Efficient Palladium-Catalyzed Substitution in Enantiomerically Pure Allyl Carbonates – A Stereodivergent Access to β-Aryl-Substituted γ-Lactones and γ-Hydroxy Amides

Braun, Manfred; Unger, Claudia; Opdenbusch, Kersten

doi:10.1002/(sici)1099-0690(199811)1998:11<2389::aid-ejoc2389>3.0.co;2-t

Cited by 17 publications

(2 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19 They also contain a stereogenic center that should not be touched in the allylic substitution, so that it could serve as a probe in order to evaluate the stereochemical result.…”

Section: Methodsmentioning

confidence: 99%

Palladium-Catalyzed Stereoselective Allylic Alkylation of Lithium Enolates

Braun¹,

Meier²

2005

Synlett

Self Cite

View full text Add to dashboard Cite

The lithium enolates, generated from cyclohexanone, cyclopentanone, and 1-tetralone, react with allyl acetate 1b or carbonate 1c enantioselectively, when catalyzed by (R)-or (S)-BINAPderived palladium complexes. The presence of lithium chloride is crucial to stereoselectivity. Diastereoselective and enantioselective allylation occurs between cyclohexanone and carbonate 1d. It is shown in the case of the acyclic substrates (Z)-12 and (E)-17 that pallyl palladium complexes are attacked by lithium enolates from the face opposite to the noble metal.The palladium-catalyzed allylic alkylation of carbon nucleophiles has developed into a versatile, frequently applied method for the formation of carbon-carbon bonds. 1 Enantioselective variants converting racemic starting materials 1 into non-racemic products 3 have been developed due to chiral ligands at the transition metal, so that the approach of the nucleophile is directed predominantly to one of the diastereotopic termini of the allyl complex 2. A major limitation is that the carbon nucleophiles are almost exclusively 'soft', stabilized carbanions. Among them, the large majority are symmetrically substituted nucleophiles, typically malonates. As a consequence, the allylic substitution leads to the formation of just one stereogenic center in the allylic position. 2 Scheme 1If, however, synthesis targets the formation of olefinic ketones 4 with stereogenic centers in the homoallylic position (R = H) or in both, the allylic and the homoallylic position (R ≠ H), the appropriate prochiral nucleophiles are preformed non-stabilized enolates 5, 3 as outlined in retrosynthetic Scheme 2. Although the chemistry of palladium-catalyzed allylic substitution and that of preformed enolates evolved at the same time, there have been only reluctant attempts to combine both concepts. 4 In recent years, a few enantioselective procedures have been elaborated based on enolates of ketones 5 and a-amino esters. 6There remain, despite this progress, still substantial limitations inasmuch as only such enolate precursors, which contain just one acidic proton, have been used in order to avoid not only double or multifold alkylation, but also a later racemization caused by deprotonation at the newly created stereogenic carbon center in the presence of a strong base. That type of 'structural support' vanishes in the asymmetric allylic alkylation of unrestricted ketones, so that the most simple-looking substrates become indeed the most difficult ones. Having recently shown 5c that diastereoselective and enantioselective reactions of ketones with the substrate 1a are feasible, we report in this communication for the first time the enantioselective palladium-catalyzed reaction of cyclohexanone and cyclopentanone with the unsubstituted allyl acetate 1b and carbonate 1c as well as the extension of this protocol to the dimethyl-substituted homologue 1d. Scheme 2Cyclohexanone was chosen as the substrate to optimize the reaction conditions (Scheme 3, Table 1). The ketone was always deprotonated by means o...

show abstract

“…19 They also contain a stereogenic center that should not be touched in the allylic substitution, so that it could serve as a probe in order to evaluate the stereochemical result.…”

Section: Methodsmentioning

confidence: 99%

Palladium-Catalyzed Stereoselective Allylic Alkylation of Lithium Enolates

Braun¹,

Meier²

2005

Synlett

Self Cite

View full text Add to dashboard Cite

show abstract

“…The diastereomeric acetates (Z)-90 and (E)-97, which are identical in the configuration of their stereogenic carbon atoms but differ just in the configuration of the double bond, served as allylic substrates. 60 They were submitted to a reaction with the lithium enolate of cyclohexanone and lithium chloride, mediated by 5 mol% of the palladium catalyst and the achiral ligand 20. Starting from (Z)-90, two diastereomeric products, syn-91 and anti-92 resulted, whose configurations were assigned based on NMR and CD spectroscopy.…”

Section: Scheme 28mentioning

confidence: 99%

New Developments in Stereoselective Palladium-Catalyzed Allylic Alkylations of Preformed Enolates

Braun¹,

Meier²

2006

Synlett

Self Cite

View full text Add to dashboard Cite

Whereas the enantioselective palladium-catalyzed allylic substitution with 'soft', stabilized carbanions can be considered as established and versatile method today, nonstabilized, preformed enolates were used for this purpose only very reluctantly. This report focuses on progress made recently in combining p-allyl palladium complexes with different metal enolates derived from carboxylic esters and ketones. The elaboration of protocols that permit enantioselective and -at the same time -diastereoselective allylic alkylations are emphasized in this report. The stereochemistry in the approach of the enolate to the p-allyl palladium complex is also discussed. 1 Introduction 2 Palladium-Catalyzed Allylic Alkylations with Different Metal Enolates 2.1 The Role of Preformed Enolates 2.2 Silyl Enol Ethers and Silyl Ketene Acetals 2.3 Tin and Boron Enolates and their 'Ate' Complexes 2.4 Zinc Enolates 2.5 Lithium and Magnesium Enolates 2.6 Enolates Generated in situ 3 Mechanistic Aspects 4 Conclusion

show abstract

Lithium carbenoids

Braun¹

2004

The Chemistry of Organolithium Compounds

View full text Add to dashboard Cite

Efficient Palladium-Catalyzed Substitution in Enantiomerically Pure Allyl Carbonates – A Stereodivergent Access to β-Aryl-Substituted γ-Lactones and γ-Hydroxy Amides

Cited by 17 publications

References 43 publications

Palladium-Catalyzed Stereoselective Allylic Alkylation of Lithium Enolates

Palladium-Catalyzed Stereoselective Allylic Alkylation of Lithium Enolates

New Developments in Stereoselective Palladium-Catalyzed Allylic Alkylations of Preformed Enolates

Lithium carbenoids

Contact Info

Product

Resources

About