Dipole minimization

Based on an X-ray crystal structure analysis of 54, the authors proposed a transition-state where the conformation of the acylammonium salt generated from 54 would be fixed by an attractive electrostatic interaction between the acyl-oxygen and the imidazoyl-2-proton or a dipole minimization effect (Fig. 14) [177]. 

Minimum steric interactions between the auxiliary s isopropyl group and the aldehyde and optimal dipole minimization make transition state 55 the lowest in energy. All other possible combinations lead to transition states of significantly higher energy. This explains the excellent observed stereoselectivity. 

Ficini-Claisen rearrangement proceeded via the dipole minimized chair-like transition state 329 leading to the major product 327. ... 

Secondly, the reaction rate is inversely correlated to the polarity of the solvent, indicating that the product of the rate limiting step has little charge or presents dipole-minimized characteristics. This observation also suggests that the addition of isonitrile 13 to 12 is a concerted process which avoids ionic or zwitterionic species. 

A general model for understanding the stereochemistry of intramolecular Michael reactions has been proposed, based on the addition of -ketoester enolates to a,[l-unsaturated esters and imide moieties bearing adjacent stereocentres in the chain connecting the Michael donor to an acceptor (225) (226) (X, Y = H, Me, OR in the syn- or unti-configuration). A dipole-minimized chair-like transition state appears to offer the best rationalization. ... 

Fig. 13 Dipole minimization of the N -H and C-F bond leads to stabilization of the protonated amine...

That the observed pK of 3-fluoropiperidine is slightly less acidic than predicted may be explained by stabilization of the ammonium species via dipole minimization, as depicted in Fig. 13a [88]. In fact, NMR studies with 3-fluoropiperidine have revealed that the 3-fluoro substituent inverts from a completely equatorial orientation to a completely axial orientation upon protonation of the amine [53]. Similarly, the fluoro substituent of cw-3-fluoro-4-benzylpiperidine adopts a completely axial orientation in the protonated species leading to stabilization and a pK of 9.3 (Fig. 13b). Upon protonation of fran.y-3-fluoro-4-benzylpiperidine, the 3-fluoro substituent occupies both the axial and equatorial orientation equally, leading to reduced stabilization and a pK of 8.8 [88]. 

Scheme 4.46 Evans-syn" selective aldol addition of valine-derived N-propionyl oxazolidinone 48 via boron enolate 208. Dipole-minimized transition state model 210.

Evans aldol reaction between the functionalized 4-phenyl-oxazohdinone 6 and 5-chloropentanal 7, securing the 1,2-syn stereochemistry " in the resultant chlorohydrin 9. The diastereoselectivity of this process is governed by the preferential formation of a (Z)-enolate and dipole minimization in the Zimmerman-Traxler transition state 8. Conversion of the aldol adduct into the corresponding mesylate was followed by reductive removal of the auxiliary to provide the hydroxymesylate 10, an advanced intermediate in the enantioselective synthesis of (-l-)-methylphenidate hydrochloride 11. The active pharmaceutical ingredient was produced in >99% ee after lecrystaUization. 

The orientational structure of water near a metal surface has obvious consequences for the electrostatic potential across an interface, since any orientational anisotropy creates an electric field that interacts with the metal electrons. Hydrogen bonds are formed mainly within the adsorbate layer but also between the adsorbate and the second layer. Fig. 3 already shows quite clearly that the requirements of hydrogen bond maximization and minimization of interfacial dipoles lead to preferentially planar orientations. On the metal surface, this behavior is modified because of the anisotropy of the water/metal interactions which favors adsorption with the oxygen end towards the metal phase. 

Solvatochromic shifts are rationalized with the aid of the Franck-Condon principle, which states that during the electronic transition the nuclei are essentially immobile because of their relatively great masses. The solvation shell about the solute molecule minimizes the total energy of the ground state by means of dipole-dipole, dipole-induced dipole, and dispersion forces. Upon transition to the excited state, the solute has a different electronic configuration, yet it is still surrounded by a solvation shell optimized for the ground state. There are two possibilities to consider ... 

Compare energies for both diaxial and diequatorial chair conformers of trans-l,2-difluorocyclohexane (X = F). Which conformer is preferred Does the preferred conformer minimize steric repulsion Explain. Examine dipole moments for the two conformers. Does the preferred conformer minimize electrostatic repulsion (or maximize electrostatic attraction) Explain. 

Potential functions induced-dipole terms, 84-85 minimization, 113-116 nonbonded interactions, 84-85 Potential of mean force, 43, 144 Potential surfaces, 1,6-11, 85, 87-88, 85 for amide hydrolysis, 176-181,178,179, 217-220, 218... 

Here, is the magnetization of spin i at thermal equilibrium, p,j is the direct, dipole-dipole relaxation between spins i and j, a-y is the crossrelaxation between spins i and j, and pf is the direct relaxation of spin i due to other relaxation mechanisms, including intermolecular dipolar interactions and paramagnetic relaxation by dissolved oxygen. Under experimental conditions so chosen that dipolar interactions constitute the dominant relaxation-mechanism, and intermolecular interactions have been minimized by sufficient dilution and degassing of the sample, the quantity pf in Eq. 3b becomes much smaller than the direct, intramolecular, dipolar interactions, that is. 

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