Enol configuration

Aldol Reactions of Boron Enolates. The matter of increasing stereoselectivity in the addition step can be addressed by using other reactants. One important version of the aldol reaction involves the use of boron enolates.15 A cyclic TS similar to that for lithium enolates is involved, and the same relationship exists between enolate configuration and product stereochemistry. In general, the stereoselectivity is higher than for lithium enolates. The O-B bond distances are shorter than for lithium enolates, and this leads to a more compact structure for the TS and magnifies the steric interactions that control stereoselectivity. 

The general trend is that boron enolates parallel lithium enolates in their stereoselectivity but show enhanced stereoselectivity. There also are some advantages in terms of access to both stereoisomeric enol derivatives. Another important characteristic of boron enolates is that they are not subject to internal chelation. The tetracoordinate dialkylboron in the cyclic TS is not able to accept additional ligands, so there is no tendency to form a chelated TS when the aldehyde or enolate carries a donor substituent. Table 2.2 gives some typical data for boron enolates and shows the strong correspondence between enolate configuration and product stereochemistry. 

Tin enolates are also used in aldol reactions.27 Both the Sn(II) and Sn(IV) oxidation states are reactive. Tin(II) enolates can be generated from ketones and Sn(II)(03SCF3)2 in the presence of tertiary amines.28 The subsequent aldol addition is syn selective and independent of enolate configuration.29 This preference arises from avoidance of gauche interaction of the aldehyde group and the enolate P-substituent. The syn stereoselectivity indicates that reaction occurs through an open TS. 

From Azides and x-Acylphosphorus ylids Addition of azides to a-acylphosphorus ylids takes place at room temperature in dichloromethane or at 80°C in benzene, giving triazolines from which a phosphine oxide is spontaneously eliminated. " The ylids exist almost exclusively in the cis-enolate configuration, and a mechanism involving concerted 1,3-dipolar addition has been proposed (Scheme 12) on the basis that there is a low entropy of activation for the reaction, and that the reaction rate is insensitive to changes in solvent polarity. ... 

We will use the 7D CRS Hamiltonian which has been determined and analyzed in Ref. [10] (DFT/B3LYP, 6-31+G(d,p)). In short, the large-amplitude motion of the H/D atom is restricted to the (x,y) plane of the molecule (cf. Fig. 1). The origin of the molecule-fixed coordinate system is at the center of mass, with the axes pointing along the principal axes of inertia for the enol configuration. The H/D motion couples strongly to 5 in-plane skeleton modes, Q = (Q4, Q, Qu, Q26, Q3o)> which are described in harmonic approximation... 

The bands show significant bathochromic shifts in base solution (Fig. 5.2C) relative to neutral (Fig. 5.2A) or acidic (Fig. 5.2B) solutions. This may be due to tautomeric [39] and resonance effects taking place in basic medium. Interactions occurred between the nonbonded electrons on the nitrogens and the n electrons of the fused rings as evidenced by the blurring of the bands. Furthermore, the enolic configuration... 

C. H. Heathcock, Modem Enolate Chemistry Regio- and Stereoselective Formation of Enolates and the Consequence of Enolate Configuration on Subsequent Reactions, in Modem Synthetic Methods (R. Scheffold, Ed.), Vol. 6, 1, Verlag Helvetica ChimicaActa, Basel, Switzerland, 1992. 

Naphthazarin, Fig. 12 (I), and its mono-methyl and di-methyl derivatives, Fig. 12 (II), (III), (IV), are /3-dicarbonyls that have been used to study the influence of symmetry on tunnelling138). They have no option but to exist in the cis enol configurations. A great deal of work has been done on the naphthazarins because of their structural relationship to certain anti-cancer antibiotics139). Debate has turned on the nature of the hydrogen bonds - are they centred or non-centred ... 

Disordered O-H 0 intramolecular hydrogen bonds are not uncommon in crystal structures of molecules having cis-enol configurations, but without evidence for an order-disorder transition, they do not necessarily imply that proton transfer takes place in the crystalline state. 

The first C6-C7-aldol reactions were reported by Nicolaou s group with the dianion of keto-carboxylic acid 5 (Scheme 12). Aldehydes 29a, 29b and 20b give the desired aldols 62, 63 and 66 in high yields ( ) at —78 °C. As expected, excellent control of the enolate configuration had taken place to result in a perfect C6-C7 syn relationship. Nevertheless, there was no or mini-... 

