Heterocyclic lithium amides as chiral ligands for an enantioselective hydroxyalkylation with n-BuLi

Chiral heterocyclic structures based on 3-aminopyrrolidines (3APs), 3-aminotetrahydrothiophens (3ATTs), and 3-aminotetrahydrofurans (3ATFs) have been synthesized. The corresponding lithium amides have been evaluated as chiral ligands in the condensation of n-BuLi on o-tolualdehyde. The returned levels of induction were in the 46-80% ee range. The cheap and easily prepared 3ATFLi's turned out to be also the best ligands, giving access to the expected R or S alcohols in a same 80% level of induction at -78 degrees C in THF. In all cases, the sense of induction depends on the absolute configuration of C(8) on the 3-amino appendage. A general concept is proposed to rationalize the process of induction in the presence of organolithium species.     

Highly enantioselective Pd-catalyzed allylic alkylation using new chiral ferrocenylphosphinoimidazolidine ligands

New ferrocenylphosphinoimidazolidines containing central chirality and planar chirality were found to act as highly effective chiral ligands in Pd-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate.     

Application of acyclic chiral auxiliaries on alkylation reactions

The application in alkylation reactions of an acyclic chiral auxiliary is described. The synthesis is straightforward from a chiral primary amine and a double acylation. A characteristic of this auxiliary is its modular design formed by an achiral part (acyl) and a chiral component (primary amine) so it can be tuned for different reactions without difficulty. The alkylation proceeds with excellent diastereoselectivity because the conformational flexibility of the enolate is restricted by the formation of a chelate and the allylic 1,3-strain.     

Chirality transfer during alkylation of chiral amides

Chiral amides derived from O-methyl mandelic acid and achiral amines underwent enantioselective alpha-methylation on treatment with LTMP followed by addition of methyl iodide; chirality transfer from an undeprotonated chiral amide into an achiral enolate in a mixed aggregate is supposed to be responsible for the asymmetric induction.     

Highly enantioselective reduction of ketones by chiral diol-modified lithium aluminum hydride reagents

Some readily available chiral diols from indene and d-mannitol were investigated as chiral modifiers in lithium aluminum hydride reduction of ketones, and it was discovered that further modification of these reducing reagents by a simple a-amino alcohol resulted in a remarkable increase in optical yield. Among the investigated chiral modifiers, chiral diol 1 gave the highest enantioselectivities.     

Highly enantioselective synthesis of 3,3-disubstituted 4-piperidones by michael alkylation of chiral piperidone imines

A method for the highly enantioselective synthesis of (3S)- and (3R)-3,3-disubstituted 4-piperidones with an optical purity of 98% based on the deracemizing alkylation of 3-substituted 4-piperidones during Michael addition of their chiral imines to electrophilic alkenes was developed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1072–1078, August, 1992.     

Highly enantioselective nickel-catalyzed hydrovinylation with chiral phosphoramidite ligands

Readily available chiral phosphoramidites are a promising class of ligands for nickel-catalyzed asymmetric hydrovinylation of vinyl arenes. Cooperative effects are operative when ligands with more than one element of chirality are used. Choosing the proper stereochemistry in each part of the modular ligand system leads to high chemoselectivities and excellent enantioselectivities up to 94%. Moreover, the catalysts derived from these ligands proved extremely efficient and remarkably robust performing up to 8300 catalytic turnovers at an initial turnover frequency beyond 1000 h-1. The large potential for structural variation and their straightforward synthesis make the phosphoramidites currently the best lead structure for catalyst development in this field.     

Catalytic enantioselective protonation of lithium enolates with chiral imides

The catalytic enantioselective protonation of simple enolates was achieved using a catalytic amount of chiral imides and stoichiometric amount of achiral proton sources. Among the achiral proton sources examined in the protonation of the lithium enolate of 2,2,6-trimethylcyclohexanone catalyzed by (S,S)-imide 1, 2, 6-di-tert-butyl-p-cresol (BHT) and its derivatives gave the highest enantiomeric excess. For example, 90% ee of (R)-enriched ketone was obtained when (S,S)-imide 1 (0.1 equiv) and BHT (1 equiv) were used. Use of 0.01 equiv of the chiral catalyst still caused a high level of asymmetric induction. For catalytic protonation of the lithium enolate of 2-methylcyclohexanone, chiral imide 6 possessing a chiral amide portion was superior to (S,S)-imide 1 as a chiral proton source and the enolate was effectively protonated with up to 82% ee.     

Enantioselective alkylation of aldehydes with chiral organomagnesium amides (COMAs)

[reaction: see text] Dialkylmagnesiums react with chiral secondary amines to form chiral organomagnesium amides (COMAs). These reagents alkylate aldehydes to form secondary alcohols with enantioselectivities up to 91:9 er.     

Asymmetric alkylation of carboxyamides by using trans-2,5-disubstituted pyrrolidines as chiral auxiliaries

trans-2,5-Bis(methoxymethyl)- and trans-2,5-bis(methoxymethoxymethyl)pyrrolidines proved to be excellent chiral auxiliaries for the asymmetric alkylation of the corresponding carboxyamide enolates giving good chemical yield and high stereoselectivity (invariably over 95% de), with remarkable flexibility to substrates and reaction conditions.     

Asymmetric alkylation of an α-keto ester with chiral lithium alkoxy-tributylaluminates

Lithium tetrabutylaluminate modified by either (-)-N-methylephedrine or Darvon alcohol[(*)-(2S, 3R)-4-dimethylamino-3-methyl-1,2-diphenyl-2-butanol] readily reacts with phenylglyoxylic acid methyl ester to give the expected α-butyl α-hydroxy ester with a good chemical yield and an optical yield of 43% when Darvon alcohol is used.     

Highly enantioselective direct syn- and anti-aldol reactions of dihydroxyacetones catalyzed by chiral primary amine catalysts

We present herein simple primary-tertiary diamine-Br?nsted acid conjugates that catalyze both syn- and anti-aldol reactions of dihydroxyacetones (DHAs) with high diastereoselectivities and enantioselectivities. This type of organocatalysts functionally mimics all four DHA aldolases, namely L-fuculose-1-phosphate aldolase, D-tagatose-1,6-diphosphate aldolase, D-fructose-1,6-diphosphate aldolase, and L-rhamnulose-1-phosphate aldolase.     

Ruthenium catalyzed asymmetric dihydroxylation with sultams as chiral auxiliaries

Ruthenium catalyzed asymmetric dihydroxylations of α,β-unsaturated carbonyl compounds with sultams 4, 5 and 6 as chiral auxiliaries are reported.     

Highly diastereo- and enantioselective construction of phthalide-oxindole hybrids bearing vicinal quaternary chiral centers via an organocatalytic allylic alkylation

A diastereo- and enantioselective synthesis of phthalide-oxindole hybrids including congested adjacent quaternary chiral centers was demonstrated through a Lewis base catalyzed asymmetric allylic alkylation reaction of Morita–Baylis–Hillman carbonates of isatins and 3-cyanophthalides. The various hybrid molecules with two valuable pharmacophores-combined frameworks can be obtained in good to high diastereo- and enantioselectivities.