Stereoelectronic hindrance

Table 3.4 and Table 3.10 summarize quenching data of singlet-excited DBO by amines and sulfides. These quenchers are stronger electron donors than ethers or alcohols and therefore mainly involved in charge-transfer-induced mechanisms. Sulfides are somewhat weaker electron donors than amines, which is manifested in lower quenching rate constants, except where structural effects such as steric or stereoelectronic hindrance are involved (see below) [59],... 

These side reactions may occur if the /V-acyliminium ion is not trapped quickly enough by a nucleophile. So problems may arise with relatively poor nucleophiles or if there is too much steric hindrance, while in the case of intramolecular reactions, unfavorable stereoelectronic factors or intended formation of medium- or large-sized rings may play a role. The reaction conditions, such as the nature of the (acidic) catalyst and the solvent, may also be of importance. 

The preparation of ketones and ester from (3-dicarbonyl enolates has largely been supplanted by procedures based on selective enolate formation. These procedures permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of keto ester intermediates. The development of conditions for stoichiometric formation of both kinetically and thermodynamically controlled enolates has permitted the extensive use of enolate alkylation reactions in multistep synthesis of complex molecules. One aspect of the alkylation reaction that is crucial in many cases is the stereoselectivity. The alkylation has a stereoelectronic preference for approach of the electrophile perpendicular to the plane of the enolate, because the tt electrons are involved in bond formation. A major factor in determining the stereoselectivity of ketone enolate alkylations is the difference in steric hindrance on the two faces of the enolate. The electrophile approaches from the less hindered of the two faces and the degree of stereoselectivity depends on the steric differentiation. Numerous examples of such effects have been observed.51 In ketone and ester enolates that are exocyclic to a conformationally biased cyclohexane ring there is a small preference for... 

According to the present theory, these reactions can be explained in the following manner. Since dioxolenium ions are essentially planar (8, 9), the chair form of ring B of salt 98 must be distorted towards a half-chair. Hydration of 98 with stereoelectronic control must take place from the a face to give the half-chair hemi-orthoester 102 (Fig. 8), because the steric hindrance between the incoming water molecule and ring B must inhibit... 

It has however been suggested by Cieplak (9) that the stereochemistry of nucleophilic addition to cyclohexanone is determined by a combination of steric and stereoelectronic effects. According to this interesting model, steric hindrance favors the equatorial approach while electron donation favors the axial approach. The stereoelectronic effect favors the axial approach because the axial C —H bonds next to the carbonyl group (C — Ha and Cn-Ha) are better electron donors than the Cn-C-j and Cc-Cfi a bonds (cf 7A 7 and 7A-8). J... 

Using a -3-ketosteroids 466, Ringold and collaborators (143) have found that the rate ratio for axial and equatorial proton loss at C-6 is 53. The profound preference for axial proton loss (465 466) despite greater steric hindrance from the a face (due to C-19 methyl group) strikingly emphasizes the importance of stereoelectronic effects. In view of this preference, these authors have essentially concluded that cases of equatorial deprotona-... 

In tricyclovetivene (4)160 and seychellene (6)161 considerable hindrance by the carboxylic acid substructure of the peracid would be expected in the disfavored diastereomeric transition states. In tricyclovetivene (4) this seems to be compensated for by a stereoelectronic effect favoring axial attack of the chair cyclohexane system (see Section 4.5.1.1.3.) to give 5A, so that the force-field calculation168 accurately reproduces the observed diastereoselectivity (80 20). 

In oxazolidines, the extent of ring chain tautomerism is also governed both by the acidity of its a-CH and by stereoelectronic stabilization of acyclic tautomers. Deprotonation at the a-carbon of the C-2 appendage induces ring opening of the oxazolidine to its chain tautomer. In 27a and 27b, steric hindrance to deprotonation and possible nonplanarity of the carbanion system due to the orthogonal disposition... 

Rotation around hindered or retrained single bonds usually implies that the molecule reaches the energy barrier that restricts interconversion from one con-former to another. In general terms, steric hindrance is the main limitation and heating is then sufficient to cross the barrier, although additional interactions such as H-bonds, stereoelectronic effects and ionic interactions may either hamper or facilitate the rotation. 

For a discussion of stereoelectronic effects in this case see also ref 621. In a similar way, -branched dithioesters can be rearranged stereoselectively to a-allyl-/l-hydroxy dithioesters. The relative configurations have not been assigned. The order of selectivity follows the degree of steric hindrance of the substituents R1 bound to the stercogenic center (Table 26)623. 

Similarly photocycloaddition of ethylene with chiral 5-alkoxyfuranones 181 proceeds with facial diastereoselection [153], Although selectivity remains low, the reaction has been used for the enantiospecihc synthesis of grandisol because it is easy to separate the initial diastereoisomers [154]. Selectivity is greatly influenced by temperature and by substituents on the ethylenic bond of the furanone ring. It was concluded that steric hindrance of the alkoxy group and stereoelectronic effects of substituents on the conjugated system are responsible for the selectivity observed. It was also proposed that the diastereoselection of the photocycloaddition of ethylene with 181 was dominated by the approach of ethylene to the vibrationally relaxed (71,71 ) excited furanone rather than by the selectivity of the reactions of biradicals. 

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