S-cis rotamers

Cyclic dipeptides, especially when N-alkylated, undergo extremely fast epimerization (79JA1885). For example, cyclo(L-Pro-L-Phe) is rapidly converted to its diastereomer, cyclo(D-Pro-L-Phe) (80% conversion), by treatment with 0.5 N NaOH at 25°C for 15 min. This diastereomer is the one in which the proline residue has epimerized and not the more activated phenylalanine. CNDO/2 calculations seem to provide a rationale for this. It is not yet completely clear why such base-catalyzed epimerizations of piperazinediones are so easy the conformation of the molecule may play a role in this (79MI1). It is also worth noting that even in linear peptides, rm-amides of N-alkyl-amino acids, which consist of s-trans and s-cis rotamers of almost equal energy, are more prone to racemization than the sec-amides, which exist only in the s-trans configuration. Of course, the amide functions of piperazine-2,5-diones are obliged to assume the s-cis conformation. 

In subsequent argon matrix isolation studies, similar bands were found when hexatriene or cyclohexadiene are ionized , and eventually, five of the six possible rotamers of hexatriene radical cation were identified by selective, wavelength-specific in ter conversions . Similar results were later obtained for octatetraene , where six of the twenty possible rotamers are formed on ionization in argon (Figure 31) which could be interconverted and identified by selective photolysis . Interestingly, in the case of the butadiene radical cation the s-cis rotamer could not be detected, even if the diene radical cation was formed from the cyclobutene radical cation . In contrast, in a recent resonance Raman study, some weak bands were detected and assigned to the s-cA-butadiene radical cation which might have escaped detection in the earlier ESR and EA experiments . ... 

As the origin of the occurrence of the quantum chain process in the isomerization of the dienes and trienes above, energy transfer from their excited triplet states to their ground states of the s-cis form was proposed. Compared to s-trans rotamers, s-cis rotamers have lower triplet energies and are more readily excited, although less populated in the ground state. For example, the following reaction may proceed [82] ... 

However, substitution of a phenyl or a naphthyl group on the terminal carbon of 2-vinylanthracene inhibits single-bond rotation in the excited singlet state. Irradiation of trans-6c and 6d with 316-nm laser light excites both s-trans and s-cis rotamers to give fluorescence of both rotamers. The... 

Lunazzi et al. have determined the conformation of 2,2 -bithienyl by means of a liquid crystal (nematic phase) NMR study (73JCS(P2)751) they found 78% of s-trans and 22% of s-cis rotamers (the estimated interconversion barrier is about 20 kj mol , see Section 2.9). The same compound using the same approach was studied by Khetrapal and Kunwar (74MP (28)441), the 0 angles determined by X-ray (Section 2.1) and electron diffraction (Section 2.2) are 0° and 34°, respectively they concluded that 2,2 -bithienyl is a mixture of cis- and frans-planar structures but they were unable to calculate the proportions (for theoretical calculations, see Section 2.14.3). 

The stereoelectronic nature of the observed trends in the J values is consistent with the conformational dependence of this NMR parameter in formate esters. For seven alkyl formates, the more abundant s-cis rotamer had jj 7 Hz greater relative to that in the minor s-trans conformed In the s-trans geometry, the interaction weakens the C-H bond and decreases the magnitude of C-H spin coupling... 

Access to Dieno-Pyranosides. We were interested in developing synthetic schemes to dieno-pyranosides V (Figure 3a), and dieno-pyranosides VI. Systems type V are less reactive fiian their demethylated analogs VI (6) (the steric interaction of the methyl group with the vinyl residue causes the s-cis rotamer required for the... 

The case of a, -unsaturated caAonyl compounds is analogous to that of 1,3-dienes, in that stereoelectronic factors favor coplanaiity of the C=C—C=0 system. The rotamers that are important are the s-trans and s-cis conformations. Microwave data indicate that the s-trans form is the only conformation present in detectable amounts in acrolein (2-propenal). The equilibrium distribution of s-trans and s-cis conformations of a,fi-unsatuiated ketones depends on the extent of van der Waals interaction between substituents. Methyl vinyl ketone has minimal unfavorable van der Waals repulsions between substituents and exists predominantly as the s-trans conformer ... 

The absolute stereochemistry for 150 (entries 2 and 3) was determined by hydrolysis and conversion to known compounds. Assuming a tetrahedral or cis octahedral geometry for the magnesium [110], the product stereochemistry is consistent with si face radical addition to an s-cis conformer of the substrate. This is the same sense of selectivity as that obtained with oxazo-lidinone crotonates or cinnamates suggesting that the rotamer geometry of the differentially substituted enoates is the same. The need for stoichiometric amount of the chiral Lewis acid to obtain high selectivity with 148 in contrast to successful catalytic reactions with crotonates is most likely a reflection of the additional donor atom present in the substrate. 

