Chiral Lithium Research Articles

New Umpolung Catalysts: Reactivity and Selectivity of Terpenol‐Based Lithium Phosphonates in Enantioselective Benzoin‐Type Couplings

AbstractTwo new classes of terpenol‐based lithium phosphonates, i.e. phenylfenchyl phosphonates and 2,2′‐biphenyldiylbis(terpenyl) phosphonates, are employed as umpolung catalysts for the enantioselective cross benzoin coupling. The structural characteristics of the phosphonates were investigated by means of X‐ray, 31P‐NMR analyses as well as DFT computations. The chiral lithium phosphonates were found to catalyze the cross benzoin coupling with enantioselectivities up to 54 % ee. For the phenylfenchyl phosphonates, the catalyst reactivities highly depend on the substituents in benzylic position. Modification of benzylic >CH2 to >C(CF3)2 significantly increases the yield from 19 to 92 %. For phenylfenchyl phosphonate pre‐catalysts, substitution of the benzylic >CH2 group by >C(CF3)2 changes the sense of enantioselectivity from S‐ to the R‐configured benzoin product.

Sequential Double α-Arylation of N-Allylureas by Asymmetric Deprotonation and N→C Aryl Migration

On lithiation with lithium amides, N-allyl-N'-aryl ureas undergo rearrangement with transfer of the aryl ring from N to the allylic α carbon. From the α-arylated products, a further aryl transfer under the influence of a chiral lithium amide allows the enantioselective construction of 1,1-diarylallylamine derivatives. Stereoselectivity in these reactions results from the enantioselective formation of a planar chiral allyllithium under kinetic control.

Catalytic asymmetric chiral lithium amide-promoted epoxide rearrangement: a NMR spectroscopic and kinetic investigation

The lithium amide derived from the chiral diamine (1 R,3 S,4 S)-3-(1-pyrrolidinyl)methyl-2-azabicyclo[2.2.1]heptane, has been reported to catalytically deprotonate cyclohexene oxide and other epoxides, yielding chiral allylic alcohols in excellent enantiomeric excess. In this work, 6Li, 1H and 13C NMR spectroscopy have been used to study the aggregation of the chiral lithium amide in THF and the influence on the aggregation by the addition of additives, such as 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU). The activated complex under catalytic deprotonation of cyclohexene oxide, that is, with excess Li-DBU and free DBU, is built from one monomer of the chiral lithium amide, one molecule of epoxide and one additional molecule of DBU. The reaction order (−0.97) obtained for the bulk base Li-DBU shows an inverse dependence on the concentration, suggesting a deaggregation of the initial mixed dimer to a monomer-based transition state containing a monomer of the lithium amide.

Highly Practical BINOL-Derived Acid-Base Combined Salt Catalysts for the Asymmetric Direct Mannich-Type Reaction

The catalytic asymmetric direct Mannich-type reaction between aldimines and 1,3-dicarbonyl compounds is one of the most important carbon-carbon bond-forming reactions in organic chemistry. The resulting Mannich adducts can be efficiently transformed into pharmaceutically useful, optically active β-amino ketones, β-amino esters, β-lactams, etc. In the course of our study of chiral acid-base combined salt catalysts for asymmetric reactions, we developed a series of simple, practical, chiral BINOL-derived salt catalysts, such as chiral pyridinium 1,1′-binaphthyl-2,2′-disulfonates 1, chiral lithium(I) binaphtholate 2, chiral magnesium(II) binaphtholate (3), chiral calcium(II) phosphate 4, and chiral phosphoric acid 5, which were particularly effective for direct Mannich-type reactions.

