,8-dimethylphenoxaphosphine-derived DIOPO (DMPP-DIOPO) afforded the best enantioselectivity for the phosphonylation of conjugated aldehydes and the chlorinative aldol reaction of an ynone and benzaldehyde.

Trichlorosilyl triflate-promoted directed cross-aldol reaction between ketones in the presence of a chiral phosphine oxide as an organocatalyst is described. This is the first enantioselective cross-aldol reaction between simple ketones with good enantioselectivity.

Chiral lithium binaphtholate effectively catalyzed the enantioselective alkynylation of ketones using lithium acetylide as an alkynylating agent. This is the first example of the catalytic enantioselective addition of lithium acetylide to carbonyl compounds without the aid of other metal sources.