The use of chiral auxiliaries to induce (or even control) diastereoselectivity in the cycloaddition of nitrile oxides with achiral alkenes to give 5-substituted isoxazolines has been investigated by a number of groups. With chiral acrylates, this led mostly to low or modest diastereoselectivity, which was explained in terms of the conformational flexibility of the vinyl-CO linkage of the ester (Scheme 6.33) (179). In cycloadditions to chiral acrylates (or acrylamides), both the direction of the facial attack of the dipole as well as the conformational preference of the rotamers need to be controlled in order to achieve high diastereoselection. Although the attack from one sector of space may well be directed or hindered by the chiral auxiliary, a low diastereomer ratio would result due to competing attack to the respective 7i-faces of both the s-cis and s-trans rotamers of the acrylate or amide. 

The photoisomerization of all-s-trans-all-trans 1,3,5,7-octatetraene at 4.3 K illustrates the need for a new mechanism to explain the observed behavior [150]. Upon irradiation, all-s-trans-all-trans 1,3,5,7-octatetraene at 4.3 K undergoes conformational change from all-s-trans to 2-s-cis. Based on NEER principle (NonEquilibrium of Excited state Rotamers), that holds good in solution, the above transformation is not expected. NEER postulate and one bond flip mechanism allow only trans to cis conversion rotations of single bonds are prevented as the bond order between the original C C bonds increases in the excited state. However, the above simple photochemical reaction is explainable based on a hula-twist process. The free volume available for the all-s-trans-all-trans 1,3,5,7-octatetraene in the //-octane matrix at 4.3 K is very small and under such conditions, the only volume conserving process that this molecule can undergo is hula-twist at carbon-2. 

The PES for rotation around the C—C bond of 58, M=Si, Ge (Figure 18) shows two minima the s-trans and the gauche, while the s-cis structure is a saddle point that connects two gauche enantiomers. The gauche rotamer is by ca 4333 and 3 kcal mol-1335 for 58, M = Si, Ge, respectively, less stable than the s-trans rotamer, an energy difference very similar to that in 1,3-butadiene. However, the rotation barrier about the central C—C bond in 58, M = Si and Ge, of ca 10-11 and 9.5 kcalmol-1, respectively, is... 

The stereochemistry of the adduct 113a, obtained as major under thermal conditions, indicates that it is derived from endo-approach to conformation A. It suggests that rotamers with the sulfinyl oxygen in s-cis arrangement (B in Fig. 10) are not the most populated in the conformational equilibrium, even though they are favored upon electrostatic grounds. The higher stability of con-... 

Recently a comparative study of the asymmetric Diels-Alder reactions of both (5)-benzyl 2-p-tolylsulfinylacrylate (167) and (S)-benzyl methyl 2-p-tolylsulfinyl maleate (168) was carried out.104 Consequently, improved mechanistic models were developed in order to explain the behavior of such sulfinyl maleate and acrylate dienophiles in asymmetric Diels-Alder reactions.104 It was postulated that conformational equilibrium around the C-S bond must be completely shifted toward the rotamer with the sulfinyl oxygen in an s-cis arrangement (the most stable from an electrostatic point of view), making favored approach of the diene from the less hindered upper face supporting the lone electron pair (Fig. 7). The chelation of the sulfinyl and carbonyl oxygens with metals shifts the conformational equilibria... 

Higher selectivities are generally obtained in the presence of a Lewis acid as the reactive conformation is essentially locked into place. The reaction in the absence of a Lewis acid, in contrast, is prone to rotamer control problems as the. v-trans to s-cis interconversion can result in lower selectivities depending on the size of substituents and reaction temperatures. Larger substituents and lower reaction temperatures counteract the s-trans to s-cis rotation. 

Since little anti-form is present under equihbrium conditions (without irradiation) in Mo(NAr )(CHR)(OCMe(CF3)2)2, and syn- into anti-conversion is slow (ca. 10 s ), cis-polymers are proposed to form from the syn-species of a catalyst via olefin attack on the CNO-face of the initiator [94]. In a t-butoxide system, where interconversion is relatively fast (ca. 1 s ), it was proposed that the anti-form was the only propagating alkylidene species. This proposal was further supported by studies carried out by Feast and co-workers [100]. Using sterically hindered and therefore unreactive monomers such as 1,7,7-trimethylnorbornene, only the reaction of the anti-rotamer at a very slow, monomer concentration-independent rate was observed. Additionally, the calculated rate constant was essentially identical with the one for syn-anti[Pg.165]

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