Reaction stereoelectronic effects

Early examples of this reaction involved cyclizations of 4-substituted phenols tethered to alkyl sulfonates and halides [3]. CycMzalions involving carbonyl electrophiles (aldehydes, ketones) and imines have been reported as well, but esters are not sufiSciently electrophilic to react [2]. Subsequent studies established that the facility of these so-called Ai-n cyclizations was strongly affected by the size of the newly formed ring in the order 3>5>6 >4. Since the vast majority of alkylative dearomatizations involve intramolecular cyclizations (thereby avoiding competitive 0-aDcylation reactions), stereoelectronic effects operative in the transition states (resembling the TS of an Sjj2 reaction) are crucially important. These sometimes subtle effects can result in differential reactivity of structurally similar substrates [4]. 

Some reactions require the bonds being broken or made in a reaction to be aligned with other parts ti- or free electrons) of a molecule. These requirements are called stereoelectronic effects. Figure 3-6f shows that the bromide ion has to open a bro-monium ion by an anti attack in order that the new bond is formed concomitantly with the breaking of one bond of the three-membered ring. 

Effects that arise because one spatial arrangement of electrons (or orbitals or bonds) IS more stable than another are called stereoelectronic effects There is a stereoelec tromc preference for the anti coplanar arrangement of proton and leaving group in E2 reactions Although coplanarity of the p orbitals is the best geometry for the E2 process modest deviations from this ideal can be tolerated In such cases the terms used are syn periplanar and anti periplanar... 

Once formed, 7 and 8 undergo a Michael reaction that gives rise to ketoenamine 9. Ring closure, to form 10, and loss of water then afforded 1,4-dihydropyridine 11. The presence of 9 and 10 could not be detected thus ring closure and dehydration were deduced to proceed faster than the Michael addition. This has the result of making the Michael addition the rate-determining step in this sequence. Conversely, if the reaction is run in the presence of a small amount of diethylamine, compounds related to 10 could be isolated. Diol 20 has been isolated in an unique case (R = CFb). Attempts to dehydrate this compound under a variety of conditions were unsuccessful. Stereoelectronic effects related to the dehydration may be the cause. In related heterocyclic ring formations, it has been determined that dehydration (20 —> 10) is about 10 times slower than diol formation (19 —> 20). Therefore, one would expect 20 to... 

Stereoelectronic effects and nonbonded interactions are non-cooperative in the reactions of (E)-allylboronates and x-heteroatom-substituted aldehydes. Thus, while transition state 8 experiences the fewest nonbonded interactions (gauche pentane type, to the extent that X has a lower steric requirement than R3), transition state 9 is expected to benefit from favorable stereoelectronic activation (Felkin-type)58f. This perhaps explains why the reaction of 2,3-[iso-propylidenebis(oxy)]propanal and ( >2-butenylboronate proceeds with a modest preference (55%) by way ol transition state 9. This result is probably a special case, how ever, since C-3 of 2.3-[isopropylidenebis(oxy)]propanal is not very stcrically demanding in 9 owing to the acetonide unit that ties back the oxygen substituent, thereby minimizing interactions with the... 

It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

In contrast to ordinary chiral aldehydes (having no ability to be chelated), the reaction of 9-allyl-9-borabicyclo[3.3.1]nonane(allyl-9-BBN) with the corresponding chiral imines 4 produces the isomer syn-6 either exclusively or predominantly (Cram selectivity Table 8)5,6. The very high 1,2-asymmetric induction is explained by a six-membered. chair-like transition state, in which the inline R group occupies an axial position due to the stereoelectronic effect of imines (R CH = NR). 

The most direct evidence that stereoelectronic effects are also important in these reactions follows from the specificity observed in hydrogen atom abstraction from conformationally constrained compounds,18 60 C-H bonds adjacent to oxygen113"118 or nitrogen110 and which subtend a small dihedral angle with a lone pair orbital (<30°) are considerably activated in relation to those where the dihedral angle is or approaches 90°. Thus, the equatorial H in 20 is reported to be 12 times more reactive towards /-butoxy radicals than the axial 11 in 21.115... 

A further example of the importance of this type of stereoelectronic effect is seen in the reactions of /-butoxy radicals with spiro[2,n]alkanes (22) where it is found that hydrogens from the position a- to the cyclopropyl ring arc specifically abstracted. This can be attributed to the favorable overlap of the breaking C-H bond with the cyclopropyl cr bonds.120131 No such specificity is seen with bicyclo[n, 1,0]alkanes (23) where geometric constraints prevent overlap. 

