Unfavored steric interactions

In case of a Z,Z-configurated diene 6, the transoid conformation is favored, because of unfavorable steric interactions of substituents at C-1 and C-4 in the... 

An interesting observation in the solvolysis of all arylvinyl systems is the effect of added /3-aryl groups. All triarylvinyl substrates react more slowly than do the corresponding monoaryl or diaryl systems. For example, triphenylvinyl fluorosulfonate, 153, Ri =C6Hs, R = F, reacts about 2.5 times more slowly (140) in acetic acid than does a-phenylstyryl fluorosulfonate, 153, Rj = H, R = F. Similarly, trianisylvinyl bromide reacts 2.8 times and 1.2 times more slowly in 80% EtOH and in AcOH, respectively (144), than does cis-1,2-dianisylvinyl bromide. This difference probably results from increased hindrance to solvation and increased unfavorable steric interactions. 

Davies [30] studied the PyBOx-induced conformational effects by testing several ligands sterically hindered on the oxazoUne moieties (Scheme 11, structures 18 and 19). However, these new ligands gave poorer results in terms of yields and enantioselectivities than ligand 16 for the Ru-catalyzed cyclopropanation reaction, indicating unfavorable steric interactions between styrene and the carbene complex. 

Migration cannot occur past a quaternary carbon, however, since the required elimination is blocked. At equilibrium the major trialkyl borane is the least-substituted terminal isomer that is accessible, since this isomer minimizes unfavorable steric interactions. 

Similar metallacyclic species have been proposed as intermediates in other reactions of metal compounds with diazoalkanes (57,55). The presence of unfavorable steric interactions in an intermediate such as 53 could well explain the failure to observe any reaction of diaryldiazoalkane with 45 (55). 

The high levels of enantioselectivity obtained in the asymmetric catalytic carbomagnesa-tion reactions (Tables 6.1 and 6.2) imply an organized (ebthi)Zr—alkene complex interaction with the heterocyclic alkene substrates. When chiral unsaturated pyrans or furans are employed, the resident center of asymmetry may induce differential rates of reaction, such that after -50 % conversion one enantiomer of the chiral alkene can be recovered in high enantiomeric purity. As an example, molecular models indicate that with a 2-substituted pyran, as shown in Fig. 6.2, the mode of addition labeled as I should be significantly favored over II or III, where unfavorable steric interactions between the (ebthi)Zr complex and the olefmic substrate would lead to significant catalyst—substrate complex destabilization. 

Figure 4. Structural data obtained for the cationic r 3-allyl complexes 26 (R = Me or CH2Ph), illustrating the differing Pd-C bond lengths which result from unfavorable steric interactions.

It is important to highlight that the regioselectiv-ity of nucleophilic addition in the above situation is entirely a result of unfavorable steric interactions between the bisoxazoline ligand and the r 3-allyl moiety. However, this is not the only means by which the regioselectivity may be influenced. As early as 1976, Faller and co-workers demonstrated... 

The reasons for such retardation effects were disclosed by quantum chemical calculations. Analysis of geometric characteristics for the initial and transition states of the rearrangements obtained by DFT method with the use of PRIRODA program (27, 28) showed that unfavorable steric interactions in transition states of the rearrangements of cations lb,c were responsible for the retardation effects (25). 

Both uncatalyzed and catalyzed [4+2]-cycloaddition reactions of furans with the allenic esters have been reported (Table 12.6) [93]. The allene adds from the less hindered C1-C2 Jt-face. The unfavorable steric interaction between the a-hydrogen atom of the furan and the methyl group at C4 of the allene is responsible for this selectivity. The more reactive 2-methylfuran adds to the allenic ester also in a regio-selective manner. The C2 carbon atom of 2-methylfuran was exclusively attached to the Cl carbon atom of the allenic ester, providing a mixture of endo- and exoadducts. 