Simple Chiral Diaminobinaphthyl Dilithium Salts for Intramolecular Catalytic Asymmetric Hydroamination of Amino‐1,3‐dienes

AbstractSimple and easily accessible chiral lithium amide salts are reported as efficient (pre)catalysts for the diastereo‐ [up to (E:Z)=92:8] and enantioselective [up to 72% ee (E)] hydroamination/cyclisation of conjugated primary aminodienes. These chiral lithium salts are straightforwardly prepared by in situ combination of an N‐substituted (R)‐(+)‐1,1′‐binaphthyl‐2,2′‐diamine ligand and a commercial methyllithium solution. Information on the solid‐state structure of these salts was obtained by X‐ray analysis of a single crystal.

ChemInform Abstract: Enantioselective Alkylation at the α-Position of Cyclic Ketones Using a Chiral Lithium Amide as a Base in the Presence of Lithium Bromide.

An efficient enantioselective alkylation reaction at the α-position of cyclic ketones (1, 2) can be realized in up to 92% enantiometric excess (e.e.) by first forming their lithium enolates using a chiral lithium amide 4 in the presence of lithium bromide, followed by treatment with alkyl halides.

ChemInform Abstract: Useful Chiral Lactones Derived from cis-Bicyclo(3.3.0)octan-3,7-dione via Asymmetric Deprotonation.

Abstract The monoketal derived from cis-bicyclo[3.3.0]octane-3,7-dione was deprotonated using chiral lithium amide bases and the enolates were trapped as either enol acetates or trimethylsilyl enol ethers. Oxidative cleavage of the enol derivatives provided useful bicyclic lactones, the ee's of which could be determined using NMR chiral shift techniques. The lactones are also potentially useful as intermediates for asymmetric synthesis.

ChemInform Abstract: Enantioselective Opening of Spiro Epoxides Derived from cis-Bicyclo(3. 3.0)octan-3,7-dione Using Chiral Lithium Amide Bases.

The monoketal derived from cis-bicyclo[3.3.0]octane-3,7-dione was converted to epoxides 3. The meso exo epoxide was cleaved via enantioselective deprotonation using chiral lithium amide bases to provide the synthetically useful alcohol 7 with up to 76%ee. The enantiomeric excess of the alcohol was determined by 1H NMR chiral shift techniques.

Synthesis of enantiomeric pure lithium and potassium benzamidinate complexes

A new synthesis leading to the chiral amidines ( S, S)- and ( R, R)- N, N-bis-(1-phenylethyl)benzamidine (( S)- and ( R)-HPEBA) in good yields is presented. Further reaction of ( S)-HPEBA with n-BuLi gave the chiral lithium salt ( S)-LiPEBA. Treatment of KH with ( S)-HPEBA in boiling THF afforded the corresponding potassium salt ( S)-KPEBA. In contrast by performing the reaction in boiling toluene a fast racemization was observed. In the solid state racemic KPEBA formed a dimer, in which all four nitrogen atoms are in a plane. To each potassium atom a toluene molecule is η 6-coordinated.

ChemInform Abstract: Synthesis and Enantioselective Rearrangement of 4-Amino-Substituted Cyclopentene Oxides.

Abstract Several N -mono- and diprotected alkenes have been prepared and the stereoselectivity of their epoxidation has been investigated: N -monoprotected alkenes give cis epoxides preferentially (due to hydrogen bonding directed epoxidations) whereas N -diprotected alkenes produce trans epoxides exclusively (due to steric effects). Chiral lithium amide base-mediated rearrangement of a cis -monoprotected epoxide generated the corresponding amino-cyclopentenol in good yield and with an enantiomeric excess of 60%.

Chiral lithium amide mediated asymmetric synthesis of 3-aryl-3,4-dihydroisocoumarins

An asymmetric synthesis of 3-aryl-3,4-dihydroisocoumarins using the reaction of laterally lithiated 4,4-dimethyl-2-(o-tolyl)oxazoline with aromatic aldehydes, in the presence of an external chiral ligand, gave products with enantiomeric excess (ee) in the range of 60-70%.

