Chiral Quaternary Carbon Center Research Articles

Total synthesis of aspidophytine

A total synthesis of aspidophytine was accomplished by employing a newly developed strategy for the enantiospecific syntheses of aspidosperma alkaloids. The key steps involve a novel ketene-lactonization reaction of a chiral vinyl sulfoxide (Marino annulation reaction) to set up the chiral quaternary carbon center, and a tandem Michael addition-alkylation reaction sequence to form the polycyclic core structure.

Palladium-Catalyzed Regio- and Diastereoselective Allylic Alkylation with Azlactones Using Triphenylarsine

The palladium-catalyzed regio- and diastereoselective allylic alkylation of (R)-2-acetoxy-4-phenyl-3-butene with azlactones using AsPh3 successfully occurred. The stereochemistries were highly controlled, and the reaction produced a coupling product which possessed vicinal chiral quaternary and tertiary carbon centers.

Lewis Acid-Promoted Rearrangement of 2,3-Epoxy Alcohol Derivatives: Stereochemical Control and Selective Formation of Two Types of Chiral Quaternary Carbon Centers from the Single Carbon Skeleton

The Lewis acid-promoted rearrangement of 2,2,3,3-tetrasubstituted 2,3-epoxy alcohols with several kinds of protecting groups was investigated. When SnCl4 is used as a Lewis acid, the reaction proceeds in a regio- and stereo-controlled manner to afford two types of carbonyl compounds selectively from a single 2,3-epoxy alcohol only by changing the protecting group of the alcohol. The method was then applied to the formation of two types of acyclic and cyclic quaternary carbon centers from the single compound in optically active forms.

イリジウム，ロジウム錯体を用いる触媒的付加環化反応の開発

Transition metal-catalyzed cycloaddition is an atom-economical and powerful synthetic tool for the construction of cyclic carbon skeletons. Various types of cycloadditions, including [2 + 2 + 1], [2 + 2 + 2], [4 + 2] cycloaddition, etc., have been reported. Their asymmetric versions using chiral transition metal catalysts have also been reported to give enantiomerically-enriched multi-cyclic compounds.First, an iridium-catalyzed enantioselective Pauson-Khand-type reaction is summarized. Pauson-Khand (-type) reaction is a [2 + 2 + 1] cycloaddition of an alkyne, alkene and carbon monoxide, and gives synthetically useful cyclopentenones. Rhodium- and iridium-catalyzed Pauson-Khand-type reactions using an aldehyde as a CO source were also mentioned. Second, two types of enantioselective [2 + 2 + 2] cycloadditions are described : One is an iridium-catalyzed [2 + 2 + 2] cycloaddition of diynes and monoalkynes for the synthesis of chiral teraryls with two axial chiralities. Another is a rhodium-catalyzed [2 + 2 + 2] cycloaddition of enynes and monoalkynes for the synthesis of bicyclic cyclohexa-1, 3-dienes with a chiral quaternary carbon center. Third, a rhodium-catalyzed enantioselective [2 + 2] cycloaddition of alkynes and alkenes for the synthesis of chiral cyclobutenes is mentioned.

Palladium‐Catalyzed Construction of Amino Acid Derivatives Possessing Vicinal Chiral Quaternary and Tertiary Carbon Centers at the α and β Positions.

Abstract The palladium catalyzed regio- and diastereo-selective allylic alkylation of ( R )-2-acetoxy-4-aryl-3-butene with N -(diphenylmethylidene)glycinate and N -(diphenylmethylidene)alaninate occurred. The stereochemistry was controlled by the use of o -(diphenylphosphino)carboxylic acid, and produced new amino acid derivatives possessing vicinal chiral quaternary and tertiary carbon centers at the α and β positions.

Catalytic Enantioselective Michael Reaction of 1,3‐Dicarbonyl Compounds via Formation of Chiral Palladium Enolate

AbstractAn efficient catalytic enantioselective Michael reaction has been developed using chiral palladium complexes. Various substrates including β‐keto esters and 1,3‐diketones reacted with α,β‐unsaturated carbonyl compounds to give the corresponding Michael adducts in good yield with up to 99% ee, thereby affording chiral quaternary carbon centers. In these reactions, chiral palladium enolates were generated as key intermediates, which acted cooperatively with a strong protic acid to activate the Michael acceptors for promotion of the CC bond‐forming reaction.

Palladium-catalyzed construction of amino acid derivatives possessing vicinal chiral quaternary and tertiary carbon centers at the α and β positions

The palladium catalyzed regio- and diastereo-selective allylic alkylation of ( R)-2-acetoxy-4-aryl-3-butene with N-(diphenylmethylidene)glycinate and N-(diphenylmethylidene)alaninate occurred. The stereochemistry was controlled by the use of o-(diphenylphosphino)carboxylic acid, and produced new amino acid derivatives possessing vicinal chiral quaternary and tertiary carbon centers at the α and β positions.

Enantioselective Total Synthesis of Marine Natural Products Untenone A and Plakevulin A.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantio‐ and Diastereoselective Michael Reaction of 1,3‐Dicarbonyl Compounds to Nitroolefins Catalyzed by a Bifunctional Thiourea.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Construction of Chiral Quaternary Carbon Centers by Pd‐Catalyzed Asymmetric Allylic Substitution with P,N‐1,1′‐Ferrocene Ligands.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Desymmetrization and Diastereotopic Group Selection in 1,4-Cyclohexadienes

Diastereotopic group selection in 1,4-cyclohexadienes is a useful approach to synthesize rather complex compounds in a single operation. The stereoinduction occurs via a covalently bound stereogenic center. Cycloadditions, Michael additions, and radical reactions have been conducted as group-selective processes. Even more elegant is the desymmetrization of an achiral 1,4-cyclohexadiene. Various chiral reagents have been used successfully to desymmetrize 1,4-cyclohexadienes. In one step, at least two new stereogenic centers are formed. Chiral quaternary carbon centers can be obtained with high selectivity. This Account will provide an overview on diastereotopic group selection and desymmetrization in various 1,4-cyclohexadiene derivatives.

