Enantioselective prochiral enol carbonates

Muzart and coworkers have reported a new catalytic enantioselective protonation of prochiral enolic species generated by palladium-induced cleavage of p-ketoesters or enol carbonates of a-alkylated 1-indanones and 1-tetralones [21 ]. Among the various (S)-p-aminocycloalkanols examined, 17 and 18 were effective chiral catalysts for the asymmetric reaction and (J )-enriched a-alkylated 1-indanones and 1-tetralones were obtained with up to 72% ee. In some cases, the reaction temperature affected the ee. 

Controlling enantioselectivity at the enol centre alone can be achieved with special reagents and a very complex catalyst. An allylic carbonate with a fluorinated esterifying group allylates a prochiral enolate derived from i-propyl cyanopropionate catalysed by Pd, Rh, and the chiral Fe TRAP ligand 257, gives excellent results. The explanations for these last two examples are complicated and you are referred to the papers if you want to know more.60... 

Asymmetric conjugate addition of dialkyl or diaryl zincs for the formation of all carbon quaternary chiral centres was demonstrated by the combination of the chiral 123 and Cu(OTf)2-C H (2.5 mol% each component). Yields of 94-98% and ee of up to 93% were observed in some cases. Interestingly, the reactions with dialkyl zincs proceed in the opposite enantioselective sense to the ones with diaryl zincs, which has been rationalised by coordination of the opposite enantiofaces of the prochiral enone in the alkyl- and aryl-cuprate intermediates, which precedes the C-C bond formation, and determines the configuration of the product. The copper enolate intermediates can also be trapped by TMS triflate or triflic anhydride giving directly the versatile chiral enolsilanes or enoltriflates that can be used in further transformations (Scheme 2.30) [110],... 

The asymmetric synthesis of a-hydroxymethyl carbonyl compounds is currently the subject of considerable interest because of their versatility as dual-function chiral synthons. There have been no reports of successful enantioselective hydroxymethylations of prochiral metal enolates with formaldehyde because of the instability and small steric size of gaseous formaldehyde. The author and Yamamoto et al. developed the enantioselective alkoxymethylation of silyl enol ethers by introducing suitable carbon-electrophiles in place of the activated-protons of LBA [142]. 

The sixth chapter of the book was devoted to advances in enantioselective nickel-catalysed a-functionalisation, and to a-alkylation/arylation reactions of carbonyl compounds. A prochiral carbonyl compound can be activated toward electrophilic substitution via the formation of an enol or enolate intermediate, generating a tertiary or quaternary centre at the a-carbon. The use of a non-carbon electrophile leads to heterofunctionalised products, while that of carbon electrophiles affords a-arylated/alkylated carbonyl compounds, and the generation of a new stereogenic centre in these reactions... 

Catalytic enantioselective protonation of prochiral ketone enolates is a beneficial route to optically active carbonyl compounds possessing a tertiary asymmetric carbon at the a-position. In the asymmetric protonation of trimethylsilyl enolates with methanol, BINAP-AgF has been found to act as a chiral catalyst [90,91], which is also known to catalyze asymmetric allylation of aldehydes with allylic trimethoxysilanes [42] as well as asymmetric aldol reaction with trimethoxysilyl enolates [54]. This protonation can be most effectively performed using 6 mol% ofBINAP and 10 mol% of... 

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