Organocatalytic cascade nucleophilic/aza-Michael addition reactions: metal-free catalytic strategy for the synthesis of hydantoins.

Lewis base-catalyzed cascade nucleophilic/aza-Michael addition reaction of N-alkoxy ß-oxo-acrylamides with isocyanates has been developed to afford various highly functionalized hydantoin derivatives in 80-98% yields under mild reaction conditions. The intriguing features of this method include metal-free reaction conditions, low catalyst loading, broad substrate scope and short reaction time.

Functional Phosphine Derivatives Having Stationary and Flexible Chiralities: Their Preparation and Chirality Controlling.

Various functional secondary and tertiary phosphines, or their derivatives, containing stationary chiral phosphorus and flexible chiral axis were prepared, which could be further modified to afford diversely chelating ligands. The flexible axial chirality was fixed by stereogenic phosphorus via a cyclic linkage of chemical bonds or coordination with a metallic ion.

Catalytic Hydrothiolation: Counterion-Controlled Regioselectivity.

In this Article, we expand upon the catalytic hydrothiolation of 1,3-dienes to afford either allylic or homoallylic sulfides with high regiocontrol. Mechanistic studies support a pathway in which regioselectivity is dictated by the choice of counterion associated with the Rh center. Non-coordinating counterions, such as SbF6-, allow for η4-diene coordination to Rh complexes and result in allylic sulfides. In contrast, coordinating counterions, such as Cl-, favor neutral Rh complexes in which the diene binds η2 to afford homoallylic sulfides. We propose mechanisms that rationalize a fractional dependence on thiol for the 1,2-Markovnikov hydrothiolation while accounting for an inverse dependence on thiol in the 3,4- anti-Markovnikov pathway. Through the hydrothiolation of an essential oil (ß-farnesene), we achieve the first enantioselective synthesis of (-)-agelasidine A.

Enantioselective Coupling of Dienes and Phosphine Oxides.

We report a Pd-catalyzed intermolecular hydrophosphinylation of 1,3-dienes to afford chiral allylic phosphine oxides. Commodity dienes and air stable phosphine oxides couple to generate organophosphorus building blocks with high enantio- and regiocontrol. This method constitutes the first asymmetric hydrophosphinylation of dienes.

Metal-Free One-Pot Synthesis of 3-Phosphinoylbenzofurans via Phospha-Michael Addition/Cyclization of H-Phosphine Oxides and in Situ Generated ortho-Quinone Methides.

A novel metal-free one-pot protocol for the effective and efficient synthesis of 3-phosphinoylbenzofurans via a phospha-Michael addition/cyclization of H-phosphine oxides and in situ generated ortho-quinone methides is described. Based on the expeditious construction of C(sp2)-P bonds, asymmetric synthesis of optically pure 3-phosphinoylbenzofurans containing chiral P-stereogenic center has also been probed by using chiral RP-(-)-menthyl phenylphosphine oxide.

Nucleophilic Substitution of P-Stereogenic Chlorophosphines: Mechanism, Stereochemistry, and Stereoselective Conversions of Diastereomeric Secondary Phosphine Oxides to Tertiary Phosphines.

A diastereomeric mixture of secondary phosphine oxide is stereospecifically converted to chlorophosphine salt by treatment with oxalyl chloride, which stereoselectively affords P-inverted or retained tertiary phosphines, depending on the substitution with aliphatic or aromatic Grignard reagents, respectively, in high to 99% yield and 99:1 dr. The repulsion of π-electron on aryl to lone electron pair on phosphorus is proposed for the P-retained substitution.

Nonepimerizing Alkylation of H-P Species to Stereospecifically Generate P-Stereogenic Phosphine Oxides: A Shortcut to Bidentate Tertiary Phosphine Ligands.

The secondary RP-(-)-menthyl alkylphosphine oxide was confirmed as configurationally stable toward base and was used in base-promoted alkylation, stereospecifically affording P-retained bis or functional tertiary phosphine oxides in excellent yields. The alkylated products were deoxygenated using oxalyl chloride followed by ZnCl2-NaBH4 to form P-inversed bidentate phosphine boranes in high stereoselectivities.

Preparation of Optically Pure Tertiary Phosphine Oxides via the Addition of P-Stereogenic Secondary Phosphine Oxide to Activated Alkenes.

