Hydrides enolate formation with

Vinylogous amides undergo reduction with lithium aluminum hydride, by Michael addition of hydride and formation of an enolate, which can resist further reduction. Thus -aminoketones are usually produced (309, 563,564). However, the alternative selective reduction of the carbonyl group has also been claimed (555). 

By means of in situ NMR spectroscopy combined with deuterium incorporation experiments, van Leeuwen has elucidated the mechanism of termination by protonolysis, showing that the fl-chelates are in equilibrium with their enolate form by a p-H elimination/hydride migration process (Scheme 7.19). The enolate intermediates are regioselectively protonated at the C2 carbon atom by either MeOH or H2O to give Pd-OMe or Pd-OH and keto terminated copolymer. The enolate formation has been reported to be rate determining in the chain transfer [19]. 

Next, we considered the activation of 13 towards hydrolysis by K-complexation of a cationic metal unit to the electron-rich diene system. On the basis of the well-known palladium-mediated addition of nucleophiles to alkenamines, it was anticipated that the enol ether function in 13 would add H2O in the presence of Pd(II).21 Interestingly, exposure of 13 to a slight excess of Pd(OAc)2 led to the isolation of 14 (Scheme 8). This material suggested the exploitation of the existing Pd-C linkage for carbon-carbon bond formation with an appropriate A-side chain. In particular, the intramolecular syn insertion of the allylic double bond in the rrans-butenyl substituent in 15b and subsequent syn (3-hydride elimination would give the desired E-alkene 17. This proposal was examined using alkene 15a as a model system, synthesized in a manner similar to 13. Upon exposure to Pd(OAc)2 under the conditions... 

Gas-phase transfers of hydride from methoxide to C02, CS2 and S02 have been observed by the flowing afterglow technique (Bierbaum et al., 1984) and by Fourier transform ion cyclotron resonance spectroscopy (FT-ICR) (Sheldon et al., 1985). With aldehydes and ketones, the normal gas-phase reaction with methoxide is enolate formation, but FT-ICR methods have been used to demonstrate reduction of non-enolizable aldehydes including benzaldehyde, pivalaldehyde, and 1-adamantylaldehyde. 

This principle can be extended to ketones whose enolates have less dramatic differences in stability. We said in Chapter 21 that, since enols and enolates are alkenes, the more substituents they carry the more stable they are. So, in principle, even additional alkyl groups can control enolate formation under thermodynamic control. Formation of the more stable enolate requires a mechanism for equilibration between the two enolates, and this must be proton transfer. If a proton source is available— and this can even be just excess ketone—an equilibrium mixture of the two enolates will form. The composition of this equilibium mixture depends very much on the ketone but, with 2-phenylcyclo-hexanone, conjugation ensures that only one enolate forms. The base is potassium hydride it s strong, but small, and can be used under conditions that permit enolate equilibration. 

The quaternary center was constructed stereospecifically by Claisen rearrangement (Scheme 46). The necessary enol ether was obtained by reaction of the secondary alcohol of 399 with ethyl vinyl ether and mercuric acetate. To change the polarity of the endocyclic double bond, the unsaturated ketone was reduced with lithium aluminum hydride to the allylic alcohol, 400, at low temperature. Then, prolonged heating with xylene led to the aldehyde, 401. Protection of the secondary alcohol was achieved by bromoether formation with W-bromosuccinimide in acetonitrile before the aldehyde of 402 was reacted with methyllithium. The epimeric mixture of secondary alcohols was protected as acetates 403. Then, the cyclic ketone... 

The oxidation of ketones to enones via the reaction of their silyl enol ethers with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) has been suggested originally to proceed via allylic hydride abstraction [195-198]. A recent reinvestigation, however, [199] has established the intermediate formation of a substrate-quinone adduct 96 which was presumably formed from a geminate radical ion pair after electron transfer. Decomposition of the adduct then finally afforded the observed enone product 97. Recently, the critical role of solvent polarity in the formation of 97 from the PET reaction of 93 and chloranil has been identified by time-resolved spectroscopy [200]. 

When the preparation of alkali metal enolates derived from alkanoylphosphonates was attempted by treatment with strong anhydrous bases such as lithium diisopropylamide or sodium hydride, the formation of phosphate phosphonate-type products was observed. This was interpreted in terms of fragmentation of the enolate formed in the first step to ketene and dialkyl phosphite anion (equation 75), and addition of the latter to the carbonyl group of an unreacted acylphosphonate molecules to form a bisphosphonate. Such molecules are known to rearrange to phosphate phosphonates ... 

Alkylations. Many bases which are weaker than t-BuOK are capable of essentially quantitative conversion of active methylene compounds into the corresponding enolates or other anions. However, the alkylation of diethyl malonate with a bicyclic secondary tosylate (eq 1) and the alkylation of ethyl n-butylaceto-acetate with -BuI (eq 2f provide examples of cases where the use of f-BuOK in f-BuOH is very effective. In the latter reaction, cleavage of the product via a retro-Claisen reaction is minimized with the sterically hindered base and yields obtained are higher than when Sodium Ethoxide or EtOK in EtOH, Sodium in diox-ane or toluene, or Sodium Hydride in toluene are used for the enolate formation. 

N-Boc leucine was converted to an acid chloride by treatment with isobutyl chloroformate. Subsequent treatment with diazomethane gave the diazoketone (6.241), which was treated with silver benzoate. This led to a Wolff rearrange-mentl40 and formation of 6.242. I ll Reduction of the ester moiety to an aldehyde with diisobutylaluminum hydride allowed condensation with the lithium enolate of ethyl acetate to give 6.243. Saponification led to N-Boc-5-amino-3-hydroxy-7-methyloctanoic acid (6.244, given the pseudonym AHM0A).1 H Amino acid... 

The dianiotf derived from a j3-ketoester by sequential treatment with sodium hydride and n-butyl-lithium alkylates exclusively at the y-position initial sodium enolate formation precludes the formation of carbonyl addition products and subsequent artifacts observed in the use of n-butyl-lithium alone. In addition to providing a convenient route to y-alkylated aceto-acetic esters, such dianions undergo ready aldol condensation, leading, after dehydration, to y3-unsaturated /3-ketoesters (Scheme 25). 

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