Sulphuranes - see also Dialkoxysulphuranes, Oxysulphuranes as intermediates 406 Sulphur bonding 484-493 Sulphur-containing groups, stereoelectronic effects of 584-594 Sulphur dioxide addition to 215-217 extrusion of 137, 140, 141, 158, 163, 397-402, 801, 805, 962, 1098 Sulphur monoxide, extrusion of 397-402 Sulphur trioxide, reactions of 217, 218 Sultenes, as intermediates 743 Sultines 679, 943 as photolytic products 881, 882... 

Chemoselectivity plays an important role in the benzannulation reaction as five-membered rings such as indene or furan derivatives are potential side products. The branching point is again the rf-vinylcarbene complex D intermediate which maybe formed either as a (Z)- or an ( )-metallatriene the (E)-configuration is required for the cyclisation with the terminal double bond. (Z)-Metallatriene D, however, leads to the formation of furan derivatives H (Scheme 8). Studies on the formation of (E)- and (Z)-isomers discussing stereoelectronic effects have been undertaken by Wulff [17]. 

C X bond, but not from B because only the has such an orbital. If the intermediate is in conformation B, the OR may leave (if X has a lone-pair orbital in the proper position) rather than X. This factor is called stereoelectwnic control Of course, there is free rotation in acyclic intermediates, and many conformations are possible, but some are preferred, and cleavage reactions may take place faster than rotation, so stereoelectronic control can be a factor in some situations. Much evidence has been presented for this concept. More generally, the term stereoelectronic effects refers to any case in which orbital position requirements affect the course of a reaction. The backside attack in the Sn2 mechanism is an example of a stereoelectronic effect. 

The interpretation of the basis for this stereoselectivity can be made in terms of the steric, torsional, and stereoelectronic effects discussed in connection with reduction by hydrides. It has been found that crown ethers enhance stereoselectivity in the reaction of both Grignard reagents and alkyllithium compounds.119 This effect was attributed to decreased electrophilicity of the metal cations in the presence of the crown ether. The attenuated reactivity leads to greater selectivity. 

There have been many applications of conjugate additions in synthesis. Some representative reactions are shown in Scheme 8.2. Entries 1 and 2 are examples of addition of lithium dimethylcuprate to cyclic enones. The stereoselectivity exhibited in Entry 2 is the result of both steric and stereoelectronic effects that favor the approach syn to the methyl substituent. In particular, the axial hydrogen at C(6) hinders the a approach. 

Enantioselective Addition Reactions of Allylic Stannanes. There have been several studies of the enantiomers of a-oxygenated alkenyl stannanes. The chirality of the a-carbon exerts powerful control on enantioselectivity with the preference for the stannyl group to be anti to the forming bond. This is presumably related to the stereoelectronic effect that facilitates the transfer of electron density from the tin to the forming double bond.182... 

Reactions through chelated TS Reactions of a- or (3-oxy-substituted aldehydes often show chelation-controlled stereoselectivity with Lewis acids that can accommodate five or six ligands. Chelation with substituents in the allylic reactant can also occur. The overall stereoselectivity depends on steric and stereoelectronic effects in the chelated TS. 

Besides di- and poly-saccharides, zeolites have been applied for hydrolysis of simple glycosides as described by Le Strat and Morreau.132 Methyl a- and /i-D-glucopyrano-sides were treated with water in the presence of dealuminated HY faujasite with an Si/Al ratio of 15, at temperatures ranging between 100 and 150 °C. It was observed that the reaction rate for the (i glycoside was about 5-6 times higher than that for the oc anomer, a result that might arise from the shape-selective properties of the zeolite and stereoelectronic effects on the surface of the solid. 

Another route involves a palladium-copper-catalyzed tandem carbon-carbon formation/cycloaddition sequence (Equation 12) <2005TL8531>. Notably, cycloadditions of azide to the internal alkynes failed under click chemistry reaction conditions <2003DDT1128>. Cyclization under oxidative conditions has been reported from dithioacetal 163 (Equation 13) <1996TL3925>. The formation of 164 as a single diastereoisomer has been explained by stereoelectronic effects. 

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