Enolate from tertiary amides

By contrast, lithium enolates derived from tertiary amides do react with oxiranes The diastereoselectivity in the reaction of simple amide enolates with terminal oxiranes has been addressed and found to be low (Scheme 45). The chiral bicyclic amide enolate 99 reacts with a good diastereoselectivity with ethylene oxide . The reaction of the chiral amide enolate 100 with the chiral oxiranes 101 and 102 occurs with a good diastereoselectivity (in the matched case ) interestingly, the stereochemical course is opposite to the one observed with alkyl iodides. The same reversal is found in the reaction of the amide enolate 103. By contrast, this reversal in diastereoselectivity compared to alkyl iodides was not found in the reaction of the hthium enolate 104 with the chiral oxiranes 105 and 106 °. It should be noted that a strong matched/mismatched effect occurs for enolates 100 and 103 with chiral oxiranes, and excellent diastereoselec-tivities can be achieved. 

Anions generated from tertiary amides preferentially assumed the Z-configura-tion. Reaction of MA-dimethylamides with 1 equiv. of LDA at -78 °C followed by addition of 1.5 equiv. of di(-)-isobomyl azodicarboxylate 97c gave in each case a 1 1 ratio of diastereomers (/ )-99 and (S)-99 (Table 3.10, entries 7 and 8). Double diastereoselection was tested with chiral enolates enantiomerically pure /V-acyloxazolidinone (S)-100 and its enantiomer (/ )-100 were aminated at -78 °C with 97c (Scheme 47). 

Organocerium reagents. 13, 206 14, 217-218 15, 221 16, 232 17, 205-207 18, 256 Reaction with carbonyl compounds. RCeClj in which R is a cyclopropeny 1 residue behaves normally as a nucleophile. Lithium enolates derived from tertiary amides have been converted to the corresponding cerium species, and their reactions with aldehydes have been studied. ... 

After it was demonstrated by the contributions of several research groups that the hard enolates of ketones are susceptible to the palladium-catalyzed allylic alkylation, it was an obvious idea to investigate amide enolates next, as they are equally stable. Thus, Hou and coworkers reported that the lithium enolates of tertiary amides 32 undergo in the presence of hthium chloride enantioselective allylic alkylation with allyl or methallyl acetate 33. The reaction was mediated by the ferrocene-based ligand 34, and the enantiomeric excess of the products 35 was found to range from 73 to 93% ee. The absolute configuration was determined in two cases (for = Me, Et, = H) to be R) (Scheme 5.12) [21]. An allylation... 

Now the two parts, 184 and 199, must be linked in a controlled aldol reaction. The lithium enolate 200 reacts with the aldehyde in 199 in the presence of excess Lewis acid Me2AICI to give one diastereoisomer of 201 as the only product. Presumably the aluminium coordinates the tertiary amide and aldehyde oxygen atoms to hold the aldehyde in one Felkin conformation while it is attacked by the lithium enolate from one face only as sketched in 202. 

Most metal enolates are generated by transmetalation from Li enoiates. However, Ti-enolates can be formed by action of TiCiyz -PrjNEt on carbonyl confounds [404,1042] and Zr-enolates can be generated by similar reactions with Zr(0-/ert-Bu)4 [1245], Lithium E-endates are obtained by deprotonation of ketones or esters with a branched Li-amide (LDA, LICA, LOB A, LTMP) in a weakly polar medium (THF or THF-hexane), while Z-enolates are formed by using LDA or LHMDS in the presence of HMPA or DPMU [1016], Tertiary amides always give Z-endates, and difunctionalized derivatives such as Evans s oxazolidinones 5.30 and 5.31 are chelated to the metal prior to enolization. 

Carboxylic acid derivatives can be created via FGIs, beginning with either a carboxylic acid or from another carboxylic acid derivative. Since it is possible to make enolates from esters, tertiary amides, and nitriles, these compounds can also be prepared by alkylation at the alpha carbon. 

Acylation of A-hydroxy-2-phenylbutyramidine (112-1) with 3-chloropropionyl chloride in the absence of an added base proceeds as might be expected to give the product (112-2) from acylation on the more basic nitrogen. Heating this compound leads to the formation of the oxadiazole (112-3) almost certainly via the enol tautomer of the amide. Displacement of the terminal chlorine with diethylamine leads to the tertiary amine and thus proxazole (112-4) [123], a compound that is said to exhibit antispasmodic activity. 

The intramolecular Heck reaction is a powerful method for the synthesis of constrained tertiary and quaternary carbon centers and has been applied as a key step in the synthesis of a number of pyridine alkaloids. Mann et al. have accessed the bicyclononane core structure of huperzine A 150 in moderate yield by intramolecular Heck reaction of bromopyridine 151 (Equation 117). Another notable application of this methodology is the intramolecular a-arylation of the amide enolate generated from 152 to give the carbon skeleton of cytosine <20040BC1825> (Equation 118). 

The oxidation of a ( )-flavanone with Tl(ni) nitrate, Pb tetracetate, phenyliodonium diacetate (PIDA), or [hydroxyl(tosyloxy)iodo]benzene in trimethyl orthofonnate affords the corresponding ( )-2,3-dihydrobenzo[h]furan derivative as a major product. The structures, including the relative stereochemistry, and a plausible mechanism of formation are reported. The preferred formation of a flavone from the ( )-flavanone by PIDA is explained by quantum-chemical calculations on the intermediate formed by the addition of this reagent to the enol ether derivative of the ( )-flavanone." Formation of mixed anhydrides by rapid oxidation of aldehydes, activated by pivalic acid, Bu OCl in presence of pyridine and MeCN is catalysed by TEMPO (2,2,6,6-tetramethylpiperidin-l-oxyl). The anhydrides can be converted in situ to esters, secondary, tertiary or Weinreb amides in high yield. Oxidation of the aldehyde to 2-propyl esters is also possible using only catalytic amounts of pivalic acid." ... 

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