The benzannulated analog 115 was likewise synthesized from 114 (Scheme 20.24) [56, 63], However, unlike 109, thermolysis of 115 resulted in its slow decomposition without the formation of the cycloaromatized adduct 116. The lack of propensity for 115 to undergo the Myers-Saito cyclization reaction was attributed to unfavorable steric interactions between the diphenylphosphinyl group and the aryl ring of the benzannulated enyne-allene system, causing the allenic moiety to be rotated out of the plane defined by the aryl ring and preventing the cyclization reaction. 

The enyne-allenylphosphine oxides 120 and the benzannulated and naphthannu-lated analogs 121 and 122 having the diphenylphosphinyl group at the allenic terminus were readily prepared from the corresponding enediynyl propargylic alcohols 117,118 and 119 (Scheme 20.25) [64]. Without the unfavorable steric interactions, these conjugated derivatives smoothly underwent the Myers-Saito cyclization reaction. 

Unlike thermal homo Diels-Alder reactions in which endo adducts predominate330, the nickel catalyzed reactions of acyclic electron-deficient dienophiles afford the exo isomers as the major cycloadducts. This has been explained by unfavorable steric interactions within intermediate 559 leading to the endo adduct. Cyclic dienophiles, on the contrary, give predominantly the endo isomer, which has again been explained by unfavorable steric interactions within exo 559. The preferred conformation of the dienophile, s-cis or s-trans, has also been suggested to play a role328. 

Now we turn to a discussion of the influence of a-substitution at C(6) or C(7) on the chemical reactivity of the lactam ring (Table 5.4,B). This substitution has been introduced mainly to improve lactamase stability (see Sect. 5.2.2.2). The insertion of an additional a-substituent at C(6) or C(7) of penicillins or cephalosporins, respectively, has a relatively small effect on the rate of base hydrolysis [82] [83], 6a-Methoxypenicillin is hydrolyzed at a rate that is approximately half that observed for the unsubstituted parent penicillin. This decrease is due mainly to unfavorable steric interaction between the... 

In contrast with data [78JBC(253)5407] on the predominance of the cyclic tautomers 66B and 67B (n = 4) in solutions of 6-carbamido- and 6-guanidino-2-oxocapronic acids, a more recent investigation (83LA1623) revealed that in neutral aqueous solutions these acids exist as the open-chain tautomers 66A and 67A (n = 4) with an admixture of the hydrate 67A (n = 4). The six-membered ring closure is presumably hindered by the unfavorable steric interaction between the planar guanidino or carbamido... 

There is a pronounced preference for the formation of a trans double bond in the Claisen-Schmidt condensation of methyl ketones. This stereoselectivity arises in the dehydration step. In the transition state for elimination to a cis double bond, an unfavorable steric interaction between the ketone substituent (R) and the phenyl group occurs. This interaction is absent in the transition state for elimination to the trans double bond. 

Kim, Chin, and co-workers have described a highly interesting oxyanion hole mimic that transforms L-amino acids to D-amino acids [97]. The mechanism involves stabilization of the enolate intermediate by an internal hydrogen bond array generated by urea group (Scheme 4.14). In the presence of an external base, such as triethylamine, the receptors readily promote the epimerization of a-amino acids, favoring the D-amino acids due to unfavorable steric interactions in the receptor-L-amino acid complex. These receptors can also be viewed as chiral mimics of pyridoxal phosphate [98]. 

Further examples of the endocychc nitrone route to spirocychc adducts are the total syntheses of (—)-histrionicotoxin (230) by Holmes and of cyhndricines by Weinreb. Histrionicotoxin is one of many spiropiperidine alkaloids isolated from the poison-arrow frog Dendrobates histrionicus and has been the subject of many attempted total syntheses by a nitrone cycloaddition strategy that failed to provide the desired regioisomer, possibly through unfavorable steric interactions (265-268). Unlike these reports, Holmes and co-workers (101) found that the intermolecular reaction of nitrone (231), prepared by the 1,3-APT of the corresponding alkynyl-hydroxylamine carrying Oppolzer s chiral sultam auxiliary, afforded the styrene... 

---