Functionalized P,C-stereogenic tertiary phosphine oxides were prepared by the addition of (RP)-menthyl phenylphosphine oxide to activated olefins, in high drP and drC, and were isolated in excellent yields. The reaction was readily catalyzed by Ca(OH)2 or occurred with gentle heating. A wide range of substrates, including vinyl ketones, esters, nitriles, and nitro alkenes, can be used in the reaction.

Variable mechanism of nucleophilic substitution of P-stereogenic phosphoryl chloride with alkynyl metallic reagents.

The variable mechanism for substitution of P-stereogenic phosphoryl chloride with alkynyl metallic reagents, which depends on temperature, stoichiometry of starting materials, and the structure of the nucleophilic reagent, is assumed as either SN2-like or Berry pseudorotation of pentacoordinated phosphorus intermediates, affording inversion and retention products, respectively. The formation of the inversion product can be controlled to occur predominantly to afford (RP)-alkynylphosphinates.

Double Asymmetric Induction During the Addition of (RP)-Menthyl Phenyl Phosphine Oxide to Chiral Aldimines.

P,C-Stereogenic α-amino phosphine oxides were prepared from the addition of (RP )-menthyl phenyl phosphine oxide to chiral aldimines under neat condition at 80 °C in up to 91:9 drC and 99% yields. The diastereoselectivity was mainly induced by chiral phosphorus that showed matched or mismatched induction with (S)- or (R)-aldimines, respectively.

One-pot process that efficiently generates single stereoisomers of 1,3-bisphosphinylpropanes having five chiral centers.

P,C-stereogenic 1,3-bisphosphinylpropanes 3 that have up to five stereogenic centers could be obtained stereoselectively in high yields by a one-step reaction of (RP)-menthylphenylphosphine oxide 1 with α,ß-unsaturated aldehydes 2 catalyzed by KOH at room temperature. A mechanism was proposed as to involve a stereoselective intermolecular 1,3'-phosphorus migration from the 1,2-adduct of 1 with 2 to another 2 generating a 1,4-adduct that subsequently reacts with 1 to produce 3.

Intramolecular dehydrative coupling of tertiary amines and ketones promoted by KO-t-Bu/DMF: a new synthesis of indole derivatives.

A new synthesis of indole derivatives has been achieved through intramolecular dehydrative coupling of tertiary amines and ketones promoted by KO-t-Bu/DMF. The reaction probably proceeds via an α-amino alkyl radical pathway.

Unprecedented construction of C═C double bonds via Ir-catalyzed dehydrogenative and dehydrative cross-couplings.

Unprecedented constructions of C═C double bonds have been achieved by Ir-catalyzed intramolecular dehydrogenative and dehydrative cross-coupling of tertiary amines and ketones. The reactions are proposed to proceed via an Ir-mediated C-H activation mechanism.

Organocatalytic asymmetric conjugate addition and cascade acyl transfer reaction of α-nitroketones.

Organocatalytic asymmetric conjugate addition of α-nitroketones to ß,γ-unsaturated α-keto esters has been developed. A pyrrolidine-based thiourea-tertiary amine was identified as the best catalyst. The reaction was found to proceed via cascade conjugate addition and acyl transfer reaction. A number of α-nitroketones and ß,γ-unsaturated α-keto esters were examined in this transformation. 5-Nitro-2-acyloxypent-2-enoates were obtained in good yields (up to 99%) and enantioselectivities (up to 99% ee). The products could be hydrolyzed to provide 5-nitro-2-oxopentanoates, which are not available from the direct addition of nitromethane to ß,γ-unsaturated α-keto esters.

Highly enantioselective synthesis of nitrocyclopropanes via organocatalytic conjugate addition of bromomalonate to alpha,beta-unsaturated nitroalkenes.

Highly enantioselective synthesis of nitrocyclopropanes was achieved via the organocatalytic conjugate addition of dimethyl bromomalonate to nitroalkenes and the consequent intramolecular cyclopropanation. 6'-Demethyl quinine was found to be the efficient catalyst. Excellent enantioselectivities, diastereoselectivities, and good yields were obtained for a variety of aryl or heteroaryl nitroethylenes.