ChemInform Abstract: Chiral Lithium(I) Binaphtholate Salts for the Enantioselective Direct Mannich‐Type Reaction with a Change of Syn/Anti and Absolute Stereochemistry.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Studies Aimed at Enhancement of Reactivity and Enantioselectivity of a Lithium Ester Enolate Using a Chiral Tridentate Lithium Amide.

Abstract Tridentate chiral amines 7–13 mediated the asymmetric condensation reaction of lithium ester enolate 2 with benzaldehyde p-anisidine imine 3 giving the corresponding β-lactam 4 in up to 75% ee. It became apparent that coexistence of 2 and chiral lithium amides derived from 7–13 is an important factor for the enhancement of the reactivity and enantioselectivity of 2.

ChemInform Abstract: Concerning the Synthesis and Enantioselective Rearrangements of Episulfoxides.

A novel synthesis of episulfoxides having the norbornane skeleton is possible by use of a rhodium catalyst to effect SO transfer from trans-stilbene episulfoxide to norbornene or norbornadiene. Analogous Rh2(OAc)4 catalysed sulfur transfer to these alkenes is also possible using propylene sulfide as the sulfur source. These methods did not give useful yields of products with alternative types of alkene substrate. A novel type of chiral lithium amide base reaction, involving the rearrangement of certain types of symmetrical ring-fused episulfoxides, gives alkenyl sulfoxide products in up to 88% ee. The structures of the products, including absolute stereochemistry, were assigned based on X-ray crystal structure determinations. p

Asymmetric Direct Mannich-Type Reaction Catalyzed by Chiral Lithium Complexes

Asymmetric Direct Mannich-Type Reaction Catalyzed by Chiral Lithium Complexes

Enantioselective alkynylation of ketones with trimethoxysilylalkynes using lithium binaphtholate as a catalyst

Abstract 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.

Studies on Aldol Reactions of Nortropinone Derivatives in Solution and on Solid Phase

Polymer-anchored (Merrifield, trityl chloride, Wang p-nitrophenyl carbonate and triazene supports) nortropinone, or N-protected nortropinone derivatives in solution, were subjected to deprotonation with LDA or chiral lithium amides, and the resulting lithium enolates were trapped with an aldehyde. The aldols were obtained with moderate to good yields (44-84%) and enantioselectivities (44-86% ee). Keywords: Aldol reaction, polymer support, solid-phase synthesis, chiral lithium amide, nortropinone

Chiral Lithium(I) Binaphtholate Salts for the Enantioselective Direct Mannich-Type Reaction with a Change of Syn/Anti and Absolute Stereochemistry

A highly diastereo- and enantioselective direct Mannich-type reaction of aldimines with 1,3-dicarbonyl compounds using Li(I) BINOLate salts as effective Lewis acid-Brønsted base catalysts has been developed. Li(I) BINOLate salts offered high catalytic activity toward 1,3-dicarbonyl compounds such as diketone, ketoester, ketothioester, ketoamide, and ketolactone. The reactions proceeded at -78 degrees C within 1-2 h in the presence of 1-10 mol % catalyst, which showed a catalytic activity (turnover frequency = 284 h(-1)) quite unlike those of other previous catalysts. Anti products were selectively obtained from acyclic ketoesters without epimerization at an alpha-tertiary-carbon center, and these are valuable since previous catalysts often gave syn/anti mixtures or the stereochemistry has not yet been determined.

Enantioselective Conjugate Addition of a Lithium Ester Enolate Catalyzed by Chiral Lithium Amides: A Possible Intermediate Characterized

Two 1:1 noncovalent mixed aggregates between a lithium enolate and two diastereomeric lithium amides have been identified spectroscopically in THF. The NMR data, as well as DFT theoretical calculations, shine some light on a puzzling reversal of induction, observed when switching from one diastereomer of the amide to the other in the enantioselective Michael addition of the lithium enolate to an unsaturated ester.

ChemInform Abstract: Chiral Lithium Salts of Phosphoric Acids as Lewis Acid—Base Conjugate Catalysts for the Enantioselective Cyanosilylation of Ketones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.