As Section IV will be mostly devoted to 2,4-pentanedione, acacH, it is worthwhile to dwell on this well studied species. The rate of interconversion between the keto and the enol form of acacH is rather slow at room temperature , thus they can be simultaneously detected by NMR spectroscopy it has been observed that the lower the polarity of the solvent, the higher the percentage of the enol tautomer . Electron diffraction studies indicate that in the gas phase acacH adopts the enol configuration with a keto/enol ratio of 8/92. More recently, an X-ray analysis of acacH, carried out at 110 showed that it exists as a mixture of the two enol forms 86 and 87, with the enolic hydrogen atom equally distributed over two positions close to the oxygen atoms as in 88. It should be noted that inclusion compounds containing different host molecules show different ratios of acacH in the enol form. For example, acacH exists as a dynamically averaged 1 1 mixture of 86 and 87 in an inclusion complex with l,T-binaphthyl-2,2 -dicarboxylic acid as host , while l,l-bis( >-hydroxyphenyl)cyclohexane and (4R,5R)-trawi-4,5-bis(hydroxydiphenylmethyl)-2,2-dimethyl-l,3-dioxolane include acacH in pure enolic form. ... 

The lithium enolate is expected to have the (enolate) configuration 147. Chelation is impossible and it adopts the Houk conformation 147a with the H atom on the inside eclipsing the ir-bond. The enormous protected amine forces the allyl bromide to the opposite face. The potassium enolate prefers the chelated structure 148 and the same group directs the allyl iodide to the bottom face. 

The formation of ( )-enolates is favored in tetrahydrofuran alone, whereas addition of metalchelating solvents such as hexamethylphosphoric triamide, A,A, /V, Ar-tetranncthylcthylenedi-amine or l,4-dimethyltetrahydro-2(l//)-pyrimidinone reverses the enolate configuration to the (Z)-product. The best seleetivities were obtained with 45% l,3-dimethyltetrahydro-2(l//)-pyrimidinone. In comparison to lithium diisopropylamide in 23% hexamethylphosphoric triamide. slightly bulkier bases, i.e., lithium hexamethyldisilanazide, have proved to be more E selective256. 

Owing to the dependence of the product stereochemistry on enolate configuration, control of the stereochemistry of enolate formation is important. For ketones with one relatively bulky group, the Z-enolate is favored, resulting in formation of the xyn-aldol product. This is the case, for example, in the reaction of 2,2-dimethyl-3-pentanone and... 

The (Z)/( ) stereoselectivity of enolate formation is dictated by the structure of the starting carbonyl compound and the base used for deprotonation. Compared to LDA, Lithium 2,2,6,6-Tetra-methylpiperidide usually favors ( )-enolates whereas Lithium Hexamethyldisilazide preferentially leads to (Z)-enolates (eq 10). With a caveat for any generalization, enolate configuration usually determines the stereochemical result in the product for example, using a hindered ester and a bulky aldehyde combination, excellent stereoselectivities in aldol reactions are observed (eq 11). ... 

When a prochiral ( )-enolate is selectively (Si)-facially protonated, the result is the (H)-enantiomer. (Jle)-Facial protonation leads to the (S)-enantiomer. From the (Z)-enolate, the direct opposite is obtained. If it is not possible to control the ( )/(Z)-configuration of the enolate, in order to obtain good selectivity, one needs then an enantiomericaUy pure acid, whose protonation preference is dependent on the enolate configuration, i.e. for example, it transfers a proton (Si)-facially to the ( )-enolate, but (Re)-fadally to the (Z)-enolate. In many successful cases the enantiomericaUy pure acid is bonded to the metal of the enolate therefore, at the same time it acts also as a Lewis base. In addition, at least from a theoretical point ofview, enantioselective inter- and intra-molecular protonations with achiral acids are conceivable, in which another ligand of the enolate complex is enantionmericaUypure. 

N-salicylideneaniline is photochromic the enol configuration can be converted to the trans-keto conformation by using light of frequency Vj, and converted back by either heat, or by light of frequency V2 here the tautomerism causes an intramolecular rotation [67]. 

The 3-keto reductase step is equivalent to that found in fatty acid synthesis, although it occurs late (and only once) in this process. Indeed, thiol-bound acetoacetate proved inactive as a substrate for the aromatic complex, whereas it was reduced by fatty acid synthetase (Dimrothe/a/., 1972). Thus, the carbonyl group adjacent to the terminal methyl position is not susceptible to reduction by the aromatic synthetase, despite the apparent presence of a suitable reductase, possibly because it is held on the enzyme surface in an inappropriate enolic configuration (Packter, 1973). If so, it may not prove acceptable, since the 3-ketoacyl-acyl carrier protein (ACP) reductase from Escherichia coli only accepts keto substrates and does not react with or bind to the enol form of 3-ketoacyl derivatives (Schulz and Wakil, 1971). 

Scheme 2.35 Correlation between enone conformation and enolate configuration.

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