Enantioselective Total Synthesis of Marine Natural Products Untenone A and Plakevulin A

An enantioselective total synthesis of untenone A and plakevulin A has been achieved. Construction of a cyclopentene derivative, the key intermediate in this synthesis, was carried out by using a ruthenium-catalyzed ring-closing metathesis reaction of a divinyl compound, prepared from octadecanal in several steps including the Sharpless asymmetric epoxidation to generate a chiral quaternary carbon center.

Enantio- and Diastereoselective Michael Reaction of 1,3-Dicarbonyl Compounds to Nitroolefins Catalyzed by a Bifunctional Thiourea

We synthesized a new class of bifunctional catalysts bearing a thiourea moiety and an amino group on a chiral scaffold. Among them, thiourea 1e bearing 3,5-bis(trifluoromethyl)benzene and dimethylamino groups was revealed to be highly efficient for the asymmetric Michael reaction of 1,3-dicarbonyl compounds to nitroolefins. Furthermore, we have developed a new synthetic route for (R)-(-)-baclofen and a chiral quaternary carbon center with high enantioselectivity by Michael reaction. In these reactions, we assumed that a thiourea moiety and an amino group of the catalyst activates a nitroolefin and a 1,3-dicarbonyl compound, respectively, to afford the Michael adduct with high enantio- and diastereoselectivity.

Construction of Chiral Quaternary Carbon Centers by Pd-Catalyzed Asymmetric Allylic Substitution with P,N-1,1‘-Ferrocene Ligands

A chiral quaternary carbon center on allyl substrates was constructed by Pd-catalyzed allylic alkylation reaction in good to high regio- and enantioselectivities for a wide range of substrates for the first time. [reaction: see text]

Acid‐Catalyzed Rearrangement of Epoxy Alcohol Derivatives Having the Electron‐Withdrawing Protective Groups (Acyl or Sulfonyl): Asymmetric Synthesis of Chiral Quaternary Carbon and Spiro Centers and Its Application to Natural Products Synthesis

AbstractFor Abstract see ChemInform Abstract in Full Text.

Direct catalytic asymmetric mannich reactions of malonates and beta-keto esters.

The first catalytic asymmetric direct Mannich reaction of malonates and beta-keto esters has been developed. Malonates react with an activated N-tosyl-alpha-imino ester catalyzed by chiral tert-butyl-bisoxazoline/Cu(OTf)(2) to give the Mannich adducts in high yields and with up to 96% ee. These reactions create a chiral quaternary carbon center and it is demonstrated that this new direct Mannich reactions provides for example a new synthetic procedure for the formation of optically active beta-carboxylic ester alpha-amino acid derivatives. A series of different beta-keto esters with various ester substituents has been screened as substrates for the catalytic asymmetric direct Mannich reaction and it was found that the best results in terms of yield, diastereo- and enantioselectivity were obtained when tert-butyl esters of beta-keto esters were used as the substrate. The reaction of different beta-keto tert-butyl esters with the N-tosyl-alpha-imino ester gave the Mannich adducts in high yields, diastereo- and enantioselectivities (up to 95% ee) in the presence of chiral tert-butyl-bisoxazoline/Cu(OTf)(2) as the catalyst. To expand the synthetic utility of this direct Mannich reaction a diastereoselective decarboxylation reaction was developed for the Mannich adducts leading to a new synthetic approach to attractive optically active beta-keto alpha-amino acid derivatives. Based on the stereochemical outcome of the reactions, various approaches of the N-tosyl-alpha-imino ester to the chiral bisoxazoline/Cu(II)-substrate intermediate are discussed.

Concise Asymmetric Synthesis of (‐)‐Herbertenediol.

Abstract The rearrangement of the optically active 3-aryl-2-methyl-2,3-epoxy tosylate (>98% ee) afforded the α-keto tosylate with a chiral quaternary carbon center and without loss of chirality. Reductive removal of the tosyloxy group gave the keto compound with a chiral quaternary carbon center, which was converted to (−)-herbertenediol (>98% ee).

D- and l-Erythrose as sources of chiral quaternary carbon centers. Total synthesis of (−)-malyngolide and (+)-tanikolide

A highly efficient and versatile approach was applied for the total synthesis of the marine natural products (−)-malyngolide and (+)-tanikolide from isopropylidene l- and d-erythrose, using a common strategy.

電子求引性保護基（アシル基，スルホニル基）を持つエポキシアルコール類の酸転位反応 不斉四級炭素および不斉スピロ中心の構築と天然物合成への応用

Rearrangements of 1, 2-epoxy alcohol derivatives having electron-withdrawing protective groups such as acyl or sulfonyl group have been developed leading to the asymmetric construction of chiral quaternary carbon centers and spiro centers. The success of the novel rearrangements here depends on the electron-withdrawing property of the protective groups. The methods were applied to the asymmetric syntheses of several natural products such as fredericamycin A, (+) - (S) -sporochnol A, (-) -aphanorphine, and (-) -a-herbertenol.

Concise asymmetric synthesis of (−)-herbertenediol

The rearrangement of the optically active 3-aryl-2-methyl-2,3-epoxy tosylate (>98% ee) afforded the α-keto tosylate with a chiral quaternary carbon center and without loss of chirality. Reductive removal of the tosyloxy group gave the keto compound with a chiral quaternary carbon center, which was converted to (−)-herbertenediol (>98% ee).