Steric Diversion

Conceivably, in an olefin addition reaction, if the more substituted end of the ethylenic linkage is sterically shielded such that the approach of the nucleophile or the radical is essentially blocked, the product cannot be expected to be the result of a simple addition reaction, but would always be complicated by the intervention of other pathways, such as elimination/rearran ment. To illustrate this point, the reaction of chlorine-free hypochlorous acid with u/wym-dineopentylethylene (110) and 2,4,4-trimethyl-l-pentene (112) may be cited (110) gives a complex reaction product in which (111) predominates (48%) and no oxygen-containing material was detected in the total product, while (112) which is less hindered furnishes 34% of the normal product (113) and 46% of elimination product (114) (65). 

Another consequence of such steric crowding would be that, even if ordinary addition does occur under favorable circumstances or is made to occur under special reaction conditions, the product, due to steric compression, would be especially prone to undergo reactions in which, in the transition state, there is a change from sp to sp hybridization at the new fully substituted carbon (69, 70). 

sterically crowded situations can divert the normal reaction pathway and the term steric diversion has been proposed (71) to describe this switch-over from the normal route. In longifolene (115), the ethylenic linkage is well-shielded and crowding at the more substituted end of the olefinic bond is, at least, as severe as in wn w-dineopentylethylene (110) (72, 73). Hence it is not surprising that the chemistry of longifolene is replete with examples of abnormal products , more appropriately called sterically diverted products. 

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An electronically and sterically diverse array of arylboronic acids serve as useful reaction partners (Table 2, entries 1-4). In addition, vinylboronic acids can be cross-coupled in good yield (entry 5), although reactions of alkylboronic acids proceed with somewhat lower efficiency (entry 6). The catalyst tolerates a range of functional groups, including esters, thioethers, and cyanides. 

Reactions leading to products from steric diversion. 

As a matter of convenience, the results of oxidation of longifolene with lead tetraacetate, and ruthenium tetraoxide will also be summarized here steric diversion may have little role in forming the products of these reactions. One of the important reactions of lead tetraacetate with olefins is allylic substitution/rearrangement (J02). Since, this pathway is blocked for longifolene, the major product of this reaction is the ring-expanded enol acetate (154) (Chart 17), exactly parallel to what happens with camphene (8J, 99). 

The steric crowding at the more substituted end of the ethylenic bond, in isolongifolene (23) also is at least as severe as in w/isy/w-dineopentyl-ethylene (110), hence it is not surprising to find that many of its reactions involving additions to the olefinic linkage are dominated by steric diversion. 

Epoxides can also be accessed asymmetrically using hypervalent iodine reagents in combination with imidazolidinone catalysts 78 (Scheme 30). The methodology developed by MacMillan et al. includes participation of hypervalent iodine reagent in a 1,4-heteroconjugate addition reaction for the organocatalytic, asymmetric epoxidation of a,p-unsaturated aldehydes 77. This organocatalytic reaction allows for the enantioselective formation of epoxides 78 from a wide array of electronically and sterically diverse a,p-unsaturated aldehydes [92]. 

Functionality preferences for metathesis of Ru carbenes to alkenes and alkynes with electronic and steric diversity were studied using time-dependent fluorescence quenching (Scheme 116). ... 

It works on electronically and sterically diverse aryl- and alkenyl-monoorganostannanes (easily accessible starting from alkenyl- or aryl- trialkylstannanes by redistribution with SnCU). 

Onium ions of small and large heterocyclics are usually produced by electrophilic attack on a heteroatom. In three- and four-membered rings nucleophilic attack on an adjacent carbon follows immediately, in most cases, and ring opening stabilizes the molecule. In large rings the onium ion behaves as would its acyclic analog, except where aromaticity or transannular reactions come into play (each with its electronic and steric pre-conditions). A wide diversity of reactions is observed. 

Because of the frequent mutual interference of electronic, inductive, and steric effects, and because of the influence of ring strain, the carbonyl stretching frequency is naturally not an absolute criterion for the methylation course. The heterocyclic systems in question are too diverse for this to hold. Careful inspection of Table I discloses certain deviations from the relationships mentioned. These deviations will now be discussed. 

A widely used 3-D QSAR method that makes use of PLS is comparative molecular field analysis (CoMFA), in which a probe atom is used to calculate the steric and electronic fields at numerous points in a 3D lattice within which the molecules have been aligned. Poso et al. [56] used the technique to model the binding of coumarins to cytochrome P450 2A5, with similar results to those obtained by Bravi and Wikel [55]. Shi et al. [57] used it to model the estrogen receptor binding of a large diverse set of compounds, and Cavalli et al. [58] used it to develop a pharmacophore for hERG potassium... 

Neutral borabenzene-PMe3, generated through the route described in Scheme 2, reacts with a variety of anionic nucleophiles to furnish 5-substituted borataben-zenes (Scheme 7).15 This approach provides efficient access to boratabenzenes that bear a range of boron substituents (H, C, N, O, P) with diverse electronic and steric properties.16 Mechanistic studies establish that this novel aromatic substitution process follows an addition-elimination pathway. 

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