Transition states dipole-minimized

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]. 

In contrast, when 6-exo cyclizations are effected in the presence of an ot-alkoxy or a-silyloxy substituent, the stereocontrol can be excellent, as has been observed in a Si-tethered cyclization of 54a (Scheme 15) where a single diastereomeric product was obtained [134]. In this case, additional conformational constraints aided the cyclization, as became evident upon finding that the product configuration was inconsistent with the standard Beckwith-Houk chair-equatorial transition state model. For 54a there are two chairlike conformations (chair-equatorial and chair-axial) conceivably leading to cyclization the latter has the C-O and C=N bonds in an anti relationship to minimize dipole repulsion (Scheme 15). The... 

To confirm the existence of the dipole repulsion effect, a related substrate 54b was conceived, differing only in the configuration at the a-carbon. The expected chair-axial and chair-equatorial transition states for cyclization of 54b each have their C-O and C=N bonds in a gauche relationship the dipole repulsion model therefore predicts minimal differentiation. In this control experiment, cyclization of... 

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. 

The diastereoselectivity of these reactions is consistent with product formation occurring through transition state 137, where the reactive conformation of the aldehyde in the transition state (corresponding to the normal Felkin-Anh model) minimizes steric interactions with the allylstannane as well as the 1,3-dipole interactions of the aldehyde and the /(-alkoxy group. The allylation reaction of the 2,3-syn aldehyde 138, however, with allyltri-n-butylstannanes 98, generates the anti-Felkin adducts 139 preferentially (Eq. (11.9)) [93], The stereochemistry of these reactions is consistent with product formation occurring preferentially through transition state 140, in which 1,3-dipole interactions of the aldehyde and the P-... 

Freshly prepared (5,7 ,/ )-a-chloroallylboronate 201 reacts with achiral aldehydes to form preferentially the (Z)-chlorohomoallylic alcohols 297 (Table 11-15) [125], The preponderance of alcohols 297 indicates that transition state 299 is favored over 300 which leads to the minor diastereomeric alcohol 298, due to the unfavorable steric interactions between the equatorially-placed a-chlorine substituent and the cyclohexyl substituent of the dioxaborolane unit in 300. Polar a-sub-stituents, e.g. -Cl, also increase the preference for reaction through transition state 299, presumably due to minimization of dipole and Coulombic repulsion [24]. 

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

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. ... 

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 presence of a polar /3-substituent in the aldehyde can significantly influence the stereochemical outcome of nucleophilic addition. The observed selectivity has been attributed to the intermediacy of an acyclic transition state structure proposed by Evans (Equation 15) [85, 86]. The key characteristics of the model are (1) attenuation of dipole effects by orientation of C(3-0 and C = 0 in an antiparallel arrangement, and (2) the minimization of non-covalent interactions as the C=0 undergoes rehybridization. Thus, over the course of nucleophilic addition, the preferred conformer 162 is transformed into a product with He->PGO and OM<- H interactions, whereas the alternative conformer 163 accrues the energetically more costly interaction between PGO and MO [86]. 

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 ... 

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