Enolization conditions

The enolization conditions are known not to fully equilibrate the two possible enolates. 

Unfortunately, it quickly became apparent that a shortfall in this proposal was an inability to prepare the desired vinyl halide 25 in a straightforward and selective manner [19]. In contrast, we reasoned that the selective formation of an enol sulfonate, such as the enol triflate 26a, could be controlled by judicious tuning of enolization conditions starting from the corresponding ketone, and that such an enol sulfonate would possibly be a substrate for a palladium-mediated coupling (Scheme 9.17). In this way a common intermediate from the previously defined synthesis, that is, the racemic ketone rac-13 or its cyano equivalent rac-5 could be used to generate the required enamide. 

Step a is-((9)-boron enolate conditions reaction with RCHO results in a 2,3-anti aldol product. 

The most direct method for the preparation of polyol frameworks is without doubt the aldol reaction. The diastereofacial selectivity of the reaction can be controlled by /J-alkoxy groups in both the methylketone enolate and the aldehyde. As investigations by Evans [6] and Paterson [7] and their groups have demonstrated, the correct selection of enolization conditions and the protective group for the )8-hydroxy group are important for the stereocontrol of the reaction. 

How can one use this thermochemical effect for a preparative route to enol radical cation intermediates in solution Since one usually has to start with the ketone tautomer, two possibilities are conceivable at first from Fig. 2 (1) direct oxidation of the ketone to the ketone radical cation followed by a 1,3-hydrogen migration to provide the enol radical cation, or (2) selective one-electron oxidation of the enol that is present in the equilibrium situation under fast enolization conditions. 

Selective oxidation of the enol tautomer is not limited to thermal enolization conditions. In a laser-jet study by Wilson [269] enol radical cations are most likely formed after electron transfer trapping of the photoenol of 2-meth-ylbenzophenone with various acceptors as benzoquinones and N-phenyltriazol-inedione. 

An effective control of the simple diastereoselectivity in boron-mediated aldol reactions of various propionate esters (162) was achieved by Abiko and coworkers (equation 45) °. They could show that under usual enolization conditions (dialkylboron triflate and amine) enol borinates are formed, which allowed the selective synthesis of 5yw-configured aldol products (Table 11). The enolization at low temperature (—78 °C) generated a (Z)-enolate selectively, which afforded mainly the syn diastereomer 164 after reaction with isobu-tyraldehyde (163), following a Zimmerman-Traxler transition-state. The anti diastereomer 164 instead was obtained only in small amounts (5-20%). 

An interesting asymmetric aldol reaction utilizing enantiomerically homogeneous bomane sultam derived boron enolates has recently been reported by Oppolzer et al. The reaction of aldehydes with boron enolates (57), generated from acyl sultams (58) under standard enolization conditions (Pr 2NEt/Bu2BOTf/0 C), provides syn aldol products (59) with extremely high ratios of (59) to (60) as shown in Scheme 29. Results from the aldol reactions with representative aldehydes are summarized in... 

The crossed aldol reaction between two different ketones is a difficult reaction under the classical metal enolate conditions. By employing divalent tin enol ethers, directed aldol reaction between ketones is easily achievable. An example is given in Scheme 31. 

This transformation requires kinetic enolate conditions. They should be specified. 

Boron Enolates of AT-Propionyloxazolidinethiones. Boron enolates of fV propionyloxazolidinethiones can be generated under standard enolization conditions with dibutylboron triflate and diisopropylethylamine. The boron enolates react with aldehydes to provide the Evans s// aldol products with excellent diastereoselectivity (eq 7). No oxidative work-up was necessary in the examples reported. ... 

Ultimately, a set of conditions which utilizes 1 equiv of tita-nium(IV) chloride, 1 equiv of (—)-sparteine, and 1 equiv of A/-methylpyrrolidinone as a ligand for the metal center was developed to avoid the need for greater than 1 equiv of (—)-sparteine (eq 12). These enolization conditions are also effective for A acyloxazolidinones and A -acylthiazolidinethiones. ... 

A diastereoselective acetyl variant has been recently developed, which utilizes TiCLt, (—)-sparteine, and NMP enolization conditions with (V-acetyl-4-isopropyl-5,5-diphenyloxazolidine-2-thione to produce the acetate aldol adducts with very high diastere-oselectivity (eq 13). ... 

Under similar azide transfer to enolate conditions, the unexpected primary amide that arose from the hydrolysis of the Evans chiral auxiliary was also isolated (eq 25). Double enolization of the bisamide followed by trapping of the dianion with trisyl azide provided the diazido diastereoisomers in 4 1 ratio (eq 26). ... 

The generation of cis-boron enolates from ketones with dialkylboron chlorides and hindered tertiary amines had been known for some time, from the work of Mukaiyama and Evans [13, 48, 87]. However, the synthesis of the corresponding trans-boron enolates remained problematic. Brown addressed this issue, reporting enolization conditions that provide access to either eno-late diastereomer [88]. The stereochemical outcome of ketone enolization was shown to be dependent both on the electronegative group on boron and on the nature of the alkyl substituents. In this regard, the combination of bulky boron ligands (cyclohexyl), a boron chloride derivative, and an unhindered base (EtjN) proved optimal for the stereoselective synthesis of trans-enolates (166) from a variety of ketones (Scheme 4.16). 

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