Construction Of Quaternary Stereogenic Centers Research Articles

Advances in Catalytic Asymmetric Construction of Quaternary Stereogenic Centers by Conjugate Addition to β,β‐Disubstituted Nitroalkenes

AbstractQuaternary stereogenic centers are of great importance because of their prevalence in a series of bioactive natural products and pharmaceuticals. Although the catalytic asymmetric construction of these highly congested centers poses a formidable challenge, this field has been extensively explored in the past few decades, and several elegant strategies, such as the asymmetric conjugate addition to β,β‐disubstituted nitroalkenes, have been developed. The resultant β‐nitro quaternary stereocenters can be conveniently transformed into the corresponding β‐amino quaternary stereocenters commonly found in bioactive compounds. This review summarizes the recent advances in the construction of all‐carbon quaternary or hetero‐carbon quaternary stereocenters via metal‐catalyzed and organocatalyzed asymmetric conjugate addition to β,β‐disubstituted nitroalkenes, focusing on the scope, applications, and mechanisms of these reactions.

Phosphine-Catalyzed Asymmetric Allylic Alkylation of Achiral MBH Carbonates with 3,3'-Bisindolines: Enantioselective Construction of Quaternary Stereogenic Centers.

The asymmetric allylic alkylation (AAA) of achiral Morita-Baylis-Hillman (MBH) carbonates with 3,3'-bisindolines under the catalysis of amino-acid-derived bifunctional phosphines was accomplished. With the AAA approach introduced herein, challenging 3,3'-bisindolines bearing an all-carbon quaternary stereocenter (C3a) have been constructed in good yields with good to excellent enantioselectivties. In addition, the synthetic value of this protocol was demonstrated by the facile synthesis of the core skeleton of gliocladin C.

Enantioselective Construction of Quaternary Stereogenic Centers by the Addition of an Acyl Anion Equivalent to 1,3-Dienes.

We report the enantioselective formation of quaternary stereogenic centers by the intermolecular addition of malononitrile, an acyl anion equivalent, and related pronucleophiles to several 1,3-disubstituted acyclic 1,3-dienes in the presence of a Pd-PHOX catalyst. Products are obtained in up to 88% yield and 99:1 er and in most cases are formed as a single regioisomer. The products' malononitrile unit undergoes oxidative functionalization to afford β,γ-unsaturated carbonyls bearing internal olefins and α-quaternary stereogenic centers.

Interrupted Morita–Baylis–Hillman-Type Reaction of α-Substituted Activated Olefins

It was demonstrated that 3-olefinic oxindoles could generate zwitterionic enolate species with tertiary phosphines and undergo C-C bond formation with various electrophiles in an interrupted Morita-Baylis-Hillman-type reaction manner, followed by a dephosphoration process. Although the in situ formation of phosphorus-ylide intermediates was observed, no Wittig reaction was detected, even in the presence of excess formaldehyde. Moreover, excellent enantioselectivity for the construction of quaternary stereogenic centers was induced with chiral phosphines. Deuterium experiments and density functional theory calculations were conducted to elucidate the reaction mechanism.

Construction of Quaternary Stereogenic Centers in the Total Synthesis of Natural Products.

Total syntheses of the tetracyclic terpene waihoensene and the densely functionalized tetracyclic compound ryanodol have recently been reported. Both approaches constitute examples of the efficient and innovative construction of multiple quaternary centers.

ChemInform Abstract: Asymmetric Aldol Reaction of α,α‐Disubstituted Acetaldehydes Catalyzed by Diphenylprolinol Silyl Ether for the Construction of Quaternary Stereogenic Centers.

AbstractThe aldol reaction of aldehydes (I) and (V) with ethyl glyoxylate polymer affords the corresponding aldol adducts with moderate diastereoselectivities and low to good enantioselectivities.

Asymmetric Aldol Reaction of α,α‐Disubstituted Acetaldehydes Catalyzed by Diphenylprolinol Silyl Ether for the Construction of Quaternary Stereogenic Centers

AbstractThe asymmetric cross‐aldol reaction of α,α‐disubstituted acetaldehydes with commercial ethyl glyoxylate polymer was successfully catalyzed by diphenylprolinol silyl ether 3 to generate all‐carbon quaternary stereogenic centers with good enantioselectivity.

Enantioselective construction of quaternary stereogenic carbon atoms by the Lewis base catalyzed additions of silyl ketene imines to aldehydes.

Silyl ketene imines derived from a variety of α-branched nitriles have been developed as highly useful reagents for the construction of quaternary stereogenic centers via the aldol addition reaction. In the presence of SiCl4 and the catalytic action of a chiral phosphoramide, silyl ketene imines undergo extremely rapid and high yielding addition to a wide variety of aromatic aldehydes with excellent diastereo- and enantioselectivity. Of particular note are the high yields and selectivities obtained from electron-rich, electron-poor, and hindered aldehydes. Linear aliphatic aldehydes did react with good diastereo- and enantioselectivity in the presence of nBu4N(+)I(-), but branched aldehydes were much less reactive. Semiempirical calculations provided a rationalization of the observed diastereo- and enantioselectivity via open transitions states.

Asymmetric Construction of Quaternary Stereogenic Centers via Auxiliary-Based SN2’ Reactions: A Case of 1,7-Relative Stereogenesis

Reactions of carbamates [(I), (VII), and (IX)] with phenyl- or butylcopper afford alkenes containing quaternary centers with modest to high enantiomeric excess.

ChemInform Abstract: Catalytic Asymmetric Direct Vinylogous Michael Addition of Deconjugated Butenolides to Maleimides for the Construction of Quaternary Stereogenic Centers.

AbstractA practical and efficient direct asymmetric vinylogous Michael reaction of deconjugated butenolides is developed.

Catalytic Asymmetric Direct Vinylogous Michael Addition of Deconjugated Butenolides to Maleimides for the Construction of Quaternary Stereogenic Centers

Competition under control: A practical and efficient direct asymmetric vinylogous Michael reaction of deconjugated butenolides has been developed (see scheme). The products of this reaction, highly functionalized chiral succinimides, are obtained in excellent yield with high diastereoselectivity (up to d.r.=18:1) and outstanding enantioselectivity (up to e.r.=99.5:0.5).

ChemInform Abstract: Highly Enantioselective Chlorination of β‐Keto Esters and Subsequent SN2 Displacement of Tertiary Chlorides: A Flexible Method for the Construction of Quaternary Stereogenic Centers.

AbstractThe reaction occurs in the presence of the new ligands (I) affording α‐chlorinated products with high enantioselectivity.

Highly Enantioselective Chlorination of β-Keto Esters and Subsequent SN2 Displacement of Tertiary Chlorides: A Flexible Method for the Construction of Quaternary Stereogenic Centers

Highly enantioselective chlorination of β-oxo esters and subsequent stereospecific substitution of tertiary chlorides are described. Enantioselective chlorination of β-keto esters and malonates was performed using a chiral Lewis acid catalyst prepared from Cu(OTf)(2) and the newly developed spirooxazoline ligand 2 to yield the desired α-chlorinated products with high enantioselectivity (up to 98% ee). Nucleophilic substitution of the resulting chlorides proceeded smoothly to afford a variety of chiral molecules such as α-amino, α-alkylthio, and α-fluoro esters, without loss of enantiopurity. The results of X-ray crystallographic analysis proved that Walden inversion occurs at the chlorinated tertiary carbon center. These results supported the fact that the substitution proceeds via an S(N)2 mechanism.

A general stereoselective enamine mediated alkylation of α-substituted aldehydes

We herein present a general enamine-mediated α-alkylation of α-substituted aldehydes with carbenium ions for the stereoselective construction of quaternary stereogenic centers.

ChemInform Abstract: Enantioselective Construction of Quaternary Stereogenic Centers from Tertiary Boronic Esters: Methodology and Applications.

AbstractTertiary boronic esters are successfully converted into the homologated alcohols (III) under standard Matteson conditions with complete retention of configuration.

Construction of Quaternary Stereogenic Centers from Tertiary Boronic Esters

The authors report on a lithiation-borylation reaction with subsequent one-carbon homologation or vinylation. The ready availability of the starting materials, broad range of substrates, bearing versatile functional groups with quaternary stereogenic centers, and very high enantioselectivities are noteworthy.

Cover Picture: Enantioselective Construction of Quaternary Stereogenic Centers from Tertiary Boronic Esters: Methodology and Applications (Angew. Chem. Int. Ed. 16/2011)

Cover Picture: Enantioselective Construction of Quaternary Stereogenic Centers from Tertiary Boronic Esters: Methodology and Applications (Angew. Chem. Int. Ed. 16/2011)

Enantioselective Construction of Quaternary Stereogenic Centers from Tertiary Boronic Esters: Methodology and Applications

Pin it down: A range of substrates that bear versatile functional groups with quaternary stereogenic centers have been prepared with very high enantioselectivity from tertiary boronic esters (see scheme; Cb=N,N-diisopropylcarbamoyl, pin=pinacolato). The preparation of allylboronic esters bearing contiguous quaternary and tertiary stereogenic centers, and applications to natural product synthesis are also reported.

Enantioselective Construction of Quaternary Stereogenic Centers from Tertiary Boronic Esters: Methodology and Applications

Enantioselective Construction of Quaternary Stereogenic Centers from Tertiary Boronic Esters: Methodology and Applications

Enantioselective Construction of Quaternary Stereogenic Carbons by the Lewis Base Catalyzed Additions of Silyl Ketene Imines to Aldehydes

Silyl ketene imines derived from a variety of alpha-branched nitriles have been developed as highly useful reagents for the construction of quaternary stereogenic centers via the aldol addition reaction. In the presence of SiCl4 and the catalytic action of chiral phosphoramide (R,R)-5, silyl ketene imines undergo extremely rapid and high yielding addition to a wide variety of aromatic aldehydes with excellent diastereo- and enantioselectivity. Of particular note is the high yields and selectivities obtained from electron-rich, electron-poor, and hindered aldehydes. The nitrile function serves as a useful precursor for further synthetic manipulation.